Band 16, Heft 1

Zymogen granule protein 16B (ZG16B) has been identified in various cancers, while so far the association between ZG16B and breast cancer hasn’t been explored. Our aim is to confirm whether it can serve as a prognostic biomarker in breast cancer. In this study, Oncomine, Cancer Cell Line Encyclopedia (CCLE), Ualcan, and STRING database analyses were conducted to detect the expression level of ZG16B in breast cancer with different types. Kaplan–Meier plotter was used to analyze the prognosis of patients with high or low expression of ZG16B. We found that ZG16B was significantly upregulated in breast cancer. Moreover, ZG16B was closely associated with foregone biomarkers and crucial factors in breast cancer. In the survival analysis, high expression of ZG16B represents a favorable prognosis in patients. Our work demonstrates the latent capacity of ZG16B to be a biomarker for prognosis of breast cancer.

Objective The aim of this study is to examine the clinical features of patients with Behçet’s disease (BD) in the presence or absence of latent tuberculosis infection (LTBI). Methods This was a retrospective study of 232 consecutive patients with active BD hospitalized between October 2012 and June 2017. LTBI was diagnosed based on the positive T-SPOT.TB assay, negative clinical, and imaging examinations. Results Among the 232 patients, 68 (29.3%) had LTBI. The frequency, number, and scope of oral ulcers in the BD-LTBI group were significantly more serious than in the non-LTBI group (all P < 0.05). Genital ulcers and eye involvement in the LTBI group were significantly higher than in the non-LTBI group (both P < 0.01). No active TB was diagnosed during follow-up (median, 27.9 months; range, 3–58 months). The patients with LTBI had signs of liver damage compared with the non-LTBI group. In the LTBI group, the frequency of alanine transaminase >2.0, the upper limit of normal, was higher in the rifampicin subgroup compared with the non-rifampicin subgroup ( P = 0.033). Conclusion Patients with BD and LTBI had worse clinical features than those with BD without LTBI. Rifampicin might be associated with the damage to liver in BD patients combined with latent TB.

This paper aimed to research the function and in-depth mechanism of GPR37 in lung adenocarcinoma (LUAD). Herein, based on TCGA and Oncomine databases, we revealed that GPR37 was expressed at high levels in LUAD, and upregulation of GPR37 was related to the poor outcomes. Furthermore, biological function experiments in vitro were utilized to assess whether GPR37 impacts malignant phenotype of LUAD cells. Gain- or loss-of-function assays indicated that the upregulation of GPR37 contributed to improving the proliferation, migration, and invasion of LUAD cells in vitro , while knockdown of GPR37 can inhibit the malignant biological behaviors. Then, we found that depletion of GPR37 resulted in a decrease in the expression of TGF-β1 as well as the extents of Smad2 and Smad3 phosphorylation, while overexpression of GPR37 presented opposite outcomes. Altogether, our findings indicated that GPR37 is a potential oncogene of LUAD, and its promoting effects on the malignant progression of LUAD may be realized via TGF-β/Smad pathway.

In this research, we attempted to explain the effect and the related molecular mechanisms of ABIN1 in lipopolysaccharide (LPS)-induced septic mice or RAW264.7 macrophages. LPS was adopted to treat RAW264.7 macrophages for 4 h, and the levels of inflammatory factors were assessed by ELISA. Besides, ABIN1 expression was measured by quantitative reverse transcription polymerase chain reaction. Apparently, LPS enhanced immunoreaction, suggested by increased expression of IL-1β, tumor necrosis factor (TNF)-α, and IL-6. ABIN1 levels were obviously reduced compared to the control. Furthermore, we evaluated the roles of ABIN1-plasmid in immunoreaction and nuclear factor-κB (NF-κB) pathway. We found that ABIN1-plasmid significantly reduced the expression of IL-1β, TNF-α, and IL-6 in LPS-treated cells and inhibited NF-κB pathway activation. Meanwhile, a septic mouse mode was conducted to validate the role of ABIN1 in inflammatory response and organ damage in vivo . These data suggested that ABIN1-plasmid significantly inhibited the secretion of inflammatory cytokines and Cr, BUN, AST, and ALT levels in the serum of LPS-stimulated mice compared to LPS + control-plasmid group, reflecting the relieved inflammation and organ injury. In summary, the present findings indicated that ABIN1 alleviated sepsis by repressing inflammatory response through NF-κB signaling pathway, emphasizing the potential value of ABIN1 as therapeutic strategy for sepsis.

Pneumonia associated with coronavirus disease 2019 (COVID-19) has been accounted for high mortality rate in severe COVID-19 worldwide, and additional serious scarcity of standard and effective anti-inflammatory drug in COVID-19 pneumonia management is a big challenge. Baricitinib, a Janus kinase (JAK) inhibitor, is a promising drug in COVID-19 pneumonia. This study aims to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥95% (in room air) and return in normal breathing function were lower in case group than the control group. The requirement of intensive care unit and mechanical ventilation support was higher in the control group than in the case group [29.4% ( N = 17)/10% ( N = 20), P < 0.05; 11.8% ( N = 17)/5% ( N = 20), P > 0.05), respectively]. Thus, an additional loading dose of baricitinib revealed better clinical outcome of patients with COVID-19 pneumonia.

Objective The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism. Methods Sprague-Dawley (SD) rats ( n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion. Results In vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+d p /d t max ), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−d p /d t max ) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells. Conclusion The combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

Bladder cancer is the most common malignant tumor of the urinary system. The intention of the present research is to explore the prognostic value and biological function of solute carrier family 12 member 8 (SLC12A8) in bladder cancer. The analysis based on the TCGA and ONCOMINE database revealed that the expression of SLC12A8 in bladder cancer was notably increased compared with the normal group. SLC12A8 expression was notably correlated with the age, pathological stage, T-stage, and lymph node metastasis of bladder cancer patients. Moreover, the patients’ overall survival was notably shorter in the high SLC12A8 group. Compared with the control, SLC12A8 upregulation enhanced the proliferative, invasive, and migratory capacities of bladder cancer cells and promoted the expression of epithelial–mesenchymal transition (EMT) protein markers including β-catenin, vimentin, snail, and slug, while reduced the expression of E-cadherin. In the case of downregulated SLC12A8 expression, the proliferative, invasive, and migratory capacities of bladder cancer cells and the expression of EMT protein markers presented the opposite trend. This study demonstrated that SLC12A8 was highly correlated with oncogenesis and progression of bladder cancer, indicating that SLC12A8 may be a meaningful biomarker for initial diagnosis and early treatment of bladder cancer.

Background Tamoxifen (TAMR) resistance remains a massive obstacle for breast cancer (BC) management. The precise parts of long non-coding RNA ataxin 8 opposite strand (ATXN8OS) in BC TAMR resistance have not been defined. Methods The levels of ATXN8OS, vasodilator-stimulated phosphoprotein (VASP), and miR-16-5p were assessed by quantitative real-time polymerase chain reaction or western blot. Colony formation and cell viability were analyzed by MTT and colony formation assays, respectively. Targeted interactions among miR-16-5p, ATXN8OS, and VASP were confirmed by dual-luciferase reporter assay. Animal studies were performed to observe the role of ATXN8OS in TAMR sensitivity in vivo . Results ATXN8OS expression was increased in BC tissues and cells. ATXN8OS depletion promoted BC cell sensitivity to TAMR. ATXN8OS sequestered miR-16-5p by directly binding to miR-16-5p. The promotional effect of ATXN8OS knockdown on BC cell TAMR sensitivity was mediated by miR-16-5p. VASP was a direct target of miR-16-5p, and miR-16-5p overexpression enhanced TAMR sensitivity by VASP. Moreover, ATXN8OS regulated VASP expression by acting as a miR-16-5p sponge. In addition, ATXN8OS knockdown augmented BC TAMR sensitivity in vivo . Conclusion ATXN8OS knockdown enhanced BC TAMR sensitivity partially through the miR-16-5p/VASP axis, highlighting a potential therapeutic target for improving the clinical benefits of TAMR treatment in BC patients.

Several Serratia species are widely distributed in nature, but Serratia marcescens is the only species frequently isolated in hospitals. This pathogen is mainly responsible for nosocomial infection, mostly in immunocompromised hosts. A 26-year-old woman with a twin pregnancy, regularly controlled, was hospitalized at 24 + 5 weeks of gestation due to scant vaginal bleeding, lower abdominal pain, and body temperature up to 37.5°C. Gynecological examination revealed bleeding accompanied by dilatation of the cervix. The laboratory analyses revealed leukocytosis with elevated C-reactive protein (CRP). Treatment was initiated with intravenous antibiotic administration. After admission, fetal membranes spontaneously ruptured, and an extremely preterm dichorionic female twin birth occurred at 25 + 0 weeks of gestation. Both infants died two days after labor. Pathological and microbiological analyses revealed chorioamnionitis caused by S. marcescens . According to the antibiogram, antibiotic treatment was continued for the next 7 days. The examination of cervical and vaginal discharge samples was negative three days and two weeks after therapy. S. marcescens may cause spontaneous miscarriages and, in this important case, caused loss of discordant twins in an extremely preterm birth by an immunocompetent patient. Infection by S. marcescens cannot be excluded as a cause of discordant growth and needs to be confirmed by further research.

Foci of splenic tissue separated from the spleen can occur as a congenital anomaly. Isolated nodules of splenic tissue are called accessory spleens or spleniculli. However, nodules of splenic tissue can merge with other organs during embryonic development, in which case we speak of spleno-visceral fusions: most often, they merge with the tail of the pancreas (thus forming spleno-pancreatic fusion or an intrapancreatic accessory spleen), with the reproductive gland (i.e., spleno-gonadal fusion), or with the kidney (i.e., spleno-renal fusion). Our case report describes the fusion of heterotopic splenic tissue with the right adrenal gland, which was misinterpreted as a metastasis of a renal cell carcinoma. To the best of our knowledge, this is the first reported case of spleno-adrenal fusion. Spleno-visceral fusions usually represent asymptomatic conditions; their main clinical significance lies in the confusion they cause and its misinterpretation as tumors of other organs. We believe that the cause of retroperitoneal spleno-visceral fusions is the anomalous migration of splenic cells along the dorsal mesentery to the urogenital ridge, together with primitive germ cells, at the end of the fifth week and during the sixth week of embryonic age. This theory explains the possible origin of spleno-visceral fusions, their different frequency of occurrence, and the predominance of findings on the left side.

Background Acute myeloid leukemia (AML) is a ubiquitous malignancy that occurs in the hematological system. Tripartite motif-containing 25 (TRIM25) has been found to be involved in various carcinomas comprising AML. However, the function and underlying causative role of TRIM25 in AML are still obscure. Methods and materials Quantitative real-time polymerase chain reaction (qPCR) was used for assaying TRIM25 and miR-137 expression in AML samples and cells. CCK-8 assay, Calcein-acetoxymethylester/propidium iodide staining, and Transwell assay were adopted to assay cell proliferation, invasion, and migration. Dual-luciferase reporter experiment was used for analyzing the interaction of TRIM25 with miR-137. Western blot was used for assaying protein expression levels. Results This study confirmed that TRIM25 expression was upregulated in AML samples and cell lines, whereas miR-137 expression was downregulated. Overexpression of TRIM25 significantly contributed to AML cell’s proliferation, invasion, and migration, whereas knockdown exerted the opposite effect. In addition, TRIM25 was a downstream target of miR-137 in AML cells and negatively modulated by miR-137. Conclusion TRIM25 was targeted and regulated by miR-137, exerted a carcinogenic function in AML, and could be used as a latent biomarker and a treatment target for AML.

Background The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC. Methods The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro , while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo . We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities. Conclusion Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

Long noncoding RNAs (lncRNAs) have been verified as vital regulators in human disease, including atherosclerosis. However, the precise role of X-inactive-specific transcript (XIST) in atherosclerosis remains unclear. The proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to low-density lipoprotein (ox-LDL) were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H -tetrazol-3-ium bromide, and flow cytometry assays, correspondingly. The western blot assay was used to quantify protein expression. Lactate dehydrogenase activity and the concentrations of inflammatory factors were measured by matched kits. The real-time quantitative polymerase chain reaction (qPCR) was used to determine α-smooth muscle actin, smooth muscle protein 22-α, XIST, miR-98-5p, and pregnancy-associated plasma protein A (PAPPA) levels in HUVECs. The relationship among XIST, miR-98-5p, and PAPPA was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. We found ox-LDL repressed proliferation and induced inflammation and apoptosis in HUVECs. Loss-of-functional experiment suggested that the downregulation of XIST overturned the ox-LDL-induced effects on HUVECs. Additionally, overexpression of miR-98-5p-induced effects on ox-LDL-stimulated HUVECs was abolished by upregulation of XIST. However, silencing of miR-98-5p strengthened the ox-LDL-induced effects on HUVECs by increasing expression of PAPPA. Mechanistically, XIST could regulate PAPPA expression in ox-LDL-induced HUVECs by sponging miR-98-5p, providing understanding for atherosclerosis.

Not fully maturated immune system in preterm neonates may contribute to the increased susceptibility to infection. The levels of some cytokines can be useful in the prediction and diagnosis of sepsis in premature neonates. In the present study, we evaluated the potential predictive role of IFN-γ and IL-5 in cord and venous blood, together with the determination of C-reactive protein and procalcitonin (PCT) for sepsis development in premature neonates. A total of 80 participants were included. The laboratory results and clinical histories showed that 21 participants had sepsis. Early onset sepsis was detected in 3 patients while late onset sepsis was observed in 18 participants. The venous plasma levels of IFN-γ and PCT was markedly increased in sepsis groups when compared to the participants without sepsis. On the other hand, levels of IL-5 did not significantly change in the evaluated groups of sepsis and in the control group of participants. Simultaneously, plasma venous levels were not altered in any of the evaluated groups. Obtained findings suggest that venous plasma levels of IFN-γ, rather than levels of IFN-γ in cord blood plasma, and PCT may have predictive potential for sepsis development in preterm neonates. Further studies are necessary to get more comprehension of the complex function of cytokines for sepsis development in preterm neonates.

While countries are in a hurry to obtain SARS-CoV-2 vaccine, we are concerned with the availability of vaccine and whether a vaccine will be available to all in need. We predicted three possible scenarios for vaccine distributions and urge an international united action on the worldwide equitable access. In case the international community does not reach a consensus on how to distribute the vaccine to achieve worldwide equitable access, we call for a distribution plan that includes the employees in international transportation industries and international travelers to halt the disease transmission and promote the recovery of the global economy.

Case presentation In the current study, we report a 69-year-old female patient who was initially diagnosed with xanthogranulomatous pyelonephritis (XGPN) with nephrolithiasis and a peri-renal abscess. She presented to our department with right flank pain. Physical examination revealed right costovertebral angle knocking pain and computed tomography revealed dilated calyces and one staghorn stone over right kidney, with multiple abscess accumulations over the right peri-renal region. Right radical nephrectomy was performed using a transperitoneal flank approach, and pathology revealed squamous cell carcinoma (SCC) with concurrent XGPN. The patient was alive at 4 months post-operative follow-up. To the best of our knowledge, this is only the fifth case of renal SCC with concurrent XGPN reported in the English medical literature. Conclusion Renal SCC with coexisting XGPN is an extremely rare presentation and only four cases have been previously reported in the English medical literature. A positive diagnosis for this rare combination of diseases was established, based on pathological and immunohistochemical examinations after radical nephrectomy. Poor prognosis has been reported in such cases. Malignancies should be considered in patients with a long-standing history of urolithiasis.

Primary renal carcinoid tumors are exceedingly rare. We report a 37-year-old woman with primary infertility, who was found to have a primary renal carcinoid tumor. She became pregnant and gave birth to a baby after removal of the tumor. This is the first case in the English literature of primary renal carcinoid tumor related with primary infertility.

Hypertension is associated with body mass index (BMI) and cardiovascular and cerebrovascular diseases (CCDs). Whether hypertension modifies the relationship between BMI and CCDs is still unclear. We examined the association between BMI and CCDs and tested whether effect measure modification was present by hypertension. We identified a population-based sample of 3,942 participants in Shuncheng, Fushun, Liaoning, China. Hypertension was defined as any past use of antihypertensive medication or having a measured systolic/diastolic blood pressure ≥130/80 mm Hg. BMI was calculated from measured body weight and body height. Data on diagnosed CCDs were self-reported and validated in the medical records. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between BMI and CCDs. Higher BMI was associated with increased odds of having CCDs (OR = 1.19, 95% CI: 1.07–1.31). This association was significantly modified by hypertension ( P for interaction <0.001), with positive associations observed among hypertensive individuals (OR = 1.28, 95% CI: 1.14–1.42). Age, sex, and diabetic status did not modify the relationship between BMI and CCDs (all P for interaction >0.10). Although higher BMI was associated with increased odds of CCDs, the relationship was mainly limited to hypertensive patients.

Background Cohen syndrome (Q87.8;ORPHA:193; OMIM#216550) is an autosomal recessive inherited genetic disorder caused by mutation in the VPS13B/COH1 gene. It is characterized by variable clinical symptoms such as deformity of the head, face, hands and feet, eye abnormalities, abdominal obesity, neutropenia and nonprogressive intellectual disability. The typical lesions in the eyeball in Cohen syndrome include high myopia, retinal dystrophy, strabismus, maculopathy and lens subluxation. The present study describes the coexistence of bilateral macular edema with pale optic disc in a patient with a homozygous deletion in the VPS13B/COH1 gene. Material and methods A 6-year-old Caucasian girl with facial dysmorphism, microcephaly, prominent upper incisors, narrow hands with slender fingers, congenital heart defect and ophthalmic symptoms was subjected to genetic testing. The genetic evaluation revealed a homozygous deletion on the long arm of chromosome 8 encompassing 20–25 exons of the VPS13 gene, as confirmed by Cohen syndrome. She underwent a full ophthalmological examination with the assessment of slit lamp examination of anterior segment and fundoscopy, refraction error, biometry, central corneal thickness and additionally electroretinography, optical coherence tomography and fundus photography. Results In the ophthalmologic examination, the girl had bilateral astigmatism accompanied by myopia and a marked reduction in central corneal thickness. Fundus examination showed pale optic nerve discs and “salt and pepper” retinopathy. Bilateral cystic macular edema was revealed in handheld optical coherence tomography. Electroretinography showed a reduced response amplitude of cones and rods. Conclusion In a patient with high myopia, macular edema, pale optic disc and facial dysmorphism, Cohen syndrome should be considered in the differential diagnosis. The severity of individual clinical features in patients with Cohen syndrome varies. It can be assumed that the type of mutation affects the occurrence and severity of individual symptoms.

The purpose of this retrospective cross-sectional study was to examine the degrees of the cervical disc degeneration and the parameters of cervical sagittal balance in plain radiographs, representing cervical lordosis or head posture in subjects with posterior neck pain. A total of 113 patients with posterior neck pain with or without radiating pain were analyzed. The kinematic sagittal parameters of cervical radiographs were obtained at the occipito–cervical (O–C2) angle, sagittal Cobb’s angles of C1–C2, C2–C7, and sagittal vertical axis (SVA) of C1–C7 and C2–C7. Cervical disc degeneration was evaluated using the sum of Pfirrmann grades and total modified Matsumoto scores calculated from MRI of the cervical spine. A significant positive correlation was found for the C2–C7 angle using the sum of the Pfirrmann grades and total modified Matsumoto scores, whereas the O–C2 angle and the C1–C2 angle were negatively correlated. The sagittal cervical parameters representing cervical kyphosis and jaw lifting posture were found to be significantly correlated with the degree of cervical disc degeneration. These findings suggest that the loss of the natural sagittal lordosis of the cervical spine may contribute to the progression of disc degeneration, rather than the forward head posture.

Hepatoid adenocarcinoma of the lung (HAL) is a rare malignant tumor that is defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. We aimed to identify prognostic factors associated with the survival of patients with HAL using data from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients diagnosed with HAL, adenocarcinoma (ADC), and squamous cell carcinoma (SCC) of the lung between 1975 and 2016 from the SEER database. The clinical features of patients with ADC and SCC of the lung were also analyzed. The clinical features of HALs were compared to ADCs and SCCs. A chi-square test was used to calculate the correlations between categorical variables, and a t test or Mann–Whitney U test was used for continuous variables. The Kaplan–Meier method and Cox regression analysis were used to identify the prognostic factors for the overall survival (OS) of HALs. Two-tailed p values < 0.05 were considered statistically significant. Sixty-five patients with HAL, 2,84,379 patients with ADC, and 1,86,494 with SCC were identified from the SEER database. Fewer males, advanced stages, and more chemotherapy-treated HALs were found. Compared to patients with SCC, patients with HAL were less likely to be male, more likely to be in an advanced stage, and more likely to receive chemotherapy ( p < 0.05). The American Joint Committee on Cancer staging was the only prognostic factor for OS in patients with HAL, and stage IV was significantly different from other stages (hazard ratio = 0.045, 95% confidence interval: 0.005–0.398, p = 0.005). Males with HAL were more likely to receive radiotherapy compared to females with HAL (61.8 vs 31.5%, p = 0.034). Younger patients with HAL were more likely to receive chemotherapy (59.4 + 10.2 years vs 69 + 11.3 years, p = 0.001). The primary tumor size of HAL was associated with the location of the primary lesion ( p = 0.012). No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL ( p > 0.05). This study showed that stage IV was the only prognostic factor for OS in HALs compared to other clinicopathologic factors. Conventional antitumor therapies failed to show survival benefit; thus, a more effective method by which to treat HAL is needed. Interestingly, the clinical features and the location of the primary lesion were shown to be associated with primary tumor size and treatment in patients with HAL, which have not been reported before.

Introduction Carpal tunnel syndrome (CTS) is a condition caused by chronic compression of the median nerve. The diagnosis is made mainly on the basis of clinical image and confirmed with electrodiagnostic testing (electromyography and nerve conduction study); however, these methods do not always aid in reaching the diagnosis of CTS. Moreover, they are invasive examinations, unpleasant for the patient and have to be performed by a qualified physician. Aim An evaluation of the usefulness of dynamic thermography in the diagnosis of CTS. Material and methods Forty patients were included in the study group. CTS was diagnosed based on clinical examination and electromyography. Forty healthy volunteers were included in the control group. Each of the participants was examined thrice with dynamic thermography. The patient’s hands were first cooled down and then a thermal camera measured their return to normal temperature. The measurement was repeated on the dorsal and volar aspects of each hand. Results The results obtained in the study show that a relief of symptoms after carpal tunnel release does not correlate with thermal image. Moreover, the return to normal hand temperature was faster in the control group. In patients with unilateral CTS, no difference was observed in thermographic images of the affected and healthy hands. Conclusions Dynamic thermography can be useful in confirming CTS diagnosis. Dynamic thermography does not allow for objective assessment of patient’s complaints in the postoperative period. This method has currently limited clinical application. Due to complexity, it presently serves mainly scientific purposes.

Objective The aim of the present work was to investigate the clinical efficacy of first-line chemotherapy regimens in the treatment of advanced non-small cell lung cancer (NSCLC) through a comprehensive network meta-analysis (NMA). Methods The prospective randomized controlled clinical trials relevant to 10 first-line chemotherapy regimens in the treatment of advanced NSCLC were systematic electronic search in the databases of Pubmed, Embase, Cochrane Library and CNKI. The combined direct or indirect objective response rate (ORR) between each of the 10 first-line chemotherapy regimens was calculated. Results Seventeen prospective clinical trials of first-line chemotherapy regimens in treatment of advanced NSCLC were included in the NMA. The 10 treatment regimens including A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = docetaxel + carboplatin, G = gemcitabine + vinorelbine, H = pemetrexed + carboplatin, I = cisplatin + pemetrexed and J = cisplatin + docetaxel were compared in the present NMA. Direct pooled results indicated that the ORR was not statistically different ( P all > 0.05). However, NMA showed that the combined ORR for regimens A (OR = 1.47, 95% CI: 0.80–2.81), B (OR = 3.22, 95% CI: 1.45–6.923), D (OR = 3.30, 95% CI: 1.22–9.33), E (OR = 4.36, 95% CI: 1.64–12.82), G (OR = 3.72, 95% CI: 1.12–12.83) and I (OR = 5.80, 95% CI: 2.04–17.86) was superior to regimen C. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens. Conclusion Cisplatin + pemetrexed may have particularly prominent ORR for advanced NSCLC as the first-line chemotherapy regimen.

Background Autologous stem cell transplantation (ASCT) is one of the standard treatments of choice for eligible multiple myeloma (MM) patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients. Materials and methods Patients who were diagnosed as having MM and had undergone single or double ASCT in our clinic between the years 2003 and 2020 were retrospectively examined. Results In this study, the median time of second ASCT is approximately 3.6 years from the first ASCT. Overall survival (OS) duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively ( p : 0.33). Progression-free survival (PFS) duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively ( p : 0.22). Disease assessment after ASCT stable or progressive disease, partial remission, and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively ( p : 0.22). Conclusion The present study points out that the second ASCT treatment option for MM patients may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.

Background The impact of smoking on spinal surgery has been studied extensively, but few investigations have focused on minimally invasive surgery (MIS) of the spine and the difference between complication rates in smokers and non-smokers. We evaluated whether a history of at least one pack-year preoperatively could be used to predict adverse peri- and postoperative outcomes in patients undergoing minimally invasive fusion procedures of the lumbar spine. In a prospective study, we assessed the clinical effectiveness of MIS in an unselected population of 187 patients. Methods We evaluated perioperative and postoperative complication rates in MIS fusion techniques of the lumbar spine in smoking and non-smoking patients. MIS fusion was performed using interbody fusion procedures and/or posterolateral fusion alone. Results Smokers were significantly younger than non-smokers. We did not encounter infection at the site of surgery or severe wound healing disorder in smokers. We registered no difference between the smoking and non-smoking groups with regard to peri- or postoperative complication rate, blood loss, or length of stay in hospital. We found a significant influence of smoking ( p = 0.049) on the overall perioperative complication rate. Conclusion MIS fusion techniques seem to be a suitable tool for treating degenerative spinal disorders in smokers.

Background Substantial studies have demonstrated that left atrial (LA) enlargement was a robust predictor of atrial fibrillation (AF) and obesity was a modifiable risk factor for cardiovascular diseases. However, the role of body mass index (BMI) on LA dimension in hypertrophic obstructive cardiomyopathy (HOCM) remains unclear. Methods A total of 423 HOCM patients (average BMI 25.4 ± 3.4 kg/m 2 ) were recruited for our study. Participants were stratified into three groups based on BMI: normal weight (BMI < 23 kg/m 2 ), overweight (BMI 23–27.5 kg/m 2 ), and obesity (BMI ≥ 27.5 kg/m 2 ). Results Compared with normal weight, patients with obesity had significantly lower prevalence of syncope ( p = 0.007) and moderate or severe mitral regurgitation ( p = 0.014), and serum NT-proBNP ( p = 0.004). Multiple linear regression analysis indicated that BMI ( β = 0.328, p < 0.001), log NT-proBNP ( β = 0.308, p < 0.001), presence of AF ( β = 0.209, p = 0.001), and left ventricular diastolic diameter index ( β = 0.142, p = 0.019) were independently related with LA diameter. However, BMI was not an independent predictor of the presence of AF on multivariable binary logistical regression analysis. Conclusions BMI was independently associated with LA diameter; however, it was not an independent predictor of prevalence of AF. These results suggest that BMI may promote incidence of AF through LA enlargement in HOCM.

Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients ( P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group ( P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

Background Previous work has shown that miR-142-5p in cervical cancer tissues increased significantly compared with adjacent normal tissues. However, the function and the mechanism of miR-142-5p in cervical cancer have not been reported. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the gene expression levels. MTT, flow cytometry, and transwell assays were performed to explore the functions of miR-142-5p in HeLa cells. The potential target gene of miR-142-5p was investigated via luciferase reporter assays. The protein expression levels were analyzed by Western blotting. Results We found that miR-142-5p expression was elevated but LIM homeobox transcription factor 1 alpha (LMX1A) was decreased in cervical cancer tissues and cells. Overexpression of miR-142-5p or knockdown of LMX1A inhibited cell apoptosis, promoted cell proliferation, migration, invasion abilities, and activated the Wnt/β-catenin pathway. However, knockdown of miR-142-5p or overexpression of LMX1A showed opposite results. LMX1A was identified as a direct target of miR-142-5p by luciferase reporter assays. Finally, rescue experiments demonstrated that LMX1A overexpression attenuated the carcinogenic effect of miR-142-5p mimic on HeLa cells. Conclusions These findings suggested that miR-142-5p might be a cervical cancer oncogene and could serve as a potential therapeutic target for the treatment of cervical cancer.

Background The foot posture is age dependent. The purpose of this study was to investigate the relationship between the 6-item version of the foot posture index (FPI) and other clinical, foot anthropometric, radiological measurements for the foot position in 5–8-year-old children. Methods A total of 301 participants with a mean age of 6.4  ±  1.14 years were enrolled in the study. Children were examined physically, clinically, and radiologically to measure the FPI and navicular drop (ND) test, resting calcaneal stance position (RCSP) angle, Chippaux–Smirak index (CSI), Staheli index (SI), calcaneal pitch (CP) angle, talocalcaneal angle (TCA), and the first lateral metatarsal angle. Tibial torsions, internal rotation of the hip as an indirect method of femoral anteversion, and Beighton scale were analyzed for factors associated with flatfoot prevalence. Results The study included children with normal and flexible flatfeet. Statistical analysis showed a significant FPI score correlation with other parameters (SI, CSI, RCSP, ND, CP, TMA, and TCA showed strong and moderate correlations, p < 0.001). Overall, the strongest associates are CSI ( β = 0.34) and ND ( β = 0.28). Other indicators have relatively small relationships with the FPI. Conclusion A positive correlation was observed between FPI-6 and ND test, CSI in 5–8-year-old children. All three prominent foot posture indicators (FPI-6, ND, and CSI) might be used as a primary or preferred tool in clinical practice.

Aim To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients. Methods The earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed. Results We found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group ( p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS. Conclusion LA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH.

Objective The purpose of this study was to clarify the value of intestinal fatty acid-binding protein (I-FABP) for the early diagnosis of strangulated intestinal obstruction through a meta-analysis. Methods A search was performed on PubMed, EBSCO, the Cochrane Library, the Web of Science, EMBASE, CNKI, and WanFang for studies on the diagnosis of strangulated intestinal obstruction based on I-FABP. Endnote X9 software and the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) were used to screen the studies and evaluate their quality, respectively. Meta-Disc 1.4 and Stata 15.1 software were used to perform the assessment of heterogeneity and meta-analysis. Result A total of eight studies were included, Spearman correlation coefficient was 0.703 ( P = 0.078), suggesting that there was no threshold effect. The pooled results of the meta-analysis were as follows: sensitivity: 0.75 (95% CI: 0.66–0.81), specificity: 0.83 (95% CI: 0.71–0.91), positive likelihood ratio (PLR): 4.35 (95% CI: 2.57–7.36), negative likelihood ratio (NLR): 0.31 (95% CI: 0.24–0.39), and diagnostic odds ratio (DOR): 14.19 (95% CI: 8.08–24.92). The area under the curve was 0.83. There was obvious heterogeneity among the studies. Conclusion I-FABP is very valuable for the early diagnosis of strangulated intestinal obstruction and can be used to distinguish strangulated intestinal obstruction from intestinal obstruction in a timely manner, enabling accurate planning of the timing of surgery.

Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.

Background and objective This study deals with an important issue of setting the role and value of the dynamic computed tomography (CT) perfusion analysis in diagnosing pancreatic ductal adenocarcinoma (PDAC). The study aimed to assess the efficacy of perfusion CT in identifying PDAC, even isodense or hardly depicted in conventional multidetector computed tomography. Methods A total of 56 patients with PDAC and 56 control group patients were evaluated in this study. A local perfusion assessment, involving the main perfusion parameters, was evaluated for all the patients. Sensitivity, specificity, positive, and negative predictive values for each perfusion CT parameter were defined using cutoff values calculated using receiver operating characteristic curve analysis. We accomplished logistic regression to identify the probability of PDAC. Results Blood flow (BF) and blood volume (BV) values were significant independent diagnostic criteria for the presence of PDAC. If both values exceed the determined cutoff point, the estimated probability for the presence of PDAC was 97.69%. Conclusions Basic CT perfusion parameters are valuable in providing the radiological diagnosis of PDAC. The estimated BF and BV parameters may serve as independent diagnostic criteria predicting the probability of PDAC.

In rotator cuff repair, strong and reliable suturing is necessary to decrease failure rates. The biomechanics of two self-cinching stitches – the single-loop knot stitch (SLKS) and the double-loop knot stitch (DLKS) – and the modified Mason-Allen stitch (mMAS) were compared. Twenty-seven porcine infraspinatus tendons were randomized among the three stitches. Each was cyclically loaded (10–80–200 N for 50 cycles each) while the gap formation was measured. Next, ultimate load to failure was tested. The gap widths after cyclic loading were 8.72 ± 0.93 mm for the DLKS, 8.65 ± 1.33 mm for the mMAS, and 9.14 ± 0.89 mm for the SLKS, without significant differences. The DLKS showed the highest ultimate load (350.52 ± 38.54 N) compared with the mMAS (320.88 ± 53.29 N; p = 0.304) and the SLKS (290.54 ± 60.51 N; p < 0.05). The DLKS showed similar reliability and better strength compared with the mMAS, while the SLKS showed a slight but not significant decrease in performance. In our experience, the DLKS and SLKS have clinical advantages, as they are easy to perform and the self-cinching loop knot allows the surgeon to grasp degenerative tendon tissue. Initial intraoperative tightening of the suture complex (preloading) before locking is important in order to decrease postoperative elongation.

Mannose-binding lectin (MBL) and lectin complement pathway have become targets of increasing clinical interest. Many aspects of MBL have been recently explored, including the structural properties that allow it to distinguish self from non-self/altered-self structures. Experimental evidences have declared the additional 5′- and 3′-variants that in amalgamation with well-known secretor polymorphisms change MBL function and concentration. Moreover, the current review highlights the differential behavior of MBL on exposure with extra/intracellular pathogens and in autoimmune diseases, stressing the fact that “high MBL levels can increase diseases susceptibility,” a paradox that needs justification. Attributable to these discrepancies, no absolute level of MBL deficiency could be defined so far and thus must be interpreted for specific diseases through case–control population-specific designs. Overall, it is evident that further research is needed about MBL and the lectin pathway of complement. Particularly, the transformative role of MBL over evolution is of interest and its role with regard to pathogenesis of different diseases and potential therapeutic targets within the respective pathways should be further explored. Apart from this, it is necessary to adopt an extensive locus-wide methodology to apprehend the clinical significance of MBL2 polymorphisms in a variety of infectious diseases by the future studies.

Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans . The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

Chromosomal inversion is closely related to male infertility. Inversion carriers may produce abnormal gametes, which may lead to partial duplication/deletion of the embryonic chromosome and result in spontaneous abortion, a fetus with multiple anomalies, or birth of a malformed child. Genetic counselling remains challenging for these carriers in clinical practice. We report two male carriers with inversion of chromosome 10 and review 26 reported cases. In the first case, 46,XX,inv(10)(p13q22) of the fetal chromosome was found in prenatal diagnosis; this was inherited from the paternal side with 46XY,inv(10)(p13q22). Another case was a male carrier with inv(10)(q21.2q22.1). There have been 25 (89.3%) cases of pericentric inversion and three (10.7%) cases of paracentric inversion involving chromosome 10. Of 28 cases, nine were associated with pregestational infertility of the couples, while the other 19 cases were associated with gestational infertility of the couples or normozoospermia. The breakpoints at 10p15, 10p11, 10q11, and 10q21 were associated with pregestational infertility of the couples. The breakpoints at 10p15, 10p14, 10p13, 10p12, 10p11, 10q11, 10q21, 10q22, 10q23, 10q24, 10q25, and 10q26 were related to gestational infertility of the couples or normozoospermia. Although there is a high risk of infertility or recurrent miscarriages, carriers with inversion of chromosome 10 might produce healthy offspring. Natural pregnancy can be used as a choice for inversion carriers with recurrent spontaneous abortion.

Pleural effusions are rarely observed in association with acute myeloid leukemia (AML), and their true incidence remains unknown. Given the low diagnostic yield from cytopathologic analysis of malignant pleural effusions and the fact that patients with leukemia are often thrombocytopenic and unable to tolerate invasive procedures, the incidence of leukemic effusions may be underestimated. Here, we report a rare case of pleural effusion in a patient with newly diagnosed AML. Initial analysis revealed an exudative, lymphocyte-predominant effusion. High levels of adenosine deaminase (ADA) were detected in pleural fluid, consistent with a diagnosis of tuberculosis. However, the analysis of pleural cytology revealed leukemic cells, permitting the diagnosis of leukemic effusion to be made. The patient underwent induction chemotherapy and pleural effusion resolved without recurrence. This case emphasizes the diagnostic dilemma presented by high levels of ADA in a leukemic pleural effusion, as this association has not been previously considered in the literature.

Primary renal extra-skeletal Ewing sarcoma is a rare neoplasm, often metastatic at diagnosis, and with a poor outcome. A multimodal approach is often the treatment of choice in this aggressive neoplasm. We present a case of primary renal extra-skeletal sarcoma in a 45-year-old woman who underwent tumor resection without clear margins. After no response to the first cycle of chemotherapy, we documented an early onset of local recurrence. The patient refused any other treatment and died four months after surgery.

Objective The aim of this study is to evaluate the clinicopathological features and the treatment of the Burkitt-like lymphoma with 11q aberration. Methods We reported two patients with Burkitt-like lymphoma with 11q aberration: a 56-year-old man with AIDS (case 1) and a 37-year-old woman (case 2) without AIDS. The biopsy of cervical lymph nodes showed Burkitt-like morphologic and immunophenotypic features. But both of them lack MYC rearrangement and carry an 11q-arm aberration with proximal gains and/or telomeric losses. The diagnosis was confirmed by pathological morphology, immunohistochemistry, and fluorescence in situ hybridization. Result After a cycle of R-CTOEP (rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisone) chemotherapy, case 1 refused to chemotherapy and radiotherapy and was followed up for 34 months without recurrence and new focus. Case 2 received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for two cycles and achieved PR (partial response). Then, the patient in case 2 received EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) for three cycles, and the right cervical mass disappeared. She achieved complete response and was followed up for 16 months without recurrence and new focus. Conclusion Burkitt-like lymphoma with 11q abnormalities resembles Burkitt lymphoma morphologically but lacks MYC rearrangement and may have a better prognosis.

Background In this study, a rare case with hemophilia pseudotumor in the skull was reported. Case presentation The case was a 34-year-old male patient who was admitted to the hospital, with the complaint of dizziness for more than 1 month. The physical examination indicated that the patient was conscious, who could give right answers to the questions. Moreover, there was a bulge on the left frontal-temporal parietal bone. The head CT showed abnormal density lesions on the left frontal-temporal parietal bone, with multiple irregular calcifications within the border. Skull MRI showed a large clump-like mixed signal at the top of the left frontal ridge. After admission, the patient was subjected to complete preoperative preparation and surgical treatment. Neurological navigation was used to determine the extent of skull defect before surgery to make a surgical incision. Clotting factor VIII substitution therapy was used for the intraoperative and postoperative treatments. The lesion was completely removed. Conclusions These results suggest that the skull hemophilia pseudotumor has been rarely seen. According to imaging examination, in combination with family history, the diagnosis can be confirmed. If there is no obvious occupying effect, conservative treatment can be tried. On the contrary, if there is an obvious occupying effect, surgical treatment might be effective, and coagulation factor VIII should be supplemented during the perioperative period.

Inflammation-mediated lung injury in severe cases of infection with SARS-CoV-2, the aetiological agent of Coronavirus disease 2019 (COVID-19), can lead to respiratory failure and death, and therapies that block or ameliorate lung injury-associated inflammatory “cytokine storms” and progression to acute respiratory distress syndrome (ARDS) are urgently needed. Therapeutic use of corticosteroids for this purpose has been controversial because of conflicting reports on their efficacy and immunosuppressive behaviour. The WHO has strongly recommended treating critical COVID-19 patients with systemic corticosteroid therapy, but recommends against corticosteroid therapy in non-severe COVID-19 disease because of a lack of strong evidence on its efficacy. This retrospective case report describing the successful treatment of a non-severe COVID-19 case in Changchun, China, by judicious administration of corticosteroids using a personalized therapeutic approach was recorded to strengthen the evidence base showing how corticosteroid use in non-severe COVID-19 cases can be safe and efficacious. Alongside supportive care and lopinavir/ritonavir antiviral drugs, a low dosage of methylprednisolone was administered over a short period to attenuate lung inflammation. Regular chest CT scans guided dosage reduction in response to lesion absorption and improved lung condition. Judicious use of corticosteroids safely attenuated disease progression and facilitated rapid and complete recovery.

Adult-onset citrullinaemia type II (CTLN2) is a rare disease in Chinese patients. As a subtype of citrin deficiency (CD), it is an autosomal recessive disease related to the SLC25A13 mutation on chromosome 7q21.3. In this study, we report a case of CTLN2 presenting with paroxysmal altered consciousness and refractory hyperammonaemia. The diagnosis was finally confirmed by gene analysis. The patient recovered after liver transplantation. It can be learned from this case that CD should be considered in patients with refractory hyperammonaemia and paroxysmal mental disorder without a history of liver disease.

Background Good’s syndrome (GS) is an immunodeficiency disease, causing thymoma, low or absent B-cells, hypogammaglobulinemia, and defects in cell-mediated immunity. The most common clinical presentation is recurrent infection, followed by refractory diarrhea, due to the immunodeficiency. However, there are only few reports on intestinal endoscopy and pathology. Case summary We report here two typical GS cases with diarrhea as the prominent manifestation. Both cases presented with thymoma combined with immunodeficiency, characterized by hypogammaglobulinemia, low or absent B lymphocytes, and decreased T-cells with inverted CD4 + /CD8 + T-cell ratio, while two GS patients were evaluated by endoscopy revealed mucosal edema and fine-granular or nodular appearance changes in the small intestine. Histological examination showed chronic inflammation and villous atrophy. A very interesting finding is that the inflammatory cell infiltration in the two GS cases was different. In one case, predominantly CD138 + plasma cells with only scattered CD3 + T-cells infiltration were revealed, while in another, it showed predominantly T-cells infiltration without plasma cells in the lamina propria. Although GS cases shared various clinical characteristics with common variable immunodeficiency (CVID) cases, they still differed from CVID cases in terms of its late onset, lack of familial clusters, low or absent peripheral blood B lymphocytes, absence of lymphoid hyperplasia, and plasma cells infiltration in the lamina propria in some patients. Although both patients had been diagnosed previously with recurrent diarrhea, respiratory infection, and thymoma, the association between these conditions and the possibility of GS was not recognized. The patients had remained misdiagnosed for 2 and 4 years, respectively, even after receiving the diagnosis of thymoma. The rarity of GS was likely the primary cause for the lack of disease recognition. Reporting of these cases will help to alert clinicians and raise awareness of this disease. Conclusion GS should be considered among the differential diagnoses for patients with unexplained recurrent diarrhea and opportunistic infection. Although it was regarded as a subset of CVID with thymoma, GS had a different clinical-pathological feature from CVID.

Camrelizumab (SHR-1210), a human monoclonal antibody against programmed death receptor 1 (PD-1), blocks the binding of PD-1 to PD-L1, consequently inhibiting immune system evasion by tumor cells. A 65-year-old man underwent radical esophagectomy 5 months ago following the diagnosis of esophageal cancer by gastroscopy. Approximately 40 days later, capecitabine was administered at a dosage of 1.5 g Po bid for 14 days, and anti-PD-1 (camrelizumab 200 mg) was administered twice. Around 20 days later, abnormal liver function was detected. He received a diagnosis of drug-induced liver injury. Chest computed tomography scanning revealed interstitial inflammatory lesions in both lower lungs. Liver biopsy revealed immune injury with ductopenia. Therefore, the diagnosis was revised as immune-related pneumonia and hepatitis associated with camrelizumab. The treatment regimen of methylprednisolone was adjusted to 40 mg/day and gradually increased to 80 mg/day. Mycophenolate mofetil was administered at a dose of 2 g/day. Consequently, chest tightness and shortness of breath resolved, and pulmonary inflammation improved. However, jaundice did not improve and continued to exacerbate. The last measured prothrombin time was 41 s, prothrombin activity was 19%, and the international normalized ratio was 4.03. The cause of death was diagnosed as liver failure, cardiopulmonary failure, and septic shock.

Objectives This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI. Method A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group. Results There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123–2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212–1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222–0.729; P = 0.003) was independent protective factors for post-OLT AKI. Conclusion This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.

Aim We compared the clinical characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive and negative anal swabs during coronavirus disease 2019 (COVID-19) recovery and investigated the clinical significance and influence factors of anal swab detection. Methods This study retrospectively analyzed 23 moderate COVID-19 patients in the recovery phase. They were divided into anal swab positive group ( n = 13) (negative for pharyngeal swabs but positive for anal swabs) and anal swab negative group ( n = 10) (negative for pharyngeal and anal swabs). The epidemiology, clinical symptoms, time of pharyngeal swabs turning negative, and laboratory results were compared. Results The time of pharyngeal swabs turning negative in the anal swab positive group was 6 (5–8.5) days, significantly longer than that in the anal swab negative group (1 (1–4.25) days), P = 0.0002). The platelet count of the anal swab positive group was significantly lower than that of the anal swab negative group (198 (135–235) × 10 9 /L vs 240.5 (227–264.75) × 10 9 /L, P = 0.0248). No significant difference was observed between the two groups in other variables. Conclusions The time of pharyngeal swab turning negative in anal swab positive patients is longer than that in anal swab negative patients. The platelet count can be used as an indicator for viral infection evaluation. For patients with a longer time of pharyngeal swabs turning negative, the combined testing of the anal swab and platelet counts may help to avoid pharyngeal swab false negatives, premature discharge, and the possibility of fecal-oral transmission.

Background Colorectal cancer (CRC) is one of the deadliest cancers in the world. Increasing evidence suggests that circular RNAs (circRNAs) are implicated in CRC pathogenesis. This study aimed to determine the role of circAPLP2 and explore a potential mechanism of circAPLP2 action in CRC. Methods The expression of circAPLP2, miR-335-5p and helicase lymphoid-specific (HELLS) mRNA in CRC tissues and cells was measured by quantitative real-time polymerase chain reaction (qPCR). The functional effects of circAPLP2 on cell cycle progression/cell apoptosis, colony formation, cell migration, invasion and glycolysis metabolism were investigated by flow cytometry assay, colony formation assay, wound healing assay, transwell assay and glycolysis stress test. Glycolysis metabolism was also assessed by the levels of glucose uptake and lactate production. The protein levels of HELLS and HK2 were detected by western blot. The interaction between circAPLP2 and miR-335-5p, or miR-335-5p and HELLS was verified by dual-luciferase reporter assay. The role of circAPLP2 on solid tumor growth in nude mice was investigated. Results circAPLP2 and HELLS were overexpressed, but miR-335-5p was downregulated in CRC tissues and cells. Functional analyses showed that circAPLP2 knockdown suppressed CRC cell cycle progression, colony formation, migration, invasion and glycolysis metabolism, induced cell apoptosis and blocked solid tumor growth in nude mice. Moreover, miR-335-5p was a target of circAPLP2, and miR-335-5p could also bind to HELLS. Rescue experiments presented that miR-335-5p inhibition reversed the effects of circAPLP2 knockdown, and HELLS overexpression abolished the role of miR-335-5p restoration. Importantly, circAPLP2 could positively regulate HELLS expression by mediating miR-335-5p. Conclusion circAPLP2 triggered CRC malignant development by increasing HELLS expression via targeting miR-335-5p, which might be a novel strategy to understand and treat CRC.

Recent studies indicate that host immune responses are dysregulated with either myeloid cell compartment or lymphocyte composition being disturbed in COVID-19. This study aimed to assess the impact of SARS-CoV-2 viral infection on the composition of circulating immune cells in severe COVID-19 patients. In this retrospective single-center cohort, 71 out of 87 COVID-19 patients admitted to the intense care unit for oxygen treatment were included in this study. Demographics, clinical features, comorbidities, and laboratory findings were collected on admission. Out of the 71 patients, 5 died from COVID-19. Compared with survived patients, deceased patients showed higher blood cell counts of neutrophils and monocytes but lower cell counts of lymphocytes. Intriguingly, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and basophil-to-lymphocyte ratio (BLR) were markedly higher in deceased patients compared to survived patients. Furthermore, the lymphocyte counts were negatively correlated with D-dimer levels, while the ratios between myeloid cells and lymphocyte (NLR, MLR, and BLR) were positively correlated with D-dimer levels. Our findings revealed that the ratios between myeloid cells and lymphocytes were highly correlated with coagulation status and patient mortality in severe COVID-19.

Objective To investigate the risk factors of left atrial appendage thrombus (LAAT) in patients with non-valvular atrial fibrillation (AF). Methods We collected the clinical data of patients with non-valvular AF who underwent transesophageal echocardiography (TEE) at the Zhongda Hospital of Southeast University between January 2016 and June 2019. The patients were divided into two groups, LAAT and non-LAAT. We performed comparative analysis, receiver operating characteristic (ROC) curve analysis and logistic regression analysis to estimate the risk factors of LAAT. Results A total of 442 patients with non-valvular AF were enrolled in the study. LAAT was detected by TEE in 20 cases (4.7%). Compared with patients without LAAT, patients with LAAT had higher CHA 2 DS 2 -VASc scores (3 vs 2, p = 0.001), higher values of D-dimer (180.0 vs 90.0 μg/L, p = 0.003), larger LA anteroposterior diameters (50.5 vs 41.0 mm, p < 0.001) and higher ratios of non-paroxysmal AF (85.0% vs 23.6%, p < 0.001). ROC curve analysis revealed that the cutoff value of LA anteroposterior diameter was 49.5 mm. After adjusting for other confounders, logistic regression analysis showed that enlarged LA (anteroposterior diameter ≥49.5 mm) and non-paroxysmal AF were independently associated with higher risks of LAAT (OR = 7.28, 95% CI: 2.36–22.47; OR = 8.89, 95% CI: 2.33–33.99, respectively). The proportions of LAAT in patients with larger LA (anteroposterior diameter ≥49.5 mm), non-paroxysmal AF and both larger LA and non-paroxysmal AF were 30% (12/40), 15.2% (17/112) and 39.1% (9/23), respectively. Conclusion Enlarged LA (anteroposterior diameter ≥49.5 mm) and non-paroxysmal AF were independent risk factors of LAAT in non-valvular AF patients.

Background SARS-CoV-2 has spread worldwide and poses a great threat to human health. Among COVID-19 patients, those with hypertension have been reported to have higher morbidity and mortality. This study was conducted to provide the international community with a deeper understanding of COVID-19 with hypertension. Methods A total of 623 COVID-19 patients enrolled in Wuhan’s hospital were studied from January to March 2020. The epidemiology, clinical features, and laboratory data of hypertensive patients with COVID-19 were collected, retrospectively analyzed, and compared with a normotensive group. The use of antihypertensive drugs, general treatment, and clinical outcomes of hypertensive patients were also analyzed. Results The median ages in hypertensive patients with mild and severe COVID-19 were both significantly greater than the median age in the normotensive group. But there was no significant gender difference between the hypertensive and normotensive groups. All patients had lived in Wuhan area. Common symptoms of all patients included fever, cough, and fatigue. Chest computed tomography (CT) scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. All (315 (100%)) of the hypertensive patients received antiviral therapy (Umifenovir was used alone or in combination with Ribavirin), antibiotic therapy (215 (68.3%)), and corticosteroids (118 (37.5%)). The results suggest that the combination of Umifenovir and Ribavirin as initial therapy for hypertensive patients with COVID-19 is effective and safe. There were no significant differences in laboratory data between the mild cases in the hypertensive and the normotensive groups. In the severe cases, the hypertensive patients had higher plasma levels of D-dimer, C-reactive protein (CRP), and Interleukin-6 (IL-6) ( P < 0.05). Furthermore, the hypertensive patients who were treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) were not represented in a statistically significant manner between the mild and severe groups ( p > 0.05). Conclusion In this study, we demonstrated that the hypertensive patients who were treated with ACEI/ARB did not have an increased risk of developing severe COVID-19. Umifenovir and Ribavirin played an important role in the treatment of viral pneumonia. Hypertensive patients with severe viral pneumonia had stronger inflammatory responses than nonhypertensive patients.

Background Kawasaki disease (KD) is a systemic inflammatory condition occurring predominantly in children. Coronary artery bypass grafting (CABG) is performed in the presence of inflammation and aneurysms of the coronary arteries. The objectives of our study were to assess which CABG strategy provides better graft patency and early and long-term outcomes. Methods A systematic review using Medline, Cochrane, and Scopus databases was performed in February 2020, incorporating a network meta-analysis, performed by random-effect model within a Bayesian framework, and pooled prevalence of adverse outcomes. Hazard ratios (HR) and corresponding 95% credible intervals (CI) were calculated by Markov chain Monte Carlo methods. Results Among 581 published reports, 32 studies were selected, including 1,191 patients undergoing CABG for KD. Graft patency of internal thoracic arteries (ITAs), saphenous veins (SV), and other arteries (gastroepiploic artery and radial artery) was compared. ITAs demonstrated the best patency rates at long-term follow-up (HR 0.33, 95% CI: 0.17–0.66). Pooled prevalence of early mortality after CABG was 0.28% (95% CI: 0.00–0.73%, I 2 = 0%, tau 2 = 0), with 63/1,108 and 56/1,108 patients, undergoing interventional procedures and surgical re-interventions during follow-up, respectively. Pooled prevalence was 3.97% (95% CI: 1.91–6.02%, I 2 = 60%, tau 2 = 0.0008) for interventional procedures and 3.47% (95% CI: 2.26–4.68%, I 2 = 5%, tau 2 <0.0001) for surgical re-interventions. Patients treated with arterial, venous, and mixed (arterial plus second venous graft) CABG were compared to assess long-term mortality. Mixed CABG (HR 0.03, 95% CI: 0.00–0.30) and arterial CABG (HR 0.13, 95% CI: 0.00–1.78) showed reduced long-term mortality compared with venous CABG. Conclusions CABG in KD is a safe procedure. The use of arterial conduits provides better patency rates and lower mortality at long-term follow-up.

The aim of this study was to evaluate the association of the chromobox homologue 7 (CBX7) expression with the epithelial–mesenchymal transition in cervical cancer (CC), as well as with the disease prognosis. CBX7, E-cadherin (E-cad), and vimentin (VIM) expression levels were detected with immunohistochemistry. The relationship between the expression of CBX7, E-cad, and VIM expression and conventional clinicopathological characteristics of CC were evaluated. The positive expression rates of CBX7 and E-cad in the CC tissues were lower than the adjacent non-tumorous cervical tissues. Moreover, the VIM expression level was higher. The CBX7 expression was positively correlated with the E-cad expression, whereas was negatively correlated with the VIM expression. Furthermore, CBX7 was associated with the disease clinical staging, histological differentiation, lymph node metastasis, and vascular invasion. Patients with negative CBX7 expression showed decreased overall survival rates compared with those with low or high CBX7 expression. Multivariate Cox regression analysis indicated that the decreased CBX7 expression was an independent predictor for the poor prognosis of CC. In conclusion, the absence of CBX7 is associated with the histologic differentiation, lymphatic metastasis, vascular invasion, and poor prognosis of CC. CBX7 may be an independent prognostic factor for the prognosis of CC patients.

FGF16 is implicated in the progression of some specific types of cancers, such as embryonic carcinoma, ovarian cancer, and liver cancer. Yet, the function of FGF16 in the development of lung cancer remains largely unexplored. In this study, we present the novel function of FGF16 and the regulation of miR-520b on FGF16 in lung cancer progression. In clinical lung cancer tissues, FGF16 is overexpressed and its high level is negatively associated with the low level of miR-520b. Furthermore, both the transcription and translation levels of FGF16 are restrained by miR-520b in lung cancer cells. For the regulatory mechanism investigation, miR-520b is able to directly bind to the 3′-untranslated region (3′UTR) of FGF16 mRNA, leading to its mRNA cleavage in the cells. Functionally, miR-520b reduces the growth of lung cancer and its inhibitor anti-miR520b is able to promote the growth through competing endogenous miR-520b. Moreover, FGF16 silence using RNA interference is capable of doing great damage to anti-miR-520b-accelerated growth of lung cancer. Thus, our finding indicates that FGF16 is a new target gene of miR-520b in lung cancer. For lung cancer, FGF16 may serve as a novel biomarker and miR-520b/FGF16 may be useful in clinical treatment.

Platelet-rich fibrin (PRF) represents second generation of platelet concentrates, which has gained increasing awareness in recent years for regenerative procedures. This biologic additive is completely autologous, easy to prepare, has minimal expense, and possesses prolonged growth factor release, together with several other advantages over traditionally prepared platelet concentrates. Since its introduction, various protocols for PRF preparation have been proposed with different amounts of growth factors and other biomolecules necessary for wound healing. However, reference data about potential effect of some PRF components on hard and soft tissue healing are still conflicting. The current article intends to clarify the relevant advances about physiological role of certain PRF components and to provide insight into the new developmental approach. Also, this review summarizes the evolution of platelet concentrates and biologic properties of different modifications of PRF procedure.

A new logistic regression-based method to distinguish between cancerous and noncancerous RNA genomic data is developed and tested with 100% precision on 595 healthy and cancerous prostate samples. A logistic regression system is developed and trained using whole-exome sequencing data at a high-level, i.e., normalized quantification of RNAs obtained from 495 prostate cancer samples from The Cancer Genome Atlas and 100 healthy samples from the Genotype-Tissue Expression project. We could show that both sensitivity and specificity of the method in the classification of cancerous and noncancerous cells are perfectly 100%.

Gestational diabetes mellitus (GDM) is a metabolic dysregulation closely related to both obesity and type 2 diabetes; however, the molecular mechanism underlying GDM is still unclear. The purpose of this study was to investigate the effects of microRNA-377 (miR-377-3p) and fibronectin type III domain containing 5 (FNDC5) in regulating the cell growth of trophoblasts under high glucose (HG) conditions during the development of GDM. Serum miR-377-3p was upregulated and positively correlated with fasting blood glucose level in GDM patients. miR-377-3p downregulation increased the cell vitality and suppressed the cell apoptosis of HG-treated HTR-8/SVneo and BeWo cells. Using TargetScan prediction, luciferase assay, and western blot, it was found that miR-377-3p could target FNDC5 and suppress its expression. However, FNDC5 downregulation abolished the effect of miR-377-3p inhibitor in HTR-8/SVneo cells. Together, miR-377 is a potential target for GDM biomarker, which promotes cell growth and suppresses cell apoptosis, partly through the upregulation of FNDC5.

Background Tripartite motif 28 (TRIM28) plays a role in multiple biological functions. The expression and function of TRIM28 in breast carcinoma (BC) remain unclear. The aim of this study was to explore potential association of TRIM28 with tumor features and survival. Materials and methods Specimens were collected from BC and adjacent normal tissues. Quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to detect TRIM28 expression. The correlation of TRIM28 with clinicopathological features was evaluated by Chi-square test. The relationship between TRIM28 expression and survival was further analyzed by the Kaplan-Meier and Cox regression method. A receiver operating characteristic (ROC) curve was used to assess the value of TRIM28 in predicting BC. Results In this retrospective research, it was demonstrated that TRIM28 was overexpressed in BC tissues. TRIM28 overexpression was correlated with lymph node metastasis, advanced TNM stage, and poor molecular subtype. The survival analysis showed that overall survival (OS) and progression-free survival (PFS) were significantly shorter in TRIM28-positive group. Moreover, TRIM28 was an independent prognostic factor for BC. And ROC analysis verified the diagnostic role of TRIM28 in BC. Conclusions TRIM28 is overexpressed in BC and might be a promising prognostic and diagnostic biomarker of BC.

Background Malignant tumors were considered as the leading causes of cancer-related mortality globally. More and more studies found that dysregulated genes played an important role in carcinogenesis. The aim of this study was to explore the significance of KPNA2 in human six major cancers including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer, breast cancer, hepatocellular carcinoma, and bladder cancer based on bioinformatics analysis. Methods The data were collected and comprehensively analyzed based on multiple databases. KPNA2 mRNA expression in six major cancers was investigated in Oncomine, the human protein atlas, and GEPIA databases. The mutation status of KPNA2 in the six major cancers was evaluated by online data analysis tool Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. Co-expressed genes with KPNA2 were identified by using LinkedOmics and made pairwise correlation by Cancer Regulome tools. Protein-protein interaction (PPI) network relevant to KPNA2 was constructed by STRING database and KEGG pathway of the included proteins of the PPI network was explored and demonstrated by circus plot. Survival analysis-relevant KPNA2 of the six cancers was performed by GEPIA online data analysis tool based on TCGA database. Results Compared with paired normal tissue, KPNA2 mRNA was upregulated in all of the six types of cancers. KPNA2 mutations, especially missense substitution, were widely identified in six cancers and interact with different genes in different cancer types. Genes involved in PPI network were mainly enriched in p53 signaling pathway, cell cycle, viral carcinogenesis, and Foxo signaling pathway. KPNA2 protein was mainly expressed in nucleoplasm and cytosol in cancer cells. Immunohistochemistry assay indicated that KPNA2 protein was also positively expressed in nucleoplasm with brownish yellow staining. Overall survival (OS) and progression free survival (PFS) were different between KPNA2 high and low expression groups. Conclusions KPNA2 was widely dysregulated and mutated in carcinomas and correlated with the patients prognosis which may be potential target for cancer treatment and biomarker for prognosis.

Background Long noncoding RNA OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) was confirmed to involve in the malignancy of breast cancer. However, whether exosomal OIP5-AS1 is implicated in trastuzumab resistance remains unclear. Methods The IC 50 value of cells to trastuzumab, cell proliferation, migration, and apoptosis was analyzed by cell counting kit-8 assay, colony formation assay, transwell assay, or flow cytometry, respectively. The expression of OIP5-AS1 and microRNA (miR)-381-3p was detected using quantitative real-time polymerase chain reaction. Exosomes were isolated by ultracentrifugation and qualified by nanoparticle tracking analysis software. Western blot was used to detect the protein levels of tumor susceptibility gene 101 (TSG101), CD81, CD63, or high-mobility group protein B3 (HMGB3). The interaction between miR-381-3p and OIP5-AS1 or HMGB3 was confirmed by dual-luciferase reporter assay and pull-down assay. In vivo experiments were conducted using murine xenograft models. Results OIP5-AS1 was elevated in trastuzumab-resistant breast cancer cells, and OIP5-AS1 knockdown rescued trastuzumab sensitivity. Extracellular OIP5-AS1 was packaged into exosomes, which were secreted by trastuzumab-resistant cells, and could be absorbed by trastuzumab-sensitive cells in breast cancer. Importantly, intercellular transfer of OIP5-AS1 via exosomes enhanced trastuzumab resistance in vitro. OIP5-AS1 was a sponge of miR-381-3p; besides, miR-381-3p targeted HMGB3. Murine xenograft analysis showed exosomal OIP5-AS1 induced trastuzumab resistance in vivo. Exosomal OIP5-AS1 was dysregulated in the serum of breast cancer patients and might be a promising diagnostic biomarker in trastuzumab resistance. Conclusion Intercellular transfer of OIP5-AS1 by exosomes enhanced trastuzumab resistance in breast cancer via miR-381-3p/HMGB3 axis, indicating a potential therapeutic strategy to boost the effectiveness of trastuzumab in resistant breast cancer patients.

Purpose This study aimed to develop a multi-long noncoding RNA (lncRNA) signature for the prediction of gastric cancer (GC) based on differential gene expression between recurrence and nonrecurrence patients. Methods By repurposing microarray expression profiles of RNAs from The Cancer Genome Atlas (TCGA), we performed differential expression analysis between recurrence and nonrecurrence patients. A prognostic risk prediction model was constructed based on data from TCGA database, and its reliability was validated using data from Gene Expression Omnibus database. Furthermore, the lncRNA-associated competing endogenous RNA (ceRNA) network was constructed, namely, DIANA-LncBasev2 and starBase database. Results We identified 363 differentially expressed RNAs (317 mRNAs, 18 lncRNAs, and 28 microRNAs [miRNAs]). Principal component analysis showed that the seven-feature lncRNAs screened by support vector machine–recursive feature elimination algorithm was more informative for predicting recurrence of GC in comparison with the eight-feature lncRNAs screened by random forest–out-of-bag algorithm. Four of the seven-feature lncRNAs including LINC00843, SNHG3, C21orf62-AS1, and MIR99AHG were chosen to develop a four-lncRNA risk score model. This risk score model was able to distinguish patients with high and low risk of recurrence, and was tested in two independent validation sets. The ceRNA network of this four-lncRNA signature included 10 miRNAs and 178 mRNAs. The mRNAs significantly related to the Wnt-signaling pathway and relevant biological processes. Conclusion A useful four-lncRNA signature recurrence was established to distinguish GC patients with high and low risk of recurrence. Regulating the relevant miRNAs and Wnt pathway might partly affect GC metastasisby.

Atherosclerosis (AS) is a serious cardiovascular disease. Circular RNAs (circRNAs) play an important role in the progression of many diseases, including AS. However, the role of circ_0003204 in AS is not clear. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) were used to construct an AS cell model in vitro . Cell viability was assessed using cell counting kit 8 (CCK8) assay. Flow cytometry and caspase-3 activity were used to measure cell apoptosis. The contents of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Oxidative stress marker expression and cell injury marker activity were detected by their corresponding Assay Kits. Besides, the expression levels of circ_0003204, miR-330-5p, and toll-like receptor 4 (TLR4) were tested by real-time polymerase chain reaction (qPCR). The interaction between miR-330-5p and circ_0003204 or TLR4 was examined by dual-luciferase reporter assay and RNA pull-down assay. Western blot (WB) analysis was used to determine the levels of TLR4 protein and nuclear factor-kappa B (NF-κB) signaling pathway-related protein. Our data suggested that ox-LDL could suppress viability and promote apoptosis, inflammatory response, and oxidative stress in HUVECs. circ_0003204 was highly expressed in ox-LDL-induced HUVECs, and its silencing could inhibit ox-LDL-induced HUVECs injury. miR-330-5p could be sponged by circ_0003204, and its inhibitor could reverse the inhibition effect of silenced circ_0003204 on ox-LDL-induced HUVECs injury. Further, TLR4 could be targeted by miR-330-5p, and its overexpression could invert the suppression effect of miR-330-5p on ox-LDL-induced HUVECs injury. The activity of the NF-κB signaling pathway was regulated by the circ_0003204/miR-330-5p/TLR4 axis. Our results indicated that circ_0003204 silencing could alleviate ox-LDL-induced HUVECs injury, suggesting that circ_0003204 might be a novel target for AS treatment.

Colorectal cancer (CRC) is responsible for thousands of slow and painful annual deaths. Propofol, an anesthetic, is commonly used in CRC surgery. The role of circularRNA0026344 (circ_0026344) in propofol-treated CRC remains unclear, which was further explored in this study. Real-time polymerase chain reaction (qPCR) was used to detect the expression of circ_0026344 and microRNA645 (miR-645) in CRC cells and normal cells. Western blot was devoted to testing the protein expression of phospho-protein kinase B (p-AKT), AKT, phospho-mammalian target of rapamycin (p-mTOR), and mTOR in CRC cells. Moreover, cell counting kit-8 (CCK8), colony formation, flow cytometry, and transwell assays were employed to assess the proliferation, apoptosis, and metastasis in CRC cells. Circinteractome online tool was applied to predict the combination between circ_0026344 and miR-645, which was further verified by dual-luciferase reporter system. circ_0026344 was lowly expressed and miR-645 was abundantly expressed in CRC cells. The relative protein expression of p-AKT/AKT and p-mTOR/mTOR was strikingly elevated by si-circ#1, which could be reversed by anti-miR-645 in propofol-treated CRC cells. circ_0026344 overexpression inhibited the proliferation and metastasis and promoted apoptosis in CRC cells. Propofol treatment induced the restraint in proliferation and metastasis and stimulation in apoptosis, which were allayed by si-circ#1; meanwhile, this alleviation could further be abolished by anti-miR-645 in CRC cells. Furthermore, circ_0026344 sponged miR-645 to inhibited Akt/mTOR signal pathway in propofol-treated CRC cells. Propofol postponed CRC process by circ_0026344/miR-645/Akt/mTOR axis. This finding might provide a possibility to improve the therapy of CRC with propofol.

Sepsis is a common and lethal syndrome. Long non-coding RNA (lncRNA) transcript predicting survival in AKI (TapSAKI) has recently been found to serve as an important regulator in sepsis. However, the underlying mechanism of TapSAKI in sepsis pathogenesis remains largely unknown. Our data demonstrated that lipopolysaccharide (LPS)-induced HK-2 cell injury by weakening cell viability and enhancing cell apoptosis and inflammation. TapSAKI was upregulated and miR-205 was downregulated in LPS-induced HK-2 cells. TapSAKI knockdown or miR-205 overexpression alleviated LPS-induced cytotoxicity in HK-2 cells. TapSAKI sequestered miR-205 via acting as a miR-205 sponge. Moreover, the mitigating effect of TapSAKI silencing on LPS-induced HK-2 cell injury was mediated by miR-205. Additionally, the interferon regulatory factor 3 (IRF3) signaling was involved in the regulation of the TapSAKI/miR-205 axis on LPS-induced HK-2 cell damage. Our current study suggested that TapSAKI silencing relieved LPS-induced injury in HK-2 cells at least in part by sponging miR-205 and regulating the IRF3 signaling pathway, highlighting a novel understanding for sepsis pathogenesis and a promising target for this disease treatment.

Most COVID-19 cases are treated as outpatients, while the majority of studies on COVID-19 focus on inpatients. Little is known about the self-reporting and self-rating of the disease’s symptoms, and the associations of prophylactic use of dietary supplements with COVID-19 severity have not been addressed. The aims of this study are to evaluate COVID-19 severity and to relate them to sociodemographic characteristics and prophylactic dietary supplements. An observational patient-based study conducted through an online questionnaire on recovered COVID-19 patients. The patients were assessed for several severity parameters, sociodemographic parameters, and prophylactic dietary supplement use. A total of 428 patients were evaluated. Age and presence of comorbidities had positive associations with the severity parameters. The severe infection group had the highest proportion of patients stressed about COVID-19 ( P < 0.05). Cigarette, but not hookah, smoking was significantly associated with less severe symptoms. Vitamin D negatively predicted disease severity ( P < 0.05). In conclusion, stress, age, and presence of comorbidities were the most important positive predictors of COVID-19 severity, while prophylactic vitamin D use and smoking were significant negative predictors. The use of protective measures and other prophylactic dietary supplements was not significantly associated with symptom severity.

Nocardiosis is a rare, life-threatening, opportunistic, and suppurative infection. Its clinical manifestation lacks specificity, which makes early diagnosis difficult. A retrospective analysis of the clinical records of 11 patients with nocardiosis admitted to our hospital from January 2013 to November 2018 was conducted. All patients had at least one underlying disorder, such as an autoimmune disease (6/11), a blood malignancy (2/11), avascular necrosis of the femoral head (1/11), bronchiectasis (1/11), or pneumonia (1/11). The first-line treatment was trimethoprim–sulfamethoxazole (TMP–SMX); one or two additional antibiotics were given according to the drug-sensitive test. The median time from onset to treatment was 3 weeks (ranging from 1 to 9 weeks). The median duration of treatment after diagnosis was 20.5 weeks (ranging from 7 to 47 weeks). Eight patients were discharged and survived, and three patients died. This indicates that early use of TMP–SMX combined with sensitive antibiotics could improve the condition of patients and improve the cure rate (8/11). Clinically, it is necessary to consider the possibility of nocardiosis in patients with long-term use of immunosuppressants and poor response to treatment of common bacterial infections. Early diagnosis, timely treatment, and combination drug therapy are keys to improving the outcomes of patients with nocardiosis.

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis -regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.

Introduction Lung adenocarcinoma (LUAD) is currently one of the most common malignant tumors worldwide. However, there is a lack of long noncoding RNA (lncRNA)-based effective markers for predicting the prognosis of LUAD patients. We identified four lncRNAs that can effectively predict the prognosis of LUAD patients. Methods We used data gene expression profile for 446 patients from The Cancer Genome Atlas database. The patients were randomly divided into a training set and a test set. Significant lncRNAs were identified by univariate regression. Then, multivariate regression was used to identify lncRNAs significantly associated with the survival rate. We constructed four-lncRNA risk formulas for LUAD patients and divided patients into high-risk and low-risk groups. Identified lncRNAs subsequently verified in the test set, and the clinical independence of the lncRNA model was evaluated by stratified analysis. Then mutated genes were identified in the high-risk and low-risk groups. Enrichment analysis was used to determine the relationships between lncRNAs and co-expressed genes. Finally, the accuracy of the model was verified using external database. Results A four-lncRNA signature (AC018629.1, AC122134.1, AC119424.1, and AL138789.1) has been verified in the training and test sets to be significantly associated with the overall survival of LUAD patients. Conclusions The present study demonstrated that identified four-lncRNA signature can be used as an independent prognostic biomarker for the prediction of survival of LUAD patients.

Cytomegalovirus (CMV) reactivation during chemotherapy or after organ or hematopoietic stem cell transplantation is a major cause of morbidity and mortality, and the risk of reactivation increases with patients’ age. Bendamustine, an alkylating agent currently used for treatment of indolent and aggressive non-Hodgkin lymphomas, can augment the risk of secondary infections including CMV reactivation. In this real-world study, we described an increased incidence of CMV reactivation in older adults (age >60 years old) with newly diagnosed and relapsed/refractory indolent and aggressive diseases treated with bendamustine-containing regimens. In particular, patients who received bendamustine plus rituximab and dexamethasone were at higher risk of CMV reactivation, especially when administered as first-line therapy and after the third course of bendamustine. In addition, patients with CMV reactivation showed a significant depression of circulating CD4 + T cell count and anti-CMV IgG levels during active infection, suggesting an impairment of immune system functions which are not able to properly face viral reactivation. Therefore, a close and early monitoring of clinical and laboratory findings might improve clinical management and outcome of non-Hodgkin lymphoma patients by preventing the development of CMV disease in a subgroup of subjects treated with bendamustine more susceptible to viral reactivation.

Objective This meta-analysis was conducted to explore the relationship between serum level of IL-8 and obstructive sleep apnea syndrome (OSAS). Methods Electronic databases were retrieved according to the inclusion and exclusion criteria, relevant studies exploring the relationship between serum level of IL-8 and OSAS were enrolled. Statistical analysis was performed using STATA 12.0. Results Totally 199 studies were retrieved, among which 10 were qualified for the inclusion criteria and were finally included in the meta-analysis with 367 cases of OSAS patients and 335 control cases. Serum level of IL-8 was higher in patients than healthy controls (Standard mean difference (SMD) = 2.16, 95% CI = 1.17–3.15, P < 0.001). The subgroup analysis based on ethnicity revealed that average serum level of IL-8 were higher in Asian and Caucasian OSAS patients than healthy controls (Asian: SMD = 2.50, 95% CI = 1.13–3.87, P < 0.001; Caucasian: SMD = 1.59, 95% CI = 0.11–3.06, P = 0.035). Further subgroup analysis based on age indicated a statistical difference in serum level of IL-8 between adult OSAS patients and healthy counterparts (SMD = 2.73, 95% CI = 1.49–3.98, P < 0.001). Conclusion The level of IL-8 was related to OSAS in adult patients, and increased serum IL-8 level may increase the risk of OSAS.

Circular RNAs (circRNAs) have gained much attention for their crucial regulatory roles in human diseases and cancers. However, the role and the mechanism of circRNA ArfGAP with FG repeats 1 (circAGFG1) in non-small-cell lung cancer (NSCLC) are still largely unknown. circAGFG1 was highly expressed in NSCLC, and high expression of circAGFG1 was closely related to the low survival rate of NSCLC patients. circAGFG1 knockdown inhibited the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. circAGFG1 bound to miR-28-5p in NSCLC cells, and circAGFG1 promoted NSCLC progression partly through sponging miR-28-5p in vitro . HIF-1α was a target of miR-28-5p, and miR-28-5p overexpression-mediated influences in NSCLC cells were partly overturned by the addition of HIF-1α overexpression plasmid. circAGFG1/miR-28-5p/HIF-1α axis regulated cellular glycolytic metabolism in NSCLC cells. circAGFG1 silencing restrained the xenograft tumor growth in vivo . circAGFG1 promoted the proliferation, migration, and invasion and suppressed the apoptosis of NSCLC cells through accelerating the glycolysis via miR-28-5p/HIF-1α axis.

In this study, we focused on the influencing factors of renal anaemia in patients with IgA nephropathy and constructed a nomogram model. We divided 462 patients with IgA nephropathy diagnosed by renal biopsy into anaemic and non-anaemic groups. Then, the influencing factors of renal anaemia in patients with IgA nephropathy were analysed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model for predicting renal anaemia was established. Eventually, nine variables were obtained, which are easy to apply clinically. The areas under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve reached 0.835 and 0.676, respectively, and the C-index reached 0.848. The calibration plot showed that the model had good discrimination, accuracy, and diagnostic efficacy. In addition, the C-index of the model following internal validation reached 0.823. Decision curve analysis suggested that the model had a certain degree of clinical significance. This new nomogram model of renal anaemia combines the basic information, laboratory findings, and renal biopsy results of patients with IgA nephropathy, providing important guidance for predicting and clinically intervening in renal anaemia.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30–90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13–3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81–4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5–1.7) and 8.8 months (95% CI: 8.5–9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

Hepatocellular carcinoma (HCC) is an angiogenesis-dependent tumor, and angiogenesis plays pivotal roles in progression and hematogenous metastasis. Upregulating NDRG2 expression could inhibit endothelial cell proliferation and tumor angiogenesis. However, the development of angiogenesis is a complicated and dynamic process, and the specific mechanisms that NDRG2 influences its progression are largely unknown. Conditioned media (CM) was collected from HCC cells. Cell viability, migration assay, tube formation, and western blot were used to evaluate the effect of NDRG2 on angiogenesis in HCC cells. ELISA assay was used to measure the level of VEGFA in CM. CM from NDRG2 knockdown cells significantly promoted HUVECs proliferation, migration, and tube formation compared with control cells. The level of VEGFA in CM was increased by NDRG2 knockdown relative to the control group. The expression of VEGFA, HIF-1α, and p-Akt was significantly increased in NDRG2 knockdown cells. CM from NDRG2 knockdown cells with VEGFA antibody failed to induce HUVEC proliferation, migration, and tube formation. YC-1 significantly inhibited the level of VEGFA in CM from NDRG2 knockdown cells. YC-1 also inhibited the expression of VEGFA and HIF-1α. Therefore, NDRG2 inhibition promoted the angiogenesis of HCC via VEGFA and may be used to be an anti-angiogenesis target.

Objective To identify differentially expressed and clinically significant mRNAs and construct a potential prediction model for metabolic steatohepatitis (MASH). Method We downloaded four microarray datasets, GSE89632, GSE24807, GSE63067, and GSE48452, from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis were performed to screen significant genes. Finally, we constructed a nomogram of six hub genes in predicting MASH and assessed it through receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, qRT-PCR was used for relative quantitative detection of RNA in QSG-7011 cells to further verify the expression of the selected mRNA in fatty liver cells. Results Based on common DEGs and brown and yellow modules, seven hub genes were identified, which were NAMPT, PHLDA1, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. After logistic regression analysis, six hub genes were used to establish the nomogram, which were NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. The area under the ROC of the nomogram was 0.897. The DCA showed that when the threshold probability of MASH was 0–0.8, the prediction model was valuable to GSE48452. In QSG-7011 fatty liver model cells, the relative expression levels of NAMPT, GADD45B, FOSL2, RTP3, RASD1 and RALGDS were lower than the control group. Conclusion We identified seven hub genes NAMPT, PHLDA1, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. The nomogram showed good performance in the prediction of MASH and it had clinical utility in distinguishing MASH from simple steatosis.

Adenocarcinoma of the esophagogastric junction (AEG) has been increased in recent years and has become a worldwide problem that seriously affects human health. The purpose of the study is to investigate the clinical and prognostic characteristics of the matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression in AEG patients. A total of 69 patients were enrolled in this study. The result showed that the high expression of MMP-2 was significantly associated with tumor differentiation ( P < 0.05) and depth of invasion (pT, P < 0.05). The high expression of VEGF was significantly associated with pT ( P < 0.05) and lymph node metastasis (pN, P < 0.05). There was a positive correlation between MMP-2 and VEGF expression ( P < 0.01). The 5-year survival rate for the 69 AEG patients was 40.6% and it was significantly associated with tumor differentiation ( P < 0.05), pN ( P < 0.01), pTNM stage ( P < 0.01), MMP-2 expression ( P < 0.05), and VEGF expression ( P < 0.05). Cox multivariate regression demonstrated that tumor differentiation and pN were independent factors for the 5-year survival rate. Our study showed that MMP-2 and VEGF could work synergistically in AEG development.

Purpose Colon cancer is one of the malignant tumors that threatens human health. miR-510 was demonstrated to play roles in the progression of various cancers; its dysregulation was speculated to be associated with the development of colon cancer. Methods One hundred and thirteen colon cancer patients participated in this research. With the help of RT-qPCR, the expression of miR-510 in collected tissues and cultured cells was analyzed. The association between miR-510 expression level and clinical features and prognosis of patients was evaluated. Moreover, the effects of miR-510 on cell proliferation, migration, and invasion of colon cancer were assessed by CCK8 and Transwell assay. Results miR-510 significantly upregulated in colon cancer tissues and cell lines relative to the adjacent normal tissues and colonic cells. The expression of miR-510 was significantly associated with the TNM stage and poor prognosis of patients, indicating miR-510 was involved in the disease progression and clinical prognosis of colon cancer. Additionally, the upregulation of miR-510 significantly promoted cell proliferation, migration, and invasion of colon cancer, while its knockdown significantly inhibited these cellular processes. SRCIN 1 was the direct target of miR-510 during its promoted effect on the development of colon cancer. Conclusion The upregulation of miR-510 acts as an independent prognostic indicator and a tumor promoter by targeting SRCIN 1 in colon cancer, which provides novel therapeutic strategies for colon cancer.

This research aimed to probe the expression characteristics of poly(A)-binding protein cytoplasmic 1 (PABPC1) and its role on the phenotype of ovarian cancer (OC) cells and to further investigate the possible underlying mechanism. The expression of PABPC1 was analyzed according to the data from gene expression omnibus, The Cancer Genome Atlas (TCGA) and Oncomine databases and the RNA sequencing data set from TCGA were downloaded for evaluating the prognostic values. We revealed that compared with the healthy samples, PABPC1 was upregulated in OC samples. High expression of PABPC1 had a connection with a shorter survival for patients with OC. Loss and gain of function assays revealed that silencing PABPC1 significantly suppressed the viability, invasion and migration of SK-OV-3 cells, while PABPC1 overexpression in A2780 cells showed the reverse outcomes. Moreover, Western blot demonstrated that silencing PABPC1 notably inactivated the epithelial–mesenchymal transition (EMT) process, while upregulation of PABPC1 promoted the mitigation of epithelial phenotype and the acquisition of mesenchymal phenotype. Taken together, PABPC1 was upregulated in OC cells and served as a carcinogene to promote the OC cell growth and invasion partly by modulating the EMT process, which implied that PABPC1 might be considered as a useful biomarker for OC therapeutics.

Aims Emerging evidence has related inflammation-based biomarkers to numerous carcinomas, including bladder carcinoma (BC). However, the role of inflammatory biomarkers in the prognosis of BC remains inconclusive. This study aimed to compare preoperative plasma fibrinogen (PF) and other inflammatory biomarkers such as the platelet–lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), C-reactive protein (CRP) level, and serum albumin level to predict the prognosis of patients with BC. Methods This article focused on a retrospective analysis of 175 patients with newly diagnosed BC who were admitted to our hospital from March 2005 to March 2016. Of these BC patients, 136 had undergone radical cystectomy (RC). Results According to multivariate analysis, high PF level was an independent predictor of overall survival (OS) in 136 BC patients receiving RC (HR = 3.759; P = 0.011), but not for all 175 BC patients. Combining the NLR and PF values showed higher predictive accuracy for OS than NLR or PF alone ( P < 0.05). Additionally, for 136 BC patients who had undergone RC, a close relationship was found between high PF levels (≥3.39 g/L) and lymph node metastasis ( P = 0.011) and clinical T stage ( P = 0.015). Furthermore, PF was a superior prognostic factor compared with the LMR, PLR, CRP, and albumin values in 136 BC patients who had undergone RC ( P < 0.001). Conclusions The preoperative PF level may be a prognostic biomarker; and when combined with the NLR, it can improve the predictive ability of the survival of BC patients, particularly of BC patients who underwent RC.

Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both P s < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change ( P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both P s < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both P s > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

Objective The retrospective investigation was carried out to assess whether subjects who fulfilled our proposed recruitment criteria responded more favorably to anterior cruciate ligament reconstruction (ACLR) than those who did not. Methods We retrospectively analyzed 109 skeletally mature subjects (78 men and 31 women) according to the following proposed criteria of recruitment: (1) pre-injury Tegner activity score ≥7 and a wish to return to a professional sports activity, (2) residual knee instability following injury and/or (3) age <20 years at the operation. The primary outcome was an improvement between assessment A (before operation) and B (mean follow-up of 1.6 years) in the average score for four of the five Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, difficulty in sports and recreational activities, and quality of life (KOOS 4 ). Results The proposed recruitment criteria for ACLR were met by 58 subjects (53%). There were 49 subjects (45%) who improved between assessment A and B. Subjects who met proposed recruitment criteria were more likely to improve clinically after ACLR (OR 5.7, 95% CI 2.5–13.3). Conclusions Fulfillment of proposed recruitment criteria was a strong predictive factor for outcome improvement in short- to medium-term follow-up after ACLR. Level of evidence Case-control study. Level of evidence 3.

Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation and may eventually lead to peritoneal membrane injury with a high solute transport rate and ultrafiltration failure. Osteopontin (OPN) is highly expressed through the stimulation of pro-inflammatory cytokines in many cell types. This study aimed to investigate the potential of OPN as a new indicator of peritoneal deterioration. One hundred nine continuous ambulatory PD patients were analyzed. The levels of OPN and IL-6 in peritoneal effluents or serum were analyzed by ELISA kits. The mean effluent OPN concentration was 2.39 ± 1.87 ng/mL. The OPN levels in drained dialysate were correlated with D/P Cr ( p < 0.0001, R = 0.54) and D/D0 glucose ( p < 0.0001, R = 0.39). Logistic regression analysis showed that the OPN levels in peritoneal effluents were an independent predictive factor for the increased peritoneal solute transport rate (PSTR) obtained by the peritoneal equilibration test ( p < 0.001). The area under the receiver operating characteristic curve of OPN was 0.84 (95% CI: 0.75–0.92) in predicting the increased PSTR with a sensitivity of 86% and a specificity of 67%. The joint utilization of effluent OPN with age, effluent IL-6, and serum albumin further increased the specificity (81%). Thus, OPN may be a useful indicator of peritoneal deterioration in patients with PD.

Purpose This study was to explore the toxicological mechanisms by which PM2.5 causes lung dysfunction. Methods The expression of circ_0038467 and miR-138-1-3p in PM2.5-induced human bronchial epithelial cell line BEAS-2B was detected by RT-qPCR. The effects of circ_0038467 and miR-138-1-3p on proliferation, apoptosis, and inflammatory cytokines (IL-6 and IL-8) in PM2.5-induced BEAS-2B were determined using cell counting kit-8, flow cytometry, western blot, and enzyme-linked immunosorbent assay, respectively. The levels of nuclear factor kappa B (NF-κB) pathway-related protein were also analyzed by western blot. The binding interaction between circ_0038467 and miR-138-1-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay and pull-down assay. Results circ_0038467 expression was increased by PM2.5 treatment in BEAS-2B cells in time- and dose-dependent methods, and knockdown of circ_0038467 reversed PM2.5-triggered BEAS-2B cell death and inflammatory response. miR-138-1-3p was decreased by PM2.5 treatment, and restoration of miR-138-1-3p attenuated PM2.5-induced BEAS-2B cell injury. In a mechanical study, we found circ_0038467 directly bound to miR-138-1-3p, and further rescue experiments exhibited miR-138-1-3p inhibition partially overturned the regulatory functions of circ_0038467 knockdown in PM2.5-induced BEAS-2B cells. Conclusion circ_0038467 provided a potential therapeutic strategy for future clinic intervention in air pollution-triggered lung dysfunction.

Background We investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC). Methods Expression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed. Results The changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium ( P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC ( P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC ( P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages ( P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression ( P = 0.002 and P < 0.001). Conclusion miR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.

Metabolic syndrome (MetS) is a highly prevalent disorder defined as a cluster of cardiometabolic risk factors including obesity, hyperglycemia, hypertension, and dyslipidemia. It is believed that excessive cortisol secretion due to psychosocial stress-induced hypothalamic-pituitary-adrenal axis activation might be involved in the pathogenesis of MetS. We sought to explore the association between MetS and psychosocial risk factors, as well as cortisol concentration measured in different biological specimens including saliva, blood serum, and hair samples. The study was conducted on a sample of 163 young and middle-aged men who were divided into groups according to the presence of MetS. Hair cortisol concentration (HCC) was determined using high performance liquid chromatography with UV detection, while blood serum and salivary cortisol levels were measured by enzyme-linked immunoassay. Lipid metabolism biomarkers were determined using routine laboratory methods. Anthropometric and lifestyle characteristics, as well as self-reported psychosocial indicators, were also examined. Significantly higher HCC and lower social support level among participants with MetS compared with individuals without MetS were found. However, no significant differences in blood serum and salivary cortisol levels were observed between men with and without MetS. In conclusion, chronically elevated cortisol concentration might be a potential contributing factor to the development of MetS.

The aim of this study is to evaluate prognostic and therapeutic implications of microvessel density (MVD) in the recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in prostate cancer (PCa). As of April 2019, EMBASE, PubMed, Cochrane Library, Science Direct/Elsevier, MEDLINE, and CNKI are used for systematic literature retrieval to investigate the correlation between MVD and PCa. Meta-analysis was performed using Review Manager and Stata software. Combined hazard ratio (HR) was identified with 95% confidence intervals (95% CI) in a random or fixed effects model. Thirteen studies were identified in this article. Of which, 8 studies analyzed for the recurrence-free survival (2,399 patients) demonstrated that MVD significantly elevated in the poor recurrence-free survival (HR 2.57, 95% CI 2.21–2.97). Other 2 eligible studies (330 patients) with 3 data sets for the MVD-OS analysis and the pooled HR (HR 1.70, 95% CI 1.27–2.28) suggested a weak risk of overall death rate in patients with high-MVD levels. The last 3 studies for disease-specific survival (220 patients) suggested that the association with high MVD and disease-specific survival may not have statistically significance (HR 1.32, 95% CI 0.49–3.56). This study suggests that high intratumoral MVD appears a significant progenitor for poor recurrence-free survival of PCa.

Background Depending on breakpoints of rearrangement different types of BCR–ABL fusion protein can be generated in patients of chronic myeloid leukemia (CML). The aim of this study is to observe frequencies of major transcripts in CML patients by reverse transcriptase polymerase chain reaction (RT-PCR) and their hematological features at the time of presentation. Materials and methods This cross sectional study was performed at Molecular Lab of Riphah International University, Islamabad from January to June 2019. Consecutive peripheral blood samples of 70 newly diagnosed CML patients in chronic phase were analyzed by RT-PCR to detect different BCR–ABL transcripts. Routine blood cell counts were assessed by an automated hematology analyzer. Results All samples expressed typical BCR–ABL rearrangement. Expression of either e14a2 or e13a2 transcript was detected in 38 (54%) and 30 (43%) patients, respectively. Coexpression of e13a2 + e14a2 was found in 2 (3%) patients. The mean total leukocyte count was higher in group expressing e13a2 ( P = 0.01). Higher mean platelet count was noted in patients with e14a2 transcript, but this difference was statistically insignificant ( P = 0.1). The association of male gender was observed with the group exhibiting e14a2 ( P = 0.01). There was no statistically significant association between transcript type and different ranges of age, hemoglobin levels, and platelet and total leukocyte counts ( P > 0.05). Conclusion e14a2 transcript was most common transcript in CML patients. Patients exhibiting e13a2 subgroup presented with significantly higher mean white blood cell count at the time of presentation. Significantly higher proportion of male patients was found to express e14a2 transcript over e13a2.

Objective This study was designed to compare the diagnostic efficacy of ultrasonography (US) and magnetic resonance imaging (MRI) in detecting changes in the knee of patients with rheumatoid arthritis (RA) and discover the possible association between the serological index and bone erosion detected by US. Patients and methods In this retrospective study, the US images and MRI findings of the knee in patients with RA from December 2017 to January 2020 were evaluated. Diagnostic outcomes were compared. The rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, and anti-cyclic citrullinated peptide antibody (ACPA) levels of the patients were recorded. The relation between laboratory index and US findings was analyzed by multivariable logistic regression. Results US showed remarkable accuracy, sensitivity, and specificity in diagnosing synovitis, bone erosion, and soft tissue swelling. In terms of reliability, the agreement between US and MRI was moderate to almost perfect. Meanwhile, a positive association between ACPA level and bone erosion was observed in patients with RA. Conclusions US may have a role as the initial imaging modality in patients with RA. Patients with higher ACPA levels may need more active treatment because they are more likely to have bone erosion detected by US.

Background Cerebral ischemia and reperfusion injury (CIRI) affects bodily function by causing irreversible damage to brain cells. The diverse pathophysiological course factors hinder the research work to go deeper. Long noncoding RNA taurine-upregulated gene 1 (TUG1) has been reported to be related to CIRI. This study explored the undefined regulatory pathway of TUG1 in CIRI. Methods Quantitative real-time polymerase chain reaction was applied to test the expression of TUG1, microRNA (miR)-493-3p and miR-410-3p. The viability and apoptosis of oxygen and glucose deprivation/reoxygen (OGD/R) model cells were evaluated by cell counting kit-8 and flow cytometry assay, respectively. The determination of inflammatory factors of interleukin-6, interleukin-1β and tumor necrosis factor-α was presented by enzyme-linked immunosorbent assay. The oxidative stress was performed by measuring the generation of malondialdehyde, reactive oxygen species and the activity of superoxide dismutase. Cytotoxicity was presented by measuring the generation of lactate dehydrogenase. Western blot assay was devoted to assessing the level of apoptosis-related factors (cleaved-caspase-3 and cleaved-caspase-9) and the protein level of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathway-related factors in neuro-2a cells treated by OGD/R. Besides, online database starBase was applied to predict the potential binding sites of TUG1 to miR-493-3p and miR-410-3p, which was further confirmed by the dual-luciferase reporter system. Results The expression of TUG1 was upregulated, while miR-493-3p or miR-410-3p was downregulated in the serum of CIRI and OGD/R model cells. Meanwhile, knockdown of TUG1 eliminated the suppression in proliferation, the promotion in apoptosis, inflammation and oxidative stress, as well as the cytotoxicity in OGD/R model cells. Interestingly, the inhibition of miR-493-3p or miR-410-3p allayed the above effects. In addition, TUG1 harbored miR-493-3p or miR-410-3p and negatively regulated their expression. Finally, the TUG1 activated JNK and p38 MAPK pathways by sponging miR-493-3p/miR-410-3p. Conclusion TUG1 motivated the development of CIRI by sponging miR-493-3p/miR-410-3p to activate JNK and p38 pathways. The novel role of TUG1 in CIRI may contribute to the advancement of CIRI treatment.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB. MALAT1 was upregulated in RB tissues and cells, and it served as a competing endogenous RNA (ceRNA) and inhibited miRNA-655-3p (miR-655-3p) expression, which eventually regulated the expression of miR-655-3p downstream target ATPase Family AAA Domain Containing 2 (ATAD2). The level of ATAD2 significantly increased, while that of miR-655-3p remarkably decreased in RB tissues and cells. MALAT1 depletion inhibited cell proliferation, metastasis, and epithelial–mesenchymal transition (EMT), but promoted apoptosis in vitro and blocked xenograft tumor growth in vivo . MALAT1 exerted its oncogenic functions in RB by regulating miR-655-3p/ATAD2 axis.

Background Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by hantavirus infection. Patients with severe HFRS may develop multiple organ failure or even death, which makes HFRS a serious public health problem. Methods In this retrospective study, we included a total of 155 consecutive patients who were diagnosed with HFRS, of whom 109 patients served as a training cohort and 46 patients as an independent verification cohort. In the training set, the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables of the risk model. Multivariate logistic regression analysis was used to construct a nomogram containing the characteristic variables selected in the LASSO regression model. Results The area under the receiver operating characteristic curve (AUC) of the nomogram indicated that the model had good discrimination. The calibration curve exhibited that the nomogram was in good agreement between the prediction and the actual observation. Decision curve analysis and clinical impact curve suggested that the predictive nomogram had clinical utility. Conclusion In this study, we established a simple and feasible model to predict severity in patients with HFRS, with which HFRS would be better identified and patients can be treated early.

Objectives Origin of outbreaks could be natural, accidental, deliberate, and caused by a new or re-emerging bioagent. The aim of this study was the retrospective analysis of whether the COVID-19 outbreak was natural, accidental, deliberate one, or caused by a new or re-emerging bioagent. Methods Analysis was performed according to the Radosavljevic–Belojevic method for outbreak scoring and differentiation. Data for the application of this method were obtained by literature review in the Medline database for the period from 2000 to 2020. Results The analysis of the unusual COVID-19 outbreak shows that the present official assumption of its natural origin is questionable and pointed out to a probability that the pathogen could have also been accidentally introduced in the human population. Conclusion There are no conclusive pieces of evidence about the reservoir of the pathogen or the source of infection. These parameters are essential for the final clarification of the outbreak origin. This study suggests that the COVID-19 outbreak is a consequence of an accidental release of a new COVID-19 virus, probably during the technical accident and/or negligent violation of hygienic norms in the laboratory facility. Further epidemiological, microbiological, and forensic analyses are needed to clarify the COVID-19 outbreak.

Background The feasibility and safety of laparoscopic major hepatectomy (LMH) are still uncertain. The purpose of the present study is to compare the short- and long-term outcomes of LMH with those of open major hepatectomy (OMH) for hepatocellular carcinoma (HCC). Method Between January 2012 and December 2018, a total of 26 patients received laparoscopic major hepatectomy in our center. To minimize any confounding factors, a 1:3 case-matched analysis was conducted based on the demographics and extent of liver resection. Data of demographics, perioperative outcomes, and long-term oncologic outcomes were reviewed. Results Intraoperative blood loss ( P = 0.007) was significantly lower in the LMH group. In addition, the LMH group exhibited a lower overall complication rate ( P = 0.039) and shorter postoperative hospital stay ( P = 0.024). However, no statistically significant difference was found between LMH and OMH regarding operation time ( P = 0.215) and operative cost ( P = 0.860). Two laparoscopic cases were converted to open liver resection. In regard to long-term outcomes, there was no significant difference between LMH and OMH regarding disease-free survival (DFS) ( P = 0.079) and overall survival (OS) ( P = 0.172). Conclusion LMH can be an effective and safe alternative to OMH for selected patients with liver cancer in short- and long-term outcomes.

Background: It is important to analyze the types of vaccines in travel clinics to determine the focus points in future practice. Methods We retrospectively reviewed the electronic medical records of all patients who visited the travel clinic of Nara Medical University between June 2013 and December 2019 to determine their background and the vaccines administered. The information regarding adverse events of the unapproved vaccines in Japan (Havrix ® , Verorab ® , Boostrix ® , Priorix ® , Typhim Vi ® , and Mencevax ® ) was also collected. Results Of 645 patients, 58.6% were men and the median age was 31 years. Business was the most common travel purpose (34.9%), and Southeast Asia was the most common destination (40.2%). More than 80% of travelers to low- and middle-income countries were vaccinated against hepatitis A, while the rabies vaccination rate was approximately 50%. Typhoid vaccination coverage among travelers to South Asia was approximately 50%. The incidence of adverse events requiring medical consultation, telephonic consultation, or prolonged stay in the examination room was less than 5% for all unapproved vaccines in Japan. Conclusion More patient education is needed to increase the vaccination rate of rabies and typhoid vaccines. Adverse events to unapproved vaccines in Japan were not high and were well-tolerated.

Objective The aim of this study was to investigate the roles of follicular helper CD4 + T cells (Tfh) and serum anti-α-1,4- d -polygalacturonic acid (PGA) antibody in the pathogenesis of Henoch–Schönlein purpura (HSP). Methods ELISA was performed to determine serum PGA-IgA and PGA-IgG. Flow cytometry was utilized to determine the peripheral CD4 + CXCR5 + and CD4 + CXCR5 + ICOS + Tfh cells. Real-time PCR was conducted to determine the expression of Bcl-6 gene. Then the change of Tfh cells was analyzed, together with the association with the anti-PGA antibody as well as the roles in the pathogenesis of HSP. Results Compared with the cases with acute respiratory infection and elective surgery, the proportion of CD4 + CXCR5 + and CD4 + CXCR5 + ICOS + Tfh cells in the HSP group showed significant elevation ( P < 0.001). A significant correlation was noticed between PGA-IgA and CD4 + CXCR5 + Tfh cells ( r = 0.380 and P = 0.042) and CD4 + CXCR5 + ICOS + Tfh cells ( r = 0.906 and P < 0.001). The expression of Bcl-6 in the HSP group showed no statistical difference compared with that in the acute respiratory infection and the surgery control ( P < 0.05). Conclusion Increased activity of Tfh cells, which is closely related to mucosal immunity, may be a major contributor in the elevation of PGA-IgA, and Tfh cells and PGA-IgA are closely related to the occurrence of HSP.

Phototherapy is a conventional treatment for neonatal jaundice and widely considered as a safe procedure. Recent developments in light-emitting diode (LED) phototherapy devices have made more effective treatments possible. Exchange transfusion (ET) is typically applied for cases of refractory severe hyperbilirubinemia despite its risk of various complications. Since the therapeutic effect of phototherapy is correlated with its irradiance, ET may be avoided by performing phototherapy with higher irradiation. Recently, we adopted double-LED phototherapy as a bridging treatment to ET to treat a case of severe hyperbilirubinemia. In this case, the continual increase of bilirubin levels was suppressed immediately after its administration, and ET was not required. Throughout the treatment, no complications or increase in oxidative stress was observed. In addition, neurodevelopment was appropriate for the patient’s age at the 1-year follow-up, and no findings of kernicterus, including physical and magnetic resonance imaging findings, were observed. We hypothesized that double-LED phototherapy may be a good treatment strategy to replace ET for infants with severe hyperbilirubinemia; however, further investigations regarding safety issues including acute and long-term complications are needed before clinical adaptation.

Background Non-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. Methods The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), Pyruvate dehydrogenase kinase 4 (PDK4), Cleaved Caspase 3 (C-caspase 3), and proliferating cell nuclear antigen were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. Xenograft model was constructed to investigate the role of circ_0005962 in vivo . Result circ_0005962 expressed with a high level in NSCLC tissues and cells. circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. miR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. circ_0005962 knockdown suppressed tumor growth in vivo . Conclusion circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

Background Bladder cancer is a common malignancy in the world. It is reported that circular RNA VANGL1 (circ_VANGL1) was involved in bladder cancer progression. However, the functional role and molecular mechanism of circ_VANGL1 in bladder cancer were still unclear. Methods The levels of circ_VANGL1, microRNA-145-5p (miR-145-5p), and Sex-determining region Y-related high-mobility group box 4 (SOX4) in bladder cancer tissues and cells were determined by quantitative real-time polymerase chain (RT-qPCR). The relative protein expression was detected by western blot. Cell counting kit-8 (CCK8) and flow cytometry analysis were used to measure cell viability, IC 50 value, and apoptosis rate. The interaction between miR-145-5p and circ_VANGL1 or SOX4 was predicted by online software starBase v2.0 or Targetscan and verified by the dual-luciferase reporter assay. Besides, xenograft mice model was used to detect the effects of circ_VANGL1 in vivo . Results The level of circ_VANGL1 and SOX4 was increased, while miR-145-5p was decreased in bladder cancer tissues and cells. Knockdown of circ_VANGL1 suppressed viability, while promoted apoptosis and increased doxorubicin sensitivity in bladder cancer cells. Moreover, circ_VANGL1 acted as a sponge for miR-145-5p. In addition, miR-145-5p partially reversed the effects of miR-145-5p knockdown in T24 and J82 cells. SOX4 was a target of miR-145-5p and negatively regulated by miR-145-5p. Furthermore, miR-145-5p regulated SOX4 to affect cell progression in bladder cancer cells, including viability, apoptosis, and doxorubicin sensitivity. Besides, circ_VANGL1 suppressed tumor growth and enhanced the doxorubicin sensitivity in bladder cancer in vivo . Conclusion circ_VANGL1 mediated cell viability, apoptosis, and doxorubicin sensitivity by regulating miR-145-5p/SOX4 axis in bladder cancer, providing a potential therapeutic target for bladder cancer therapy.

Introduction It is believed that fibroblast growth factor 23 (FGF23) can become an early biomarker of chronic kidney disease progression. Data on FGF23 age dependency are inconsistent. We present the results of the cross-sectional study concerning FGF23 levels in healthy Polish children. Material and methods This study was conducted in 121 children aged 0–18 years. Kidney function and intact FGF23 levels in serum were assessed. Differences between age groups and according to gender were analysed. Results The difference in FGF23 between age groups and according to gender was statistically insignificant. In the youngest and the oldest group, a trend to higher FGF23 levels was observed. FGF23 level in girls tended to be higher than boys, apart from the age group between 1 and 4 years. There was a negative correlation between eGFR and FGF23 ( r = −0.26, p < 0.05) – strong in girls ( r = −0.38, p < 0.05), but not in boys. In each age group, we found no significant correlation between eGFR and FGF23. Conclusions Our study supports the evidence that the FGF23 level in paediatric population is not age or sex dependent. The results can serve as a reference point under clinical conditions and for other studies on the topic.

Background Fournier’s gangrene is a rare form of necrotizing fasciitis that affects the genital area up to the perineal region and sometimes the abdominal wall. Objectives Our article aims to show that in the treatment of extensive forms of Fournier’s gangrene, correct use of flap and skin grafts and a quick reconstruction of the exposed tissues avoid scarring retraction of the testicles and deformation of the penis. Materials and methods We retrospectively reviewed the clinical and photographic data of Fournier’s gangrene cases treated at our Institute. The data were evaluated to obtain an estimate of the results of the reconstructive technique used, in terms of percentage of occurred healings and eventual complications. Results A total of 34 patients underwent surgery for Fournier’s gangrene. In nine cases (26.5%), we had minor complications: in four patients, suffering from diabetes and obesity, a retard in attachment of graft occurred, while in five patients with perianal problems there was a delay in healing due to the onset of local infection. Conclusion The reconstruction approach described here may reduce surgical times. In Fournier’s gangrene, the exposed tissues must be reconstructed as quickly as possible.

Context There are no recommended therapeutic agents for acute spinal cord injury (SCI) due to the pathophysiological complexity of the injury. Objective The objective of this study is to investigate the efficacy of various exosomes and potential factors impacting the efficacy of exosomes. Methods We searched the PubMed, EMBASE, Web of Science, Medline, Scopus, and Cochrane Library databases to systematically collect articles comparing the locomotor function of SCI rodents undergoing exosome treatment and untreated SCI rodents. No language was preferred. Results Pooled analysis revealed that the locomotor function recovery of SCI rodents receiving exosomes was greatly improved (583 rats, 3.12, 95% CI: 2.56–3.67, p < 0.01; 116 mice, 2.46, 95% CI: 1.20–3.72, p < 0.01) compared to those of control rodents. The trial sequential analysis demonstrated the findings of the meta-analysis with the cumulative Z -curve crossing the upper monitoring boundary for the benefit and reaching the adjusted required information size. However, the origin of the exosome, SCI model, and administration method determined the therapeutic effect to some extent. Conclusions Despite the proven therapeutic effects of exosomes on SCI rodents, the results should be interpreted cautiously considering the diversity in vivo and in vitro in relation to future trials.

Nasopharyngeal carcinoma (NPC) is characterized by high morbidity and morality, especially in Southern China. Transcription factors intensively participate in the initiation and development of NPC. This study aimed to investigate the roles of Src-1 in NPC. mRNA level was determined by qRT-PCR. Western blot was carried out for the protein level. CCK-8 assay was performed to determine cell viability, colony formation for NPC cell proliferation, and transwell for cell migration and invasion ability. The results showed Steroid receptor coactivator 1 (Src-1) was overexpressed in SNE-2 and 6-10B. The expression of Src-1 and SP2 was in positive correlation. Overexpression of Src-1 promoted the cell viability, colony formation, and epithelial–mesenchymal transition (EMT), manifested by the increase of migration and invasion ability, while knockdown of Src-1 exerted opposite effects. Additionally, knockdown or overexpression of SP2 reversed the effects of overexpressed or downregulated Src-1, which was reversed by the depletion of SP2. Moreover, Src-1 interacted with SP2 to regulate EMT-related genes such as E-cad, N-cad, Vimentin, and ZEB1, and proliferation- and apoptosis-related genes, such as bax, cytochrome c, and cleaved caspase3 and bcl-2. Thus, blocking the interaction between Src-1 and SP2 may be a therapeutic target for inhibiting the metastasis of NPC.

Objective The purpose of our study was to explore the effect of dexmedetomidine on cardiac tolerance to bupivacaine. Method Human coronary endothelial cells were used to establish in vitro model. They were randomly divided into control (Con) group, dexmedetomidine (Dex) group, bupivacaine (Bupi) group, dexmedetomidine + bupivacaine group (DB group), and dexmedetomidine + bupivacaine + PI3K inhibitor (DB-inhibitor) group. Cell activity was measured by Cell counting kit-8 (CCK-8). Transwell was used to detect cell permeability. Western blotting was used to detect the protein expression of related factors. Results There were no notable differences in cell activity among the five groups ( P > 0.05). Dexmedetomidine significantly reduced the permeability of endothelial cells to bupivacaine and increased the protein expression of Zonulaoeeludens-1 (ZO-1) ( P < 0.01). However, the aforementioned effects of dexmedetomidine were disappeared after the addition of PI3K inhibitors. Furthermore, Dex and DB markedly increased the protein expression of PI3K, p-Akt, and p-PTEN in comparison with Con group ( P < 0.001), but there was no significant difference in p-PTEN among DB-inhibitor, Con, and Bupi groups ( P > 0.05). Conclusion Dex reduced Bupi-induced vasopermeability through protein expression of ZO-1 and PI3K/Akt pathway, which may lead to the decrease of Bupi-induced cardiotoxicity.

Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents. This study aims to reveal that hypoxia promotes the invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. The expression of HIF-1α and NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6–36 h. Furthermore, hypoxia induced the migration and invasion of MG63 cells and regulated the level of E-cad, N-cad, Vimentin, Snail, Slug, MMP2, and MMP9 proteins. Importantly, knockdown of NUSAP1 inhibited hypoxia-induced cell migration and invasion. In the hypoxia microenvironment, the addition of HIF-1α inhibitor or the transfection of siRNA specifically targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 and markedly inhibited the migration and invasion of MG63 cells under the hypoxia microenvironment. In conclusion, hypoxia induced the expression of NUSAP1 in a HIF-1α-dependent manner, stimulating the migration and invasion of MG63 cells.

Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI). In this study, we aimed to explore the roles and underlying mechanisms of lncRNA X-inactive specific transcript (XIST) in SCI progression. SCI mice model was constructed and evaluated by the Basso–Beattie–Bresnahan method. The SCI cell model was constructed by treating BV2 cells with lipopolysaccharide (LPS). The levels of XIST and miR-219-5p were determined by the reverse transcription quantitative polymerase chain reaction. The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Protein levels were measured via western blot assay. Cell viability and apoptosis were evaluated by cell counting kit-8 assay and flow cytometry analysis, respectively. The relationship between XIST and miR-219-5p was analyzed by online tool starBase, dual-luciferase reporter assay, and RNA immunoprecipitation assay. As a result, the XIST level was enhanced and the miR-219-5p level was declined in the SCI mice model. XIST was also upregulated in LPS-induced BV2 cells. LPS treatment restrained BV2 cell viability and accelerated apoptosis and inflammatory response. XIST knockdown effectively weakened LPS-induced BV2 cell injury. miR-219-5p was identified as a target of XIST. Moreover, inhibition of miR-219-5p restored the impacts of XIST knockdown on cell viability, apoptosis, and inflammation in LPS-treated BV2 cells. In addition, LPS-induced XIST promoted the activation of the nuclear factor-κB (NF-κB) pathway by sponging miR-219-5p. In conclusion, XIST silencing promoted microglial cell viability and repressed apoptosis and inflammation by sponging miR-219-5p, thus promoting the recovery of SCI.

Background and aim Acute treatment of young patients with proximal femoral fracture (PFF) remains a challenge for trauma surgeons due to major fracture displacement and heavy pain in clinical practice. Traditional methods have a variety of intrinsic defaults and cannot successfully manage the requirements of young patients. Benefiting from our anatomic research, we explored a new method of external fixation for this specific trauma and evaluated its feasibility and clinical outcomes. Material and methods Twenty-three young multiple-trauma patients with PFF were included in this study. Surgical treatment was applied using an external fixator via the anterior inferior iliac spine (AIIS). Electronic patient records, surgical characteristics, clinical outcomes, and complications were reviewed for each patient. Results The mean surgical time was 30.3 ± 7.3 min. The mean blood loss was 25.3 ± 10.8 mL. No iatrogenic nerve palsy, pin tract infection, failure of external fixation, or bedsores were observed. The postoperative visual analog scale score was significantly lower than the preoperative score ( P < 0.01). The mean fracture reduction rate of the femur was 58.1 ± 17.0%, and the mean degree of reduction was 13.5 ± 6.9°. The mean external fixation time was 7.6 ± 4.0 days and intramedullary nailing was performed. The mean hospital, follow-up, and healing times were 28.7 ± 8.7 days, 23.5 ± 7.9 months, and 22.8 ± 5.7 weeks, respectively. The Harris Hip Score indicated excellent or good results in 20 patients. Conclusion Collectively, the results of this study revealed that external fixation via the AIIS is a safe, rapid, and effective method for acute treatment of PFF in young patients.

Objective Acute lung injury (ALI) caused by sepsis is clinically a syndrome, which is featured by damage to the alveolar epithelium and endothelium. In this study, we employed mice models of cecal ligation and puncture (CLP) and primary mice pulmonary microvascular endothelial cells (MPVECs) in vitro to investigate the effect of miR-128-3p in ALI caused by sepsis. Methods miR-128-3p agomir or randomized control were injected into adult male C57BL/6 mice 1 week before the CLP surgery. We used miR-128-3p agomir or scrambled control to transfect MPVECs and then employed lipopolysaccharide (LPS) stimulation on the cells. Pellino homolog 2 (PELI2) was predicted to be a direct target of miR-128-3p via luciferase reporter assay. MPVECs were cotransfected with lentiviral vector that expressed PELI2 (or empty vector) as well as miR-128-3p-mimics 1 day before LPS stimulation in rescue experiment. Transcriptional activity of caspase-3, cell apoptosis rate, and the expression levels of miR-128-3p, interleukin-1β (IL-1β), interleukin-6 (IL-6), and PELI2 were analyzed. Results Compared with the sham group, the lung of mice in the CLP group showed pulmonary morphological abnormalities, and the expression of IL-6 and IL-1β, caspase-3 activity, and apoptosis rate were significantly upregulated in the CLP group. Inflammatory factor levels and apoptosis rate were also significantly induced by LPS stimulation on MPVECs. Upregulation of miR-128-3p effectively inhibited sepsis-induced ALI, apoptosis as well as inflammation. miR-128-3p also played a role in antiapoptosis and anti-inflammation in MPVECs with LPS treatment. PEL12 upregulation in MPVECs alleviated miR-128-3p-induced caspase-3 activity inhibition and pro-inflammatory factor production. Conclusions miR-128-3p enabled to alleviate sepsis-induced ALI by inhibiting PEL12 expression, indicating a novel treatment strategy of miR-128-3p for sepsis-induced ALI.

Parkinson’s disease (PD) is a prevalent neurodegenerative disease. Currently, the molecular mechanisms underlying the progressions of PD are not fully understood. The human neuroblastoma cell line SH-SY5Y has been widely used as an in vitro model for PD. This study aims to investigate the molecular mechanisms of the non-coding RNA-mediated SH-SY5Y differentiation induced by retinoic acid (RA). By microArray analysis, lncRNA HAGLR was observed to be significantly upregulated during the RA-induced SH-SY5Y differentiation. Silencing HAGLR blocked the RA-induced SH-SY5Y differentiation. Moreover, bioinformatical analysis illustrated that miR-130a-3p contains binding sites for HAGLR. The RNA-pull down assay and luciferase assay demonstrated that HAGLR functioned as a ceRNA of miR-130a-3p in SH-SY5Y cells. Overexpression of miR-130a-3p effectively inhibited SH-SY5Y differentiation. We identified MeCP2, a vital molecule in neuronal diseases, to be a direct target of miR-130a-3p in SH-SY5Y cells by western blot and luciferase assays. The rescue experiments verified that recovery of miR-130a-3p in HAGLR-overexpressing SH-SY5Y cells could successfully overcome the RA-induced SH-SY5Y differentiation by targeting MeCP2. In summary, this study reveals a potential molecular mechanism for the lncRNA-HAGLR-promoted in vitro neuron differentiation by targeting the miR-130a-3p-MeCP2 axis, contributing to the understanding of the pathogenesis and progression of PD.

Background Heart failure (HF) is a serious and advanced stage of various cardiac diseases with high mortality and rehospitalization rates. Phosphoglycerate mutase 2 (PGAM2) overexpression was identified in the serum of patients with HF. Material/methods One hundred and fifty-three cases of HF were included in the present work. According to New York Heart Association (NYHA) classification, 22 were grade II, 84 were grade III, and 47 were grade IV. Serum PGAM2, NT-proBNP, B-type natriuretic peptide (BNP), troponin T (TNT), and Cys-C of HF patients were detected using ELISA assay. Left ventricular ejection fraction, left ventricular end-diastolic inner diameter, and left atrium (LA) inner diameter of the included cases were also detected by the cardiac color Doppler. Results The number of patients with atrial fibrillation was significantly higher in NYHA IV group than in groups II and III with statistical difference ( p < 0.05). The serum PGAM2, NT-proBNP, and Cys-C were significantly higher in NYHA IV group than in NYHA II and NYHA III groups ( p all < 0.05). NT-proBNP had the highest prediction efficacy of HF severity and PGAM2 was also a potential biomarker for HF severity evaluation with relatively high sensitivity, specificity, and area under the ROC. The overall survival among NYHA II, III, and IV groups were statistically different ( p = 0.04) with the median survival time of 25 months for NYHA III and IV groups. Conclusion PGAM2 is a new promising biomarker for evaluation of the severity of HF. Combination detection using multiple serum factors such as PGAM2, NT-proBNP, BNP, TNT, and Cys-C can improve the HF severity differential diagnosis performance.

Objective Leukocyte morphological parameters known as CPD (cell population data) is detected by hematology analyzer UniCel DxH800 with VCS technology. This study aimed to investigate the diagnostic efficacy of morphological changes in CPD parameters in distinguishing active tuberculosis from community-acquired pneumonia. Methods From October 2018 to February 2019, 88 patients with active tuberculosis, 78 patients with community-acquired pneumonia, and 89 healthy controls were enrolled in this study. CPD was obtained using Unicel DxH800 analyzer for all whole blood samples, one-way ANOVA (non-parametric) and area analysis under ROC curve were performed. Results The neutrophil mean conductivity (NMC), monocyte mean volume (MMV), monocyte mean conductivity (MMC), lymphocyte percentage (LY%), and monocyte percentage (MO%) were significantly higher in the active tuberculosis group than in the community-acquired pneumonia group. The white blood cell (WBC) count and neutrophil percentage (NE%) were significantly lower in the active tuberculosis group than in the community-acquired pneumonia group. The analysis of the area under the ROC curve proved that WBC count, neutrophil percentage (NE%), lymphocyte percentage (LY%), and monocyte percentage (MO%) did not achieve a higher area under the curve (AUC: 0.63, 0.71, 0.62, and 0.7, respectively). However, the AUC of NMC, MMV, and MMC in the CPD parameters was 0.951, 0.877, 0.98, respectively, and the simultaneous measurement of the three parameters was 0.99. The sensitivity and specificity were 98.5% and 91.1%, respectively. Conclusion The combined diagnosis of NMC, MMV, and MMC could assist the clinical diagnosis of active tuberculosis and community-acquired pneumonia.

Background Non-small cell lung cancer (NSCLC) is a malignant tumor with the highest mortality rate in our country. It has been found in many studies that microRNA-4521 (miR-4521) is abnormally expressed and plays a role in clear cell renal cell carcinoma and other cancers. Objective The purpose of this study was to explore the relationship between miR-4521 expression and clinical prognosis, as well as its influence on cell biological behavior. Methods The expression differences of miR-4521 in NSCLC tissues and cells were examined by qRT-PCR technology. Kaplan–Meier survival analysis and Cox regression analysis were used to analyze the clinical information and survival status of patients to explore the relationship. Using the vitro cell MTT assay, Transwell assay, and western-blot analysis, the effects of miR-4521 on cell proliferation, migration, and invasion were analyzed. Results The expression of miR-4521 in NSCLC tissues and cells was significantly downregulated. miR-4521 can be used as an independent prognostic factor. The survival rate of the miR-4521 low expression group was lower, which was significantly related to poor prognosis. In addition, the low expression of miR-4521 significantly promoted cell proliferation, migration, and invasion with highly expressed related protein levels. FOXM1 might be a direct target of miR-4521. Conclusion The results of this study showed that the low expression of miR-4521 indicated the poor prognosis of NSCLC and promoted cell proliferation, migration, and invasion by targeting FOXM1.

Objective To evaluate the prognostic value of the mean platelet volume (MPV) and red blood cell distribution width (RDW) in sepsis among premature neonates. Methods This was a retrospective cohort study conducted in the neonatal intensive care unit between May 2015 and May 2020. Premature neonates with late-onset sepsis were enrolled. The demographic data, blood cell count analysis, C-reactive protein, and blood culture were compared between survivors and non-survivors. Results A total of 73 premature neonates with sepsis in the survivor group and 10 cases in the non-survivor group. Significant differences were observed between the survivor and non-survivor groups with regard to birth weight, MPV, and RDW ( P < 0.05). The results of binomial stepwise logistic regression suggested that MPV (OR = 3.226, P = 0.017 < 0.05) and RDW (OR = 2.058, P = 0.019 < 0.05) were independent predictor for prognosis in preterm with sepsis. A receiver operating characteristic analysis showed that the areas under the curves were 0.738 for MPV alone, 0.768 for RDW alone, and 0.854 for MPV combined with RDW. Conclusion MPV and RDW were independent predictors of prognosis and the combination of the two helps in predicting the prognosis of preterm with late-onset sepsis in the early stage.

Objective To explore the role of a three-dimensional (3D)-printed porous titanium alloy scaffold (3D scaffold) in the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs) and the underlying mechanism. Methods hADMSCs were divided into control and 3D scaffold groups. The osteogenic differentiation of hADMSCs and expression of osteogenic makers were estimated. Based on the information from published articles, five candidate circular RNAs were selected, and among them, hsa_circ_0019142 showed the most promising results. Finally, control group cells were overexpressed or silenced with the hsa_circ_0019142. Then, Alizarin red S (ARS) staining, calcium content analysis and estimation of alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and collagen-1 (COL1) were performed to evaluate the role of hsa_circ_0019142 on osteogenic differentiation. Results Osteogenic differentiation of the hADMSCs was significantly higher in the 3D scaffold group than in the control group, as evidenced by ARS staining, increased calcium concentration, and elevated expression of above four osteogenic factors. qPCR revealed that the expression of hsa_circ_0019142 was significantly higher in the 3D scaffold group. Overexpression of hsa_circ_0019142 promoted the osteogenic differentiation of hADMSCs, while knockdown of hsa_circ_0019142 caused the opposite results. Conclusion The 3D-printed scaffold promoted osteogenic differentiation of hADMSCs by upregulating hsa_circ_0019142.

Aim of study was set to investigate the association of women urinary incontinence (UI) with serotonin receptor HTR2A T102C and beta 3-adrenergic receptor ADRB3 Trp64Arg genes polymorphisms. The study included 110 women with Urge, Stress, and Mixed UI types and the control group – 105 continent women. Both groups have filled in the ICIQ-FLUTS questionnaire and their blood genotyping was performed. Urge UI subgroup was older and had higher body mass index (BMI) in comparison to other UI types and control group. More than half of all women had family history of UI in Stress UI and Mixed UI subgroups. The frequency of HTR2A T102C gene polymorphism’s minor allele C and genotype CC was significantly more expressed in Urge UI subgroup, as compared with control group (C-77.3 vs 58.7%, p = 0.007 and CC-57.6 vs 31.1%, p = 0.015). The ADRB3 Trp64Arg gene polymorphism did not differ between groups. The regression analysis revealed CC genotype (OR = 3.06, 95% CI: 1.11–8.43; p = 0.030) and allele C (OR = 2.53, 95% CI: 1.16–5.53; p = 0.020) were risk factors for development of Urge UI. We conclude that HTR2A T102C gene polymorphism affected the development of Urge UI.

Introduction Several studies have shown the consequences of COVID-19 pandemic on perceived stress of different populations, but none of them analyzed urological patients who underwent elective surgery. Methods We enrolled prospectively patients who underwent elective surgery between March and October 2020. A survey on COVID-19 and the 4-item Perceived Stress Scale (PPS-4) questionnaire were administered at hospital admission. Demographic and medical history data were also collected. Uni- and multivariate analyses were performed to identify independent predictors of higher PSS-4 values (≥7). Results A total of 200 patients were enrolled. Mean PSS-4 value resulted 6.04. Patients with PSS-4 value ≥7 resulted 43.5% (87/200). In multivariate analysis, PSS-4 value ≥7 was independently associated ( p < 0.05) with female gender (OR 6.42), oncological disease (OR 2.87), high (>5 in a range between 0 and 10) fear of intrahospital transmission of SARS-CoV-2 infection (OR 4.75), history of bladder instillation (OR 0.26), and current smokers (OR 0.27) Conclusion High PSS-4 values at hospital admission in urologic surgical patients are positively correlated with female gender, fear of intrahospital transmission of SARS-CoV-2 infection, and oncological disease. PSS-4 questionnaire could be useful to select patients for whom a preadmission counselling is necessary to improve the management of their high stress level.

MicroRNAs (miRNAs) operate as tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis, and metabolic process. In the present research, we investigated the effect and mechanism of miR-496 in human gastric cancer cells. miR-496 was downregulated in two gastric cancer cell lines, AGS and MKN45, compared with normal gastric epithelial cell line GES-1. miR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. miR-496 mimics induced the apoptosis through upregulating the levels of Bax and Active Caspase 3 and downregulating the levels of Bcl-2 and Total Caspase 3. Bioinformatics analysis showed that there was a binding site between miR-496 and Lyn kinase (LYN). miR-496 mimics could inhibit the expression of LYN in AGS cells. LYN overexpression blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment for gastric cancer.

The purpose of the current study was to characterize role of microRNA (miR)-519d in trophoblast cells and preeclampsia (PE) development and its potential underlying mechanism. Regulation of leptin (LEP) by miR-519d was verified using a dual-luciferase reporter gene assay. Loss- and gain-of-function assays were conducted to detect the roles of miR-519d and LEP in proliferation, migratory ability, and invasive capacity of HTR-8/SVneo cells by means of CCK-8 assay, scratch test, and Transwell invasion assay, respectively. The cell apoptosis rate and cycle distribution were analyzed by flow cytometry. LEP expression was elevated, whereas miR-519d level was suppressed in the PE placenta samples compared with those from normal pregnancy. Depletion of LEP promoted proliferation, migratory ability, and invasive capacity and repressed apoptosis. miR-519d could bind 3′ untranslated regions (3′UTRs) of LEP, the extent of which correlated negatively with LEP expression. miR-519d suppressed the expression of LEP in HTR-8/SVneo cells. Moreover, overexpression of miR-519d promoted survival and migratory ability of HTR-8/SVneo cells. Taken together, we find that miR-519d targeted LEP and downregulated its expression, which could likely inhibit the development of PE.

Objective To compare the perioperative parameters between single- and triple-port video-assisted thoracoscopic surgery (VATS) lobectomy in the treatment of lung cancer. Methods The Pubmed, Embase, Cochrane library, and the Web of Science databases were electronically searched from inception to September 2019 for all relevant studies. Study quality was evaluated using the Jadad scale or the Newcastle-Ottawa scale. The results were pooled using the generic inverse-variance method and expressed as mean differences or risk ratios, with 95% confidence intervals. Results Three randomized controlled trials (RCTs) and ten cohort studies with 2,278 subjects were included in the meta-analysis. Whether based on RCTs or cohort studies, the pooled results showed no significant difference in the operation time, chest tube duration, intraoperative blood loss, postoperative hospital stays, lymph node dissection number, postoperative drainage volume, and postoperative complications between single- and triple-port VATS lobectomy ( P > 0.05). Single-port VATS could relieve postoperative pain better than triple-port VATS, especially in the first day and fifth day ( P < 0.05). No evidence of significant publication bias was found ( P > 0.05). Conclusion Single-port VATS lobectomy can yield similar perioperative results to those of triple-port VATS lobectomy and is more effective in relieving postoperative pain.

Skin grafting is often the only treatment for skin trauma when large areas of tissue are affected. This surgical intervention damages the deeper dermal layers of the skin with implications for wound healing and a risk of scar development. Photobiomodulation (PBM) therapy modulates biological processes in different tissues, with a positive effect on many cell types and pathways essential for wound healing. This study investigated the effect of fluorescent light energy (FLE) therapy, a novel type of PBM, on healing after skin grafting in a dermal fibrotic mouse model. Split-thickness human skin grafts were transplanted onto full-thickness excisional wounds on nude mice. Treated wounds were monitored, and excised xenografts were examined to assess healing and pathophysiological processes essential for developing chronic wounds or scarring. Results demonstrated that FLE treatment initially accelerated re-epithelialization and rete ridge formation, while later reduced neovascularization, collagen deposition, myofibroblast and mast cell accumulation, and connective tissue growth factor expression. While there was no visible difference in gross morphology, we found that FLE treatment promoted a balanced collagen remodeling. Collectively, these findings suggest that FLE has a conceivable effect at balancing healing after skin grafting, which reduces the risk of infections, chronic wound development, and fibrotic scarring.

In this study, we aim to discover the importance of long non-coding RNA cyclin-dependent kinase 6 (CDK6)-AS1 in lipopolysaccharide (LPS)-induced HK-2 cells. We treated the HK-2 cells with LPS and knocked down CDK6-AS1 in HK-2 cells and then analyzed the effects of CDK6-AS1 on the viability of cell, cell apoptosis, the expression of cytokines via MTT, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and qPCR. The results showed that silencing CDK6-AS1 alleviated LPS-induced inhibition of HK-2 cell proliferation, release of IL-1β, IL-8, IL-6, and TNF-α, cell apoptosis, and decrease in mitochondrial membrane potential. In addition, decreasing the level of CDK6-AS1 inhibited the reduction of Bcl-2 levels, the expression of Bax, cleaved caspade-9, and cleaved caspase-3, induced by LPS. In conclusion, lowering CDK6-AS1 level alleviates LPS-induced inflammatory damage in HK-2 cells.

Non-small cell lung cancer (NSCLC), a commonly diagnosed lung cancer, is characterized by a high incidence of metastatic spread to the brain, which adversely impacts prognosis. The present study aimed to assess the value of combined dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the treatment outcomes of whole-brain radiotherapy (WBRT) and gefitinib in brain metastases from non-small cell lung cancer (NSCLC) from the perspectives of response rate and short- and long-term efficacy. These results suggested that the indicators measured by DCE-MRI combined with DWI can be used as key imaging-derived markers that predicted the efficacy of WBRT combined with gefitinib in NSCLC patients with brain metastases. Specifically, patients with higher ΔADC mid and ΔADC post values showed better treatment outcomes. ROC curve analysis indicated ADC post , ΔADC post , ΔADC post (%), and tumor regression rate as the best predictors of efficacy of WBRT combined with gefitinib in these patients. The short-term and long-term effects noted were also significant. Taken together, the findings of this study reveal that tumor regression rate, ADC post , ΔADC post , and ΔADC post (%) can be used as important imaging indicators that predict the therapeutic effect of WBRT combined with gefitinib in NSCLC patients with brain metastases.

Purpose The purpose of our present study was to explore the characteristics and outcomes of congenital heart disease (CHD) patients with severe postoperative hyperbilirubinemia. Methods All patients who underwent cardiopulmonary bypass surgical treatment for CHD and had severe postoperative hyperbilirubinemia (total bilirubin [TB] ≥85.5 μmol/L) in our center between January 2015 and December 2018 were retrospectively screened. Univariate and multivariate analyses were employed to identify risk factors for the study endpoints, including postoperative acute kidney injury (AKI), in-hospital mortality, and long-term mortality. Results After screening, 86 patients were included in our present study. In-hospital mortality was 10.9%. Fifty-one (59.3%) patients experienced AKI, and four (4.7%) patients received continuous renal replacement therapy. Multivariate analysis identified that the peak TB concentration ( P = 0.002) and duration of mechanical ventilation ( P = 0.008) were independent risk factors for in-hospital mortality, and stage 3 AKI was an independent risk factor for long-term mortality. The optimal cutoff value for peak TB concentration was 125.9 μmol/L. Patients with a postoperative TB level ≥125.9 μmol/L had worse long-term survival. Conclusion Hyperbilirubinemia was a common complication after CHD surgery. CHD patients with severe postoperative hyperbilirubinemia ≥125.9 μmol/L and AKI had a higher risk of mortality.

Objective To investigate the effect of baicalin on diabetic nephropathy (DN) rats and podocytes and its mechanism. Methods The rat models with DN were established by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. The fasting blood glucose (FBG) and weight of rats in each group were measured at 0, 1, 2, 3, and 4 weeks. Their biochemical indicators, expression of inflammatory, and antioxidant factors were measured using an automatic biochemical analyzer together with ELISA. Hematoxylin–eosin staining and periodic acid-schiff staining were used to observe the morphological changes in the kidneys of rats in each group. Finally, the expressions of related molecules and PI3K/Akt/mTOR signaling pathway proteins in renal tissues and podocytes were examined by qRT-PCR and Western blot. Results Compared with the DN group, the FBG and weight, serum creatinine, blood urea nitrogen, total cholesterol, triacylglycerol, microalbumin, and albumin/creatinine ratio were all significantly decreased in the Baicalin treatment groups in a concentration-dependent manner. The levels of inflammatory factors in kidney tissue and podocytes were decreased. In addition, the activities of lactate dehydrogenase and malondialdehyde in tissue were decreased, while the superoxide dismutase was increased. The pathological sections showed that glomerular atrophy and glomerular basement membrane thickening caused by hyperglycemia were improved in the Baicalin treatment groups. Meanwhile, baicalin inhibited the downregulation of Nephrin and Podocin expressions and upregulation of Desmin expression caused by DN, and inhibited the expressions of p-PI3K, p-Akt, and p-mTOR proteins. Conclusion Baicalin slows down podocyte injury caused by DN by inhibiting the activity of PI3K/Akt/mTOR signaling pathway.

Double-J stent (DJ) placement is usually the treatment of choice for relieving external compression of the ureter. However, in some cases DJ function may become impaired and a percutaneous nephrostomy (PCN) may be required. Previous studies have reported different predictive factors for choosing PCN or DJ insertion as the initial treatment. In this study, we analyzed the risk factors for DJ failure in patients with external ureteral compression. Our results showed that the patients with moderate and severe hydronephrosis ( p -value = 0.0171 and 0.0249, respectively), preexisting pyuria ( p -value = 0.0128), or lower ureter obstruction ( p -value = 0.0305) were more prone to DJ laterality. Age was also an important predictor. Urologists should pay more attention to these patients and consider PCN as the initial treatment.

As a gaseous mediator, hydrogen sulfide (H 2 S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H 2 S donors have been synthesized to study atherosclerosis diseases. In this study, proglumide-(5-(4-hydroxyphenyl)-3 H -1,2-dithiole-3-thione) (P-A) was synthesized as a H 2 S donor. The protective effect and mechanism of P-A on HUVEC that was injured by ox-LDL were detected. The HUEVCs were affected by 100 μmol/L P-A for 24 h; the release of H 2 S was the largest. After 100 μmol/L P-A acted on HUVEC damage model for 12 h, the cell proliferation activity was the best. The results showed that P-A can downregulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.

We retrospectively analyzed the clinical data of 635 patients with acute acromioclavicular dislocation, who underwent surgery in our hospital between May 2014 and June 2020. Patients were divided into group A (clavicular hook plate) and group B (Triple-Endobutton plates via double-incision). The propensity score analysis using one to one match was performed for comparisons. We obtained 292 matched patients’ data. The matched preoperative clinical characteristics were a balance between the two groups. All clinical parameters showed insignificant differences ( P > 0.05). Compared with group A, group B has longer operative time ( P < 0.001) and more blood loss ( P < 0.001); however, the mean incision length ( P < 0.001) and length of hospitalization ( P < 0.001) were shorter in group B than in the group A. The mean VAS in group B were significantly lower than in group A at each time point ( P < 0.001), and the UCLA shoulder score was higher in the group B. The CMS scores were also higher in group B than in group A, including before removal and 12 weeks after removal ( P < 0.001). The clinical efficacy of the double-incision Triple-Endobutton plate is better than the clavicular hook plate technology, and achieves anatomical reduction by reconstructing coracoclavicular ligament.

Background Diabetic nephropathy (DN) is a common diabetic complication. Long noncoding RNAs (lncRNAs) have been identified as essential regulators in DN progression. This study is devoted to the research of lncRNA-myocardial infarction-associated transcript (MIAT) in DN. Methods DN cell model was established by high glucose (HG) treatment for human renal tubular epithelial cells (HK-2). Cell viability and colonizing capacity were analyzed by Cell Counting Kit-8 (CCK-8) and colony formation assay. Apoptosis was assessed via caspase-3 detection and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used for evaluating inflammation. The protein determination was completed using western blot. MIAT, microRNA-182-5p (miR-182-5p), and G protein-coupled receptor class C group 5 member A (GPRC5A) levels were all examined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Intergenic binding was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Results HG induced the inhibition of cell growth, but accelerated apoptosis and inflammation as well as the activation of nuclear factor kappa B (NF-κB) pathway. MIAT reestablishment prevented the HG-induced cell damages and NF-κB signal activation. Mechanistically, MIAT was proved as a miR-182-5p sponge and regulated the expression of GPRC5A that was a miR-182-5p target. The rescued experiments demonstrated that MIAT downregulation or miR-182-5p upregulation aggravated the HG-induced cell damages and activated the NF-κB pathway via the respective regulation of miR-182-5p or GPRC5A. Conclusion Taken together, MIAT functioned as an inhibitory factor in the pathogenesis to impede the development of DN and inactivate the NF-κB pathway via regulating the miR-182-5p/GPRC5A axis.

Objective The aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients. Methods miR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed. Results In the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others. Conclusion These results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.

MicroRNAs are involved in the pathogenesis of various human malignant tumors. This study aims to explore the role of miR-513b-5p in the malignant proliferation of retinoblastoma (RB) cells and its potential molecular mechanisms. The function-gain and function-loss experiments were performed in Weri-RB1 cells using miR-513b-5 mimics and inhibitors. miR-513b-5p mimics inhibited the proliferation and clone formation and promoted apoptosis of Weri-RB1 cells. In contrast, the miR-513b-5p inhibitor promoted the proliferation and clone formation of Weri-RB1 cells and inhibited cell apoptosis. miR-513b-5p can directly bind to the 3′UTR region of TRIB1 mRNA, and inhibit its protein expression. Overexpression of TRIB1 promoted the proliferation and cloning of Weri-RB1 cells but inhibited their apoptosis. The knockdown of TRIB1 inhibited the proliferation and clone formation of Weri-RB1 cells and promoted cell apoptosis. In addition, miR-513b-5p mimics neutralized the effects of TRIB1 overexpression on the proliferation and apoptosis of Weri-RB1 cells. Finally, miR-513b-5p can inhibit the phosphorylation level of AKT, mTOR, and p70, while TRIB1 played the opposite role. miR-513b-5p inhibits the malignant proliferation of Weri-RB1 cells by repressing the expression of TRIB1. miR-513b-5p and TRIB1 may be the biomarkers and/or key targets for clinical diagnosis and treatment of RB.

Aim Renal fibrosis (RF) is a common clinical condition leading to irreversible renal function loss. Tyrosine kinase proteins and microRNAs (miRs) are associated with pathogenesis and we aim to investigate the role of Fer and its partner miR(s) in RF. Method In silico reproduction of Mouse Kidney FibrOmics browser was performed to identify potential miR(s) and target gene(s). In vivo validation was performed in C57BL/6 mice with unilateral ureteral obstruction (UUO). In vitro validation was performed in rat kidney fibroblast NRK-49F cells. Mimics and inhibitors of miR-29c-3p were constructed. The target gene Fer was monitored by RT-PCR and western blotting. The levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. Results The Fer expression and protein level were gradually increased during 14 days of UUO modeling. miR-29c-3p expression was strongly correlated with that of Fer. In vivo validation showed increased expressions of fibrosis-associated genes and increased phospoho-Smad3 level in the UUO model. Fer-knockdown (KD) significantly decreased expressions of fibrosis-associated genes. Pharmaceutical inhibition of Fer showed similar effects to miR-29c-3p, and miR inhibition showed a significant decrease of excretion of inflammatory factors. Conclusion Dysregulation of miR-29c-3p and Fer plays a role in RF. Pharmaceutical or genetic inhibition of Fer may serve as the potential treatment for RF.

Background miR-92a is believed to have a significant role in the diagnosis and prognosis of different types of tumors, but the potential impact of its expression is still controversial due to the sample size. We conducted the meta-analysis to figure out whether miR-92a could be used as a detecting tool for assessing the prognosis of gastric cancer. Method A literature search was conducted by retrieving the Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, VIP (Technology of Chongqing databases), and Wanfang databases (last updated by February 2020). The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were pooled to explore the diagnostic performance of miR-92a. The pooled hazard ratios (HRs) and 95% CIs of miR-92a for overall survival (OS) were calculated to explore the prognostic performance of miR-92a. Results Nine articles containing 11 studies were included. The pooled SEN and SPE were 0.76 and 0.79. Besides, the pooled PLR and NLR were 3.7 and 0.30, and the pooled DOR was 12. AUC was 0.84, indicating a significant value of miR-92a in gastric cancer detection. For the prognostic analysis of miR-92a in gastric cancer, the univariate and multivariate data’s poor OS were 1.37 and 2.01. Conclusion The present meta-analysis demonstrated that miR-92a could be a potential biomarker for the detection of gastric cancer. miR-92a could also be used as a valuable indicator for predicting the prognosis of gastric cancer patients.

Voltage-dependent calcium channel subunit alpha-2/delta-1 (α2δ1) has been identified as a marker of cancer stem cells in multiple malignant tumor types. However, α2δ1’s role in the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) was not reported. In our study, ten pairs of HSCC and peritumoral normal tissues were used for immunohistochemistry assessment. And α2δ1 expression levels of 34 more HSCC samples were also evaluated, represented by the integral optic density using Image-Pro Plus. Clinicopathological associations and prognostic value of α2δ1 were analyzed. As a result, α2δ1 expression was frequently increased in HSCC tissues. Although the correlation between patients’ clinicopathological characteristics and their α2δ1 expression levels was not significant, α2δ1 expression was significantly correlated with unfavorable overall survival (OS) ( P = 0.018) and progression-free survival (PFS) ( P = 0.023). Univariate and multivariate cox regression analyses suggested α2δ1’s prognostic role for both OS and PFS ( P = 0.013 and 0.011, respectively). This study specifically demonstrated that α2δ1 regularly increased in HSCC compared with peritumoral tissues, and α2δ1 could act as a promising prognostic marker in HSCC patients.

There is no specific drug for coronavirus disease 2019 (COVID-19). We aimed to investigate the possible clinical efficacy of moderate-dose vitamin C infusion among inpatients with severe COVID-19. Data of 397 adult patients with severe COVID-19 admitted to a designated clinical center of Wuhan Union Hospital (China) between February 13 and February 29, 2020, were collected. Besides standard therapies, patients were treated with vitamin C (2–4 g/day) or not. The primary outcome was all-cause death. Secondary outcome was clinical improvement of 2 points on a 6-point ordinal scale. About 70 participants were treated with intravenous vitamin C, and 327 did not receive it. No significant association was found between vitamin C use and death on inverse probability treatment weighting (IPTW) analysis (weighted hazard ratio [HR], 2.69; 95% confidence interval [CI], 0.91–7.89). Clinical improvement occurred in 74.3% (52/70) of patients in the vitamin C group and 95.1% (311/327) in the no vitamin C group. No significant difference was observed between the two groups on IPTW analysis (weighted HR, 0.76; 95% CI, 0.55–1.07). Our findings revealed that in patients with severe COVID-19, treatment with moderate dose of intravenous vitamin C had no significant benefit on reducing the risk of death and obtaining clinical improvement.

Background Circular RNAs have been identified as crucial players in the initiation and progression of cancers, including colorectal cancer (CRC). The Has_circ_0000467 (circ_0000467) expression has been found to be upregulated in CRC, but its function and mechanism remain unclear. Methods The expression levels of circ_0000467, microRNA-4766-5p (miR-4766-5p), and Krueppel-like factor 12 (KLF12) were examined using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by cell counting kit-8 assay and colony formation assay. The apoptosis was measured by flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastatic ability. Angiogenesis was detected using tube formation assay. All protein expressions were quantified by western blot assay. Dual-luciferase reporter assay was used to analyze intergenic binding. Xenograft models were constructed for the experiment of circ_0000467 in vivo . Results The expression of circ_0000467 was upregulated in CRC tissues and cells. Knockdown of circ_0000467 repressed cell proliferation, metastasis, and angiogenesis, but it induced apoptosis in CRC cells. circ_0000467 targeted miR-4766-5p and inhibited the expression of miR-4766-5p. Silencing of circ_0000467 inhibited CRC progression by upregulating miR-4766-5p. miR-4766-5p suppressed the expression of target gene KLF12 and KLF12 overexpression reversed the effects of miR-4766-5p on CRC cell behaviors. circ_0000467 positively regulated the expression of KLF12 by targeting miR-4766-5p. circ_0000467 downregulation in vivo reduced CRC tumorigenesis by regulating miR-4766-5p and KLF12. Conclusion circ_0000467 acted as an oncogene in CRC through regulating KLF12 expression by sponging miR-4766-5p. Therefore, circ_0000467 can be used as an effective target in CRC diagnosis and therapy.

Tubulointerstitial fibrosis leads to tubular basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). Matrix metallopeptidase-2 (MMP-2) is involved in the breakdown of ECM. Chronic hypoxia often occurs in the kidney tissues of patients with chronic kidney disease. Our previous study reported the effect of autophagy and endocytosis on MMP-2 activity in hypoxia-treated HK-2 cells. In this study, the relationship between the Ras-related protein Rab-7a (RAB7) and MMP-2 activity was further investigated. RAB7 overexpression decreased MMP-2 activity. In contrast, the results for RAB7 knockdown displayed the opposite pattern. Short hairpin RNA technology was used to knockdown Caveolin-1 (Cav-1) or Beclin-1 (Bec-1) in HK-2 cells. The two genes displayed differential effects on MMP-2 activity. Cav-1 and RAB7 interference increased MMP-2 activity. This study suggested that autophagy and endocytosis, RAB7, Cav-1, and Bec-1 may serve as potential mediators for altered MMP-2 activity.

Background In this retrospective study, we studied the impact of educational osteoporosis program on the rates of bone mineral density (BMD) assessment and bone turnover markers (BTM) and drug medications in the patients with hip fracture. Methods This retrospective research enrolled 651 patients aged ≥50 years who experienced hip fractures from January 2013 to December 2015. We recorded whether patients had received BMD assessment, BTM measurement, and anti-osteoporosis therapy during the period of hospitalization. Orthopedic surgeons were classified into the trained group and the untrained group. The rates of BMD assessment, BTM measurement, and anti-osteoporosis medications in the patients with hip fracture were compared between the trained group and the untrained group. Results BMD assessment was performed in 109/220 patients in the trained group and 142/431 patients in the untrained group. BTM measurements were performed in 130 patients in the trained group and 124 patients in the untrained group. Forty eight patients in the trained group and 63 patients in the untrained group received bisphosphonate medications. Conclusions Although the rates of BMD assessment, BTM measurement, and bisphosphonate use in the patients after hip fractures are still insufficient, education programs help to improve the situation.

Objective The purpose of this study was to explore the effect of CRABP2 and FABP5, and their ratio on prognosis in esophageal squamous cell carcinoma. Methods The expression data of CRABP2 in esophageal cancer in TCGA and GEO were collected by the public database GEPIA. The expression levels of CRABP2 and FABP5 were examined using immunohistochemistry. The relationship between the two proteins and related clinicopathological parameters were analyzed by χ 2 test. Survival analysis was used to investigate the effect of CRABP2 and FABP5, and their ratio on prognosis. Results Compared with normal esophageal mucosal epithelium, there was lower CRABP2 gene mRNA in the esophageal cancer tissue, and the difference was statistically significant ( p < 0.01). For the expression level, no significant difference was observed in patients with stages I–IV in esophageal cancer. Immunohistochemistry showed that CRABP2 and FABP5 were both highly expressed in normal esophageal squamous epithelial cells at 100 and 94.1%, while lower in ESCC (75.6 and 58.7%). There was a significant difference in the expression between cancer and adjacent tissues ( p < 0.001). No inherent relationship was manifested between the CRABP2 expression and the clinical parameters of the ESCC. The expression of FABP5 was related to lymph node metastasis ( p = 0.032), the depth of invasion ( p = 0.041), and the AJCC stage ( p = 0.013). The ratio of CRABP2 and FABP5 was related to ethnicity ( p = 0.001), nerve invasion ( p = 0.031), and postoperative treatment ( p = 0.038). CRABP2 is positively associated with FABP5 ( r = 0.156, p = 0.041) and the ratio ( r = 0.334, p = 0.000), while there was a negative correlation between FABP5 and the ratio ( r = −0.269, p = 0.000). Patients with CRABP2-positive expression had a significantly longer overall survival than patients with CRABP2-negative expression ( p = 0.025). Conclusion CRABP2 as a suppressor factor is expected to be a potential prognosis marker for esophageal squamous cell carcinoma.

Introduction Gap junction protein, alpha 1 (GJA1), which is correlated with recurrences and unfavorable prognoses in hepatocellular carcinomas (HCCs), is one of the specific proteins expressed by activated hepatic stellate cells (HSCs). Methods Expression of GJA1 was compared between HCCs and nontumor tissues (NTs), between hepatic cirrhosis and NTs, and between primary and metastatic HCCs using transcriptomic datasets from the Gene Expression Omnibus and the Integrative Molecular Database of Hepatocellular Carcinoma. The in vitro activities of GJA1 were investigated in cultured HSCs and HCC cells. The underlying mechanism was characterized using Gene Set Enrichment Analysis and validated by western blotting. Results The expression of GJA1 was significantly increased in HCCs and hepatic cirrhosis compared to that in NTs. GJA1 was also overexpressed in pulmonary metastases from HCCs when compared with HCCs without metastasis. Overexpression of GJA1 promoted while knockdown of GJA1 inhibited proliferation and transforming growth factor (TGF)-β-mediated activation and migration of cultured HSCs. Overexpression of GJA1 by lentivirus infection promoted proliferation and migration, while conditioned medium from HSCs overexpressing GJA1 promoted migration but inhibited proliferation of Hep3B and PLC-PRF-5 cells. Lentivirus infection with shGJA1 or conditioned medium from shGJA1-infected HSCs inhibited the proliferation and migration of HCCLM3 cells that had a high propensity toward lung metastasis. Mechanistically, GJA1 induced the epithelial–mesenchymal transition (EMT) in HSCs and HCCLM3 cells. Conclusion GJA1 promoted HCC progression by inducing HSC activation and the EMT in HSCs. GJA1 is potentially regulated by TGF-β and thus may be a therapeutic target to inhibit HCC progression.

Zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) functions as an oncogenic long noncoding RNA (lncRNA) to promote proliferation and metastasis of endometrial carcinoma cell; however, the underlying mechanism has not been fully understood. First, RT-qPCR analysis of endometrial carcinoma tissues and cells showed that ZFAS1 was enriched in endometrial carcinoma tissues and cells. miR-34b was reduced in endometrial carcinoma and suggested negative correlation with ZFAS1 in endometrial carcinoma. Second, functional assays demonstrated that siRNA-mediated silence of ZFAS1 suppressed endometrial carcinoma cell proliferation and metastasis. Third, ZFAS1 bind to miR-34b and negatively regulate expression of miR-34b in endometrial carcinoma cells. miR-34b also bind to and negatively regulate expression of vascular endothelial growth factor A (VEGFA) in endometrial carcinoma cells. Lastly, knockdown of miR-34b counteracted with the suppressive effects of ZFAS1 silence on endometrial carcinoma cell proliferation and metastasis. In conclusion, lncRNA ZFAS1 functioned as an oncogene to promote endometrial carcinoma cell proliferation and metastasis through miR-34b/VEGFA axis.

All autopsy studies demonstrated widespread thrombosis and alveolar-capillary microthrombi as the cause of death among patients with COVID-19. The autopsy studies are the gold-standard for diagnostic accuracy and therapeutic strategies for any clinical scenarios. The author initially observed that patients already taking therapeutic dose of oral direct factor Xa inhibitors for an unrelated reason, have significantly better survival rates than those not taking any anticoagulants. This influenced the author to conduct a retrospective chart review of the hospitalized patients in Jackson Hospital (Alabama) to evaluate the effect of variable doses of anticoagulation among COVID-19 patients. The study found that serum inflammatory bio-marker D-dimer trends are associated with changes in oxygen requirement among patients with COVID-19, if patients present at an early stage, and titration of Enoxaparin (anticoagulation) dose based on D-dimer trends leads to increased patient survival.

Introduction This study is to investigate the effect of late-onset hemorrhagic cystitis (LOHC) on progression-free survival (PFS) of patients after haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). Methods This retrospective study enrolled 74 patients with hematological malignancies treated with a myeloablative conditioning regimen and haplo-PBSCT. The effect of LOHC on PFS was studied in terms of HC occurrence, grade, disease type, duration, onset time, gender, and age. Results There were 28 patients with LOHC, and no case was with early-onset HC. The cumulative incidence of LOHC was 37.8% (95% CI: 26.9–48.7%). The 2-year expected PFS of 74 patients and 34 AML patients was not significantly different between LOHC patients and patients without HC ( P > 0.05). Among 27 ALL patients, the 2-year expected PFS of LOHC patients was 75%, significantly higher than patients without HC (54.2%) ( P < 0.05). The 2-year expected PFSs of patients with mild LOHC and severe LOHC were 69.8 and 77.8%, respectively ( P > 0.05). Similarly, the onset time, duration, age, and gender of LOHC patients did not show significant effects on PFS ( P > 0.05). Conclusions After haplo-PBSCT, LOHC has a significant effect on the PFS of ALL patients. The HC grade, duration, onset time, gender, and age have no significant effect on PFS.

Background Discordant results exist about the role of human epidermal growth factor receptor 2 (HER2) overexpression and/or HER2 amplification in lung adenocarcinoma. We aimed to compare the performance of HercepTest and PATHWAY anti-HER2 (4B5) by correlating immunohistochemistry (IHC) results with silver in situ hybridization (SISH) in adenocarcinoma lung specimens. Methods A total of 148 surgically resected adenocarcinoma lung specimens were included. Results HER2 overexpression was found in 7.4% patients for HercepTest Dako and in 2.7% patients for 4B5 antibody. The overall coincidence between these two types of antibodies equals 93.9%. The incidence of HER2 amplification in lung adenocarcinoma was 17.6%, of which in 2.7% of the cases high-grade amplification was present. HER2 amplification was present in 90.9% of patients with overexpression of HER2, obtained by using HercepTest Dako and 75% patients using 4B5 antibody. A significant correlation between overexpression of HER2 receptors obtained by HercepTest Dako and 4B5 antibody and HER2 amplification was shown. Conclusion The research of the efficiency of targeted molecular therapies with an HER2 antibody may serve as a basis for the introduction of routine HER2 status determination in lung adenocarcinoma, dictating the need for the standardized protocol for HER2 status determination in such pathology.

Objective V-set and transmembrane domain-containing protein 1 (VSTM1) is negatively correlated with inflammation. However, its effect on atherosclerosis (AS) remains largely unexplored. In this study, we aimed to assess the effect of VSTM1 on the biological function of human peripheral blood mononuclear cells /macrophages stimulated by oxidized low-density lipoprotein (ox-LDL). Methods U937 cells were divided into three groups as follows: control group, pLenti-VSTM1 shRNA group (VSTM1 depletion), and pLenti-VSTM1 group (VSTM1 overexpression). Cellular migration, chemotaxis, apoptosis, and secretion of inflammatory factors of monocytes/macrophages stimulated by ox-LDL were studied. Results Overexpression of VSTM1 decreased the proliferation of U937 cells and induced cellular apoptosis. Depletion of VSTM1 enhanced the invasiveness and chemotaxis, increased the inflammatory response, and reduced the incidence of cell necrosis and apoptosis. Nuclear factor κ of B cells (NF-κB) was activated in VSTM1-depleted U937 cells. Conclusion VSTM1 might play an important role in the activation of monocytes/macrophages and participate in the pathogenesis of AS via regulating NF-κB activity.

Background Experts in many countries are recommending a scaling up midwifery-led care as a model to improve maternal and newborn outcomes, reduce rates of unnecessary interventions, realise cost savings, and facilitate normal spontaneous vaginal birth. Objective The aim of this study was to compare midwifery-led and obstetrician-gynaecologist-led care-related vaginal birth outcomes. Participants Pregnant women in Kaunas city maternity care facilities. Methods A propensity score-matched case–control study of midwifery-led versus physician-led low-risk birth outcomes. Patient characteristics and outcomes were compared between the groups. Continuous variables are presented as mean ± standard deviation and analysed using the Mann–Whitney U test. Categorical and binary variables are presented as frequency (percentage), and differences were analysed using the chi-square test. Analyses were conducted separately for the unmatched (before propensity score matched [PSM]) and matched (after PSM) groups. Results After adjusting groups for propensity score, postpartum haemorrhage differences between physician-led and midwifery-led labours were significantly different (169.5 and 152.6 mL; p = 0.026), same for hospital stay duration (3.3 and 3.1 days, p = 0.042). Also, in matched population, significant differences were seen for episiotomy rates (chi 2 = 4.8; p = 0.029), newborn Apgar 5 min score (9.58 and 9.76; p = 0.002), and pain relief (chi 2 = 14.9; p = 0.002). Significant differences were seen in unmatched but not confirmed in matched population for obstetrical procedures used during labour, breastfeeding, birth induction, newborn Apgar 1 min scores, and successful vaginal birth as an overall spontaneous vaginal birth success measure. Conclusion The midwifery-led care model showed significant differences from the physician-led care model in episiotomy rates, hospital stay duration and postpartum haemorrhage, and newborn Apgar 5 min scores. Midwifery-led care is as safe as physician-led care and does not influence the rate of successful spontaneous vaginal births.

The aim of this study was to investigate the characteristics of postmenopausal women prescribed with teriparatide in Slovenia, during the first decade after its approval, and the predictors of bone mineral density (BMD) improvement with treatment. We retrospectively studied postmenopausal osteoporotic patients prescribed with teriparatide at tertiary center from 2006 to 2015. BMD was measured at standard sites by DXA at baseline, after 12 and 24 months. 25-hydroxyvitamin D and procollagen type I N-terminal propeptide (PINP) were measured at the same time-points. The inclusion criteria were met by 188 women (aged 71 years on average), 151 (80.3%) with postmenopausal and 37 (19.7%) with glucocorticoid-induced osteoporosis. Everyone had at least one fracture, 159 (84.6%) had ≥2 fractures, with vertebral fractures in 172 patients (91.5%). All patients had been previously on antiresorptives for 8.6 years on average. The average BMD change at lumbar spine, total hip, and femoral neck was +5.0%, −1.1%, and +0.3% after 24 months of treatment, respectively. Higher baseline PINP was associated with higher BMD increase at all sites after the first 12 months. Teriparatide was prescribed mostly to elderly women with severe osteoporosis who had sustained two or more fractures despite long-term antiresorptive therapy. Baseline PINP might predict initial BMD increase with teriparatide.

Background Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. Methods Male Sprague Dawley rats ( n = 160) were randomized into eight groups ( n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. Results MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. Conclusion HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

Objective This study aims to identify superenhancer (SE)–transcriptional factor (TF) regulatory network related to eight common malignant tumors based on ChIP-seq data modified by histone H3K27ac in the enhancer region of the SRA database. Methods H3K27ac ChIP-seq data of eight common malignant tumor samples were downloaded from the SRA database and subjected to comparison with the human reference genome hg19. TFs regulated by SEs were screened with HOMER software. Core regulatory circuitry (CRC) in malignant tumor samples was defined through CRCmapper software and validated by RNA-seq data in TCGA. The findings were substantiated in bladder cancer cell experiments. Results Different malignant tumors could be distinguished through the H3K27ac signal. After SE identification in eight common malignant tumor samples, 35 SE-regulated genes were defined as malignant tumor-specific. SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. In vitro experimental data verified the presence of a SE–TF regulatory network in bladder cancer, and SE–TF regulatory network enhanced the malignant phenotype of bladder cancer cells. Conclusion The SE–TF regulatory network with SMAD3 as the core TF may participate in the carcinogenesis of malignant tumors.

Type 2 diabetes mellitus (T2DM) is a strong risk tfactor for osteosarcopenia. The relationship between musculoskeletal index and β-cell function remains controversial. We aimed to describe the clinical characteristics of osteosarcopenia and to explore the association between osteosarcopenia and β-cell function, as well as insulin resistance in patients with T2DM. A total of 150 middle-aged and older nonobese patients with T2DM were recruited. Bone mineral density (BMD) and body composition were measured by the dual-energy X-ray absorptiometry scanner. The homeostasis model assessment of insulin resistance and Matsuda index were used to evaluate insulin resistance status. β-Cell function was estimated by the area under the curve insulin/glucose (AUC-Ins/Glu) and the area under the curve C-peptide/glucose (AUC-CP/Glu). T2DM patients with osteosarcopenia had lower body mass index, waist circumference, body fat percentage, AUC-Ins/Glu, and AUC-CP/Glu. Both AUC-Ins/Glu (OR = 0.634 , P = 0.008) and AUC-CP/Glu (OR = 0.491, P = 0.009) were negatively associated with the presence of osteosarcopenia. Multivariate linear regression analysis showed that β-cell function was positively associated with the skeletal muscle mass index, whereas it showed no correlation with lumbar or hip BMD. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with T2DM. These findings suggest that β-cell function might be a protective factor against osteosarcopenia.

Objectives The aim of this study is to investigate clinical features of atypical pulmonary tuberculosis (aPTB) mimicking bacterial pneumonia, determine imaging features with the highest degree of correlation, and identify predictors for acid-fast bacilli (AFB) positivity. Methods The clinical data of 259 patients considered as aPTB were retrospectively analyzed. The correlation of CT patterns was evaluated with Spearman analysis, and the predictors for AFB positivity were assessed with the multivariate analysis. Results The most common symptom of aPTB was cough (84.6%), followed by fever and anorexia (47.1 and 41.7%, respectively). Infiltrated patchy was the most common radiological pattern (84.9%), followed by nodules (3–10 mm), micronodules (<3 mm), and consolidation (79.2, 78.8, and 66.0%, respectively). Nodules (3–10 mm) and micronodules ( r = 0.988, p < 0.001), consolidation and air bronchogram ( r = 0.590, p < 0.001), and pulmonary atelectasis and consolidation ( r = 0.323, p < 0.001) showed high correlation. In the multivariate analysis, hyperpyrexia (OR, 2.29; 95% CI, 1.22–4.29) and bronchiectasis (OR, 2.06; 95% CI, 1.04–4.06) were the predictors of AFB-smear positivity, while bulla (OR, 0.22; 95% CI, 0.05–0.97) was the predictor of AFB-smear negativity. Conclusion This study demonstrated the clinical and radiological features of aPTB mimicking pneumonia. Several paired radiological findings may guide us to the diagnosis of aPTB. Hyperpyrexia and bronchiectasis may be helpful for predicting AFB positivity, and bulla may be a predictive sign of AFB negativity.

Background To assess the effects of proteoglycan-depleted regions of annular disruptions on nerve ingrowth in the injury site in vivo . Methods New Zealand white rabbits ( n = 18) received annular injuries at L3/4, L4/5, and L5/6. The experimental discs were randomly assigned to four groups: (a) an annular defect was created; (b) an annular defect implanted with a poly lactic-co-glycolic acid (PLGA)/fibrin/PBS plug; (c) an annular defect implanted with a PLGA/fibrin/chondroitinase ABC (chABC) plug; and (d) an uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, and analysis of the proteoglycan (PG) content. Immunohistochemical detection of nerve fibers and chondroitin sulfate (CS) was performed. Results The injured discs produced progressive and reliable disc degeneration. In the defective discs, the lamellated appearance of AF (Annulus fibrosus) was replaced by extensive fibrocartilaginous-like tissue formation outside the injured sites. In contrast, newly formed tissue was distributed along small fissures, and small blood vessels appeared in the outer part of the disrupted area in the PLGA/fibrin/PBS discs. More sprouting nerve fibers grew further into the depleted annulus regions in the PLGA/fibrin/chABC discs than in the control discs and those receiving PLGA/fibrin/PBS. In addition, the innervation scores of the PLGA/fibrin/chABC discs were significantly increased compared with those of the PLGA/fibrin/PBS discs and defected discs. Conclusion ChABC-based PLGA/fibrin gel showed promising results by achieving biointegration with native annulus tissue and providing a local source for the sustained release of active chABC. Disc-derived PG-mediated inhibition of nerve and blood vessel ingrowth was abrogated by chABC enzymatic deglycosylation in an annular-injured rabbit disc degeneration model.

Background The increasing use of new technologies by pregnant women inevitably exposes them to the risks of the electromagnetic fields (EMFs). According to the World Health Organization, EMFs are the major sources of pollutants which harm human health. This study was aimed to evaluate the effects of EMF exposure on abortion. Methods Web of Science, Cochrane Library, MEDLINE, PubMed, EMBASE, Scopus, and Google Scholar were searched until 2021. Pooled odds ratio (OR) with 95% confidence interval (CI) was estimated using a random-effects model. Heterogeneity was explored using Cochran’s Q test and I 2 index. A meta-regression method was employed to investigate the factors affecting heterogeneity between the studies. The Newcastle-Ottawa scale was used to assess the credibility of the studies. Results Eligible studies ( N = 17) were analyzed with a total of 57,693 participants. The mean maternal age (95% CI) was 31.06 years (27.32–34.80). Based on meta-analysis results, the pooled estimate for OR of EMF with its effects was 1.27 (95% CI: 1.10–1.46). According to the results of meta-regression, sample size had a significant effect on heterogeneity between studies ( p : 0.030), but mother’s age and publication year had no significant effect on heterogeneity ( p -value of bothwere >0.05). No publication bias was observed. Conclusion Exposure to EMFs above 50 Hz or 16 mG is associated with 1.27× increased risk of abortion. It may be prudent to advise women against this potentially important environmental hazard. Indeed, pregnant women should receive tailored counselling.

We explore miR‐150‐5p in atherosclerosis (AS). The AS model was constructed using Apo E −/− mice with an injection of the miR-150-5p mimic or an inhibitor. Pathological characteristics were assessed using Oil red O staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expressions of microRNA-150-5p (miR-150-5p), STAT1, α-SMA (α-smooth muscle actin) and proliferating cell nuclear antigen (PCNA). Targetscan and dual-luciferase reporter assay were used to analyze the interaction between miR-150-5p and STAT1. The viability, migration, cell cycle and α-SMA and PCNA expressions in oxidized low-density lipoprotein (ox-LDL)-stimulated primary human aortic smooth muscle cells (ASMCs) were assessed using molecular experiments. miR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. The miR‐150‐5p inhibitor alleviated the increase of lipid plaque and reduced collagen accumulation in the aortas during AS. Upregulation of α-SMA and PCNA was reversed by miR-150-5p upregulation. STAT1 was targeted by miR‐150‐5p, and overexpressed miR-150-5p weakened the ox-LDL-induced increase of viability and migration abilities and blocked cell cycle in ASMCs, but overexpressed STAT1 blocked the effect of the miR‐150‐5p mimic. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1.

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual‐luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

Our aim was to evaluate lung injury due to oxidative stress and antioxidant activity levels in an infrarenal ischemia–reperfusion model and to compare prevention effects of single and combined use of propofol and remifentanil. In this study, a total of 40 adult Wistar Albino rats were randomly divided into five groups of eight rats as SHAM, physiological saline, intraperitoneal propofol, remifentanil, and propofol and remifentanil groups. Blood and tissue samples were obtained after 80 min of reperfusion. The malondialdehyde (MDA) level, a measure of lipid peroxidation, was measured in lung tissue samples and red blood cells; additionally, total oxidant status and total antioxidant capacity of lung tissues were measured and histopathological examination was performed. Distant organ (lung) injury developed due to lower extremity ischemia–reperfusion was created by infrarenal aortic clamping. The lipid peroxidation product MDA and total oxidant levels were increased, but there was insufficient antioxidant protection both in the lung tissues and red blood cells. While propofol prevented this injury consistent with its proposed antioxidant properties; no protective effect of remifentanil was observed. On the contrary, it showed oxidative stress increasing effect. This study concluded that the antioxidant effect of propofol was suppressed by remifentanil in the case of combined use.

Background Gastric carcinoma (GC) ranks the fifth most common cancer worldwide, with high incidence and mortality rates. Numerous microRNAs (miRNAs), including miR-654-5p, have been implicated in the pathophysiological processes of tumorigenesis. Nevertheless, the mechanism of miR-654-5p in GC is unclear. Objectives Our study is devoted to exploring the function and molecular mechanism of miR-654-5p on the malignant cell behaviors of GC. Methods The gene expression was detected by reverse transcription quantitative polymerase chain reaction. GC cell proliferation and motion were assessed by colony formation assay and transwell assay. The binding capacity between miR-654-5p and G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) was explored by luciferase reporter and RNA pulldown assays. The protein levels were detected by Western blotting. Results miR-654-5p expression was higher in GC cells and tissues than control cells and tissues. miR-654-5p promoted GC cell growth and motion. Moreover, our findings showed that miR-654-5p was bound with GPRIN1. Importantly, downregulation of GPRIN1 rescued the inhibitory influence of miR-654-5p knockdown on GC cell malignant behaviors. Additionally, miR-654-5p activated the nuclear factor kappa-B (NF-κB) pathway by regulation of GPRIN1. Conclusions miR-654-5p facilitated cell proliferation, migration, and invasion in GC via targeting the GPRIN1 to activate the NF-κB pathway.

DNA ligase (LIG) plays a key role in connecting the 3′-OH end of a DNA strand to the 5′-P end of another DNA strand, resulting in the formation of a phosphodiester bond. It has been reported that LIGs (including LIG1, LIG3 and LIG4) play important roles in the occurrence and progression of many cancers. However, the role of LIGs in breast cancer (BC) is still unclear. In this study, we aim to reveal the expression level, function, and prognostic value of LIGs in BC. Bioinformatic tools were used to study the expression level, potential function and prognostic value of LIG1 and LIG3 in BC patients. ENCORI was used to predict microRNAs (miRNAs) that regulate LIG1 and LIG3 and established a valuable miRNA–mRNA regulation network for BC. We found that the expression of LIG1 and LIG3 was upregulated in BC and predicted high relapse-free survival (RFS) in BC patients. Functional annotation analysis was performed to reveal the role of LIG1 and LIG3 in BC. In addition, hsa-miR-22-3p was identified to be potentially involved in the regulation of LIG3. We suggest that LIG1 and LIG3 are novel valuable prognostic biomarkers for BC and has-miRNA-22-3p may be a potential therapeutic target for BC.

Mitophagy affects the activation of hepatic stellate cells (HSCs). Mitochondria-targeted ubiquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces the production of intracellular reactive oxygen species (ROS). However, its relationship with mitophagy remains unclear. This study evaluated mitophagy during HSC activation and the effects of MitoQ on mitophagy in cell culture and in an animal model of the activation of HSCs. We found that MitoQ reduced the activation of HSCs and alleviated hepatic fibrosis. PINK1 (PTEN-induced putative kinase 1) is a putative serine/threonine kinase located in the mitochondria’s outer membrane. While the activation of primary HSCs or LX-2 cells was associated with reduced PINK1/parkin-mediated mitophagy, MitoQ reduced intracellular ROS levels, enhanced PINK1/parkin-mediated mitophagy, and inhibited the activation of HSCs. After knocking down the key mitophagy-related protein, PINK1, in LX-2 cells to block mitophagy, MitoQ intervention failed to inhibit HSC activation. Our results showed that MitoQ inhibited the activation of HSCs and alleviated hepatic fibrosis by enhancing PINK1/parkin-mediated mitophagy.

GNE gene-specific c.2179G>A(p.V727M) is a key alteration reported in patients with hereditary inclusion body myopathy (HIBM) and represents an ethnic founder mutation in the Indian cohort. However, the underlying role of this mutation in pathogenesis remains largely unknown. Thus, in this study, we aimed to access possible mechanisms of V727M mutation that could be leading to myopathy. We evaluated various in silico tools to predict the effect of this mutation on pathogenicity, structural or possible interactions, that could induce myopathy. Our results propose that V727M mutation could induce deleterious effects or pathogenicity and affect the stability of GNE protein. Analysis of differential genes reported in the V727 mutant case suggests that it can affect GNE protein interaction with Myc-proto-oncogene (MYC) transcription factor. Our in silico analysis also suggests a possible interaction between GNE ManNac-kinase domain with MYC protein at the C-terminal DNA-binding domain. MYC targets reported in skeletal muscles via ChIP-seq suggest that it plays a key role in regulating the expression of many genes reported differentially expressed in V727M-mutated HIBMs. We conclude that V727M mutation could alter the interaction of GNE with MYC thereby altering transcription of sialyltransferase and neuromuscular genes, thus understanding these effects could pave the way for developing effective therapies against HIBM.

Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro . circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment. Graphical abstract

The oxytocin receptor (OXTR) is directly involved in the pathological mechanisms of multiple cancers, including breast cancer, prostate cancer, and ovarian cancer; however, the role of OXTR in the modulation of colon adenocarcinoma (COAD) growth, metastasis, and clinical prognosis remains to be elucidated. This study used systematic bioinformatics analysis to explore the effects of OXTR on modulating COAD growth and prognosis in patients with COAD. Compared with normal tissues, OXTR mRNA level was higher in COAD tissues, which was associated with tumor progression. Elevated mRNA level of OXTR also indicated a poor prognosis in COAD patients. Furthermore, high mRNA level of OXTR was significantly associated with pathways involved in cell cycle regulation and signal transduction pathways, including the hedgehog, mTOR, TGF-β, and Wnt signaling pathways. OXTR expression was significantly correlated with the infiltration level of type 2T helper cell, central memory CD8 T cell, CD56 bright natural killer cell, activated CD8 T cell, activated B cell, and Type 1T helper cell. Moreover, silencing OXTR inhibited cell proliferation, migration, and invasion, and arrested the cell cycle. In conclusion, high mRNA level of OXTR indicates poor prognosis.

Non-coding ribonucleic acids (ncRNAs) are a diverse group of RNA molecules that are mostly not translated into proteins after transcription, including long non-coding RNAs (lncRNAs) with longer than 200 nucleotides non-coding transcripts and microRNAs (miRNAs) which are only 18–22 nucleotides. As families of evolutionarily conserved ncRNAs, lncRNAs activate and repress genes via a variety of mechanisms at both transcriptional and translational levels, whereas miRNAs regulate protein-coding gene expression mainly through mRNA silencing. ncRNAs are widely involved in biological functions, such as proliferation, differentiation, migration, angiogenesis, and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. The etiology of IPF is still unclear. Increasing evidence shows the close correlations between the development of IPF and aberrant expressions of ncRNAs than thought previously. In this study, we provide an overview of ncRNAs participated in pathobiology of IPF, seeking the early diagnosis biomarker and aiming for potential therapeutic applications for IPF.

The stiff person syndrome (SPS) is an extremely rare neurological disorder with primarily immune-mediated etiology. The cardinal symptoms are progressive, fluctuating axial/proximal limb muscle stiffness and spasms. The diagnosis is based on the clinical picture, electromyography examination and detection of antibodies to glutamic acid decarboxylase (anti-GAD). Adverse effects of medications might preclude its use or increase in dosing, therefore symptomatic and/or immunomodulatory medical therapy might be ineffective in acute exacerbation of the disease. We present a case of a 49-year-old female with exacerbation of SPS, in whom some standard pharmacotherapy could not be introduced (clonazepam, baclofen used in the past) and doses of existing standard medications could not be increased (diazepam, gabapentin, and levetiracetam) due to adverse effects. Moreover, a newly introduced medication (methylprednisolone) also led to a serious adverse effect (severe hyperglycemia). The patient underwent therapeutic plasma exchange (TPE) with good effect and no complications. We review the literature regarding the efficacy and safety profile of TPE in exacerbation of SPS unresponsive to medical therapy. The procedure seems to have a good safety profile as an adjunct therapy for exacerbation of SPS not responding to standard medical therapy in this patient population.

Background The delivery mode is one of the factors affecting the type of colonization of the human gut. Gut colonization affects all stages of the human life cycle, and the type of gut microbiome can contribute to immune system function, the development of some diseases, and brain development; and it has a significant impact on a newborn’s growth and development. Methods Terms defined as MeSH keywords were searched by the databases, and web search engines such as PubMed, ClinicalTrials.gov, Embase, Scopus, ProQuest, Web of Science, and Google Scholar were searched between 2010 and 2020. The quality of each study was assessed according to the Newcastle–Ottawa scale, and seven eligible and high-quality studies were analyzed. Finding The abundances of Bacteroides and Bifidobacterium during the first 3 months of life; Lactobacillus and Bacteroides during the second 3 months of life; Bacteroides and Bifidobacterium during the second 6 months of life; and Bacteroides , Enterobacter , and Streptococcus after the first year of life were higher in vaginal delivery-born infants. While infants born by cesarean section (CS) had higher abundances of Clostridium and Lactobacillus during the first 3 months of life, Enterococcus and Clostridium during the second 3 months of life, and Lactobacillus and Staphylococcus after the first year of life. Discussion Delivery mode can affect the type of the human intestinal microbiota. The CS-born babies had lower colonization rates of Bifidobacterium and Bacteroides , but they had higher colonization rates of Clostridium , Lactobacillus , Enterobacter , Enterococcus , and Staphylococcus . Given the effect of microbiota colonization on neonatal health, it is therefore recommended to conduct further studies in order to investigate the effect of the colonization on the delivery mode and on baby’s growth and development. Application to practice The aim of this study was to investigate the role of CS in the development of the neonatal gut microbiota.

Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major histological categories of lung cancers. Drug resistance is a great challenge for cancer treatment, and histological transformation from NSCLC to SCLC is one of the mechanisms underlying drug resistance in NSCLC patients. SCLC-transformed patients show combined characteristics of NSCLC and SCLC; however, they lack timely diagnoses and effective treatment strategies. Thus, we reviewed the clinical characteristics of SCLC transformation patients with a literature search to enhance clinical consciousness, diagnosis, and personalized treatment for patients with it.

Frailty is a clinical syndrome caused by homeostasis imbalance. It is characterized by marked vulnerability to endogenous or exogenous stressors, reduced self-care ability, and increased mortality risk. This aging-related syndrome is common in individuals older than 65 years and carries an increased risk for poor health outcomes. These include falls, incident disability, incapacity, and mortality. In addition, it can result in a poor prognosis for other comorbidities. With the aging population, frailty increases the burden of adverse health outcomes. Studies on frailty are at their infancy. In addition, there is a lack of thorough understanding of its pathogenesis. Several studies have suggested that frailty is caused by chronic inflammation due to enhanced intestinal permeability following gut microbiota imbalance as well as pathogen-related antibodies entering the circulation system. These result in musculoskeletal system disorders and neurodegenerative diseases. However, this assumption has not been validated in large cohort-based studies. Several studies have suggested that inflammation is not the only cause of frailty. Hence, further studies are necessary to extend our understanding of its pathogenesis. This review summarizes the research findings in the field and expands on the possible role of the gut microbiota in frailty syndrome.

The spread of the COVID-19 disease substantially influenced the International Healthcare system, and the national governments worldwide had before long to decide how to manage the available resources, giving priority to the treatment of the COVID-infected patients. Then, in many countries, it was decided to limit the elective procedures to surgical oncology and emergency procedures. In fact, most of the routine, middle-low complexity surgical interventions were reduced, and the day surgery (DS) activities were almost totally interrupted. As a result of this approach, the waiting list of these patients has significantly increased. In the current phase, with a significant decrease in the incidence of COVID-19 cases, the surgical daily activity can be safely and effectively restarted. Adjustments are mandatory to resume the DS activity. The whole separation of pathways with respect to the long-stay and emergency surgery, an accurate preoperative protocol of patient management, with a proper selection and screening of all-day cases, careful scheduling of surgical organization in the operating room, and planning of the postoperative pathway are the goals for a feasible, safe, and effective resumption of DS activity.

Objective A cluster outbreak of patients with similar symptoms and computed tomographic (CT) images of COVID-19 were diagnosed with leptospirosis. This study was aimed to identify the clinical difference between leptospirosis and COVID-19, providing evidence for strategy optimization. Methods A cohort of leptospirosis patients were collected and compared with age- and gender-matched COVID-19 cases in the epidemiological investigation, chest CT scan, laboratory tests, and length of hospital stay. Results Compared with COVID-19, contacting floodwater and lack of family clustering were features of leptospirosis in epidemiological assessment. In the laboratory test, higher level of white blood cells (WBCs: (10.38 ± 4.56) × 109/L vs (6.45 ± 1.95) × 109/L, p < 0.001), C-reactive protein (CRP: (138.93 ± 73.03) mg/L vs (40.28 ± 30.38) mg/L, p < 0.001), Creatine ((88.27 ± 35.16) mmol/L vs (63.31 ± 14.50) mmol/L, p < 0.001), and a lower level of platelet ((152.93 ± 51.93) × 109/L vs (229.65 ± 66.59) × 109/L, p < 0.001) were detected on patients with leptospirosis. Conclusion Given the epidemiological differences and seasonal prevalence, it is important to suspect leptospirosis in cases with a similar presentation of COVID-19. The clinical disparities may facilitate the therapeutic management of these two diseases.

Purpose To describe our initial experience with use of microspheres in transcatheter arterial embolization (TAE) for unruptured sporadic renal angiomyolipomas (AMLs). Materials and methods Seven consecutive patients with seven unruptured sporadic renal AMLs, 6 females and 1 male, with a median age of 45 years (range, 30–69 years), underwent TAE using microspheres between November 2016 and February 2020. We evaluated the technical success rate, complications related to the procedure, clinical success rate, and the shrinkage rate of renal AML. Technical success was defined as the completion of TAE. Clinical success was defined as presence of shrinkage of the renal AML after TAE. Results In all patients, TAE using microspheres was accomplished and technical success rate was 100% (7/7). Three patients exhibited slight pain, but it improved with only observation, and the minor complication rate was 43% (3/7) and major complication rate was 0% (0/7). After the TAE, shrinkage of renal AML was confirmed in 6 of 7 patients, and clinical success rate was 86% (6/7). The median of shrinkage rate was 47% (range, 26–83%) with a median follow-up period of 19 months (range, 4–30 months). Conclusion TAE using microspheres appears to be effective and safe for unruptured sporadic renal AMLs.

Objective Over 90% of the COVID-19 patients with computed tomographic (CT) manifestations showed radiological improvement on dissipating stage. Cases with refractory pulmonary infiltration were discussed in this study. Methods During hospitalization, chest CT scan and reverse transcriptase polymerase chain reaction (RT-PCR) test were repeatedly performed. While drawing parallels to RT-PCR, the impact of delayed absorption of lung lesions on length of hospital stay (LOS) and medical expense was investigated. Features for delayed absorption of lung lesions were identified using cox proportional hazard regression model. Results Cases with delayed absorption of lung lesions had a prolonged LOS (18.00 ± 4.90 vs 9.25 ± 4.20, p < 0.01) and increased medical expense (9124.55 ± 2421.31 vs 4923.88 ± 2218.56, p < 0.01). Time interval from admission to a negative RT-PCR (ATN) was also prolonged (13.29 ± 4.72 vs 9.25 ± 4.20, p = 0.03). The cox proportional hazard regression model indicated that imported cases bore high risk of delayed absorption of lung lesions (hazard ratio = 2.54, 95% confidence interval 1.05, 6.11, p = 0.04). Sensitivity analysis revealed similar pattern (hazard ratio = 6.64, 95% confidence interval 1.62, 27.18, p = 0.01). Conclusion Imported cases of COVID-19 were more likely to have refractory pulmonary infiltration, which subsequently prolongs LOS and increases medical expense.

Objective A triple combination of interferon (IFN) α-2b, lopinavir tablets, and umifenovir was used to treat COVID-19 patients. It is important to explore whether the benefit of this therapy is time dependent. Methods A cohort of moderate COVID-19 patients ( n = 54) was admitted for hospitalization. The demographic (age, gender, and smoking status) and clinical characteristics (epidemiological trace and comorbidity) were collected from the digital medical records. The length of hospital stay (LOS) and the viral shedding time (VST) were set as the outcomes for COVID-19 cases. Results After control for age, sex, epidemiological trace, smoking, and comorbidity, the time of treatment start had null effect on VST (IRR = 1.09; 95% CI = 0.91–1.30; p = 0.33) or LOS (IRR = 1.10; 95% CI = 0.94–1.28; p = 0.23). Conclusion There is no convincing evidence to support a pivotal role of the timing of the therapy in the prognosis of moderate COVID-19 cases.

Objective The purpose of this study is to assess the increase both in the use of the Internet and social media and in Google searches regarding eating disorders (ED) in Italy during the Covid-19 pandemic. Our aim is also to verify the possible impact of such an increase on ED, since patients treated for ED by the National Health Service (NHS) have increased in the first 6 months of 2020 as well. Method We used data from Wearesocial surveys on Internet users in the first 6 months of 2020 and the Google searches related to the query of “food disorders” and “body shaming.” The first results of a project of the Italian Ministry of Health on ED have been considered too. Results The social media users in July 2020 increased to 60% of the Italian population; a tendential increase in Google searches on these issues has emerged. Finally, new patients of NHS with ED showed a high increase in the first 6 months of 2020 (+40.9%). Conclusion Considering the contents diffused on the Internet, it is fundamental to watch over net usage in the adolescent population and those with ED, because massive access to social media can be considered almost as a risk factor.

All governments, regulatory authorities, and vaccine-related committees are under tremendous pressure to roll out vaccines to safeguard the people against COVID-19. To be noted that all COVID-19 vaccines have been developed hurriedly, some with new technologies being used on humans for the first time ever. Most clinical trials did not include elderly patients with comorbidities, hence a careful and logical rollout planning, especially for elderly people, is necessary.

Brain metastases (BMs) are the most common intracranial malignancy with poor prognosis. Patients with intracranial tumors are at greater risk for thrombotic complications and intracranial hemorrhage. Rivaroxaban is a potent oral anticoagulant with the high selectivity of direct factor Xa inhibition. The incidence and severity of rivaroxaban-triggered intratumoral hemorrhage (ITH) in patients with BMs remain unknown. A 57-year-old woman was diagnosed with multiple lung, bone, and BMs from unknown primary cancer origin, and refused any invasive procedures to confirm tumor pathology. However, this patient had a relatively favorable outcome after treating with cabozantinib, an inhibitor of multiple tyrosine kinases. The patient survived over 2 years and developed deep vein thrombosis of right lower limb. Oral rivaroxaban was prescribed, and the multifocal catastrophic ITH was encountered after 1 week. The last head computed tomography imaging revealed a rare but typical image of diffuse hemorrhagic metastases. Hemorrhagic-prone BMs, therapeutic rivaroxaban, and cabozantinib treatment increase risks to develop ITH. In this case rivaroxaban was the trigger to this terminal event. This case is a miserable lesson and keeps reminding us to stay vigilant in clinical practice even when there is a potential benefit for anticoagulation in such population.

Duplex kidney is a common congenital malformation appeared as duplication of pelvis and ureter. However, renal duplication within sinus renalis is an extremely rare variation of the renal collecting system. In this study, we report a case of an asymptomatic kidney disease in a 33-year-old man, who demonstrates abnormal echo of renal sinus anomaly discovered incidentally in ultrasound examination. Computed tomography urography (CTU) exhibited the other small duplex kidney located in renal sinus. In the excretory phase images, the contrast medium within its small renal pelvis could be seen to flow into the right major renal calices. This case exhibited a very rare anatomical variation of duplicated renal malformation.

Multiple primary malignancies in a single patient are relatively rare; however, the frequency of this has increased significantly in recent decades. Here, we retrospectively reported an unusual case of a 70-year-old man who was admitted to the hospital with mantle cell lymphoma (MCL) and colon cancer and aimed to explore measures to reduce missed diagnosis. Based on the data, the investigation of the related literatures, colonoscopy examination, and abdominal computed tomography (CT) scan were conducted for the detection of colon cancer. Following this, a precise diagnosis of MCL was confirmed by immunohistochemistry and bone marrow biopsy, which were performed to analyze the clinical characteristics and essentials for the diagnosis and differential of the disease. The results of colonoscopy showed that the patient had colon cancer, while the abdominal CT scan demonstrated colon cancer accompanied by multiple lymphadenopathy throughout the entire body. Besides, the results of immunohistochemistry confirmed that the patient suffered from MCL. The bone marrow biopsy revealed the active hematopoietic tissue hyperplasia but no tumor issue involvement in the bone marrow. In conclusion, our study combined the analysis and summary of the diagnosis and treatment of the colon cancer with MCL to provide clinical guidance for the rare multiple primary malignancy.

Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor rarely described in the liver. Sonazoid is a new ultrasound contrast with both vascular and post-vascular phases due to the uptake of Kupffer cell. CD68 is a defined immunohistorical staining marker for macrophage including Kupffer cell. No previous cases have been reported to reveal Kupffer images in the post-vascular phase by using Sonazoid and pathologic characters of CD68 positive cell in PEComa. Herein, we describe the first case to present Sonazoid contrast-enhanced ultrasonography (CEUS) findings in Kupffer images and CD68 positive cell in hepatic PEComa which may lead to rethink of the phagocytic properties of macrophages.

In recent months, the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis with takeover more than 1 million lives worldwide. The long-lasting existence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been reported. Herein, we report a case of SARS-CoV-2 infection with intermittent viral polymerase chain reaction (PCR)-positive for >4 months after clinical rehabilitation. A 35-year-old male was diagnosed with COVID-19 pneumonia with fever but without other specific symptoms. The treatment with lopinavir-ritonavir, oxygen inhalation, and other symptomatic supportive treatment facilitated recovery, and the patient was discharged. However, his viral PCR test was continually positive in oropharyngeal swabs for >4 months after that. At the end of June 2020, he was still under quarantine and observation. The contribution of current antivirus therapy might be limited. The prognosis of COVID-19 patients might be irrelevant to the virus status. Thus, further investigation to evaluate the contagiousness of convalescent patients and the mechanism underlying the persistent existence of SARS-CoV-2 after recovery is essential. A new strategy of disease control, especially extending the follow-up period for recovered COVID-19 patients, is necessary to adapt to the current situation of pandemic.

We report a 26-year-old man with left chest pain for 4 days. His chest CT showed a cavity in the left upper lung. Tuberculosis was suspected first, but metagenomics next generation sequencing (mNGS) in bronchoalveolar lavage fluid only detected Tropheryma whipplei . Tropheryma whipplei is the pathogen of Whipple’s disease. The most frequently involved organs are the eyes, heart, and central nervous system. Pulmonary parenchymal involvement is rare. To our knowledge, this is the first reported case of pulmonary cavity caused by Tropheryma whipplei . Nineteen cases of pulmonary parenchymal involvement were found by literature search. The most common respiratory symptom was cough, followed by dyspnea/breathlessness and chest pain. The most common finding in chest imaging was pulmonary nodules, followed by interstitial changes and patchy infiltration. Our case and literature review highlighted that Tropheryma whipplei infection should be considered in the differential diagnosis of pulmonary cavity, pulmonary nodules, interstitial changes, and patchy infiltration. mNGS is helpful to improve diagnosis rate.

Mixed germ cell tumor (MGCT) mainly occurs in young women’s ovaries and men’s testicles and rarely occurs outside the gonad. Fewer than 10 cases of mediastinal MGCT are available in PubMed, Embase, and other databases in English, while mediastinal MGCT with three pathological components, such as yolk sac tumor, immature teratoma, and embryonal carcinoma, has not been reported previously. A 12-year-old male sought medical attention for chest discomfort and underwent a computed tomography (CT) scan. A large soft tissue mass occupying most of the left thoracic cavity and mediastinum was detected. A CT-guided biopsy was performed, and an MGCT was diagnosed with pathological components, including yolk sac tumor, immature teratoma, and a small amount of embryonal carcinoma. Due to the large size of the tumor, the patient was treated with an EP regimen (etoposide + cisplatin) and paclitaxel + ifosfamide + cisplatin interstitial chemotherapy. The patient was followed up for 6 months and was alive with the disease. To the best of our knowledge, this is the 10th patient with MGCT in the mediastinum. The incidence of mediastinal MGCT is low, but it should still be considered one of the differential diagnoses of isolated pleural fibroma and neurogenic tumors.

Background During embryonic development in women, a regression of temporary embryonic structures – mesonephric (Wolffian) ducts occurs. Adnexal tumors of Wolffian duct origin (FATWO) are rare. Case report We presented the case of a 64-year-old female patient who was diagnosed with FATWO. After the surgical treatment, the uterus with bilateral adnexal structures was submitted for histopathological analysis. The left ovary was occupied by a tumor measuring 80 × 60 × 50 mm, with smooth, shiny, whitish surface. Tumor cells were medium-sized, relatively uniform, round, and polygonal, with eosinophilic cytoplasm and centrally laid nucleus with fine chromatin, organized into solid, trabecular, and tubular formations. Tumor cells were positive for pancytokeratin (CK), CK7, CD10, neuron-specific enolase (NSE), synaptophysin, calretinin, progesterone, estrogen, and epithelial membrane antigen (EMA). Conclusion This case adds a report of a rare tumor to the literature. We must think of it in the differential diagnostic algorithm to make an accurate diagnosis for selecting the best treatment modality.

Aggressive angiomyxoma (AAM) is a rare mesenchymal myxoid tumor, and most cases occur in the pelvic region or perineum of adult females. AAM is very rare in males. Most of these cases have been diagnosed in patients aged 30–60 years, and the tumors involved the pelvic cavity, scrotum, or spermatic cord. AAM can mimic inguinal hernia, hydrocele, or paratesticular neoplasm. Four male cases have been reported with paratesticular AAM mimicking a testicular/epididymal tumor, and to the best of our knowledge, this is the oldest patient in the literature. Because of its rarity, making an exact diagnosis before surgery is difficult. Herein, we present a case of AAM in an 82-year-old man and review the literature.

Gestational trophoblastic disease (GTD) commonly occurs in reproductive females, but is extremely rare in perimenopausal females. In this study, we reported a case of hydatidiform mole in a 48-year-old perimenopausal female admitted due to a giant uterine mass of 28 weeks’ gestational size. The serum human chorionic gonadotropin (HCG) level ranged from 944 to 1,286 mIU/mL before treatments. The signs of preeclampsia and hyperthyroidism were relatively prominent. Hysterectomy was performed and chemotherapy was scheduled when the serum HCG level remained at a plateau, about 528 mIU/mL. The symptoms of preeclampsia and hyperthyroidism were relieved after treatment. Accordingly, we concluded that GTD could occur in perimenopausal woman and hysterectomy usually is the optimal treatment.

Background Ganglioneuroblastoma (GNB) is a neoplasm that arises from the primitive cells of the sympathetic nervous system during childhood. The current case is very unique because of the initial primary tumor manifestation in the orbit and an adrenal tumor being observed later during follow-up. Case presentation A 2-year-old girl presented to the Ophthalmology Department of our hospital complaining of swelling of the left upper eyelid for approximately one month. Orbital computed tomography (CT) revealed a left orbital mass with bone destruction. Thoracic and abdominal CT indicated no abnormalities. The mass was surgically resected, and histopathological analysis confirmed it as GNB. During follow-up, abdominal CT detected an adrenal tumor with internal calcification, a calcified nodule on the left side of the abdominal aorta, and mesenteric lymph nodes. Accordingly, primary orbital GNB and metastatic adrenal GNB were the possible considerations. We removed the adrenal tumor, and the patient underwent chemotherapy. However, the patient died 18 months after the ophthalmic surgery. Conclusion Primary orbital GNB in children is easily misdiagnosed because of its rare occurrence and atypical clinical findings. Imaging methods combined with histopathological examination contribute to the detection and diagnosis of primary and metastatic GNBs. Thus, timely surgery combined with adjuvant chemotherapy and long-term follow-up is essential for controlling the metastasis of GNB and improving the survival rate of patients.

Primary aortic intimal sarcoma is a very rare disease and most patients present with features similar to those of atherosclerotic plaque and thrombus; however, primary aortic intimal sarcoma presents with features similar to those of intramural hematoma (IMH) on CT imaging and clinical presentation had never been previously reported. Here we report a case involving a 49-year-old woman with primary aortic intimal sarcoma masquerading as IMH on radiological images and clinical presentation. We also discuss some of the diagnostic pitfalls and hope that these diagnostic pitfalls will be very useful for clinicians.

Hepatitis A virus immunoglobulin M (HAV-IgM) is often used to diagnose acute hepatitis A virus (HAV) infection serologically. However, false-positive test results can interfere with the diagnosis. A 56-year-old woman was readmitted to the hospital owing to abnormal liver function tests for the last 18 months. She had been diagnosed with acute HAV and was hospitalized in isolation based on a positive HAV-IgM test 18 months ago. Regular follow-up after discharge showed abnormal liver function and an elevated level of antinuclear antibodies and immunoglobulin G. For the last 15 days, the patient had fatigue, decreased appetite, and yellow urine, signaling recrudescence. Liver function tests were also abnormal. Liver biopsy revealed histological changes consistent with typical autoimmune hepatitis. After 2 months of methylprednisolone treatment, liver function returned to normal, and HAV-IgM turned negative. The diagnosis of acute HAV in nonendemic areas requires a comprehensive analysis of epidemic history, clinical characteristics, etiology, etc.

Peritoneal loose body (PLB) is a rare clinical entity. It is generally agreed that the most common origin of the loose bodies is appendix epiploica. We here report a case of PLB that looks like a “boiled egg,” which was misdiagnosed preoperatively as a lesion of hepatic origin and was confirmed by operation and postoperative pathology. PLBs are rare entities, a good understanding of their specific imaging features can help prevent misdiagnosis, but sometimes an accurate preoperative diagnosis is still difficult to achieve. Exploratory laparoscopy is a recommended method for management of PLBs.

Chondroblastoma is one of the uncommon benign bone tumors, particularly when located in the mandibular condyle. Such a location makes its diagnosis difficult when based on only its clinical presentation and radiographic features. Herein the current report presents a case of chondroblastoma of the mandibular condyle: its clinical presentation, radiographic features, and immediate condylar reconstruction after resection. Additionally, the relevant literature is discussed to provide clinical recommendations for its diagnosis and treatment. Chondroblastoma has been reported so infrequently in the temporomandibular joint (TMJ), more common entities should first be considered in the differential diagnosis of masses in this location. Osteochondroma is the most frequent bone neoplasm in the TMJ. Since a correct diagnosis is difficult, additional tools, such as magnetic resonance imaging (MRI) and immunohistochemical analyses, should be used for diagnostics and surgical planning.

Trauma-induced complete lead fracture is a rare complication of pacemaker implantation. Only a few cases have been previously reported. Common treatment included replacement of pacemaker and/or extraction of fractured lead. In this report, however, we describe this unique case of complete traumatic pacemaker lead fracture. The patient had her right-ventricular lead fractured after a bicycle accident and had lived with the fractured lead for 8 months prior to her hospitalization. After examinations, she was treated with a relatively conservative strategy. The pacemaker and fractured lead were left for further observation and follow-up.

We present a rare case of a primary intradural extramedullary Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) in the thoracolumbar spine and review the current literature. We describe the imaging manifestations, pathological features, surgical methods, and patient survival to shed light on the clinical management of this rare tumor. A 32-year-old man experienced progressive low back pain for more than 1 month. An intradural extramedullary tumor from T12 to L2 was detected on magnetic resonance imaging. He underwent a thoracolumbar laminotomy for decompression, complete excision of the intradural extramedullary tumor, and internal fixation with pedicle screws. A histopathological examination confirmed that the tumor was a PIEES/PNET via an immunohistochemical study of the surgically resected tissues. Postoperatively, the patient received chemotherapy and radiotherapy. No recurrence, metastasis, or failure of internal fixation were noted at a 17-month post-surgery radiographic examination. PIEES/PNET of the thoracolumbar spine is extremely rare. Treatment is difficult because the current literature is sparse and cases are rare. Complete resection combined with chemotherapy and radiotherapy effectively reduces recurrence and metastasis.

Introduction Reports on the use of computer-assisted trauma surgery of comminuted scapula fracture are still quite rare. In this article, we present a case of comminuted scapula fracture, the surgical reconstruction of which was pre-operatively planned using a complex software solution. Materials and methods For surgical planning of the fracture, we used the TraumaTech software facilitating virtual reconstruction (both manual and automatic), surgery planning, design of the implant, planning of screw placement and lengths, and production of a 3D print model of the fracture and the implant. The software also supported ordering such custom-made plate from a plate producer who was capable of fast and precise production of the plate. Results The surgery using the custom-ordered plate was successful. The actual used screw lengths did not differ from the planned ones by more than 2 mm. One year after the surgery, the patient was capable of more demanding activities and doing sports activities. Conclusion This approach provides a great way to prevent complications of the surgery and to shorten its duration. To the best of our knowledge, this is the first description of the treatment of a scapula comminuted fracture utilizing computer-assisted preoperative planning.

Brain metastases (BMs) and bone metastases seriously affect the prognosis of lung cancer patients. How to optimize the use of existing targeted drugs is an important way to address the clinical needs of the central nervous system in the individualized treatment of non-small cell lung cancer (NSCLC). In this report, we describe an NSCLC patient with BMs who survived for 58 months, which is the longest survival case among lung cancer patients with BMs. The patient was initially diagnosed with lung cancer more than 5 years ago with simultaneous brain, bone, and lung metastases. After gefitinib resistance, she received osimertinib in sequence with no progress for 58 months in total and maintained very good quality of life.

There are no effective therapeutic options for locally advanced head and neck squamous cell carcinoma (HNSCC). Additionally, there is no standard therapy for patients subjected to multiple lines of treatment. Angiogenesis plays a key role in tumor growth and metastasis. Therefore, inhibition of tumor angiogenesis is an important strategy for tumor therapy. Apatinib is a novel tyrosine kinase inhibitor that inhibits angiogenesis by targeting vascular endothelial growth factor receptor-2 (VEGFR-2). The effect of apatinib on HNSCC has not been clearly established. In this study, we administered apatinib in combination with anti-epidermal growth factor receptor (EGFR) targeted and systemic chemotherapy for the treatment of oral cancer and to achieve better disease outcomes. To avoid fatal bleeding, after achieving good clinical outcomes, the follow-up treatment plan was adjusted. The efficacy of apatinib combined with anti-EGFR targeted and systemic chemotherapy for the treatment of oral cancer has not been previously reported. Our findings show the therapeutic potential of apatinib for advanced HNSCC patients with multiple lines of chemotherapy, especially for patients with large neck masses.

Background Foreign bodies in the kidney have rarely been reported. However, they can be a clinical problem for urologists. We report on a patient with a residual segment of guidewire coating embedded in the renal parenchyma following computed tomography (CT)-guided percutaneous nephrostomy drainage (PCND), and our successful minimally invasive management with retrograde intrarenal surgery (RIRS). Case presentation A 40-year-old female with urosepsis due to a right upper ureteral stone with hydronephrosis received emergent CT-guided PCND and subsequent ureteroscopic lithotripsy, double J stent insertion, and percutaneous catheter removal. Follow-up radiography showed a coiled object within the upper pole parenchyma of the right kidney, which might be the remnant of a guidewire used during the PCND procedure. Flexible ureteroscopy (fURS) was performed. Under fluoroscopy, the foreign body was localized, the renal parenchyma was incised with laser, and the foreign body was retrieved using a stone basket. Conclusion Although guidewire breakage is uncommon, clinicians should keep it in mind during interventional procedures. Several methods can be used to eradicate foreign objects from the urinary tract, and the first choice should always be the least invasive one. RIRS with fURS is considered as a safe, efficient, and minimally invasive option for the extraction of foreign bodies from the kidney. To the best of our knowledge, this is the first comprehensive case report detailing the removal of a foreign object by RIRS in the English literature.

Mortality rate in older adults following extensive burn injury is extremely high, and management of these patients is challenging. One of the main problems is that autologous split-thickness skin grafts are scarce and the wounds cannot be covered quickly and effectively. Intermingled skin grafting is a low-tech and economic method, which not only maximizes the use of precious autologous skin but also prevents the wounds from infection and consumption. Herein we present a case of extensive burn injury in a 68-year-old female successfully treated with intermingled skin grafting. The patient was accidentally burned by gas flame, resulting in a major burn injury covering 80% of her total body surface area. Early burn wound excision was performed and the wound was temporarily covered with irradiated porcine skin in the first week after injury. Autologous stamp-like skin grafts were applied to the wound bed 4 weeks after injury. In this operation, the results were not satisfactory. The take rate of the skin grafts is only about 50%. We covered the wounds with intermingled skin allografts and autografts 8 weeks after injury: autografts (0.5 cm × 0.5 cm) + fresh close relative’s allografts (1 cm × 1 cm) + cryopreserved allografts (2 cm × 2 cm).

Endometrial cancer is one of the most common gynecological malignancies in developed countries. The prevention of the recurrence of endometrial cancer has always been a clinical challenge. Endometrial cancer is asymptomatic in the early stage, and there remains a lack of time-series correlation patterns of clinical pathway transfer, recurrence, and treatment. In this study, the artificial immune system (AIS) combined with bootstrap sampling was compared with other machine learning techniques, which included both supervised and unsupervised learning categories. The back propagation neural network, support vector machine (SVM) with a radial basis function kernel, fuzzy c-means, and ant k-means were compared with the proposed method to verify the sensitivity and specificity of the datasets, and the important factors of recurrent endometrial cancer were predicted. In the unsupervised learning algorithms, the AIS algorithm had the highest accuracy (83.35%), sensitivity (77.35%), and specificity (92.31%); in supervised learning algorithms, the SVM algorithm had the highest accuracy (97.51%), sensitivity (95.02%), and specificity (99.29%). The results of our study showed that histology and chemotherapy are important factors affecting the prediction of recurrence. Finally, behavior code and radiotherapy for recurrent endometrial cancer are important factors for future adjuvant treatment.

Breast cancer is one of the most common cancers in women all over the world. Due to the improvement of medical treatments, most of the breast cancer patients would be in remission. However, the patients have to face the next challenge, the recurrence of breast cancer which may cause more severe effects, and even death. The prediction of breast cancer recurrence is crucial for reducing mortality. This paper proposes a prediction model for the recurrence of breast cancer based on clinical nominal and numeric features. In this study, our data consist of 1,061 patients from Breast Cancer Registry from Shin Kong Wu Ho-Su Memorial Hospital between 2011 and 2016, in which 37 records are denoted as breast cancer recurrence. Each record has 85 features. Our approach consists of three stages. First, we perform data preprocessing and feature selection techniques to consolidate the dataset. Among all features, six features are identified for further processing in the following stages. Next, we apply resampling techniques to resolve the issue of class imbalance. Finally, we construct two classifiers, AdaBoost and cost-sensitive learning, to predict the risk of recurrence and carry out the performance evaluation in three-fold cross-validation. By applying the AdaBoost method, we achieve accuracy of 0.973 and sensitivity of 0.675. By combining the AdaBoost and cost-sensitive method of our model, we achieve a reasonable accuracy of 0.468 and substantially high sensitivity of 0.947 which guarantee almost no false dismissal. Our model can be used as a supporting tool in the setting and evaluation of the follow-up visit for early intervention and more advanced treatments to lower cancer mortality.