Band 15, Heft 1

Coronary artery disease (CAD) is one of the main causes of hospitalization worldwide and has high morbidity. MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases. miR-451 is a special miRNA that is involved in many cancers’ development. At present, there is no research about miR-451 in coronary heart disease. In this study, we aimed to identify the action mechanism of miR-451 in coronary heart disease and human umbilical vein endothelial cells (HUVECs). In this study, we found that miR-451 is up-regulated in the peripheral blood of patients with coronary heart disease. Moreover, TargetScan and dual-luciferase reporter gene assay results showed that VEGFA is a direct target gene of miR-451. C (CCK-8) and flow cytometry assay results showed that miR-451 mimic significantly inhibits cell proliferation and promotes apoptosis in HUVECs. Moreover, we found that the role of miR-451 in HUVECs is associated with the PI3K-Akt-mTOR pathway. Taken together, the data indicates that miR-451 might be a novel bio-marker for coronary heart disease.

Kawasaki disease (KD) is a form of acute multisystem vasculitis that presents with various complications, including coronary artery aneurysm. Heart failure and brain damage are rare, but life-threatening complications are associated with KD. Here, we describe a 4-year-old girl who developed intravenous immunoglobulin-resistant KD with both left ventricular failure and acute encephalopathy. On day 8 of the illness, the low left ventricular ejection fraction, mitral regurgitation, and low blood pressure, which required continuous administration of dobutamine, were observed during the treatments for KD, including intravenous immunoglobulin. She also appeared unconscious, where the electroencephalogram showed slow waves of activity in all regions of the brain. The cardiac performance improved after she received plasma exchange for three days. However, her unconsciousness with slow waves of activity on electroencephalogram and fever continued after the plasma exchange. Therefore, she was treated with methylprednisolone pulse, followed by prednisolone, as well as intravenous immunoglobulin. Finally, she recovered without any cardiac or neurological sequelae not only at the time she was discharged, but also throughout the follow-up period. The combination therapy using plasma exchange and methylprednisolone pulse may be a treatment option for severe KD with left ventricular failure and acute encephalopathy complications.

The healthcare-associated infections (HCAIs) occur in patients both in nosocomial environments and in community. More often HCAIs are associated to the use of medical devices and bacterial biofilm development on these equipments. Due to the clinical and economic relevance of this topic, new strategies for the treatment of infections caused by biofilm proliferation are unceasingly searched by scientists. The present study investigated the role of vitamin E to reduce the biofilm formation for a larger panel of human pathogens, including strains of Staphylococcus aureus , Staphylococcus epidermidis , Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , Acinetobacter baumannii , Pseudomonas aeruginosa and Pseudomonas putida . This potential activity was tested by placing a preparation of vitamin E (α-Tocopheryl acetate) as interface between the bacterial culture and the polystyrene walls of a 96 well plate at different concentrations of glucose, used as a biofilm enhancer. The Staphylococcus genus was further investigated by spreading the vitamin E on a silicone catheter lumen and evaluating its influence on the bacterial colonization. From our results, vitamin E has been able to interfere with bacterial biofilm and prevent in vitro biofilm formation. Furthermore, the ability of Staphylococcus aureus and Staphylococcus epidermidis to colonize the catheter surface decreased as a result of vitamin E application.

Retroperitoneal fibrosis is a connective disease of the auto-inflammatory/auto-immune type of the retroperitoneum with unknown etiology and pathological mechanism. The manifestations of the pathology can be local or systemic. Amongst the local symptoms, the dull and constant pain in the hips, back or abdomen is the most frequent. We report here a case of a 47-year-old woman, whose pathogenic mechanism could be related to an “IgG4-related disease” disorder as suggested by an increased serum level of this subclass of IgG and the positive immunohistochemistry. The diagnosis is not easy, because this pathology generates masses; adenomegalies with retro peritoneal development, that makes it similar to lymphomas or metastases from ovarian tumors.

Convolutional neural networks (CNNs) are a branch of deep learning which have been turned into one of the popular methods in different applications, especially medical imaging. One of the significant applications in this category is to help specialists make an early detection of skin cancer in dermoscopy and can reduce mortality rate. However, there are a lot of reasons that affect system diagnosis accuracy. In recent years, the utilization of computer-aided technology for this purpose has been turned into an interesting category for scientists. In this research, a meta-heuristic optimized CNN classifier is applied for pre-trained network models for visual datasets with the purpose of classifying skin cancer images. However there are different methods about optimizing the learning step of neural networks, and there are few studies about the deep learning based neural networks and their applications. In the present work, a new approach based on whale optimization algorithm is utilized for optimizing the weight and biases in the CNN models. The new method is then compared with 10 popular classifiers on two skin cancer datasets including DermIS Digital Database Dermquest Database. Experimental results show that the use of this optimized method performs with better accuracy than other classification methods.

Background The inflammatory response of macrophages is responsible for sepsis. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in sepsis development. However, its underlying mechanism remains largely unclear. This study aims to investigate the effect of NEAT1 on inflammatory response of macrophages and explore the regulatory network of NEAT1/microRNA-17-5p (miR-17-5p)/Toll-like receptor 4 (TLR4). Methods The serum samples of 68 sepsis patients and 32 heathy controls were collected. THP-1 macrophages were treated with lipopolysaccharide (LPS) to induce inflammatory injury model of sepsis. The expressions of NEAT1, miR-17-5p and TLR4 were measured by quantitative real-time polymerase chain reaction or western blot. The inflammatory response was investigated by levels of inflammatory cytokines, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1β) and IL-6 as well as nitric oxide (NO) production. The interaction among NEAT1, miR-17-5p and TLR4 were investigated by bioinformatics analysis, luciferase reporter assay and RNA pull-down. Results NEAT1 expression was enhanced in patient serum and associated with severity of sepsis. Knockdown of NEAT1 inhibited levels of TNF-ɑ, IL-1β, IL-6 and NO release in LPS-treated macrophages. miR-17-5p is bound to NEAT1 and its abrogation reversed NEAT1 knockdown-mediated inhibition of inflammatory response in LPS-treated macrophages. Overexpression of miR-17-5p weakened LPS-induced inflammatory response. TLR4 as a target of miR-17-5p was regulated by NEAT1 and miR-17-5p. TLR4 res-to ration alleviated silencing NEAT1-induced inflammatory suppression. Conclusion Silence of NEAT1 suppressed LPS-induced inflammatory response of macrophages by mediating miR-17-5p and TLR4, indicating that NEAT1 might be a promising target for sepsis treatment.

Matrix metalloproteinase 9 (MMP-9) plays an important role in inflammatory and pathological processes by enabling the inflow of leukocytes to the site of infection or tissue damage. MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) have been described as potential prognostic biomarkers in various clinical settings. The aim of the study was to evaluate the usefulness of plasma levels of MMP-9 and TIMP-1 as well as the MMP-9/ TIMP-1 ratio in predicting the outcome in patients admitted to the intensive care unit (ICU). The study included 56 critically ill patients with multiple organ failure. Plasma levels of MMP-9 and TIMP-1 were determined on hospitalization day 1, 2, 3 and 7. Nineteen (35.7%) patients died. The level of TIMP-1 was statistically significantly higher on day 1 and 7 of hospitalization in non-survivors, as compared to survivors (p=0.01). A statistically significant positive correlation was found between MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio was comparable in both groups during of observation (0.62 on day 1). The MMP-9/TIMP-1 ratio was positively correlated with the level of lactate and negatively correlated with platelet count. Likewise, TIMP-1 was positively correlated with the level of lactate. The level of MMP-9 was higher in the non-survivor group only on day 7 of observation. In conclusion, although TIMP-1 and MMP-9 concentrations were higher in non-survivors and the MMP-9/TIMP-1 ratio was related to some parameters of critical illness, further research is needed to verify whether they can serve as reliable biomarkers for early prognostication of ICU patients.

Background Fecal incontinence (FI) is a common condition that has devastating consequences for patients’ QOL. In some patients, the conventional functional pelvic floor electrical stimulation has been effective but is an invasive and embarrassing treatment. The object of the study was to evaluate the feasibility of functional extracorporeal magnetic stimulation (FMS) in strengthening the pelvic floor muscles without an anal plug and the embarrassment of undressing. Materials and Methods Thirty patients (26 female and 4 males) with FI were enrolled. All patients were assessed during a specialized coloproctology evaluation followed by endoanal ultrasonography and anorectal manometry. All patients underwent an FMS treatment once weekly for 8 weeks. Patients’ outcome was assessed by the Cleveland Clinic Fecal Incontinence Score (CCFIS) and by the fecal incontinence QOL questionnaire (FIQL). Results After 8 weeks, the number of solid and liquid stool leakage per week was significantly reduced (p<0.05) with a significant improvement of the CCFIS and of the FIQL (p<0.05). Moreover, the authors recorded a missed recruitment of the agonist and antagonists’ defecation muscles. Conclusion FMS is a safe, non-invasive and painless treatment for FI. It could be recommended for selected patients with non-surgical FI to ensure a rapid clinical improvement.

Germ cell tumors (GCTs) localized extragonadally are rare, with only 14 reported cases of a yolk sac tumor in the endometrium. Here we report a case of mixed endometrium GCTs in a 65-year-old postmenopausal woman with abnormal vaginal bleeding. An ultrasound examination showed an oval-shaped mass in the patient’s uterine cavity. Biochemical examination revealed elevated serum α-fetoprotein (AFP) at 359 ng/mL, whereas the tumor markers CA-125, CA-199, and CEA were all within normal range. Total hysterectomy and bilateral salpingo-oophorectomy were performed;. a histological examination revealed that the malignant components contained a yolk sac tumor, embryonal carcinoma, and focal immature teratoma. Immunohistochemical staining showed that AFPs were diffusively distributed in both the yolk sac tumor and embryonal carcinoma. The stem cell marker OCT3/4 was positive in the embryonal carcinoma component and that the pan-cytokeratin AE1/AE3 staining was positive in glandular areas. GFAPs (Glial Fibrillary Acidic Proteins) were positive in neuroectodermal tubules; the Ki-67 protein was positive in 90% of the tumor cells, whereas CD117 and placental alkaline phosphatase (PLAP) were negative. The cumulative evidence indicated mixed GCTs of endometrium as the final histopathological diagnosis. The patient received three courses of adjunct chemotherapy that provided good therapeutic efficacy as evidenced by the decreased serum AFP level. Our report on this rare case of mixed GCTs of the endometrium, supported by associated histological patterns and immunophenotypes and successful adjunct chemotherapy after surgery, could provide insight on future treatment of this rare but lethal disease.

Bowel perforation by a peritoneal catheter (BPPC) is a serious complication after ventriculoperitoneal shunting, with high mortality and morbidity rates. This patient presented with scalp ulceration over the shunt valve at the retromastoid region 26 years after shunt placement. During revision, the catheter distal to the valve was divided in the clavicular region. As there was no cerebrospinal fluid drainage, we decided to remove the ventricular catheter and valve. The ulceration was debrided and primarily closed. Distal to the clavicle, the disconnected peritoneal catheter was encased in a fibrous, calcified tunnel. To avoid piecemeal resection with multiple incisions, the catheter was not retrieved. Two years later, the patient presented with an abscess and pus draining from the clavicular wound. Cultures were positive for enteric bacteria. BPPC with retrograde spread of infection was suspected, and abdominal computed tomography confirmed perforation. We removed the disconnected catheter, but the perforation site could not be detected during laparotomy. The patient was treated with intravenous antibiotics and recovered without complications. To minimize complications, abandoned catheters should be avoided. Otherwise, patients unnecessarily have a life-long risk of developing abdominal complications. In patients with abandoned catheters and severe abdominal symptoms, BPPC is an important differential diagnosis.

Abstract: HOX transcript antisense intergenic RNA (HOTAIR) is one of the most studied long noncoding RNAs (lncRNAs) and is aberrantly expressed in colorectal cancer (CRC). We thus performed a comprehensive study based on meta-analysis and validation of the TCGA database to investigate clinicopathological and prognostic value of HOTAIR in CRC. Six studies enrolling 629 CRC patients were included in the analysis. The results indicated that high HOTAIR expression predicted worse OS (hazard ratio [HR] = 2.46, 95% confidence interval [CI]: 1.82-3.32, P < 0.01) and RFS (HR = 1.97, 95% CI: 1.27-3.05, P < 0.01) for CRC patients. High HOTAIR expression was also significantly associated with venous invasion (OR = 2.53, 95% CI: 1.12-5.68, P = 0.02), advanced tumor infiltration (OR = 3.35, 95% CI: 1.34-8.42, P = 0.01) and distant metastasis (OR = 5.52, 95% CI: 1.22-25.01, P = 0.03). Then, the results were validated by the TCGA database, showing that the up-regulated expression of HOTAIR was significantly related to poor OS (P = 0.01) and RFS (P = 0.04) in CRC. Our meta-analysis indicated that high HOTAIR expression was closely associated with poor clinical outcomes and could be a reliable prognostic biomarker for CRC patients.

Despite its rarity, insulinoma is the most common type of pancreatic endocrine neoplasm, with an occurrence of 1 to 5 per million per year in the population. Surgical resection or enucleation is the first line of curative treatment choice for insulinoma. Eight patients with symptomatic insulinomas treated by radiofrequency ablation have been described since 2009. In the past two years, we treated two patients with symptomatic insulinomas (one in the pancreatic tail and the other in the pancreatic neck) successfully using laparoscopic radiofrequency ablation. Both patients achieved complete elimination without any significant complications. Our study suggests laparoscopic radiofrequency ablation could be developed as a safe and effective alternative treatment to surgery for the patients with insulinomas who refuse or are not eligible for surgery.

Background Primary pulmonary papillary adenocarcinoma (PA) is a specific and rare subtype of invasive pulmonary adenocarcinoma (ADC). The knowledge concerning the clinicopathologic features and prognosis of patients with primary pulmonary PA has not been clarified because of its rarity. Methods The clinical data of a total of 3391 patients with primary pulmonary PA were retrospectively analyzed to confirm their clinical characteristics and factors influencing prognosis and were in comparison with 3236 patients with non- PA pulmonary adenocarcinoma. All patients were histologically diagnosed between 1988 and 2015 in The Surveillance Epidemiology and End Results (SEER) database. A nomogram with satisfactory predictive performance was established to visually predict long-term survival of these patients. Results and conclusion Collectively, primary pulmonary PA is a rare pathological cancer and its prognosis is analogous to that of non-PA pulmonary adenocarcinoma. Older age, larger lesions, distant metastases, lymph node invasion, and poor pathological differentiation are correlative with unacceptable prognosis. Surgical intervention is conducive to reaping favorable prognosis. Unfortunately, radiotherapy or chemotherapy results of no significant effects on patient survival. In our study, a nomogram with prognostic function is formulated to confer individual prediction of overall survival (OS).

Pheochromocytoma is a rare catecholamine-producing tumor of the adrenal gland. Patients with known pheochromocytoma undergoing surgery require preoperative treatment with alpha-blockers to reduce the risk of intraoperative complications related to catecholamine release. If undiagnosed, pheochromocytoma can lead to life-threatening surgical complications. We report the case of a patient with a suspected solid pseudopapillary neoplasm in the pancreatic tail, for whom pancreatoduodenectomy was scheduled. However, shortly after abdominal incision, hypertensive crisis developed and was followed by severe hypotension requiring intravenous vasopressors, which prompted discontinuation of the operation. Further diagnostic evaluation revealed marked elevations in urinary excretion of methylated catecholamines and suggested that the tumor was in fact a pheochromocytoma extending from the left adrenal gland. After preoperative treatment with doxazosin, the patient underwent lateral transperitoneal laparoscopic adrenalectomy, with no major complications and an uneventful postoperative course. The pathological report confirmed a diagnosis of pheochromocytoma. Due to the potential for life-threatening surgical complications in patients with pheochromocytoma not treated preoperatively with alpha-blockers, this tumor type should be included in the differential diagnosis of abdominal tumors of unknown origin.

Objective To investigate the expression of the ABCC3 gene in human glioma and its correlation with the patient’s prognosis. Methods The cancer genome atlas (TCGA) database was used to analyze the differential expression of the ABCC3 gene in human glioma. The STRING database was used to construct the protein-protein interaction (PPI) network of the ABCC3 gene coding protein. The co-expression genes relevant to the ABCC3 gene were analyzed by the Pearson correlation test. A log-rank test was used to analyze the difference of overall survival (OS) and disease-free survival (DFS) between the high and low ABCC3 gene expression groups. Results The expression level of the ABCC3 gene in glioma tissues was lower than that of corresponding normal brain tissues. The PPI network contains 51 nodes with the average node degree of 13.3 and the local clustering coefficient of 0.72 which indicated that the PPI enrichment was significant (p<0.001). Ten hub genes (ABCC3,NR1I2,NR1H4,-CYP7A1,SLC10A1,CYP3A4,UGT1A1,UGT1A8,UGT1A6 and ALB) were identified by the cytoscape software. The KEGG analysis was enriched in drug metabolism - cytochrome P450 and PPAR signaling pathway. CFI gene expression level was positive correlated with the ABCC3 expression level (r=0.71, p<0.05). And the CNRIP1 gene expressed was negative correlated with ABCC3 expression (r=-0.43, p<0.05). The overall survival (HR=2.8, P<0.05) and disease-free survival rates (HR=2.0, P<0.05) of patients with ABCC3 low expression glioma were significantly higher than those of patients with high expression of ABCC3. Conclusion The expression level of the ABCC3 gene in glioma was decreased compared to normal brain tissue. The overall survival and disease-free survival of in the ABCC3 low-expression group was significant decreased.

Background and aim To explore the diagnostic value of recombinant heparin-binding hemagglutinin adhesin (HBHA) protein antigen in spinal tuberculosis. Materials and methods Forty patients with spinal tuberculosis were included in the experimental group and 40 healthy people were included in the control group. Serum IgG antibody expression level was detected with recombinant HBHA protein as the antigen, using enzyme-linked immunosorbent assay (ELISA) detection. Results Patients with spinal tuberculosis and healthy volunteers were included in this study. A total of 40 eligible patients with spinal tuberculosis were included (24 males and 16 females, aged 18-72 years, with an average age of 41.24 ± 15.74 years). Forty healthy people were included (21 males and 19 females, aged 18-70 years, with an average age of 41.33 ± 12.36 years). On comparing the groups, no significant difference was found in the general data (P >0.05). IgG antibody level in the experimental group was higher than that in the control group, and the difference was significant (P < 0.00001). Conclusions Detection of serum HBHA protein antibody is of great value in the auxiliary diagnosis of spinal tuberculosis, and high HBHA expression can be used as an indicator for diagnosis of spinal tuberculosis.

Several types of B-cell lymphomas, including both primary cutaneous lymphomas and systemic lymphomas, may affect the skin, with partially overlapping clinical, morphological and immunohistochemical features. Currently, the World Health Organization (WHO) classification of primary cutaneous B-cell lymphomas does not include diffuse large B-cell lymphomas (DLBCL) and considers leg-type DLBCL the only primary cutaneous DLBCL. Here we report the case of a 72-year-old white woman with a primary cutaneous neoplasm comprised of large cells with round nuclei, irregularly clumped chromatin and one or more inconspicuous nucleoli. The immunohistochemistry demonstrated positivity for CD20 and MUM1, with no significant genetic translocations detected by fluorescence in-situ hybridization. After staging, we considered this neoplasm a primary cutaneous DLBCL with a non-germinal center phenotype, not otherwise specified, inconsistent with a leg-type DLBCL. Because of this view, we underscore the need for greater knowledge of the molecular landscape of B-cell lymphomas in order to reconsider the classification of such neoplasms in the skin.

Aim This study aims to explain the role and mechanism of lncRNA LINC00152 in esophageal cancer. Methods The 30 pairs of esophageal cancer and adjacent normal tissues were collected and measuring the lncRNA LINC00152 expression by ISH and RT-qPCR assay. In the next cell experiment, Eca 109 and Kyse 150 cells were divided into 3 groups: NC group were treated with non-treatment; BL group were transfected with empty vector and lncRNA group were transfected with lncRNA LINC00152. The cells proliferation were measured by MTT assay; the cells apoptosis and cell cycle were evaluated by flow cytometry. The relative proteins expressions were measured by WB assay. Results Compared with NC groups, the cell proliferation rate of lncRNA groups were significantly suppressed (P<0.05, respectively); the cell apoptosis and G1 phase rates were significantly enhanced in the lncRNA groups (P<0.05, respectively). In the proteins expressions, the EGFR, PI3K and AKT proteins expressions of lncRNA group were significantly inhibited and the P21 proteins expressions were significantly stimulated in the lncRNA groups compared with those of NC groups in Eca 109 and Kyse 150 cells. Conclusion The lncRNA LINC00152 had anti-tumor effects on esophageal cancer in the Eca 109 and Kyse 150 cells, the mechanisms were relative with EGFR pathway.

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare autosomal dominant vascular disorder. Patients with HHT may present with a wide spectrum of clinical manifestations from epistaxis to clinically significant arteriovenous malformations (AVM) in the lungs, liver, brain and spine. The diagnosis of HHT is based on clinical criteria. There is a long diagnostic delay of nearly 3 decades since disease onset. The treatment is based on various types of haemostasis. There is ongoing research with potential therapies which may prevent and decrease the severity of epistaxis. Thalidomide may be an effective treatment to decrease the bleeding symptoms of patients with HHT.

Background The relationship between electrocardiographic evaluation and circadian blood pressure (BP) variation in young and middle-aged hypertensive patients remains unknown. Methods A total of 171 hypertensive patients were included in the study. First, patients were divided into a young and middle-aged group and an elderly group. The two groups were then separately classified into three subgroups on the basis of circadian variation of BP as dippers, non-dippers and reverse-dippers. The electrocardiographic evaluation was calculated from 12-lead electrocardiography (ECG). Results QTc intervals were shortest in the dippers and longest in the reverse-dippers in the young and middle-aged group (QTc dipper: 416.53±18.37ms; non-dipper: 438.30±29.71ms; reverse-dipper: 444.93±25.47ms; for dipper vs non-dipper, and dipper vs reverse-dipper P<0.05). QTc interval was found to be an independent risk factor for the non-dipper BP pattern (Odds ratio 1.049; 95% CI 1.01-1.089; P=0.012) and reverse-dipper BP pattern (Odds ratio 1.051; 95% CI 1.007-1.098; P=0.023) in young and middle-aged hypertensive patients. No significant differences in other ECG parameters were found among the three subgroups in the young and middle-aged group. Conclusion Our study suggested that QTc interval might serve as a risk factor for non-dipper BP pattern and reverse-dipper BP pattern in young and middle-aged hypertensive patients.

Purpose Shoulder pain and weakness are common symptoms in athletes who play sports connected with overhead throwing. Suprascapular neuropathy may be one of the reason of such signs.The aim of the study was to find out if ultrasound examination of the shoulder in athletes reveals signs of suprascapular neuropathy. Methods This was a cross-sectional study in which 67 professional volleyball, handball and rugby players of polish teams without shoulder disorders, which have played sport for 10 or more years, were included. An ultrasound examination of both shoulders was performed. Excluding criteria were recent shoulder and/or neck trauma and neurological disorders. Results No ultrasound signs of suprascapular neuropathy were seen in any player. The only finding was enthesopathy of supraspinatus muscle and this finding was connected with athletes’ age, type of sport and with dominant hand. It had statistical significance with p-value respectively 0.01 for athletes’ age, 0.0208 for sport type and 0.03 for dominant hand. Conclusions Ultrasonography should not be used as the screening examination of shoulders in athletes, but it can sometimes be an additional tool to help to diagnose shoulder disorders.

Background There is a controversial relationship between the negative lymph nodes (NLNs) and survival in patients with esophageal squamous cell carcinoma (ESCC). This study investigates the implications of total number of NLNs on thoracic ESCC patient prognosis. Methods 579 thoracic ESCC patients were categorized into four groups (0-9, 10-14, 15-19 and ≥20 NLNs). Univariate analysis was done by the log-rank tests while multivariate analysis was undertaken using Cox regression models. Survival analysis was determined employing the Kaplan-Meier method. Results When the numbers of NLNs were 9 or less, 10 to 14, 15 to 19 and 20 or more, patients of 3-year survival rates were 21.7%, 40.0%, 61.2% and 77.5%, respectively ( P <0.001). In the node-negative and node-positive subgroups, 3-year survival rates were 34.9% and 14.3%, 50.9% and 19.3%, 65.6% and 51.8%, 81.4% and 68.9% respectively ( P <0.001). Gender, tumor length, tumor differentiation, T and N stage as well as the total NLNs were found to be significantly linked to survival rates. Multivariate analysis showed tumor length, T stage, N stage and total NLNs were independent prognostic factors for ESCC patients. Conclusion NLNs numbers is a significant independent prognostic indicator for thoracic ESCC patients’ survival after curative esophagectomy.

Purpose We hypothesized that the current criteria may be unsuitable for lacunar pontine infarctions (LPI) diagnosis and that size criteria may indicate different stroke mechanisms. Methods A total of 102 patients with isolated pontine infarctions were divided into a parent artery disease (PAD) and non-PAD groups according to stenosis of basilar artery. Further, 86 patients from the non-PAD group were divided into paramedian pontine infarction (PPI) and LPI groups. Data were collected from the three groups. The “golden” criterion for LPI was established based on the location of the infarction. A receiver operating characteristic (ROC) curve were used to evaluate the optimal cutoff value to use as an LPI diagnostic indicator. Results There was a high prevalence of patients with PAD in both asymptomatic carotid atherosclerosis (ACAS) and PPI groups. Patients with PPI had a higher prevalence in diabetes and ACAS than those with LPI. Based upon the ROC curve, the optimal lesion size cutoff value for use as an LPI diagnostic indicator was 11.8 mm. Conclusions Diffusion weighted imaging (DWI) cutoff points for predicting LPI may differ from that of the middle cerebral artery territory. The diameter of LPI may also indicate different stroke mechanisms.

Objectives Monitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC. Methods A total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels. Results According to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value. Conclusion RAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

Background Recent studies demonstrated that long non-coding RNAs (lncRNAs) were involved in many biological processes. Dysregulated lncRNAs are related to many cancers, including colorectal cancer (CRC). However, the molecular mechanism of lncRNA ZEB1-AS1 in CRC is not clear. Methods LncRNA ZEB1-AS1, miR-205, and YAP1 expression were measured by quantitative reverse transcriptase PCR (QRT-PCR). YAP1 protein expression was measured by western blotting. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was used to confirm the relationship between ZEB1-AS1, miR-205, and YAP1. Results LncRNA ZEB1-AS1 and YAP1 was upregulated in CRC tissues. The expression of YAP1 was positively correlated with ZEB1-AS1. Knockdown of ZEB1-AS1 inhibited cell viability and induced apoptosis in CRC cell line SW480 and HCT116 which could be reversed by overexpression of YAP1. ZEB1-AS1 targeted and regulated miR-205 which could directly bind to YAP1. Meanwhile, ZEB1-AS1 regulated the expression of YAP1 via modulating miR-205. Conclusion Long non-coding RNA ZEB1-AS1 silencing could inhibit cell proliferation and induce apoptosis of colorectal cancer via regulating miR-205 and YAP1.

Background Laser hemorrhoidoplasty (LHP) is a new technique for treatment of hemorrhoids. The exact extent of coagulation is not visible at the time of the procedure. There currently is no experimental or clinical data on the subject. Objective To evaluate the length of coagulation defect according to power and activation time of 1470nm diode laser on the perianal tissue model. Methods Fresh anorectal tissue of twenty-four pigs was used to produce 54 experimental samples. Each sample was randomly assigned to the laser power of 6, 8 and 10 W and 1, 2 or 3-second pulses. The procedure was performed using Biolitec Ceralas © diode laser with 1.85 mm optical fiber. The fiber was inserted in a manner, similar to intrahemorrhoidal laser application. Samples were evaluated using low-power and high-power light microscopy by a single pathologist. The length of tissue injury was measured on high-magnification microscopy. Results The longest tissue injury (mean 3.93 mm) was caused by the longest laser exposure time (3 sec) with no significant difference between laser power used. Conclusions 8 W 3-second application of the 1470nm diode laser results in coagulation area approximately 4 mm, and further coagulation should be initiated approximately 5 mm from the first one.

Lung cancer is one of the most harmful malignant tumors to human health. The accurate judgment of the pathological type of lung cancer is vital for treatment. Traditionally, the pathological type of lung cancer requires a histopathological examination to determine, which is invasive and time consuming. In this work, a novel residual neural network is proposed to identify the pathological type of lung cancer via CT images. Due to the low amount of CT images in practice, we explored a medical-to-medical transfer learning strategy. Specifically, a residual neural network is pre-trained on public medical images dataset luna16, and then fine-tuned on our intellectual property lung cancer dataset collected in Shandong Provincial Hospital. Data experiments show that our method achieves 85.71% accuracy in identifying pathological types of lung cancer from CT images and outperforming other models trained with 2054 labels. Our method performs better than AlexNet, VGG16 and DenseNet, which provides an efficient, non-invasive detection tool for pathological diagnosis.

Background Enhanced recovery after surgery (ERAS) is a perioperative treatment intended to speed up recovery of surgical patients. Pulmonary lobectomy is a high-risk procedure, which ERAS is intended to address. Objective We evaluated the application of ERAS to patients with lung cancer. Interventions/Methods Of 337 patients who underwent pulmonary lobectomies for lung cancer at our hospital, 168 received traditional perioperative nursing, and 169 received ERAS. Their complication rates, numerical rating scale of pain (NRS), satisfaction with care, demographics and some inpatient indices before and after surgery were compared. Results The two groups did not significantly differ in general data or NRS score at 6 post-operative hours (P = 0.214) and 1 post-operative day (POD; P = 0.027). The ERAS group had lower incidence of postoperative lung complication (P = 0.008), shorter length of stay (P < 0.001), shorter enterokinesia recovery times (P < 0.001), lower hospitalization costs (P < 0.001), lower NRS scores at POD 2–5 (P < 0.001), higher nursing satisfaction (P < 0.001), and higher postoperative pulmonary function indices of maximal voluntary ventilation (MVV; P < 0.001), forced vital capacity (FVC; P = 0.002), and forced expiratory volume in 1 second (FEV1; P = 0.002) than did the traditional group. Conclusion ERAS is applicable to lung surgery patients. Implications for Practice Applying ERAS to thoracic surgery patients can alleviate their postoperative pain, shorten enterokinesia recovery, lower postoperative complication incidence, reduce hospitalization expenses, and raise nursing satisfaction, thereby expediting recovery.

A 62-year-old male who was receiving prednisolone and methotrexate for scleroderma and rheumatoid arthritis complained of diarrhea and vomiting, and was transferred to our hospital for detailed examination and treatment of renal dysfunction and thrombocytopenia. Hemolytic anemia and crushed erythrocytes were found during the patient’s course; therefore, we suspected thrombotic microangiopathy (TMA). His ADAMTS13 activity was 60.3% and his ADAMTS13 inhibitor was under 0.5. In addition, his blood culture was positive for Streptococcus pneumoniae , and we finally diagnosed Streptococcus pneumoniae -associated TMA (pTMA). The patient was treated with antibiotics and hemodialysis. The patient recovered and was discharged on the 45 th hospital day. Adult pTMA cases are remarkably rare. We herein report a successfully treated adult case of pTMA.

The constantly growing bacterial resistance against antibiotics is recently causing serious problems in the field of human and veterinary medicine as well as in agriculture. The mechanisms of resistance formation and its preventions are not well explored in most bacterial genera. The aim of this review is to analyse recent literature data on the principles of antibiotic resistance formation in bacteria of the Enterococcus genus. Furthermore, the habitat of the Enterococcus genus, its pathogenicity and pathogenicity factors, its epidemiology, genetic and molecular aspects of antibiotic resistance, and the relationship between these bacteria and bowel diseases are discussed. So-called VREfm – vancomycin resistant Enterococcus faecium and its currently rapidly growing resistance as well as the significance of these bacteria in nosocomial diseases is described.

Inflammatory fibroid polyps (IFPs) tend to occur in the gastrointestinal tract, and they are rare and benign neoplasms. In general, IFPs often come from epithelial tissue. The gastric antrum is the most common location. Endoscopic ultrasound (EUS) often shows a predominantly hypoechoic mass with well-defined borders originating from the submucosal area. Here, we report the case of a 46-year-old woman with abdominal pain who underwent computed tomography (CT), endoscopic ultrasound and endoscopic submucosal dissection (ESD) of resected specimens; the diagnosis was ultimately an inflammatory fibroid polyp. She is currently in clinical remission.

The aim of the present study was to investigate the role and mechanism of microRNA-204-5p (miR-204-5p) in atherosclerosis (AS)-related abnormal human vascular smooth muscle cells (hVSMCs) function. Firstly, we analyzed the expression of miR-204-5p and found that the miR-204-5p expression level was clearly downregulated in atherosclerotic plaque tissues and blood samples compared to the normal controls. Then, matrix metallopeptidase-9 (MMP-9) was predicted to be the potential target of miR-204-5p by TargetScan and this prediction was confirmed by luciferase assays. Besides, we observed that miR-204-5p could negatively regulate the expression of MMP-9 in hVSMCs. Subsequently, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, transwell assay and flow cytometry were performed to detect the proliferation, migration and apoptosis of hVSMCs. Down-expression of miR-204-5p led to the promotion of proliferation and migration accompanied with the suppression of apoptosis in hVSMCs, and these effects were reversed by MMP-9-siRNA. In addition, overexpressed miR-204-5p could inhibit hVSMC proliferation and migration and promote the apoptosis of hVSMCs. However, the effects were also abrogated by overexpressed MMP-9. Together, our findings showed that miR-204-5p plays an important role in the growth and migration of hVSMCs by targeting MMP-9, which might be a novel biomarker and promising therapeutic target for AS.

Background Long noncoding RNA (lncRNA) LINC00152 (CYTOR) has been reported to be upregulated and to serve as a diagnostic biomarker in multiple types of cancers, including laryngeal squamous cell cancer (LSCC). However, the functional role and molecular mechanisms of LINC00152 in LSCC progression need to be further investigated. Methods LINC00152 levels in LSCC and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Gene knockdown of LINC00152 was achieved in LSCC cells by use of small interfering RNA (siRNA). Cell proliferation, apoptosis, migration and invasion were examined by a series of methods. The micoRNA (miRNA) interaction with LINC00152 was screened by starBase v2.0 and confirmed by luciferase reporter activity. Results LINC00152 levels in LSCC tissues were significantly higher than those in adjacent normal tissue, and patients with lymph node metastasis or an advanced clinical stage displayed higher LINC00152 expression. Moreover, siRNA-mediated LINC00152 knockdown significantly inhibited the proliferation, migration and invasion of LSCC cells and induced apoptosis in those cells. Mechanistically, LINC00152 functioned as a competing endogenous RNA (ceRNA) sponging miR-613. The inhibitory effect of LINC00152 knockdown on malignant behavior was abrogated by inhibiting miR-613. Conclusion LINC00152 exerts an oncogenic effect on the tumorigenesis of LSCC by sponging miR-613 and may serve as a potential target for treating LSCC.

Three-dimensional (3D) cell cultures were created with the use of fur keratin associated proteins (F-KAPs) as scaffolds. The procedure of preparation F-KAP involves combinations of chemical activation and enzymatic digestion. The best result in porosity and heterogeneity of F-KAP surface was received during pepsin digestion. The F-KAP had a stable structure, no changes were observed after heat treatment, shaking and washing. The 0.15-0.5 mm fraction had positive effect for formation of 3D scaffolds and cell culturing. Living rat mesenchymal cells on the F-KAP with no abnormal morphology were observed by SEM during 32 days of cell culturing.

Aim The aim of this study is to explain the effects of miRNA-186 in renal injury induced by sepsis. Methods The Wistar rats were divided into 3 groups: the Sham group, Sepsis model group and the miRNA-186 group based on the model group; there were 9 rats in every group. The rat sepsis model was reproduced by cecal ligation and puncture (CLP). The rats of the miRNA-186 group were injected miRNA-186 from caudal vein. The rats of the difference group were killed after operation 24 h. The kidneys of the difference groups were taken for histopathological and cell apoptosis analysis by H&E and TUNEL assay. The relative protein expressions were measured by WB assay. miRNA-186 target to Phosphatase and tensin homologous protein (PTEN). Results Compared with the Sham group, the kidney histopathological and cell apoptosis rates of the model group were significantly damaged (P<0.05, respectively), however, the kidney histopathological and cell apoptosis rate of miRNA-186 group were significantly improved compared with the model group (P<0.05, respectively). The relative protein expressions were significantly different among 3 groups (P<0.05, respectively). The PTEN was the target of the miRNA-186. Conclusion miRNA-186 over-expression has effects that improve renal injury induced by sepsis via PTEN pathway.

Ultra-low anterior resection for low rectal cancer is usually done with a covering ileostomy as a safety measure to reduce the consequences of distal anastomotic failure. In many centres, distal loopogram is performed routinely, prior to the closure of the loop ileostomy, to assess the integrity of anastomosis. Distal loopogram is generally considered a safe procedure with very low complication rates, especially when water-soluble contrast is used. We report two cases of delayed bowel perforation which led to severe sepsis and generalized peritonitis after distal loopogram prior to ileostomy closure. Our cases highlight the potential dangers of distal loopogram. Therefore, the routine usage of this procedure should be scrutinized and the patient needs to be properly counselled prior to the procedure.

Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has become one of the most popular methods for the rapid and cost-effective detection of clinical pathogenic microorganisms. This study aimed to evaluate and compare the diagnostic performance of MALDI-TOF MS with that of conventional approaches for the direct identification of pathogens from urine samples. A systematic review was conducted based on a literature search of relevant databases. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the summary receiver operating characteristic (SROC) curve of the combined studies were estimated. Nine studies with a total of 3920 subjects were considered eligible and included in the meta-analysis. The pooled sensitivity was 0.85 (95% CI 0.79-0.90), and the pooled specificity was 0.93 (95% CI 0.82-0.97). The PLR and NLR were 11.51 (95% CI 4.53-29.26) and 0.16 (95% CI 0.11-0.24), respectively. The area under the SROC curve was 0.93 (95% CI 0.91-0.95). Sensitivity analysis showed that the results of this meta-analysis were stable. MALDI-TOF MS could directly identify microorganisms from urine samples with high sensitivity and specificity.

Stroke is the major cause of death and disability worldwide. ABCA1 R219K has been suggested as a risk factor for ischemic stroke, but the results remain inconclusive in the Chinese population. This study aimed to assess the association between ABCA1 R219K and ischemic stroke using meta-analysis. A systematic literature search was conducted to select eligible studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Fourteen studies containing 2865 cases and 3227 controls were included in the meta-analysis and the results suggested that there is a strong association between ABCA1 R219K and the ischemic stroke risks (K vs. R: OR = 0.837, 95% CI: 0.735- 0.954, p=0.008; KK vs. RR: OR = 0.689, 95% CI: 0.520-0.912, p=0.009; KK+RK vs. RR: OR = 0.782, 95% CI: 0.691-0.885, p<0.001). Subgroup analysis revealed that significant association was found for the 4 genetic models (p<0.05) in the Southern population, while in the northern population significant association was only found under the dominant model (KK+RK vs. RR: OR = 0.744, 95% CI: 0.583- 0.949, p<0.017). This meta-analysis suggested that ABCA1 R219K polymorphism might be a protective factor against developing IS, indicating this SNP may contribute to the pathogenesis of ischemic stroke and might be potentially used as a biomarker to predict the susceptibility to ischemic stroke.

This study aimed to explore the pathological mechanism in regulating glioma progression. The expression of miR-92 and neogenin was evaluated by qRT-PCR and western blot. Cell viability and apoptosis were measured by MTT and flow cytometry assays, respectively. The migration and invasion abilities were examined by transwell assays. The interaction between miR-92 and neogenin was conducted by dual-luciferase reporter system. As a result, we found that the expression of miR-92 was up-regulated in glioma tissues and cell lines. Down-regulation of miR-92 inhibited glioma cell proliferation, migration, invasion and promoted cell apoptosis rate of U251 and U87 cells. Notably, miR-92 was identified to directly target to 3’-UTR of neogenin. Furthermore, neogenin was down-regulated in glioma tissues and cells in a miR-92-correlated manner. Overexpression of neigenin could cause similar results to miR-92 knockdown in U251 and U87 cells. However, the silencing of neogenin partially reversed the effects of miR-92 knockdown on cell proliferation, migration, invasion and apoptosis of glioma cells in vitro. In conclusion, we clarified that miR-92 knockdown could suppress the malignant progression of glioma cells in vitro by targeting neogenin. Therefore, miR-92 could serve as a potential diagnostic and prognostic marker in glioma patients

Objective Programmed cell death-ligand 1 (PD-L1) expression has been shown to play important roles in various types of cancer. However, the role of PD-L1 expression has not been conclusively reported in patients with oral squamous cell carcinoma (OSCC). Accordingly, in this meta-analysis, we investigated the clinicopathological value of PD-L1 expression in patients with OSCC. Methods Google Scholar, PubMed, EMBASE, and CNKI databases were searched to find relevant studies published through to September 16, 2019. The relationships between PD-L1 expression in patients with OSCC and clinicopathological features were assessed using risk ratio (RR) and 95% confidence intervals (CIs). Results Sixteen studies including 1989 participants were included. The results indicated that high PD-L1 expression was correlated with sex (RR = 1.28, 95% CI: 1.16–1.42, P < 0.001), N stage (RR = 1.19, 95% CI: 1.06–1.33, P = 0.003), M stage (RR = 1.64, 95% CI: 1.01–2.66, P = 0.044), low differentiation (RR = 1.16, 95% CI: 1.01–1.33, P = 0.034), and human papilloma virus infection (RR = 1.38, 95% CI: 1.14–1.68, P = 0.001), but unrelated to TNM stage or T stage. There was no significant publication bias in the studies included in this analysis. Conclusions This meta-analysis revealed that high PD-L1 expression in patients with OSCC was correlated with clinicopathological features. Further large-scale studies are necessary to confirm our results.

Background Previous studies have shown that NF2 plays a key role in tumorigenesis. NF2 has been illustrated to be downregulated in several types of human cancer. However, the role of NF2 in breast cancer remains unclear. Methods We used UALCAN and KM-plotter database to study NF2 expression in human breast cancer and corresponding normal tissues and analyzed its relationship with clinicopathological parameters. We investigated the role of NF2 in breast cancer cells behavior by inhibiting its expression in MDA-MB-231 and MCF-7 cells. Results In this study, we found that NF2 was downregulated in breast cancer tissues compared to the adjacent normal tissues. We found that the low expression of NF2 was related with the tumor stage. NF2 overexpression inhibited the cell colon formation and stemness. Conclusion Our results indicate a role of NF2 in the progression of breast cancer.

Background This study aims to explore the correlations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and body composition with levels of asymmetric dimethylarginine (ADMA), endothelin 1(ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP) and calculated cardiovascular risks. Methods 102 women and 67 men with type 2 diabetes participated. Serum levels of NT-proBNP were measured by electro-hemi-luminescence while ELISA were used for ADMA and ET-1. Cardiovascular risks were calculated using the Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines. Statistical analysis was performed on an IBM SPSS 19.0. Results The BMI outperformed all other indices of obesity (WC, WHtR, WHR), as well as body composition parameters (body fat%, fat mass, fat free mass and total body water) in relation to the estimated risks for coronary heart disease and stroke, based on different calculators. The correlations of the obesity indices with the serum cardiovascular biomarkers were not significant except for BMI and fat mass versus ET-1, and for fat free mass and total body water versus ADMA. Conclusions The WC, WHR, WHtR, BF%, FM and FFM apparently do not add significant information related to the levels of cardiovascular biomarkers or the calculated CV-risks.

Purpose S100A6 protein (calcyclin), a small calcium-binding protein of the S100 family, is often upregulated in various types of cancers, including hepatocellular carcinoma (HCC). The aim of this study was to illustrate the molecular mechanism of S100A6 in regulating the proliferation and migration of HCC cells. Methods The expressions of S100A6 in human HCC and adjacent non-tumor liver specimens were detected using immunoblotting and quantitative PCR (qPCR). The recombinant glutathione S-transferase (GST)-tagged human S100A6 protein was purified and identified. After treatment with S100A6, the proliferation of HepG2 cells was detected by the MTT and colony formation assay, and the migration of HepG2 cells was investigated by the transwell migration assay; the protein levels of cyclin D1 (CCND1), E-cadherin, and vimentin were also tested by immunoblotting. The effect of S100A6 on p21 and nuclear factor-κB pathway was verified by performing the dual luciferase assay. Then, the expression of p21 and its transcription activator, p53, was examined using immunoblotting and qPCR, the ubiquitination of which was investigated through co-immunoprecipitation. Results It was found that the level of S100A6 was higher in the HCC tissues than in the adjacent non-tumor liver specimens. Exogenous overexpression of S100A6 promoted the proliferation and migration of HepG2 cells. S100A6 was observed to regulate p21 mRNA and protein expression levels and decrease p53 protein expression level, not mRNA level, by promoting the ubiquitination of p53 via the proteasome-dependent degradation pathway. Conclusion Our study indicated that S100A6 overexpression could promote the proliferation and migration of HCC cells by enhancing p53 ubiquitin-dependent proteasome degradation, ultimately regulating the p21 expression level.

Amyloidosis is a group of idiopathic clinical syndromes caused by the deposition of insoluble fibrillar proteins (amyloid) in the extracellular matrix of organs and tissues. These deposits disrupt the function of the target organ. Amyloidosis can manifest as a systemic disease or a single-organ involvement (local form). Its etiology still remains unclear. Deposits of amyloid in the larynx are rare, accounting for between 0.2 and 1.2% of benign tumors of the larynx. In this retrospective study, we report the clinical aspects, diagnosis, treatment and follow-up of five female patients with localized laryngeal amyloidosis without systemic involvement. The patients were all treated successfully using microlaryngoscopy with CO 2 laser or cold instruments. Prognosis is excellent; however, appropriate follow-up is an important part of the long-term management of this disease in order to prevent and control the possibility of local recurrence.

Background and aim Acute kidney injury (AKI) is a common complication of sepsis. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays a vital role in various diseases, including AKI. This study aimed to investigate the function and mechanism of NEAT1 in sepsis-induced AKI. Materials and methods A septic AKI model was established by treating HK-2 cells with lipopolysaccharide (LPS). The levels of NEAT1 and miR-22-3p were measured by quantitative real-time PCR. Cell apoptosis was assessed by flow cytometry. The levels of apoptosis-related protein and autophagy-related factors were examined by the western blot assay. An enzyme-linked immunosorbent assay was used to calculate the contents of inflammatory factors. The interaction between NEAT1 and miR-22-3p was validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. The levels of nuclear factor (NF)-κB pathway-related proteins were evaluated by the western blot assay. Results NEAT1 was upregulated, while miR-22-3p was downregulated in patients with sepsis and in LPS-stimulated HK-2 cells. LPS treatment triggered cell apoptosis, autophagy, and inflammatory response in HK-2 cells. NEAT1 knockdown attenuated LPS-induced cell injury. NEAT1 modulated LPS-triggered cell injury by targeting miR-22-3p. Furthermore, NEAT1 regulated the NF-κB pathway by modulating miR-22-3p. Conclusion Depletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.

Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring.

Purpose The purpose of this study was to evaluate the association of hearing loss with atherogenic index (AI) in the general population. Methods A multistage study using cluster random sampling method was conducted in the Zhejiang province from 2016 to 2018. Pure-tone air-conduction hearing thresholds were measured at frequencies of 0.125–8 kHz for each subject. After obtaining their consent, all participants were asked to provide their own plasma lipid data. Results A total of 3,414 eligible participants were included, 1,765 (51.7%) were men and 1,649 (48.3%) were women and 1,113 (32.6%) had hearing loss. Ridge regression showed increased AI in subjects with hearing loss. The subgroup with the highest quartile of AI, presenting the highest risk of hearing loss as compared to the lowest quartile, comprised young and middle-aged women. Further analysis revealed that the AI in people with different categories of hearing loss was higher than that in the normal population, except for those with (extremely) severe hearing loss. Moreover, the young and middle-aged women exhibited the most significant correlations between AI and hearing loss. Conclusion AI was positively associated with hearing loss in the general population, especially the young and middle-aged women.

Sirtuin 6 (SIRT6) plays a critical role in the progression and development of gastrointestinal cancers. However, the association between SIRT6 expression and clinicopathological parameters and prognosis in gastrointestinal cancer patients remains inconclusive. Consequently, we conducted this meta-analysis to evaluate the importance of SIRT6 expression in various types of gastrointestinal cancers. PubMed, EMBASE, and Web of Science databases were systematically searched to screen the relevant literature. The reported or estimated hazard ratio (HR) and odds ratio (OR) and their corresponding 95% confidence interval (CI) were pooled to assess the strength of the association. Nine studies involving 867 patients were included in the meta-analysis. Overall analysis showed that high SIRT6 expression was related to better overall survival in gastrointestinal cancers (HR = 0.62, 95% CI = 0.47–0.82). High SIRT6 expression was also related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% CI = 0.28–0.70) among gastrointestinal cancer patients. Our meta-analysis revealed that high SIRT6 expression might be a potential biomarker predicting better prognosis in gastrointestinal cancers, which may offer options for gastrointestinal cancer treatment.

Osteoarthritis (OA) is a common medical problem leading to chronic pain and physical disability among the world’s population. Analyzing the molecular background of the degenerative arthritis creates the potential for developing novel targeted methods of treatment. Fifty samples of meniscus, anterior cruciate ligaments (ACLs) and articular surfaces were collected from patients who underwent total knee arthroplasty in 2016. Enzyme-linked immunosorbent assay was used to assess the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), transforming growth factor-β1 and LUMINEX for MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. The collected data were correlated with the severity of radiological OA, demographic data and clinical scales. Strong positive correlations in the concentration of metalloproteinases and proinflammatory cytokines, TNF-α (MMP-2 and MMP-13) and IL-6 (MMP-13), were identified. MMP-13 had a positive correlation with the concentration of MMP-1, MMP-2 and MMP-9. Negative correlation coefficient exists between clinical conditions measured with the Western Ontario and McMaster Universities Osteoarthritis Index scale and the level of TNF-α and MMP-1. The TNF-α concentration was lower in the cartilage of the articular surface among patients who took non-steroidal anti-inflammatory drugs periodically. The decrease in MMP-2 in the cartilage of the articular surface corresponded with the severity of radiological OA on the Kellgren–Lawrence scale. Current treatment methods for OA do not stop disease progression. Identifying signaling pathways and molecular particles engaged in OA and their correlations with the patient’s clinical condition brings new therapeutic possibilities.

Introduction The association between interleukin-6 ( IL-6 ) gene −572 G^C polymorphism and myocardial infarction (MI) risk has not been established. We adopted this meta-analysis for further insight into the case–control studies. Materials and methods To investigate the genetic association, we searched multiple databases, including Web of Science, EMbase, CBM disc, PubMed and CNKI. Also, we manually identified the searched references. All the statistical analyses were conducted using Stata 11.0. Results A total of five studies were identified, involving 2,526 MI cases and 3,027 controls. The results revealed a significant association between IL-6 gene −572 G^C polymorphism and MI, implying that the IL-6 gene −572 C allele may be a protective factor for MI (for C allele vs K allele: OR = 0.85, 95% CI = 0.73–0.99, p = 0.041; for C/C vs G/G: OR = 0.55, 95% CI = 0.31–0.98, p = 0.044; for C/C vs G/C + G/G: OR = 0.60, 95% CI = 0.41–0.89, p = 0.011). However, in the subgroup analysis with regard to ethnicity, no significant correlation was identified between IL-6 gene −572 G^C polymorphism and MI among Europeans. Conclusion The IL-6 gene −572 C allele may be a protective factor for MI. Future studies involving larger sample bases are still recommended.

A case of a severe anaphylactic reaction during general anesthesia was reported. Despite the high suspicion for cefuroxime as a trigger of the anaphylactic reaction, cisatracurium emerged being the culprit drug. This case illustrates the importance of testing all drugs used during procedures/operations, trying to find a culprit of anaphylaxis.

Objective The aim of this study was to investigate the effects of rehabilitation training on Notch1 and synaptophysin (SYN) levels in brain tissues of rats with chronic cerebral ischemia. Methods Eighty-one male Sprague-Dawley rats were divided into nine groups: three Sham groups, three Model groups, and three training groups. There were nine rats in each group. At different time points, the apoptosis cell rate was analyzed by the TUNEL assay, and the expression levels of Notch1 and SYN in brain tissues were analyzed by immunohistochemical staining and RT-qPCR assay. Results The apoptosis cell rate of training groups was significantly higher on day 28 ( P < 0.05). The protein and mRNA levels of both Noth1 and SYN in training groups were significantly higher on day 28 ( P < 0.05). Conclusion Rehabilitation training could improve nerve cell apoptosis by increasing the expression of both Notch1 and SYN.

Multiple myeloma (MM) is an immunoglobulin-producing tumor of plasma cells, which occurs commonly in the elderly. The incidence of myocardial amyloidosis with MM is extremely low and early clinical manifestations are nonspecific. The diversity of clinical manifestations and first episode symptoms often cause misdiagnosis in young patients with myocardial amyloidosis following MM. In this study, we analyzed the clinical data of a young woman with MM and impaired cardiac function combined with echocardiography, electrocardiography (ECG), laboratory data, cell Congo Red staining, and other manifestations to diagnose amyloidosis. Considering the rapid progression, short survival, and poor prognosis in most patients, a clear, definitive, and timely diagnosis is essential for the treatment of patients with MM complicated with myocardial amyloidosis.

Background This study identified key genes in gastric cancer (GC) based on the mRNA microarray GSE19826 from the Gene Expression Omnibus (GEO) database and preliminarily explored the relationships among the key genes. Methods Differentially expressed genes (DEGs) were obtained using the GEO2R tool. The functions and pathway enrichment of the DEGs were analyzed using the Enrichr database. Protein–protein interactions (PPIs) were established by STRING. A lentiviral vector was constructed to silence RUNX2 expression in MGC-803 cells. The expression levels of RUNX2 and FN1 were measured. The influences of RUNX2 and FN1 on overall survival (OS) were determined using the Kaplan–Meier plotter online tool. Results In total, 69 upregulated and 65 downregulated genes were identified. Based on the PPI network of the DEGs, 20 genes were considered hub genes. RUNX2 silencing significantly downregulated the FN1 expression in MGC-803 cells. High expression of RUNX2 and low expression of FN1 were associated with long survival time in diffuse, poorly differentiated, and lymph node-positive GC. Conclusion High RUNX2 and FN1 expression were associated with poor OS in patients with GC. RUNX2 can negatively regulate the secretion of FN1, and both genes may serve as promising targets for GC treatment.

Recent studies have revealed that microRNAs regulate radiosensitivity of non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether miR-101-3p is correlated with radiosensitivity of NSCLC. According to our results, miR-101-3p was downregulated in NSCLC tissues and cell lines. Moreover, miR-101-3p was decreased in A549 cells’ response to irradiation in a dose-dependent manner. Upregulation of miR-101-3p decreased survival fraction and colony formation rate and increased irradiation-induced apoptosis in irradiation-resistant cells, while miR-101-3p depletion had the opposite effects in irradiation-sensitive cells. Furthermore, mechanistic target of rapamycin (mTOR) is a target gene of miR-101-3p. The expressions of mTOR, p-mTOR, and p-S6 were curbed by overexpression of miR-101-3p in A549R cells, which was enhanced by repression of miR-101-3p in A549 cells. Intriguingly, elevation in mTOR abated miR-101-3p upregulation-induced increase in irradiation sensitivity in irradiation-resistant cell line. In contrast, rapamycin undermined miR-101-3p inhibitor-mediated reduction of irradiation sensitivity in irradiation-sensitive cell line. Besides, miR-101-3p overexpression enhanced the efficacy of radiation in an NSCLC xenograft mouse model. In conclusion, miR-101-3p sensitized A549 cells to irradiation via inhibition of mTOR-signaling pathway.

Retinoic acid receptor-related orphan receptors (RORs) are frequently abnormally expressed in several human malignancies, including gastric cancer (GC). RORs are involved in the development and progression of GC through Wnt signaling pathway receptors and other common receptors. However, the prognostic roles of individual RORs in patients with GC remain elusive. We accessed the prognostic roles of three RORs (RORα, RORβ, and RORγ) through “The Kaplan–Meier plotter” (KM plotter) database in patients with GC. For all patients with GC who were followed for 20 years, the low mRNA expression of all three RORs showed a significant correlation with better outcomes. We further accessed the prognostic value of individual RORs in different clinical pathological features including Lauren classification, clinical stages, pathological grades, HER2 status, and different treatments methods. The RORs demonstrated critical prognostic roles in GC. Expressions of RORs were higher in GC tissues when compared with normal gastric tissues. Moreover, knockdown of RORs significantly inhibited cell proliferation and migration, suggesting an oncogenic role of RORs in human GC. These findings suggest potential roles of RORs as biomarkers for GC prognosis and as oncogenes in GC.

Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric ( n = 8), desmosomal ( n = 3), lamin A/C ( n = 3) and transthyretin ( n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

This study evaluates the efficacy of pembrolizumab for the treatment of advanced/metastatic melanoma. The literature search was conducted in electronic databases for studies that evaluated the efficacy and safety of pembrolizumab either alone or in combination with other treatments advanced/metastatic melanoma patients. Random-effects meta-analyses were performed to achieve pooled effect sizes of response and survival rates. The overall objective response rate (ORR) was 34.2% [95% confidence interval (CI): 30.4, 38.0]. However, ORR differed with respect to the history of prior systemic therapy. ORR was lower in studies with over 50% patients with prior therapy (25.5% [22.4, 28.5]) than in studies with under 50% patients with prior therapy (40.1% [34.1, 46.1]). ORR was higher in pembrolizumab monotherapy (32.9% [28.1, 37.7]) than in pembrolizumab–ipilimumab combination (27.6% [24.0, 31.2]). Overall ORR was inversely associated with visceral metastasis and prior systemic therapy. With pembrolizumab treatment, either alone or in combination, the progression-free survival (PFS) was 5.73 months; 12-, 24-, and 60-month PFS rate were 44%, 27%, and 25%, respectively; and 12-, 24-, and 60-month overall survival rates were 65%, 50%, and 41%, respectively. The percentage of AEs that led to treatment discontinuation was 13%. Pembrolizumab monotherapy is a valuable option for the treatment of advanced/metastatic melanoma patients.

Osteoprotegerin (OPG) appears to be a very promising marker both in the diagnosis of abdominal aortic aneurysms (AAAs) and as a potential target in its treatment. This article presents an overview of the current literature that discusses the role of OPG in the pathogenesis of atherosclerosis and its potential value as a prognostic factor in AAA. Pharmacological modulation of OPG expression has been considered. In conclusion, it seems that further research designed to assess the relationship between OPG and AAA is needed as this may contribute to improved AAA monitoring and more effective treatment of patients with AAA.

Melanoma is one of the most highly metastatic, aggressive and fatal malignant tumors in skin cancer. This study employs bioinformatics to identify key microRNAs and target genes (TGs) of plasma extracellular vesicles (pEVs) and their diagnostic and prognostic significance in melanoma. The gene expression microarray dataset (GSE100508) was downloaded from the Gene Expression Omnibus database. Differential analysis of miRNAs in pEVs was performed to compare melanoma samples and healthy samples. Then, TGs of the differential miRNAs (DE-miRNAs) in melanoma were selected, and differential genes were analyzed by bioinformatics (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, protein–protein interaction network and prognostic analysis). A total of 55 DE-miRNAs were found, and 3,083 and 1,351 candidate TGs were diagnostically correlated with the top ten upregulated DE-miRNAs and all downregulated DE-miRNAs, respectively. Prognostic analysis results showed that high expression levels of hsa-miR-550a-3p, CDK2 and POLR2A and low expression levels of hsa-miR-150-5p in melanoma patients were associated with significantly reduced overall survival. In conclusion, bioinformatics analysis identified key miRNAs and TGs in pEVs of melanoma, which may represent potential biomarkers for the early diagnosis and treatment of this cancer.

This study aimed to investigate the role and relevant mechanism of miR-30a-3p action in asthma. The results of this study revealed that the expression levels of miR-30a-3p were significantly decreased in the peripheral blood of asthmatic patients. In addition, we found that the CC chemokine receptor (CCR3) was a target of miR-30a-3p. Subsequently, an asthma mouse model was established using ovalbumin (OVA). The results showed that the expression of miR-30a-3p and CCR3 was downregulated and upregulated, respectively, in the peripheral blood of asthmatic mice. Enzyme-linked immunosorbent assay (ELISA) in asthmatic mouse serum demonstrated that miR-30a-3p mimic treatment significantly decreased the secretion of OVA-specific IgE, eotaxin-1, interleukin (IL)-5, and IL-4. These results suggested that miR-30a-3p inhibited CCR3 signaling pathway and relieved the inflammatory response against asthma in vivo . Eosinophils have also been implicated in the asthmatic inflammatory response. Therefore, the in vitro effects of miR-30a-3p on eosinophil activity were determined. Findings suggested that miR-30a-3p mimic significantly reduced eosinophil viability and migration and induced apoptosis. In addition, CCR3 and eotaxin-1 downregulation were observed. The aforementioned results were significantly reversed following CCR3 overexpression. This study suggested that miR-30a-3p was involved in asthma by regulating eosinophil activity and targeting CCR3.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are critical processes that are involved in atherosclerosis. The aim of this study was to explore the role of microRNA-491-5p (miR-491-5p) in the progression of atherosclerosis by regulating the growth and migration of VSMCs. In this study, we showed that the expression of miR-491-5p was downregulated in the atherosclerotic plaque tissues and plasma samples of the patients with atherosclerosis. The bioinformatic analysis and dual-luciferase reporter assay identified that matrix metallopeptidase-9 (MMP-9) was a target gene of miR-491-5p. The results showed a significant upregulation of MMP-9 in the atherosclerotic plaque tissues and plasma samples. Subsequently, the results also showed that downregulation of miR-491-5p significantly promoted the proliferation and migration of VSMCs and inhibited the apoptosis in VSMCs. Furthermore, we detected the effects of miR-491-5p mimic on the growth and migration of VSMCs, and the results illustrated that miR-491-5p mimic could inhibit the proliferation and migration of VSMCs and promote the apoptosis of VSMCs. Notably, MMP-9 plasmid could reverse all the effects of miR-491-5p mimic on VSMCs. Collectively, our study provides the first evidence that miR-491-5p inhibited the growth and migration of VSMCs by targeting MMP-9, which might provide new biomarkers and potential therapeutic targets for atherosclerosis treatment.

The present study aimed to analyze the data of embedded intrauterine device (IUD) in the bladder wall with the additional presence of calculus. This case series study included 11 female patients with partially or completely embedded IUD in the bladder wall. Their median age was 34 (range, 32–39) years. The median duration of IUD placement was 36 (range, 24–60) months. The median duration of symptoms was 9 (range, 3–12) months. Six patients underwent laparoscopy: the operation duration was 129 (range, 114–162) min, blood loss was 15 (range, 10–25) mL, the hospital stay was 4 (range, 4–4.5) days, the visual analog scale (VAS) for pain at 6 h after surgery was 3 (range, 2–6), and the time to removal of the urethral catheter was 7 (range, 7–8) days. Five patients underwent open surgery: the operation duration was 126 (range, 96–192) min, blood loss was 30 (range, 20–50) mL, the hospital stay was 7 (range, 7–15) days, the VAS was 6 (range, 4–9) at 6 h after surgery, and the time to removal of the urethral catheter was 9 (range, 8–17) days. The IUD and bladder stones were successfully removed in all 11 (100%) patients.

Introduction The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection. Objective This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis. Case presentation A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy. Conclusions Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Introduction In Italy, both parents have parental responsibility, so they have the power to give or withhold consent to medical procedures on their children. Methods The present work reports the case of a 5-year-old boy diagnosed with neuroblastoma in the right adrenal loggia, who underwent several chemotherapy treatments that prolonged his life until the age of 10. Informed consent for treatments was requested exclusively of the parents, without taking into consideration the minor’s will, not even when he asked for increased pain relief medication instead of other palliative treatments. Results The authors thought it interesting to examine the case in the light of new Italian legislation on informed consent and to verify whether it promotes greater participation of minors in healthcare choices, given that the issue of acquisition of informed consent is becoming increasingly broad and complex. Conclusion The case examined here indicates that current Italian legislation, even including the modifications introduced, does not allow for concrete and active participation of minors, especially those under the age of 12, in the discussion of choices about their health, not even in choices regarding the end of life, and not even when the minor manifests a mature capacity for discernment.

This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood–brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj- R 2 goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low k trans range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.

Background Cutaneous melanoma is an aggressive cancer with increasing incidence and mortality rates worldwide. Metastasis is one of the primary elements that influence the prognosis of patients with cutaneous melanoma. This study aims to clarify the potential mechanism underlying the low survival rate of metastatic melanoma and to search for novel target genes to improve the survival rate of patients with metastatic tumors. Methods Gene expression dataset and clinical data were downloaded from The Cancer Genome Atlas portal. Differentially expressed genes (DEGs) were identified, and their functions were studied through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Survival and multivariate Cox regression analyses were used to screen out candidate genes that could affect the prognosis of patients with metastatic melanoma. Results After a series of comprehensive statistical analysis, 464 DEGs were identified between primary tumor tissues and metastatic tissues. Survival and multivariate Cox regression analyses revealed four vital genes, namely, POU2AF1 , ITGAL , CXCR2P1 , and MZB1 , that affect the prognosis of patients with metastatic melanoma. Conclusion This study provides a new direction for studying the pathogenesis of metastatic melanoma. The genes related to cutaneous metastatic melanoma that affect the overall survival time of patients were identified.

Primary secondary tumor increased recently with the use of immunomodulatory drugs in patients with multiple myeloma (MM). However, MM with prior diagnosis of primary secondary tumor is relatively rare. In this study, we reported an MM patient with prior diagnosis of rectal cancer. In brief, an 85-year-old man was first diagnosed with rectal cancer. Given the age, heart failure and small-cell hypochromic anemia (hemoglobin level: 54 g/L), rectal cancer resection was not advised and symptomatic treatments were performed (including sufficient iron supplementation). Eight months later, the patient was diagnosed with MM due to worsening anemia. Anemia and heart failure were corrected after three cycles of treatment with thalidomide, dexamethasone and capecitabine. Radical resection of rectal carcinoma (Hartmann) was finally performed due to acute abdominal distension. Meanwhile, RR interval prolongation (longest interval >5.0 s) and atrial fibrillation occurred in the fifth cycle treatment. One month after discontinuation of thalidomide, RR interval returned to normal range, while atrial fibrillation developed into persistent atrial fibrillation.

We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

Background Many factors contribute to successful nerve reconstruction. The correct technique of anastomosis is one of the key elements that determine the final result of a surgery. The aim of this study is to examine how useful an electromyography (EMG) can be as an objective intraoperative anastomosis assessment method. Methods The study material included 12 rats. Before the surgery, the function of the sciatic nerve was tested using hind paw prints. Then, both nerves were cut. The left nerve was sutured side-to-side, and the right nerve was sutured end-to-end. Intraoperative electromyography was performed. After 4 weeks, the rats were reassessed using the hind paw print analysis and electromyography. Results An analysis of left and right hind paw prints did not reveal any significant differences between the length of the steps, the spread of the digits in the paws, or the deviation of a paw. The width of the steps also did not change. Electromyography revealed that immediately after a nerve anastomosis (as well as 4 weeks after the surgery), better nerve conduction was observed through an end-to-end anastomosis. Four weeks after the surgery, better nerve conduction was seen distally to the end-to-end anastomosis. Conclusions The results indicate that in acute nerve injuries intraoperative electromyography may be useful to obtain unbiased information on whether the nerve anastomosis has been performed correctly – for example, in limb replantation. When assessing a nerve during a procedure, EMG should be first performed distally to the anastomosis (the part of the nerve leading to muscle fibers) and then proximally to the anastomosis (the proximal part of the nerve). Similar EMG results can be interpreted as a correct nerve anastomosis. The function of the distal part of the nerve and the muscle remains intact if the neuromuscular transmission is sustained.

2019 novel coronavirus disease (COVID-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020. The initial symptoms of most patients include fever, cough, and fatigue. Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases. The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease. Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed. We report the first case of novel coronavirus disease (COVID-19) in Heilongjiang Province, China. The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan. The leukocyte count was normal, and the lymphocyte count was decreased. CT imaging showed large GGO and partial patchy consolidation in both lungs. The patient recovered and was discharged after 26 days of treatment. This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVID-19).

Our commentary is focused on three studies that used microRNA overexpression methods for directed differentiation of stem cells into insulin-producing cells. Islet transplantation is the only cell-based therapy used to treat type 1 diabetes mellitus. However, due to the scarcity of cadaveric donors and limited availability of good quality and quantity of islets for transplant, alternate sources of insulin-producing cells are being studied and used by researchers. This commentary provides an overview of distinct studies focused on manipulating microRNA expression to optimize differentiation of embryonic stem cells or induced pluripotent stem cells into insulin-producing cells. These studies have used different approaches to overexpress microRNAs that are highly abundant in human islets (such as miR-375 and miR-7) in their differentiation protocol to achieve better differentiation into functional islet beta (β)-cells.

Introduction Poor postoperative outcomes have been reported after surgery for infective endocarditis (IE). Whether the absence of positive cultures impacts the prognosis remains a matter of discussion. The aim of this study was to evaluate the impact of negative cultures on the prognosis of surgically treated IE. Methods This was a single-center, retrospective study. From January 2000 to June 2019, all patients who underwent valvular surgery for IE were included in the study. The primary endpoint was early postoperative mortality. A covariate balancing propensity score was developed to minimize the differences between the culture-positive IE (CPIE) and culture-negative IE (CNIE) cohorts. Using the estimated propensity scores as weights, an inverse probability treatment weighting (IPTW) model was built to generate a weighted cohort. Then, to adjust for confounding related to CPIE and CNIE, a doubly robust method that combines regression model with IPTW by propensity score was adopted to estimate the causal effect of the exposure on the outcome. Results During the study period, 327 consecutive patients underwent valvular repair/replacement with the use of cardiopulmonary bypass and cardioplegic cardiac arrest for IE. Their mean age was 61.4 ± 15.4 years, and 246 were males (75.2%). Native valve IE and prosthetic valve IE accounted for 87.5% and 12.5% of cases, respectively. Aortic (182/327, 55.7%) and mitral valves (166/327, 50.8%) were mostly involved; 20.5% of isolated mitral valve diseases were repaired (22/107 patients). The tricuspid valve was involved in 10 patients (3.3%), and the pulmonary valve in 1 patient (<1%). Fifty-nine patients had multiple-valve disease (18.0%). Blood cultures were negative in 136/327 (41.6 %). A higher postoperative mortality was registered in CNIE than in CPIE patients (19% vs 9%, respectively, p = 0.01). The doubly robust analysis after IPTW by propensity score showed CNIE to be associated with early postoperative mortality (odds ratio 2.10; 95% CI, 1.04–4.26, p = 0.04). Conclusions In our cohort, CNIE was associated with a higher early postoperative mortality in surgically treated IE patients after dedicated adjustment for confounding. In this perspective, any effort to improve preoperative microbiological diagnosis, thus allowing targeted therapeutic initiatives, might lead to overall better postoperative outcomes in surgically treated IE.

Background Prostatitis is the most commonly diagnosed disease in men younger than 50 years and accounts for about 8% of all urologists’ consultations. Objective After evaluating clinical trials and demonstrating the efficacy of chronic non-bacterial prostatitis treatment, it remains of clinical importance to continue studies on the use of low-energy extracorporeal shock wave therapy (ESWT) in men. Materials and methods From May 2017 to April 2018, 40 patients with chronic prostatitis (CP) type IIIB/chronic pelvic pain syndrome (CPPS) were enrolled in the study. The patients underwent ESWT once a week for 4 weeks. Results The mean age of the patients was 47.8 years. A statistically significant improvement in all the parameters, i.e., the International Prostate Symptom Score (IPSS), the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function (IIEF), was observed at week 4. The effect of the treatment was maintained during the entire 12-week period. The NIH-CPSI total score showed the best improvement at week 4, but a slight deterioration without a statistically significant change was noticed at week 12. The greatest improvement at week 4 was documented for the NIH-CPSI and IPSS (43% and 37%, respectively). At week 12, an improvement of 52% and 39% was recorded for VAS and IPSS, respectively. Conclusions Our findings confirmed the effectiveness and safety of ESWT in resistant cases of CPPS in the short term. ESWT is cost-effective, which takes little time or requires a small amount of staff, and is easily conducted.

This study evaluates the efficacy and safety of bevacizumab (BEV) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BM) by performing meta-analyses of response and survival indices. Seventeen studies were included. BEV treatment was associated with a lower new BM incidence (hazard ratio: 0.30 [95% confidence interval (CI): 0.14, 0.46]) during follow-up. Disease control rate (DCR) of BEV-treated patients with BM was 91% [95% CI: 85, 95]. However, intracranial DCR was relatively higher (94% [95% CI: 87, 98]) than extracranial DCR (86% [95% CI: 74, 96]). DCR of NSCLC patients with BM was significantly better with BEV than with control therapies (odds ratio: 2.71 [95% CI: 1.26, 5.86], P = 0.01). Progression-free survival (PFS) of BEV-treated patients with and without BM was 7.1 months [95% CI: 6.2, 8.0] and 7.4 months [95% CI: 6.3, 8.4], respectively. Intracranial PFS of BEV-treated patients with BM was 8.0 months [95% CI: 6.0, 10.0]. Overall survival of BEV-treated NSCLC patients with and without BM was 13.5 months [95% CI: 11.4, 15.6] and 12.5 months [95% CI: 10.2, 14.8], respectively. The incidence of bleeding/hemorrhage in the central nervous system was 1% with BEV treatment.

Introduction Aneurysmal subarachnoid hemorrhage is a type of spontaneous hemorrhagic stroke, which is caused by a ruptured cerebral aneurysm. Cerebral vasospasm (CVS) is the most grievous complication of subarachnoid hemorrhage (SAH). The aim of this study was to examine the risk factors that influence the onset of CVS that develops after endovascular coil embolization of a ruptured aneurysm. Materials and methods The study was designed as a cross-sectional study. The patients included in the study were 18 or more years of age, admitted within a period of 24 h of symptom onset, diagnosed and treated at a university medical center in Serbia during a 5-year period. Results Our study showed that the maximum recorded international normalized ratio (INR) values in patients who were not receiving anticoagulant therapy and the maximum recorded white blood cells (WBCs) were strongly associated with cerebrovascular spasm, increasing its chances 4.4 and 8.4 times with an increase of each integer of the INR value and 1,000 WBCs, respectively. Conclusions SAH after the rupture of cerebral aneurysms creates an endocranial inflammatory state whose intensity is probably directly related to the occurrence of vasospasm and its adverse consequences.

The progress of the coronavirus disease 2019 (COVID-19) pandemic is still severe. While everyone has been striving very hard to combat the pandemic, some healthcare professionals have shown varying degrees of infection symptoms and even died. The Chinese Army Medical Aid Team arrived in Wuhan on January 25, 2020, and quickly entered the battle against the pandemic after a short and rigorous training. As one of the earliest medical teams to enter the pandemic area, researchers have been exploring effective infection control measures that are currently in practice. Through observation and research, it has been noticed that layers of protective equipment have a hidden danger of infection while protecting the safety of the personnel. The members of each medical team have typically focused on the standard use of personal protective equipment (PPE). However, after a long period of intensive diagnosis and treatment in clinics and due to physical exertion and tiredness, problems such as improper operation are prone to occur during the tedious PPE doffing, thereby producing a relatively high risk of infection. This study primarily analyzes PPE doffing procedures, existing problems, and measures for improvement to explore methods to improve PPE donning and doffing and reduce the risk of infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is now a serious public health problem. Angiotensin-converting enzyme 2 (ACE2) recognized as the receptor of SARS-CoV is also necessary for SARS-CoV-2. However, the impact of ACE2 on SARS-CoV-2 susceptibility and the situation of malignant tumor patients in this outbreak are unclear. So, it is important to understand the expressions of ACE2 in different normal tissues and cancers. The results showed that the kidneys, duodenum, intestine, gallbladder and testis had the highest ACE2 expressions, followed by the colon, rectum and seminal vesicles. The lungs had a very low expression. ACE2 expressions were upregulated in renal cancer, gastrointestinal tumor and lung cancer. ACE2 expression levels may affect SARS-CoV-2 infection and severity. A total of 3,421 cases with COVID-19 have been collected. Among them, 43 cases (1.26%) had malignant tumor coexisting conditions. The rate of severe events for malignant tumor patients was 39.02% (16/41), while the rate of severe events for all patients was 10.79% (194/1,798). The clinical symptoms and signs were studied for the following three systems: respiratory (31–92%), digestive (10–13%) and urinary systems (3.38%). It seems that symptom severity is not related to protein expression levels. This might be the reason for SARS-CoV-2 showing higher regeneration index and susceptibility. More research is needed to explore the mechanisms and treatments.

Kidney transplantation is the surgical operation by which one of the two original kidneys is replaced with another healthy one donated by a compatible individual. In most cases, donors are recently deceased. There is the possibility of withdrawing a kidney from a consenting living subject. Usually, living donors are direct family members, but they could be volunteers completely unrelated to the recipient. A much-feared complication in case of kidney transplantation is the appearance of infections. These tend to arise due to immune-suppressor drugs administered as anti-rejection therapy. In this review, we describe the gastrointestinal complications that can occur in subjects undergoing renal transplantation associated with secondary pathogenic microorganisms or due to mechanical injury during surgery or to metabolic or organic toxicity correlated to anti-rejection therapy. Some of these complications may compromise the quality of life or pose a significant risk of mortality; fortunately, many of them can be prevented and treated without the stopping the immunosuppression, thus avoiding the patient being exposed to the risk of rejection episodes. Graphical abstract

We aimed to investigate the CXCL13 concentration of the serum and cerebral spinal fluid (CSF) in human immunodeficiency virus (HIV)-negative latent syphilis patients with treatment failure and explore the change in CXCL13 after treatment. Sixty-eight latent syphilis patients with treatment failure (failure group), 68 syphilis patients with successful treatment (seroconversion group) and 18 patients with non-inflammatory diseases of the nervous system (control group) were included and serum and CSF were collected. Enzyme-linked immunosorbent assay was employed to detect the CXCL13 in the serum and CSF. Results showed that the serum CXCL13 concentration was comparable among three groups, and the CSF leukocyte count, IgG index and CXCL13 concentration in the failure group were significantly higher than those in the seroconversion group and control group ( P < 0.05, P < 0.01). CSF CXCL13 concentration in the failure group was positively related to the CSF leukocyte count ( r = 0.3594, P < 0.001). Of the 68 patients in the treatment failure group, neurosyphilis was found in 17 (25.0%). In conclusion, involvement of nervous system is one of the reasons for the treatment failure in patients with latent syphilis. Detection of CSF CXCL13 concentration is helpful for the diagnosis and therapeutic evaluation of HIV-negative latent syphilis patients with treatment failure and neurosyphilis.

Purpose A model for predicting the prognosis of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) is currently not available. This study aimed to develop an age-biomarker-clinical history prognostic index (ABC-PI) and validate it for the assessment of individual prognosis. Patients and methods A total of 5,974 HFrEF patients were enrolled and 1,529 were included in this study after excluding missing values and loss to follow-up. Variables that significantly contributed to prediction of all-cause mortality were assessed by Cox regression and latent trait analysis (LTA) was used to validate discrimination of variables. Results After Cox regression, the following seven most significant variables were selected: age, N-terminal pro-B-type natriuretic peptide, renal dysfunction, left ventricular mass index, percutaneous coronary intervention, atrial fibrillation, and New York Heart Association (C-index: 0.801 ± 0.013). After verification by LTA, discrimination of these seven variables was proven. A nomogram was used to form the ABC-PI, and then the total score was set to 100 points. A lower score indicated a higher risk. After verification, the 3-year mortality rate was 34.7% in the high-risk group and only 2.6% in the low-risk group. Conclusion Our novel ABC-PI shows a good performance and does not require re-input in the original model. The ABC-PI can be used to effectively and practically predict the prognosis of HFrEF patients.

Objective The objective of this study was to evaluate the clinicopathological features and treatment of composite lymphoma (CL) with cervical lymph node enlargement. Methods In this study, two cases of CL are presented. Biopsies of enlarged cervical lymph nodes by excision revealed two distinct types of lymphomas. The diagnoses were confirmed by routine histopathology, immunohistochemistry, in situ hybridization, polymerase chain reactions and flow cytometry. Case 1 was diagnosed with Hodgkin’s lymphoma and cytotoxic T-cell lymphoma complicated by Epstein–Barr virus infection. Case 2 was diagnosed with diffuse large B-cell lymphoma and angioimmunoblastic T-cell lymphoma. Results Case 1 received one cycle of adriamycin, bleomycin, vincristine and dacarbazine (ABVD regimen) combined with chidamide, followed by one cycle of gemcitabine and dexamethasone (GDP regimen) combined with chidamide, and then oral acyclovir. The patient achieved stable disease, but was lost to follow-up. Case 2 received eight cycles of cyclophosphamide, pirarubicin, vincristine and dexamethasone (CTOP regimen) combined with chidamide, and the patient achieved complete remission. Nine months later, relapse was confirmed. She received chidamide monotherapy for 3 months, which was then terminated. One year later, the patient underwent progressive disease and died. Conclusions CL is a kind of rare disease. Due to the complexity of CL, clinicians should consider both disease components in order to increase the likelihood of effective treatment. This is important.

Trastuzumab, a humanized monoclonal antibody derived from recombinant DNA, is used in patients with breast cancer with HER2 gene amplification. The survival benefit from trastuzumab has been well established in patients with early and metastatic breast cancer who had over expression of HER2. We reported a case of severe thrombocytopenia after eight cycles of trastuzumab treatment for breast cancer. Before the 9th trastuzumab treatment, the patient’s platelet decreased to 48 × 10 9 /L. Recombinant human thrombopoietin was used, and the platelet level increased to normal level. Before the 10th treatment, the platelet count of the patient was 99 × 10 9 /L. However, during the 10th and 11th trastuzumab treatment, the platelet count decreased to 5 × 10 9 /L in 24 h. After treatment with TPO and corticosteroids, the platelet levels increased to the normal level in 7 days. Trastuzumab-induced thrombocytopenia is rare but still occurred even after 8 cycles of trastuzumab treatment.

Hepatoma is a serious liver cancer with high morbidity and mortality. Eldecalcitol (ED-71), a vitamin D analog, is extensively used as anti-cancer agent in vitro . Hepatocellular carcinoma cell, SMMC-7721 cell lines were used in this study. Transwell assay, cell apoptosis and cell cycle detection assays were investigated after treatment with ED-71 and phosphate buffered saline (PBS) as control. Sizes of tumors were measured after ED-71 treatment in a mouse model. E-cadherin and Akt gene expressions were detected by real-time PCR (RT-PCR). The results showed that cell invasion and migration were decreased markedly after ED-71 treatment compared to control group. Cell cycle detection showed that the G2 stage was 13.18% and total S-stage was 41.16% in the ED-71 group and G2 stage: 22.88%, total S-stage: 27.34% in the control group. Cell apoptosis rate was promoted in the ED-71 group. Size of the tumors reduced more after the ED-71 treatment than the PBS treatment in mice. ED-71 markedly inhibited the expression of Akt and E-cadherin, either detected by immunohistochemistry or RT-PCR. ED-71 treatment can inhibit the hepatoma agent proliferation by increasing the E-cadherin expression and decreasing Akt expression. Therefore, these findings provide novel evidence that ED-71 can be used as an anti-hepatoma agent.

The chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

Background Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, and no effective treatment exists until now. Glucagon-like peptide-1 receptor agonists are becoming the preferred therapeutic option for the management of obesity and are becoming the preferred treatment options for the management of both NAFLD and type 2 diabetes mellitus, but the molecular mechanisms are still unclear. Methods Forty-five healthy male Wistar rats were divided into three groups: normal control, high-fat diet (HFD) group, HFD + liraglutide (100 mg/kg body weight) group. Biochemical parameters and adipokine levels were examined in the serum of rats. In order to judge the degree of steatosis of NAFLD, the magnetic resonance imaging and histopathology of the liver were also studied. Results and conclusion Liraglutide caused a significant decrease in the serum fasting glucose and improved the insulin resistance, dyslipidemia, and liver enzymes. It reduced the adipokine level, and alleviated the histopathology of liver of rats in the steatosis, ballooning, and lobular inflammation when compared to the HFD group. Thus, liraglutide demonstrated amelioration of NAFLD by decreasing the adipokine levels in this animal model and seems to be a promising molecule for the management of NAFLD.

Introduction According to recent studies, silent atrial fibrillation (AF) is a common cause of cryptogenic ischemic stroke (CIS). 12-lead electrocardiogram (ECG) and 24 h Holter are not efficient to reveal an occult arrhythmic cause of stroke. Objectives The aim of the study was to evaluate 72 h Holter, 7 day Holter monitoring, and intermittent single-lead ECG recording in patients with CIS to identify cases with the arrhythmic cause of stroke in patients with CIS in whom 24 h ECG Holter was free from arrhythmia. Methods 72 patients (aged 60 ± 9 years, 44 males) with CIS and no arrhythmic findings in 24 h Holter were enrolled. All patients had 7 day Holter monitoring and received handheld ECG recorder (CheckMe, Viatom) for ambulatory 30 ± 3 days ECG recording. AF, supraventricular tachycardia (SVT runs of ≥5 QRS), and other arrhythmias were assessed in the first 72 h of Holter recording, in 7 day-recording, and in handheld ECG strips. Results 72 h-recording revealed AF in four cases (5.6%) and SVT in 18 (25%) cases. 7 day Holter confirmed AF in seven patients (10%) and SVT in 27 patients (37.5%). There was no difference in regards to CHADS2VASc score between patients with SVT and non-arrhythmic group (3.6 ± 1.1 vs 3.4 ± 1.6; p = NS). Symptoms did not correlate with findings. Patient-activated handheld ECG recorders were used with good compliance. The mean number of recordings was 49 ± 30. Except for PACs, there was only one case of AF documented in 3,531 strips. Conclusions 7 day Holter performs better than 72 h and reveals supraventricular arrhythmias in every third and AF in 10% of CIS patients who were free from arrhythmia in 24 h ECG monitoring. 30 day intermittent ECG monitor does not yield diagnostic value in CIS.

Forkhead box K2 (FOXK2) was first identified as an NFAT-like interleukin-binding factor. FOXK2 has been reported to act as either oncogene or tumor suppressor. However, functional and regulating mechanisms of FOXK2 in epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. An FOXK2-specific siRNA was employed to decrease the endogenous expression of FOXK2. MTT assay, colony formation and transwell assay were used to evaluate proliferation, migration and invasion of Hep3B and HCCLM3 cells, respectively. The protein expression associated with EMT and Akt signaling pathways was evaluated using western blot. FOXK2 downregulation could inhibit cell proliferation and colony formation and suppress migration and invasion in Hep3B and HCCLM3 cells. The expression of E-cadherin was significantly upregulated, and the expression of snail and p-Akt was significantly downregulated in siFOXK2-transfected cells compared with control cells. SF1670 induced the expression of p-Akt and snail and suppressed the expression of E-cadherin in Hep3B and HCCLM3 cells. SF1670 promoted the invasion and colony formation of Hep3B and HCCLM3 cells. SF1670 partly inhibited the effect of FOXK2 suppression on Hep3B and HCCLM3 cells. In conclusion, this study revealed that FOXK2 downregulation suppressed the EMT in HCC partly through inhibition of the Akt signaling pathway.

Carl Wernicke described the disease bearing his name in 1881 and reported three cases characterized by the presence of mental confusion, ataxia, and ophthalmoplegia. Wernicke’s disease is mainly observed in alcoholic patients, due to decreased vitamin intake as a consequence of an unbalanced diet, and a reduction of absorption due to the effects of alcohol. Likewise, inadequate vitamin intake is prevalent in older patients. Wernicke’s encephalopathy due to inappropriate total parenteral nutrition (TPN) occurs infrequently; recently, there is an increase in the literature concerning Wernicke’s encephalopathy in patients after general and bariatric surgeries. We present two cases of Wernicke’s encephalopathy after oncologic gastrointestinal surgery by failure to administer vitamin B1 during TPN; to our knowledge, these are the first two cases of Wernicke’s encephalopathy after colorectal surgery for cancer. In our opinion, timely diagnosis and treatment are mandatory to avoid nonfunctional recovery and consequent malpractice legal actions as well as an increase in the health-care costs correlated with the prolonged hospital stay and with the nonfunctional recovery.

Objective The acute-on-chronic liver failure associated with hepatitis B virus (HBV-ACLF) was a type of clinical syndrome with rapid deterioration of liver function. It was characterized by short-term elevated bilirubin, ascites, prolonged clotting time, hepatic encephalopathy, organ failures, and high short-term mortality. It was important to predict and evaluate the disease early. This study intended to comprehensively analyze the prognostic factors of patients with ACLF associated with HBV DNA infection through clinical manifestations and laboratory tests, and to establish a corresponding prediction and evaluation model for further clinical guidance. Methods A total of 220 patients were first diagnosed with HBV-ACLF and admitted to and treated at the Department of Infectious Diseases of the First Affiliated Changhai Hospital of the Second Military Medical University from 2009 to 2018. These patients’ records were collected and divided into two groups: (1) 120 patients who were improved and discharged were classified as good prognosis group and (2) 100 patients who died or underwent liver transplantation were classified as poor prognosis group. By analyzing baseline characteristics and clinical indicators of the two groups, the main potential factors affecting prognosis were identified and the corresponding prognostic evaluation model was established. This model’s advantages and disadvantages were compared with classic prognostic scoring systems. Results The proportion of ascites and the proportion of hepatic encephalopathy of poor prognosis group were significantly higher than those of good prognosis group. The total bilirubin, creatinine, white blood cell count, and NEU (%) levels of poor prognosis group were significantly higher than those of good prognosis group, and the international normalized ratio, albumin (ALB), alanine aminotransferase, Na, Cl, RBC, and PLT levels of poor prognosis group were significantly lower than those of good prognosis group. A new prediction model LR( p ) = 1/(1 + e − Z ) was established, where z = 10.0127 + 0.3687 × NEUT (%) − 0.0082 × PLT + 1.8157 × hepatic encephalopathy. The area under receiver operating characteristic (ROC) curve was 0.89, specificity was 80.83%, and sensitivity was 81%. The newly established prognostic model was compared with other three scoring systems including model for end-stage liver disease (MELD), MELD-Na, and ALBI scores. The results showed that the specificity, sensitivity, and area under the ROC curve of the newly established model were significantly higher than the other three scoring systems. Conclusion Hepatic encephalopathy, NEU (%), and PLT levels were independent risk factors for predicting the prognosis of HBV-ACLF. The new prediction model LR( p ) had better prediction accuracy than the other three scoring models of MELD, MELD-Na, and ALBI and could more accurately assess the prognosis of HBV-ACLF, but in the later stage, it was still necessary to expand the sample size for verification.

In December 2019, novel coronavirus pneumonia-19 (COVID-19) was discovered in the viral pneumonia cases that occurred in Wuhan, China, and then quickly spread around the world. This report described the clinical course of two COVID-19 patients and the purpose of the study was to discuss the combination of chest CT and clinical features for diagnosis of COVID-19. The first case was a typical COVID-19 case. A 66-year-old female presented to our hospital with a 3-day history of fever. She had contact with a COVID-19 patient. Chest CT showed a typical COVID-19 appearance. She was diagnosed with COVID-19 by a positive nucleic acid test. The second case was a 50-year-old male with a 2-day history of fever. He denied having been to Wuhan. Chest CT also showed typical features of COVID-19 pneumonia. COVID-19 nucleic acid tests were repeated up to seven times and the results remained controversial. Eventually, he was diagnosed with COVID-19. Our study shows that chest CT has high sensitivity for diagnosis of COVID-19 in clinical practice, particularly when the nucleic acid test is negative. The chest CT should be considered as a diagnostic tool for the COVID-19 screening, comprehensive evaluation, and follow-up and patients would benefit from effective treatments in time.

Objective To explore the clinical significance and mechanisms of altered miRNAs in squamous cell carcinoma of head and neck (SCCHN) and provide references for SCCHN diagnosis and prognosis. Method Differential expressed miRNAs (DEMs) in SCCHN were screened through gene expression omnibus (GEO) DataSets and verified by the cancer genome atlas (TCGA) database. Next, the overall survival analysis, receiver operating characteristics, and clinical correlation analysis were adopted to filter the miRNAs with diagnostic and prognostic values. Finally, functional enrichment analyses were conducted for inquiring into the mechanisms of miRNAs. Results Total 103 DEMs ( p < 0.05, fold change ≥ 2) in SCCHN were screened out from GSE124566. Partly, the expression levels of the selected (12/17) miRNAs were verified by TCGA. Followed, of the 12 miRNAs, two miRNA expression levels were associated with the overall survival, and five miRNAs showed diagnostic values (AUC ≥ 0.85). Besides, miR-223-3p and miR-204-5p expression levels were correlated to certain clinical features. Epithelial–mesenchymal transition (EMT) related biological process and energy metabolism controlling related AMPK signaling pathway might mediate the roles of miR-223-3p and miR-204-5p , respectively. Conclusion With diagnostic and prognostic values, miR-223-3p and miR-204-5p may be involved in the progression of SCCHN through EMT-related biological process and energy balance related AMPK signaling pathway, respectively.

Introduction Hepatocellular carcinoma (HCC) is the sixth most common cancer. Spontaneous rupture of HCC is an acute complication with a high mortality rate. The HCC principally arises in the background of chronic liver disease and cirrhosis of the liver. In the last few years, the rising incidence of HCC in noncirrhotic liver suggests the presence of other factors that may play a role in liver carcinogenesis. Methods We reviewed all cases treated at the University Surgical Department of Ospedali Riuniti of Foggia from 2009 to 2018. Only a single case of hemoperitoneum caused by spontaneous rupture of HCC in noncirrhotic liver was found. An extensive search of the relevant literature was carried out using MEDLINE, and a total of 58 published studies were screened from the sources listed. Conclusions The management of this devastating emergency should be carefully analyzed, with stabilization of vital signs as soon as possible. Patient with ruptured HCC and hemoperitoneum without a prior history of cirrhosis and viral infections benefited from the role of transcatheter arterial embolization (TAE) as the preliminary treatment in order to have a more precise diagnosis and an optimal stabilization of the patient. Delayed or staged hepatectomy after TAE represents the definitive treatment.

The purpose of this study was to investigate the role of voltage-dependent anion channel (VDAC) in mitochondria-mediated apoptosis of neurons in refractory epilepsy. Western blot analyses were carried out to detect the changes in cytochrome C , caspase 9, Bax, and Bcl-2. TUNEL assays were also carried out to investigate cell apoptosis under the upregulation and downregulation of VDAC1 with or without Bax or Bcl-2. VDAC1 induced Bax, Bcl-2, and caspase 9, increasing the release of cytochrome C . VDAC1 played an essential role in the apoptotic cell death of refractory epilepsy. It is concluded that VDAC1 plays an important role in refractory epilepsy and could be a possible therapeutic target of anti-epileptic drugs. The current study provides a new understanding of the possible mechanisms of refractory epilepsy.

Purpose The purpose of this research is to investigate the prognostic factors of patients with stage I gastric cancer (GC) and to determine whether adjuvant chemotherapy improves the prognosis for high-risk patients. Methods We performed a retrospective analysis at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences from January 2001 to December 2015. Cox regression and Kaplan-Meier were used to evaluate the relationship between the patients’ clinicopathologic characteristics and prognosis. Results A total of 1,550 patients were eligible for the study. The 5-year disease-free survival (DFS) rate of all enrolled patients was 96.5%. The pT and pN stages were significantly associated with the prognosis. The 5-year DFS rates of the three subgroups (T1N0, T2N0, and T1N1) were 97.8%, 95.7%, and 90.5%, respectively ( p < 0.001). In the T1N1 subgroup, patients not undergoing chemotherapy showed a lower 5-year DFS rate compared to those undergoing chemotherapy, although the difference was not statistically significant. Conclusions Both the pT and pN stages were closely associated with the prognosis of patients with stage I GC. We also found that the danger coefficient of the pN stage was higher than that of the pT stage, and that postoperative adjuvant chemotherapy might be a reasonable approach to improve outcomes of high-risk patients, particularly in the T1N1 group.

Background While there is evidence of a link between irisin and bone metabolism, prior clinical evaluations have been limited to women with postmenopausal osteoporosis. The primary goal of this evaluation is to examine the relationship between irisin and bone mineral density (BMD) in geriatric Chinese men experiencing osteoporosis or osteopenia. Methods In this case–control study, 43 geriatric Chinese men were verified as having osteoporosis or osteopenia via dual-energy X-ray light absorption spectrophotometry, and 24 subjects were accepted as the controls. Serum irisin levels were detected by a commercial ELISA kit. Results Serum irisin levels were lowered in geriatric Chinese men with osteopenia and osteoporosis, and multiple linear regression analysis revealed that the serum irisin level is an independent factor impacting BMD. Conclusions and discussion Our data confirm a positive correlation between irisin levels and BMD in geriatric Chinese men. Irisin has a protective effect on bone health dependent on BMD, but large clinical trials are still required to verify the irisin and BMD relationship.

Congenital dysfibrinogenemia (CD) is a rare hereditary fibrinogen disorder characterized by normal fibrinogen antigen levels associated with lower functional activities. The aim of this study is to analyze the phenotype and genotype of a family of CD. Routine coagulation screening tests were performed on the proband, her parents, and her grandparents. Then, the purified genomic DNA extracted from peripheral blood was amplified by PCR, and Sanger sequencing was performed to further confirm the mutation. The prothrombin time and activated partial thromboplastin time of the proband were normal, thrombin time prolonged, and the activity of fibrinogen (Fg:Ac) decreased significantly, but fibrinogen antigen (Fg:Ag) level was normal. The coagulation function indices of the proband’s father and grandfather were similar to her, and the indices of her mother and grandmother were normal. Sequencing results showed that the proband had a heterozygous missense mutation in FGA gene c.92G > A, which caused the mutation of amino acid 31 from glycine to glutamic acid (p.Gly31Glu). Her father had the same heterozygous mutation. In conclusion, the proband suffered from CD. The change of Gly31Glu in A chain due to the c.92G > A heterozygous missense mutation in the FGA gene is the cause of CD in the family. To the best of our knowledge, the mutation site is new and first reported so far.

The aim of the study is to evaluate the usefulness of cone-beam computed tomography (CBCT) in the assessment of the relationship between the cemento-enamel junction (CEJ) and bone crest of the anterior mandibular cortex. The study population comprised 39 males and 61 females, aged 18–71. A GENDEX GXCB-500 machine, i-CAT Vision and CorelDraw 9 software were used. The distances between the CEJ and bone crest at buccal and lingual sides of six anterior mandibular teeth were measured. Descriptive statistical methods, Student’s t -test and ANOVA were used. The mean distance between the bone crest and CEJ was 2.32 mm ± 0.78 mm at the buccal and 2.52 mm ± 0.85 mm at the lingual side. It was found that in males aged over 50 years, the mean distance at the buccal side was 2.84 mm ± 0.79 mm and was significantly higher than in males aged 49 and less – 2.08 mm ± 0.41 mm. The mean distance at the lingual side was 3.28 mm ± 1.08 mm and was significantly lower in the age group of 49 years and less – 2.10 mm ± 0.41 mm. CBCT allows determining the distance between the CEJ and crestal bone margin at buccal and lingual sides. The data provide crucial information for planning orthodontic treatment, implant placement and periodontal therapy.

Carbapenems are frequently used to treat infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), but carbapenem-resistant Enterobacteriaceae bacteria are a clinical concern. Although cephamycins (cefmetazole; CMZ) have been shown to be effective against mild cases of ESBL-E infection, data on their use for severe ESBL-E infections with sepsis or septic shock remain scarce. Herein, we discuss a de-escalation therapy to CMZ that could be used after empiric antibiotic therapy in ICU patients with sepsis or septic shock caused by ESBL-E bacteremia. A sequence of 25 cases diagnosed with sepsis or septic shock caused by ESBL-E bacteria was evaluated. The attending infectious disease specialist physicians selected the antibiotics and decided the de-escalation timing. The median SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) severity scores were 8 and 30; the rate of septic shock was 60%. Infections originated most frequently with urinary tract infection (UTI) (56%) and Escherichia coli (85%). Eleven patients were de-escalated to CMZ after vital signs were stable, and all survived. No patients died of UTI regardless of with or without de-escalation. The median timing of de-escalation antibiotic therapy after admission was 4 days (range, 3–6 days). At the time of de-escalation, the median SOFA score fell from 8 to 5, the median APACHE II score from 28 to 22, and the rate of septic shock from 55% to 0%. We conclude that for sepsis in UTI caused by ESBL-E bacteremia, de-escalation therapy from broad-spectrum antibiotics to CMZ is a potential treatment option when vital signs are stable.

Background and objective Extra-articular manifestations (EAMs) are serious outcomes or complications of rheumatoid arthritis (RA) with increasing mortality and morbidity. The purpose was to explore the factors influencing EAMs, tissue-specific/systemic EAMs, and the concurrence of several EAMs. Patients and methods In total, 519 inpatients with RA were enrolled. The clinical characteristics, laboratory parameters, and medications of RA patients and the details of EAMs were recorded carefully. Differences between groups were examined by a Chi-square test, independent samples t test, one-way analysis of variance, Mann–Whitney U test, and Kruskal–Wallis H test. Binary and ordinal logistic regression analyses were performed to determine the relationship between influential factors and EAMs, tissue-specific/systemic EAMs, and the concurrence of several EAMs. Results The morbidity of EAMs was 44.70%. Male sex, age, and traditional Chinese medicine (TCM) were independent influential factors of EAMs, and a number of statistically significant influence factors were found in the multivariate analysis of tissue-specific/systemic EAMs. Finally, age, CRP levels, number of RA-affected types of joints, and TCM were the factors that independently influenced the concurrence of several EAMs. Conclusion Influential factors identified in this study could be recommended in clinical work, which is hopeful to decrease the morbidity and mortality of EAMs in RA.

Background The practice of young adults smoking e-cigarette may have been adopted as a way of smoking cessation or just to follow a trend. Most people still remain unaware of the detrimental effects of e-cigarette. This study was carried out to assess the prevalence of the habit of smoking e-cigarette and the awareness of its harmful effects among adults aged 18–23 years. Methods A questionnaire adopted from a study conducted in Italy was used in the study following due permission. After taking their consent, participants were requested to fill the survey irrespective of their smoking status. Results In total the study comprised 710 participants aged 20.7 ± 1.7 years (females = 412 and males = 298) from six countries. Most respondents were from India followed by the USA and then the UK. The most common mode of information for the participants on the existence of e-cigarette was from the family members, friends followed by Internet search engines and TV/newspaper advertisements. Among the participants, e-cigarette had a prevalence of 5.63%. Among these, 26 participants were using e-cigarette for less than 1 year and 2 participants for more than 5 years. E-cigarette smokers also experienced sore throat, cough, headache, dizziness and sleeplessness. Conclusion Majority of the young population was unaware about the use and harmful effects of e-cigarette.

Aim Early diagnosis and treatment are crucial for the survival of severe Coronavirus Disease 2019 (COVID-19) patients, but data with regard to risk factors for disease progression from milder COVID-19 to severe COVID-19 remain scarce. Methods We conducted a retrospective analysis on 116 patients. Results Three factors were observed to be independently associated with progression to severe COVID-19 during 14 days after admission: (a) age 65 years or older (hazard ratio [HR] = 8.456; 95% CI: 2.706–26.426); (b) creatine kinase (CK) ≥ 180 U/L (HR = 3.667; 95% CI: 1.253–10.733); and (c) CD4+ T-cell counts <300 cells/µL (HR = 4.695; 95% CI: 1.483–14.856). The difference in rates of severe COVID-19 development was found to be statistically significant between patients aged 65 years or older (46.2%) and those younger than 65 years (90.2%), between patients with CK ≥ 180 U/L (55.6%) and those with CK < 180 U/L (91.5%), and between patients with CD4+ T-cell counts <300 cells/µL (53.8%) and those with CD4+ cell counts ≥300 cells/µL (83.2%). Conclusions Age ≥ 65 years, CK ≥ 180 U/L, and CD4+ T-cell counts <300 cells/µL at admission were risk factors independently associated with disease progression to severe COVID-19 during 14 days after admission and are therefore potential markers for disease progression in patients with milder COVID-19.

Procedural sedation and analgesia (PSA) is important during painful dilatation and stenting in patients undergoing percutaneous trans-hepatic biliary drainage (PTBD). A prospective, nonblinded randomized clinical trial was performed comparing different analgesic regimens with regard to the patient’s comfort. Patients were randomly assigned to two treatment groups in a parallel study, receiving either remifentanil or combined midazolam, piritramide, and S-ketamine. The primary study endpoint was pain intensity before, during, and after the intervention using the numerical rating scale (0, no pain; 10, maximum pain). The secondary study endpoint was the satisfaction of the interventional radiologist. Fifty patients underwent PTBD of whom 19 (38.0%) underwent additional stenting. During intervention, the two groups did not differ significantly. After the intervention, the need for auxiliary opioids was higher (12.5% vs 7.7%; p = 0.571) and nausea/vomiting was more frequently observed (33.4% vs 3.8%; p = 0.007) in patients with remifentanil than in patients with PSA. Overall, 45 patients (90.0%) needed additional administration of non-opioid analgesics during postinterventional observation. Remifentanil and combined midazolam, piritramide, and S-ketamine obtained adequate analgesic effects during PTBD. After the intervention, medications with antiemetics and long-acting analgesics were more frequently administered in patients treated with remifentanil (EudraCT No. 2006-003285-34; institutional funding).

During radiotherapy treatment for cervical cancer, up to 84% of patients exhibit some form of acute radiation toxicity (ART). The primary aim of this clinical study is to determine the impact of angiotensin-converting enzyme (ACE) inhibitors, β-blockers and other risk factors such as the patient’s anatomical characteristics on ART emergence in patients with locally advanced cervical cancer treated by chemoradiotherapy. This is a combination of two nested case–control studies within the cohort of patients with locally advanced cervical cancer based on the analysis of potential risk factors for the onset of ART in patients treated with 3D conformal radiotherapy (3D-CRT) and 2D conventional radiotherapy (2D-RT), prospectively followed up from January 2017 to September 2018 in a tertiary care hospital. The ACE inhibitors and bladder volume were identified as factors that significantly affect the occurrence of ART in patients treated with 3D-CRT. In patients treated with 2D-RT, the factors that significantly affect the occurrence of ART were ACE inhibitors, body mass index (BMI), brachytherapy rectal and bladder dose. This study has shown that BMI, radiation dose received by the bladder and rectum are of exceptional importance for the occurrence of the ART and also that therapy with ACE inhibitors was associated with the decreased chances of the ART.

This study was carried out to observe the impact of insulin-like growth factor-1 (IGF-1) on human vaginal fibroblasts (HVFs) in the context of pelvic organ prolapse (POP) and to explore its effects on mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. First, it was found that IGF-1 expression reduced in the vaginal wall tissues derived from POP compared to that in non-POP cases. Then the role of IGF-1 was explored in HVFs and thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to detect cell viability and cell apoptosis. Western blot assay and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression. The results showed that knockdown of IGF-1 inhibited the cell viability of HVFs, promoted the cell apoptosis of HVFs, and decreased the expression of types I and III collagen in HVFs, which was through inhibiting the expression of IGF-1 receptor and MAPK/NF-κB pathways. However, IGF-1 plasmid had the opposite effects on HVFs. In conclusion, our results showed that IGF-1 could activate MAPK and NF-κB pathways, thereby enhancing collagen metabolism and the growth of vaginal wall fibroblasts then to inhibit POP development.

Purpose In prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-β1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-β1/SMAD signaling pathway. Methods In this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-β1/SMAD signal of PCSCs. Results NANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-β1, p15, and p-SMAD2 expression was observed. Conclusion These findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-β1/SMAD signaling pathway.

Background As one of the most common malignant tumors worldwide, the morbidity and mortality of gastric carcinoma (GC) are gradually increasing. The aim of this study was to construct a signature according to immune-relevant genes to predict the survival outcome of GC patients using The Cancer Genome Altas (TCGA). Methods Univariate Cox regression analysis was used to assess the relationship between immune-relevant genes regarding the prognosis of patients with GC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic immune-relevant genes and to establish the signature for the prognostic evaluation of patients with GC. Multivariate Cox regression analysis and Kaplan–Meier survival analysis were used to assess the independent prognostic ability of the immune-relevant gene signature. Results A total of 113 prognostic immune-relevant genes were identified using univariate Cox proportional hazards regression analysis. A signature of nine immune-relevant genes was constructed using the LASSO Cox regression. The GC samples were assigned to two groups (low- and high risk) according to the optimal cutoff value of the signature score. Compared with the patients in the high-risk group, patients in the low-risk group had a significantly better prognosis in the TCGA and GSE84437 cohorts (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the signature of nine immune-relevant genes might serve as an independent predictor of GC. Conclusions Our results showed that the signature of nine immune-relevant genes may potentially serve as a prognostic prediction for patients with GC, which may contribute to the decision-making of personalized treatment for the patients.

Skin cancer is a type of disease in which malignant cells are formed in skin tissues. However, skin cancer is a dangerous disease, and an early detection of this disease helps the therapists to cure this disease. In the present research, an automatic computer-aided method is presented for the early diagnosis of skin cancer. After image noise reduction based on median filter in the first stage, a new image segmentation based on the convolutional neural network optimized by satin bowerbird optimization (SBO) has been adopted and its efficiency has been indicated by the confusion matrix. Then, feature extraction is performed to extract the useful information from the segmented image. An optimized feature selection based on the SBO algorithm is also applied to prune excessive information. Finally, a support vector machine classifier is used to categorize the processed image into the following two groups: cancerous and healthy cases. Simulations have been performed of the American Cancer Society database, and the results have been compared with ten different methods from the literature to investigate the performance of the system in terms of accuracy, sensitivity, negative predictive value, specificity, and positive predictive value.

This study attempted to research the molecular mechanism underlying the inhibitory role of miR-1225-5p in the malignant progression of glioblastoma. Bioinformatics analyses based on the gene expression omnibus (GEO) and Chinese glioma genome atlas (CGGA) databases showed that miR-1225-5p, as a favorable prognostic factor, was expressed at low levels in glioblastoma, and its expression was also related to WHO grade and age. The subsequent CCK-8 assay indicated that miR-1225-5p might prevent the malignant progression of glioblastoma, which was represented by that miR-1225-5p mimic reduced the viability of glioblastoma cells. Then, we predicted that FNDC3B might be a potential target gene of miR-1225-5p, and it was negatively correlated with the level of miR-1225-5p, which were confirmed by dual-luciferase reporter assay, qRT-PCR and western blot assays. Moreover, based on the analyses of the cancer genome atlas (TCGA), Oncomine and CGGA databases, FNDC3B was enriched in glioblastoma and high expression of FNDC3B led to poor prognosis. Finally, CCK8 and transwell experiments showed that the ability of miR-1225-5p to inhibit glioblastoma cell viability, invasion and migration was at least partially achieved by targeting FNDC3B . In general, these results revealed that the miR-1225-5p/ FNDC3B axis contributes to inhibiting the malignant phenotype of glioblastoma cells, which lays a foundation for molecular diagnosis and treatment of glioblastoma.

MicroRNA (miR/miRNA) expression disorders play a crucial role in the development of gastric cancer (GC). Increasing evidence has indicated that miRNAs participate in the process of numerous cancers. Previous research has demonstrated that miR-300 acts as a cancer-promoting factor or tumor suppressor in a number of tumors. However, to the best of our knowledge, the effects of miR-300 on GC cells remain largely unknown. The present study investigated the effects of miR-300 on GC cells and analyzed its molecular mechanism. First, reverse transcription–quantitative polymerase chain reaction showed that miR-300 expression was increased in GC tissues and cell lines, with the highest expression observed in human gastric cancer cell line AGS. Subsequent results indicated that fatty acid 2-hydroxylase (FA2H) was a target of miR-300. FA2H-plasmid inhibited AGS cell proliferation and induced apoptosis. Finally, miR-300 inhibitor reduced cell proliferation and induced apoptosis, whereby these effects were reversed by FA2H-small interfering RNA. Therefore, the data demonstrated that miR-300/FA2H might be a new potential biomarker and therapeutic target for GC treatment.

Background First identified in 2014, fibroadipose vascular anomaly (FAVA) is a very rare type of venous and lymphatic malformation. Marked by tough fibrofatty tissue in the extremities overtaking portions of the muscles, it is associated with constant pain and contracture of the affected extremity. There is a paucity of literature, and no guidelines on treatment procedure are available. This case highlights the role of hybrid treatment with primary ethanol percutaneous ethanol embolization and additional surgery for radicality in excision of FAVA lesions. Case summary A 9-year-old girl with FAVA underwent the hybrid treatment. The achievements of complete excision, clinical response, and patient satisfaction in long-term follow-up were assessed. Following the hybrid treatment, the patient experienced significant improvement in pain. Concurrent symptoms of physical limitation, leg swelling, and skin hyperesthesia also improved. The clinical benefit, supported by postoperative physiotherapy, was well stabilized at 6-month follow-up, resulting in complete patient satisfaction at 12- and 36-month follow-ups. No major complications were encountered. Conclusion Ethanol embolization plus surgery is a safe, effective, and long-term hybrid treatment of symptomatic FAVA lesions.

Introduction Hepatic artery aneurysms are rare, and their treatment represents a challenge for the surgeons. Materials and methods A new technique is presented for common hepatic artery (CHA) aneurysm: it requires minimal vascular surgical dissection and only one linear vascular stapler is applied at the bottom of aneurysm. Aneurysm exclusion is easily obtained, which allowed retrograde thrombosis. Liver blood supply is ensured to the right and left hepatic artery, through the gastroduodenal artery, and can be previously monitored, with temporary clamping of the section area, by visual control, enzyme evaluation and intraoperative ultrasound examination. We reported an open surgical treatment, with simultaneous removal of hepatic and adrenal metastases, secondary to colon cancer. Results The duration of vascular surgery was 30 min and did not involve complications. Postoperative controls confirmed the efficacy of the procedure. Discussion This original technique can be added to the various open and endovascular techniques so far described for the treatment of a CHA aneurysm. It is advisable as open surgery, mostly in case of associated pathologies. Conclusions The authors believe that this “one shot” technique by vascular staple of the distal part of CHA is minimally invasive and effective to obtain the exclusion of the aneurysm.

The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver’s burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer’s Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation ( p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver’s burden ( r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms ( r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers’ burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.

The aim of this retrospective study is to determine the predictive factors of postoperative dyspnea in infants with Pierre Robin sequence (PRS). Forty children with PRS, who underwent general anesthesia, were retrospectively analyzed. The patient’s physiological status and anesthesiology data were collected accordingly, demographic characteristics including age, gender, height and weight at surgery, weight gain, preoperative airway status, tracheal intubation route, American Society of Anesthesiologists grading and airway Cormack–Lehane classification. Weight gain, dyspnea before the operation, Cormack–Lehane grade distribution showed a significant difference between patients with and without postoperative dyspnea ( p = 0.0175, p = 0.0026, and p = 0.0038, respectively). Incompetent weight gain was identified as a predictor ( p = 0.0371) of PRS postoperative dyspnea through the binary logistic regression model. In conclusion, this study established an early alerting model by monitoring the weight gain, dyspnea before the operation, Cormack–Lehane grade as potential combinations to predict the risk of postoperative dyspnea for PRS.

Long non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

Background Ovarian cancer is one of the common malignant tumors in female reproductive organs. Kallikrein-related peptidase (KLK) 7 is a secreted serine peptidase that is related to different cancer. To investigate the expression and significance of KLK7 in ovarian cancer. Materials and methods The expression of KLK7 in human ovarian cancer was evaluated by Oncomine and Cancer Cell Line Encyclopedia database. Then the co-expression genes relevant to the KLK7 gene were analyzed by the Pearson correlation test. Finally, the impact of KLK7 on clinical prognosis was investigated in distinct subtypes of ovarian cancer patients by UALCAN database and Kaplan–Meier plotter database. Results It was found that the expression of KLK7 was higher in ovarian cancer compared with other types of cancer, such as gastric cancer and pancreatic cancer. The expression of KLK7 was found to be increased in four various ovarian cancer data sets compared with the healthy tissues. In addition, upregulation of KLK7 expression was associated with age and cancer stage. Moreover, survival analysis revealed that higher KLK7 expression was negatively associated with progression-free survival. Conclusion Knowledge of the expression of KLK7 may be useful for better understanding the outcome in ovarian cancer patients.

Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Circular RNA circ_SETD2 (circ_SETD2), also termed as hsa_circ_0065173, is reported to be abnormally expressed in BC. Nevertheless, the role and mechanism of circ_SETD2 in BC are unclear. Expression of circ_SETD2, miR-155-5p, and SCUBE2 mRNA was evaluated by quantitative real-time polymerase chain reaction. Cell cycle progression, proliferation, apoptosis, migration, and invasion were determined by flow cytometry, MTT, and transwell assays. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dual-luciferase reporter assay. The role of circ_SETD2 in BC in vivo was confirmed by a xenograft assay. circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Moreover, circ_SETD2 upregulation repressed BC growth in vivo . Importantly, circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. Also, the inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Besides, SCUBE2 silencing abolished miR-155-5p downregulation mediated effects on the malignant behavior of BC cells. Therefore, circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p.

Background Bone marrow stromal cells (BMSCs) have an important application prospect in the field of cell therapy for various neurodegenerative diseases, and inducing factors that regulate BMSC differentiation are proposed as a promising therapeutic strategy. In this study, we explored the effect of glial cell-derived neurotrophic factor (GDNF) on the course of BMSC differentiation. Methods BMSCs were isolated from rat bone marrow and induced by GDNF. The effects of GDNF on BMSC viability and proliferation were verified by cell counting kit-8, MTT, bromodeoxyuridine, and flow cytometry assays. Neuronal differentiation from BMSCs was detected by quantitative real-time polymerase chain reaction and immunofluorescence via measuring the expression of several neural specific markers. Results Compared to untreated BMSCs, GDNF induced the differentiation of BMSCs into neuron-like cells and enhanced the expression levels of neuronal markers including nestin and NCAM. Moreover, the expression of SCF was suppressed by GDNF stimulation. Conclusion GDNF could elevate the differentiation of BMSCs into neuron-like cells and could be considered as an effective candidate cell for future neuroscience research.

Moraxella lacunata ( M. lacunata ) is a Gram-negative bacterium, which rarely causes serious infection. This is a rare case report of acute glomerulonephritis diagnosed by pathological findings in a child accompanied by M. lacunata infection. The patient showed hematuria, proteinuria and hyperkalemia requiring emergency hemodialysis. After hospitalization, M. lacunata bacteremia became apparent. Pathological findings showed an increase in glomerulus inflammatory cells and glomerular C3 deposition was observed in the renal tissue biopsy. Final diagnosis was endocapillary proliferative glomerulonephritis. Clinical reports of M. lacunata infection requiring emergency hemodialysis in children are rare. Previous reports have suggested that lowered immune competency with chronic kidney disease may be a risk factor associated with serious invasive cases of M. lacunata infection. However, detailed clinical laboratory data and pathological findings have not been identified in previous case reports. Our case directly indicated complement activity and acute glomerulonephritis with M. lacunata infection. Although there are various causes for acute glomerulonephritis, infection-related glomerulonephritis (IRGN) is an important concept. M. lacunata infection might have a potential risk for IRGN with dysregulation of complement activity leading to serious and invasive clinical conditions than previously considered.

Lung transplantation is a potentially life-saving therapy for patients with terminal respiratory illnesses. Long-term survival is limited by the development of a variety of opportunistic infections and rejection. Optimal means of differential diagnosis of infection and rejection have not been established. With these challenges in mind, we tried to use transbronchial lung biopsy (TBLB) rapid on-site cytological evaluation (ROSE), metagenomic next-generation sequencing (mNGS), and routine histologic examination to timely distinguish infection and rejection, and accurately detect etiologic pathogens. We reviewed the medical records of all patients diagnosed with infection or rejection by these means from December 2017 to September 2018 in our center. We identified seven recipients whose clinical course was complicated by infection or rejection. Three patients were diagnosed with acute rejection, organizing pneumonia, and acute fibrinoid organizing pneumonia, respectively. Four of the seven patients were diagnosed with infections, including Pneumocystis carinii pneumonia, cytomegalovirus, Aspergillus , and bacterial pneumonia. These patients recovered after proper treatment. TBLB + ROSE + mNGS might be a good method to accurately detect etiologic pathogens, which may help us to facilitate the use of targeted and precision medicine therapy in postoperative complications and avoid unnecessary potential adverse effects of drugs.

As the most effective treatment for end-stage renal diseases, renal transplantation can improve the quality of life of patients and prolong the survival time. However, during the prolonged survival time, malignancy has become one of the main causes of death of recipients, which vary geographically. Tumors in the digestive system and urothelial tumors have been highly reported in Asia. In general, the gynecological malignant tumors have been rarely reported, especially the endometrial carcinoma. Herein, a 63-year-old female renal transplant recipient diagnosed with endometrial carcinoma (15 years after transplantation) was reported. The patient had suffered irregular postmenopausal bleeding for a short time before hospitalization. She underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, right pelvic lymphadenectomy, right para-aortic lymphadenectomy and omental excision. Postoperative pathology showed ovarian and pelvic lymph node metastasis and pathological stage IIIC. After six courses of chemotherapy with paclitaxel 270 mg + carboplatin 500 mg, the patient’s renal function was normal. During the third cycle of chemotherapy, the patient suffered a third-degree bone marrow suppression and returned to normal soon when treated with the recombinant human granulocyte stimulating factor. In conclusion, early screening of gynecologic tumors is important for female patients after renal transplantation, which has a positive significance for the prognosis improvement.

Background Non-small-cell lung carcinoma (NSCLC) seriously threatens the health of human beings. Aberrant expression of lncRNAs has been confirmed to be related with the progression of multiple malignant tumors, including NSCLC. LncRNA FGF12-AS2 has been considered to be upregulated in NSCLC. However, the mechanism by which FGF12-AS2 promotes the tumorigenesis of NSCLC remains elusive. Methods Gene and protein expressions in NSCLC cells were measured by q-PCR and western blot, respectively. CCK-8 and immunofluorescence staining were performed to detect the cell proliferation. Cell apoptosis was tested by flow cytometry. Transwell assay was used to detect the cell migration and invasion. Finally, the dual luciferase report assay was used to verify the relation among FGF12-AS2, miR-188-3p, and NCAPG2. Results Downregulation of FGF12-AS2 significantly inhibited the proliferation of NSCLC cells via inducing apoptosis. In addition, FGF12-AS2 silencing notably suppressed the migration and invasion of A549 cells. Meanwhile, FGF12-AS2 modulated the progression of NSCLC via regulation of miR-188-3p/NCAPG2 axis. Finally, knockdown of FGF12-AS2 inhibited the tumorigenesis of NSCLC via suppressing the EMT process of NSCLC. Conclusion Downregulation of lncRNA FGF12-AS2 suppressed the tumorigenesis of NSCLC via sponging miR-188-3p. Thus, FGF12-AS2 may serve as a potential target for the treatment of NSCLC.

Organ abscesses caused by Streptococcus anginosus are relatively rare. We report the case of an elderly woman with splenic abscess caused by S. anginosus bacteremia after urinary tract infection. An 82-year-old woman had a history of frequency of urination, urgency, and fever with chills for over 10 days prior to admission. An abdominal computed tomography (CT) scan performed in the emergency room revealed a low-density lesion in the spleen, kidney cysts, some exudation around the kidney, and cystitis should be valued. She was treated with ceftriaxone and imipenem/cilastatin. After admission, the blood culture yielded positive results for S. anginosus . A contrast-enhanced abdominal CT scan showed that the low-density lesion previously found in the spleen was smaller than before. After percutaneous drainage of the splenic abscess and treatment with piperacillin/tazobactam based on the antibiotic sensitivity pattern, repeated abdominal CT scan revealed a significant reduction in the low-density lesion. The patient was discharged without recurrence or complications. A systematic review of organ abscess caused by S. anginosus bacteremia was performed. To our knowledge, there has been no report of splenic abscess caused by S. anginosus bacteremia secondary to urinary system tract infection, although urinary tract infections are also an important source.

Osteosarcoma (OS) is the most common primary malignant tumor of the skeletal system in the clinic. It mainly occurs in adolescent patients and the pathogenesis of the disease is very complicated. The distant metastasis may occur in the early stage, and the prognosis is poor. MicroRNAs (miRNAs) are non-coding RNAs of about 18–25 nt in length that are involved in post-transcriptional regulation of genes. miRNAs can regulate target gene expression by promoting the degradation of target mRNAs or inhibiting the translation process, thereby the proliferation of OS cells can be inhibited and the apoptosis can be promoted; in this way, miRNAs can affect the metabolism of OS cells and can also participate in the occurrence, invasion, metastasis, and recurrence of OS. Some miRNAs have already been found to be closely related to the prognosis of patients with OS. Unlike other reviews, this review summarizes the miRNA molecules closely related to the development, diagnosis, prognosis, and treatment of OS in recent years. The expression and influence of miRNA molecule on OS were discussed in detail, and the related research progress was summarized to provide a new research direction for early diagnosis and treatment of OS.

Background Rheumatoid arthritis (RA) can lead to various pulmonary manifestations. Evidence shows the possible association between RA and pleural empyema. Methods We conducted a retrospective cohort study to investigate the risk of pleural empyema in patients with RA. The RA group ( n = 29,061) included newly diagnosed adult patients between 2000 and 2012. The comparison group ( n = 1,16,244) included individuals without RA at a 1:4 ratio of frequency matched by age, gender, and diagnosis year. The occurrence of pleural empyema was monitored until the end of 2013. Results Patients with RA had a higher risk of developing pleural empyema than those without RA (23.6 vs 1.82 per 10,000 person-years, adjusted hazard ratio = 11.0, 95% confidence interval [CI] = 8.90–13.5). Furthermore, intensive care unit admission rates of pleural empyema were 37.7% in the RA group and 37.2% in the comparison group (adjusted odds ratio [OR] = 1.02, 95% CI = 0.66−1.57). The 30-day mortality rates of pleural empyema were 11.2% in the RA group and 10.9% in the comparison group (adjusted OR = 1.01, 95% CI = 0.51−1.88). Conclusion Patients with RA are at a greater risk of developing pleural empyema than those without RA.

Objective This article aims to investigate the effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA. Methods HeLa cells of cervical cancer were divided into five groups: blank control group, negative control group (miRNA-200b mimic NC), miRNA-200b mimic group, RhoA-negative control group, and RhoA overexpression group. Cells were collected 48 h after transfection. The expression levels of miRNA-200b were detected by RT-PCR. Target relationship between miRNA-200b and RhoA was verified by the dual-luciferase reporter assay. RhoA mRNA and protein expression were detected by western blot and RT-PCR methods. Flow cytometry was used to detect the apoptosis of cells in each group, and the CCK8 method was used to detect the proliferation of cells in each group. The mRNA and protein expression of Bax and cyclin D1 were detected by RT-PCR and western blot. Results The results of the dual luciferase reporter assay showed that RhoA was the target gene of microRNA 200b. Compared with the blank control group and the miRNA-200b mimic-NC group, the proportion of apoptotic cells increased significantly in the miRNA-200b mimic group, and the proliferation of cells was inhibited ( P < 0.05). After overexpression of RhoA, the percentage of apoptotic cells decreased and the ability of cell proliferation increased significantly ( P < 0.05). Conclusion miRNA-200b can inhibit the proliferation and promote the apoptosis of cervical cancer cells by targeting the RhoA gene.

Long non-coding RNAs (lncRNAs) were reported to promote the development of gastric cancer (GC). Nuclear-enriched abundant transcript 1 (NEAT1) played a great role in diverse cancers, but the mechanism of NEAT1 in GC remains indistinct. NEAT1 and AKT1 were distinctly up-regulated and miR-1294 was down-regulated in GC tissues and cells. Cell proliferation and metastasis were refrained but apoptosis was promoted in GC cells after knockdown of NEAT1. NEAT1 negatively regulated miR-1294 expression, and the miR-1294 inhibitor reverted the si-NEAT1-induced effect on GC cells. NEAT1 modulated AKT1 expression through miR-1294, and the si-NEAT1-induced effect was relieved by AKT1. NEAT1 affected phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway via regulating miR-1294 and AKT1. NEAT1 could modulate cell proliferation, apoptosis, and metastasis in GC cells by regulating the PI3K/AKT/mTOR signaling pathway via the miR-1294/AKT1 axis, showing the great potential for NEAT1 as a valid biomarker in the progression and treatment of GC.

Prostate cancer (PCa) is a leading adult malignant tumor. Recent research has shown that speckle-type BTB/POZ protein (SPOP) mutant is the top frequently mutated gene in PCa, which makes it an important biomarker. In this paper, we aimed at identifying critical genes and pathways related to SPOP mutation in PCa. Recent The Cancer Genome Atlas data showed that 12% of patients with PCa were SPOP mutant. There were 1,570 differentially expressed genes, and online enrichment analysis showed that these genes were mainly enriched in metabolism, pathways in cancer and reactive oxygen species. INS, GNG13, IL6, HTR5A, SAA1, PPY, CXCR5, CXCL13, CD19 and CCL20 were identified as hub genes. The lower SPOP expression level was associated with poor prognosis. In all, our findings showed that various pathways and genes could play critical roles in SPOP mutation in PCa, providing potential options for individualized treatment.

Aim To compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip replacement (THR) or total knee replacement (TKR). Material and methods To the prospective, randomized study were included 66 adult patients qualified to undergo THR or TKR (age 63 ± 12 years, 44 women). The patients were randomized to daily in-hospital subcutaneous prophylaxis with 5,000 I.U. of DALT or 40 mg of enoxaparin. Clinical and laboratory data were collected before surgery, and on 1st and 5th days after surgery. Results Thirty-four patients were randomized to prophylaxis with ENOX and 32 with DALT. The groups did not differ significantly in age, sex, creatinine and most of the laboratory parameters. The compared groups had similar surgical parameters, but more patients in the ENOX group received red blood cell infusion (17(50%) vs 8(25%); p < 0.05). The Lee–White coagulation time mildly decreased in ENOX and DALT following the surgery ( p = ns). There was a shortening of Duke’s bleeding time in DALT after the surgery and it became significantly quicker than that in ENOX on Day 5 ( p = 0.03). Conclusion The observed difference in Duke’s bleeding time and exceeding blood loss during the surgery on the enoxaparin demands confirmation, as it can be important information for clinical management.

The coronavirus disease 2019 (COVID-19) has become a global pandemic, which is induced by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with systemic lupus erythematosus (SLE) are susceptible to infections due to the chronic use of immunosuppressive drugs and the autoimmune disorders. Now we report a case of SLE infected with SARS-CoV-2, influenza A virus and Mycoplasma pneumoniae concurrently. The patient used hydroxychloroquine and prednisone chronically to control the SLE. After infection of SARS-CoV-2, she was given higher dose of prednisone than before and the same dosage of hydroxychloroquine. Besides, some empirical treatments such as antiviral, antibiotic and immunity regulating therapies were also given. The patient finally recovered from COVID-19. This case indicated that hydroxychloroquine may not be able to fully protect SLE patient form SARS-CoV-2. Intravenous immunoglobulin therapies and increased dose of corticosteroids might be adoptable for patient with both COVID-19 and SLE. Physicians should consider SARS-CoV-2 virus test when SLE patient presented with suspected infection or SLE flare under the epidemic of COVID-19.

Background Mounting evidence has revealed that abnormal expression of circular RNAs play pivotal roles in many human diseases including preeclampsia (PE). While human sapiens circular RNA 0007121 (hsa_circ_0007121) has been verified to be downregulated in human placental tissues, the underlying mechanisms were still unclear. This research aims to investigate the effect and underlying mechanisms of hsa_circ_0007121 in preeclampsia. Methods The expression of hsa_circ_0007121, microRNA (miR)-182-5p, and placental growth factor (PGF) was assessed by quantitative reverse transcription polymerase chain reaction in PE placentas relative to the expression in normal pregnancy placentas. After transfection, cell counting kit-8 assay was employed to detect cell proliferation. Cell migration and invasion were tested by the transwell assay. The relative level of epithelial–mesenchymal transition (EMT)-related proteins in HTR-8/SVneo cells and PGF in placentas samples were measured by western blot. The relationship between miR-182-5p and hsa_circ_0007121 or PGF was predicated by circular RNA interactome or ENCORI and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results The levels of hsa_circ_0007121 and PGF were significantly declined in PE placental tissues and HTR-8/SVneo cells, whereas miR-182-5p had an opposite result. Downregulation of hsa_circ_0007121 obviously inhibited HTR-8/SVneo cell proliferation, migration, invasion, and EMT, while upregulation of hsa_circ_0007121 promoted this process. Besides, miR-182-5p was a target gene of hsa_circ_0007121 and could target PGF. Further analysis indicated that hsa_circ_0007121 regulated the proliferation, migration, invasion, and EMT of HTR-8/SVneo cells via altering PGF expression by interacting with miR-182-5p. Conclusion Hsa_circ_0007121 mediated the progression of PE via miR-182-5p/PGF axis.

Background and aim This investigation was aimed at disclosing whether SRPX2 affected pancreatic cancer (PC) chemoresistance by regulating PI3K/Akt/mTOR signaling. Methods Totally 243 PC patients were recruited, and they were incorporated into partial remission (PR) group, stable disease (SD) group and progressive disease (PD) group in accordance with their chemotherapeutic response. PC cell lines (i.e. AsPC1, Capan2, VFPAC-1, HPAC, PANC-1, BxPC-3 and SW1990) and human pancreatic ductal epithelial cell lines (hTERT-HPNE) were also collected. Results PC patients of SD + PD group were associated with higher post-chemotherapeutic SRPX2 level than PR group, and their post-chemotherapeutic SRPX2 level was above the pretherapeutic SRPX2 level ( P < 0.05). PR population showed lower SRPX2 level after chemotherapy than before chemotherapy ( P < 0.05). Besides high serum SRPX2 level and SRPX2 level change before and after chemotherapy were independent predictors of poor PC prognosis. Additionally, si-SRPX2 enhanced chemosensitivity of PC cell lines, and expressions of p-PI3K, p-AKT and p-mTOR were suppressed by si-SRPX2 ( P < 0.05). IGF-1 treatment could changeover the impact of si-SRPX2 on proliferation, migration, invasion and chemoresistance of PC cells ( P < 0.05). Conclusion The SRPX2-PI3K/AKT/mTOR axis could play a role in modifying progression and chemoresistance of PC cells, which might help to improve PC prognosis.

Although female genital tuberculosis may lead to infertility, pregnancy is still possible, especially through in vitro fertilization (IVF). In this eventuality, even latent tuberculosis (TB) infection is prone to reactivate. Because some of the symptoms of TB overlap with those of pregnancy, diagnosis and treatment may be delayed. We report the case of a 30-year-old infertile woman with repeated genital tuberculosis (GTB) who underwent two laparoscopic surgeries and anti-TB treatments. The woman conceived through IVF and, unfortunately, a cervical pregnancy was diagnosed, together with a third recurrence of GTB. When the condition became stable after anti-TB treatment, the pregnancy was terminated using oral mifepristone in combination with an ultrasound-guided local injection of methotrexate. The gestational sac was expelled 4 days later with minimal blood loss. In view of the reciprocal influence and interconnection between IVF, pregnancy, and TB, we conducted a literature review to provide valuable information for early diagnosis and treatment, as well as for routine screening before IVF of TB in infertile patients.

In 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70–90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10–20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts’ opinions.

Exosomes-like nanoparticles can be released by a variety of plants and vegetables. The relevance of plant-derived nanovesicles (PDNVs) in interspecies communication is derived from their content in biomolecules (lipids, proteins, and miRNAs), absence of toxicity, easy internalization by mammalian cells, as well as for their anti-inflammatory, immunomodulatory, and regenerative properties. Due to these interesting features, we review here their potential application in the treatment of inflammatory bowel disease (IBD), liver diseases, and cancer as well as their potentiality as drug carriers. Current evidence indicate that PDNVs can improve the disease state at the level of intestine in IBD mouse models by affecting inflammation and promoting prohealing effects. While few reports suggest that anticancer effects can be derived from antiproliferative and immunomodulatory properties of PDNVs, other studies have shown that PDNVs can be used as effective delivery systems for small molecule agents and nucleic acids with therapeutic effects (siRNAs, miRNAs, and DNAs). Finally, since PDNVs are characterized by a proven stability in the gastrointestinal tract, they have been considered as promising delivery systems for natural products contained therein and drugs (including nucleic acids) via the oral route.

Chromosomal microdeletions and microduplications likely represent the main genetic etiologies for children with developmental delay or intellectual disability. Through prenatal chromosomal microarray analysis, some microdeletions or microduplications can be detected before birth to avoid unnecessary abortions or birth defects. Although some microdeletions or microduplications of chromosome 5 have been reported, numerous microduplications remain undescribed. We describe herein a case of a 30-year-old woman carrying a fetus with a chromosome 5q21.1–q21.3 microduplication. Because noninvasive prenatal testing indicated a fetal chromosome 5 abnormality, the patient underwent amniocentesis at 22 weeks 4 days of gestation. Karyotyping and chromosomal microarray analysis were performed on amniotic fluid cells. Fetal behavioral and structural abnormalities were assessed by color and pulsed Doppler ultrasound. Clinical characteristics of the newborn were assessed during the follow-up. The left lateral ventricle appeared widened on ultrasound, but the infant appeared normal at birth. The 5q21.1–q21.3 microduplication in the fetus was inherited from his mother. There are seven genes in this duplication region, but their main functions are unclear. According to this case report, microduplication in this region could represent a benign mutation. Clinicians should pay attention to the breakpoints and the genes involved when counseling patients with microdeletions and microduplications.

Background Effect of serum calcium levels on prognosis of patients with coronary artery disease (CAD) is not well evaluated. We aimed to assess the associations of baseline serum calcium levels with both short-term and long-term outcomes in CAD patients. Methods This study included 3,109 consecutive patients with angiographically confirmed CAD. Patients were categorized into quartiles according to admission serum calcium. Multivariable regression analysis was used to determine the association of serum calcium with mortality. Results Compared to patients in the lowest quartile of serum calcium, patients in upper quartiles were presented with lower all-cause mortality (Hazard ratios [HRs] were −0.636 [95% CI: −0.424 to −0.954], −0.545 [95% CI: −0.351 to −0.846] and −0.641 [95% CI: −0.450 to −0.913] for three upper quartiles versus lowest quartile respectively), cardiovascular mortality (HRs 0.594 [0.368−0.961], 0.261 [0.124–0.551] and 0.407 [0.229–0.725]), and in-hospital mortality (Odd ratios [ORs] 0.391 [0.188–0.812], 0.231 [0.072–0.501] and 0.223 [0.093–0.534]). Consistent associations between serum calcium and long-term mortality were also obtained in subgroup analysis of ACS patients, stable CAD patients and discharged patients. Conclusions Serum calcium is inversely associated with CAD and can independently predict both in-hospital and long-term mortality among CAD patients.

Rapunzel syndrome, defined by the presence of a trichobezoar extending from the stomach to the small intestine, is a rare cause of intestinal obstruction. It usually presents with vague symptoms; however, it can also present with complications such as perforation, peritonitis and obstructive jaundice. We report a rare case of a 37-year-old woman with Rapunzel syndrome complicated by acute cholangitis and pancreatitis and analyse the diagnosis and management of this complicated pathology. Although she reported a history of trichotillomania and trichophagia, she had been asymptomatic for ten years. We review the steps of diagnosis, highlighting the importance of a thorough clinical history and detailed examination, with supporting evidence from the contrast-enhanced computed tomography (CECT) scan. She was successfully managed with gastrotomy and trichobezoar removal. She had an uneventful postoperative recovery and was discharged after psychiatric counselling. To our knowledge, this is the first case of Rapunzel syndrome in a young female presenting with both cholangitis and pancreatitis.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype known for its extremely high drug resistance, progression, poor prognosis, and lack of clear therapeutic targets. Researchers are aiming to advance TNBC treatment worldwide. In the past 2–3 years, more positive results have emerged in the clinical research on TNBC treatment. Based on the results, several impressive drugs have been approved to benefit patients with TNBC, including the PARP inhibitors olaparib and talazoparib for germline BRCA mutation-associated breast cancer (gBRCAm-BC) and immunotherapy using the checkpoint inhibitor atezolizumab in combination with nab-paclitaxel for programmed cell death-ligand 1-positive (PD-L1+) advanced TNBC. Although neoadjuvant therapy has focused on combinations of systemic agents to optimize pathologically complete response, metastatic TNBC still has a poor prognosis. Innovative multidrug combination systemic therapies based on neoadjuvants and adjuvants have led to significant improvements in outcomes, particularly over the past decade.

We present the first case of peritoneal-cutaneous fistula (PCF) within ovarian carcinoma neoplastic infiltrates located inside a large abdominal hernia in a home hospice patient with massive ascites. It is an instructive case featuring a rapid diagnosis and efficient treatment of the PCF at home. As the patient refused hospitalization, she had successful paracentesis performed at home. Subsequent hydrocolloid dressing application, diuretics, and oral protein supplementation were recommended. Our intervention led to PCF closure, improved quality of life, and deepened the trust between the patient and the home hospice team. Our case demonstrates that in some instances, PCF may be efficiently treated at home, which may require paracentesis, appropriate dressings, and identification of all factors affecting healing. It also provides further support for the safety of paracentesis in home settings.

Renal cell carcinoma (RCC) is a malignant tumor originating from renal tubular epithelial cells with poor prognosis and high metastatic rate. Tripartite motif-containing 24 (Trim24) is a member of the tripartite motif (Trim) family and also a valuable oncogene, but its role in RCC remains unclear. We constructed the overexpression and knockdown of Trim24 cell lines to investigate its roles in RCC progression. CCK8, wound healing, and transwell assay were performed to determine the proliferation, migration, and invasion of RCC cell lines, respectively. Moreover, the expression of Trim24 and its clinicopathological significance were evaluated in a human RCC tissue microarray. From our results, Trim24 promoted the proliferation, migration, and invasion of RCC cells in vitro . Importantly, overexpression of Trim24 led to a significant increase in the expression levels of MMP-2, MMP-9, fibronectin, snail, vimentin, N-cadherin, and β-catenin, inducing the EMT process in turn, while the expression of these proteins was significantly downregulated when Trim24 was knocked down in ACHN cells. In addition, Trim24 was significantly upregulated in RCC, and its high expression was negatively associated with the tumor size. Trim24 might operate as an oncogene in RCC progression by inducing the EMT process, suggesting that Trim24 was a potential target for human RCC.

Cataracts are mainly classified into three types: cortical cataracts, nuclear cataracts, and posterior subcapsular cataracts. In addition, retrodots and waterclefts are cataract subtypes that cause decreased visual function. To maintain an orderly and tightly packed arrangement to minimize light scattering, adhesion molecules such as connexins and aquaporin 0 (AQP0) are highly expressed in the lens. We hypothesized that some main and/or subcataract type(s) are correlated with adhesion molecule degradation. Lens samples were collected from cataract patients during cataract surgery, and mRNA and protein expression levels were measured by real-time RT-PCR and western blotting, respectively. The mRNA levels of adhesion molecules were not significantly different among any cataract types. Moreover, AQP0 and connexin 46 protein expressions were unchanged among patients. However, connexin 50 protein level was significantly decreased in the lens of patients with WC cataract subtype. P62 and LC3B proteins were detected in the WC patients’ lenses, but not in other patients’ lenses. These results suggest that more research is needed on the subtypes of cataracts besides the three major types of cataract for tailor-made cataract therapy.

Little is known about the functional roles of gamma-aminobutyric acid type A receptor subunit delta (GABRD) in colorectal cancer (CRC). The expression of GABRD between CRCs and adjacent normal tissues (NTs), metastasis and primary tumors was compared using public transcriptomic datasets. A tissue microarray and immunohistochemical staining (IHC) were used to determine the clinical and prognostic significance of the GABRD in CRC. We used gain-of-function and loss-of-function experiments to investigate the in vitro roles of GABRD in cultured CRC cells. We characterized the potential mechanism of GABRD’s activities in CRC using a Gene Set Enrichment Analysis (GSEA) with The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset. We found that the GABRD expression was significantly increased in CRCs compared to that in NTs, but was similar between metastasis and primary tumors. Overexpression of GABRD was significantly associated with later pTNM stages and unfavorable patient survival. Overexpression of GABRD accelerated while knock-down of GABRD inhibited cell growth and migration. Mechanistically, the function of GABRD might be ascribed to its influence on major oncogenic events such as epithelial–mesenchymal transition (EMT), angiogenesis, and hedgehog signaling. Collectively, GABRD could be a novel prognostic predictor for CRC that deserves further investigation.

Purpose This study explores the effects and mechanisms of the long noncoding RNA (lncRNA) UBE2R2-AS1 activity in the cervical cancer development. Methods Thirty-four pairs of normal adjacent and cancer tissues were collected from cervical cancer patients. Pathology was evaluated by HE staining, and UBE2R2-AS1 expression was evaluated by in situ hybridization assays. HeLa and SiHa cells were respectively divided into negative control, pcDNA 3.1 vehicle control and lncRNA-expressing groups. Cell proliferation and apoptosis were measured by CCK8 expression and flow cytometry. The number of invading cells and the wound healing rate were measured by transwell and wound healing assays, respectively. Relative protein levels (caspase-3, caspase-8, MMP-2 and MMP-9) were measured by Western blot. Results Compared with adjacent normal tissues, UBE2R2-AS1 expression was significantly suppressed in cancer tissues correlated with the increasing stage. UBE2R2-AS1 suppressed cell proliferation and enhanced apoptosis, as well as decreased cell invasion and wound healing in cervical cancer cell lines. UBE2R2-AS1 overexpression significantly upregulated caspase-3 and caspase-8 protein expressions and significantly downregulated MMP-2 and MMP-9 protein expressions by Western blot. Conclusion UBE2R2-AS1 suppressed cervical cancer cell biological activities and might represent an antitumor factor in cervical cancer.

This research aimed to illustrate the biological function and associated regulatory mechanism of lncRNA FOXD3-AS1 (FOXD3-AS1) in nasopharyngeal carcinoma (NPC). This research initially found that FOXD3-AS1 was obviously upregulated in NPC cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) detection. Next, the direct target of FOXD3-AS1 was predicted by bioinformatics and further verified by dual-luciferase reporter assay. MiroRNA-135a-5p (miR-135a-5p) was identified as the target gene of FOXD3-AS1 and down-expressed in C666-1 cells compared to NP69. In addition, function assays were conducted in C666-1 cells, including methyl tetrazolium assay, flow cytometry, Caspase3 activity detection, and western blot assay. Our results suggested that miR-135a-5p upregulation inhibited NPC cell growth, enhanced cell apoptosis, promoted Caspase3 activity, increased cleaved-Caspase3, and reduced pro-Caspase3 level. Moreover, we found that FOXD3-AS1 knockdown notably inhibited C666-1 cell proliferation, increased cell apoptosis, enhanced Caspase3 activity, enhanced cleaved-Caspase3 expression, and suppressed pro-Caspase3 level in C666-1 cells. However, these findings were reversed in C666-1 cells by miR-135a-5p mimic co-transfection. To sum up, our data showed that FOXD3-AS1 knockdown regulated cell growth and apoptosis in NCP cells via altering miR-135a-5p expression, suggesting that FOXD3-AS1 might be a therapeutic target for NPC diagnosis and treatment.

Allergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo . Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.