Abstract
Brain metastases (BMs) and bone metastases seriously affect the prognosis of lung cancer patients. How to optimize the use of existing targeted drugs is an important way to address the clinical needs of the central nervous system in the individualized treatment of non-small cell lung cancer (NSCLC). In this report, we describe an NSCLC patient with BMs who survived for 58 months, which is the longest survival case among lung cancer patients with BMs. The patient was initially diagnosed with lung cancer more than 5 years ago with simultaneous brain, bone, and lung metastases. After gefitinib resistance, she received osimertinib in sequence with no progress for 58 months in total and maintained very good quality of life.
1 Introduction
The nervous system is the most common metastatic site of lung cancer, especially in women [1]. About 50% of brain metastases (BMs) originated from non-small cell lung cancer (NSCLC) [2]. Compared with nervous system metastases, bone metastases had poor survival signals [1]. Historically, due to the physical, chemical, and metabolic properties of the blood–brain barrier, which prevented drug delivery to the central nervous system, the brain had been considered as a refuge for metastatic NSCLC [3]. Although chemotherapy was not used to treat BMs because of the effects of the blood–brain barrier [3], targeted agents and immune checkpoint inhibitors have shown significant benefits [4]. For patients with advanced NSCLC without history of smoking, targeted therapy is recommended first if the molecule tests positive for epidermal growth factor receptor (EGFR) [5]. With the discovery of targeted promoter genes and related drug research, the treatments of advanced NSCLC patients with multiple metastases have also made gratifying progress [6–8]. How to optimize the use of existing targeted drugs is an important way to address the clinical needs of central nervous system in the individualized treatment of NSCLC [9]. We herein present a patient of NSCLC with multiple metastases to the brain, bone, and lung who survived for more than 5 years after appropriate combination of molecular targeted therapies while maintaining a very good quality of life. This is by far the longest survival in patients with NSCLC complicated with multiple metastases to the brain, bone, and lung.
2 Case report
The 63-year-old female never-smoker was admitted to our department for the first time on December 23, 2015, due to cough and dyspnea for over 20 days. Her chest computed tomography (CT) showed space-occupying lesions in the right hilum and enlarged lymph nodes in the mediastinum, atelectasis of the right lung, massive pleural effusion in the right side, and multiple nodules in both lungs (Figure 1a). Magnetic resonance imaging (MRI) showed gadolinium-enhanced multiple abnormal intensification foci in the brain which were considered to be multiple metastatic tumors (Figure 2a, c, and e). The serum concentration of the carcinoembryonic antigen (CEA) was 18.75 ng/mL. Right thoracic closed drainage and pleural biopsy were performed, resulting in a total of 1,500 mL yellow pleural fluid drained out (Figure 1b) and a pleural fluid CEA of 17.55 ng/mL.

Chest CT. The arrow points to the tumor site. (a) At initial diagnosis, (b) after closed drainage of the right chest, and (c) after targeted therapy of gefitinib.

Multiple BMs revealed by MRI. (a and b), (c and d), and (e and f) are image comparison of the same part, respectively. (a), (c), and (e) At initial visit, (b) and (d) after targeted therapy of gefitinib, and (f) a new metastasis was found in the right cerebellar hemisphere.
The histology of the pathological changes confirmed by both pleural biopsy (Figure 3a and b) and fiberoptic bronchofiberscopy biopsy (Figure 3c and d) was adenocarcinoma of the lung. Then the EGFR mutation status was investigated and the result showed a point mutation at exon 21 (L858R). One month later, the patient underwent a systemic bone imaging examination, which revealed abnormal bone metabolism in the middle of the left femur (Figure 4a). Bilateral femoral MRI showed bilateral femoral shaft metastatic tumor.

Hematoxylin–eosin-stained biopsy specimens. (a) (10*10) and (b) (40*10) showed the pathology of pleural biopsy specimens: Well-differentiated adenocarcinoma infiltration in small fibrous tissue, immunohistochemical feature: CK (+) EMA (−) Vim (−) MC (−) CR (−) P53 (−) Ki-67 (2% +) CK7 (−) TTF-1 (−) Villin (−) CK 20 (−) CDX-2 (−) CEA (−). (c) (10*10) and (d) (40*10) showed the pathology of bronchoscopic biopsy specimens: (right lower lobe bronchial orifice) infiltrating adenocarcinoma, tumor thrombus was found in vascular cavity, immunohistochemical feature CK7 (+) TTF-1 (+) CEA (+) CK (+) CD31 (vascular+, tumor thrombus visible).

Systemic bone imaging. The metabolic activity of hypermetabolic focus in the middle part of left femur decreased significantly after treatment. (a) At the initial visit and (b) after targeted treatment of gefitinib.
The patient received gefitinib and intermittent zoledronic acid for bone metastases until 20 months, and then MRI showed that BMs which had disappeared and shrunk (Figure 2b and d) after gefitinib were progressing again. The cancer lesions in lungs of the patient were significantly reduced (Figure 1c) after gefitinib and did not progress during the treatment period. Systemic bone imaging showed that the metabolic activity of hypermetabolic lesions in the middle part of the left femur was significantly decreased after gefitinib treatment (Figure 4b) and the patient had never been affected by lower limb discomfort.
The patient received osimertinib for 38 months which was recommended after T790M acquisition confirmed by liquid biopsy after brain MRI showed progression of the disease on August 7, 2020 (Figure 2f).
No matter taking gefitinib or osimertinib, the patient only had mild diarrhea and mild paronychia, which did not affect the life of the patient. During the 58 months of treatment, the patient maintained a good quality of life and took care of her family as usual.
Until September 8, 2020, the patient developed unilateral facial paralysis, and MRI examination showed a new metastasis in the brain.
The patient was then given osimertinib for a double dose of 1 month and revisited with brain MRI on October 7. The BMs still showed growth while the patient still had no other intracranial symptoms.
Illumina second-generation sequencing was performed on May 6, 2020, and 600 genes were tested, but no targeted drug-related mutations were detected. Written informed consent has been provided by the patient’s husband to have the case details and any accompanying images published.
3 Discussion
NSCLC patients with multiple organ metastases have a high risk of death, and lung adenocarcinoma is the most common type of metastatic lung cancer [10]. EGFR mutation is a major drug target for lung adenocarcinoma [11]. Patients with EGFR mutation are more likely to develop BMs than patients with wild-type EGFR. BM was present in about 25% of the patients with EGFR mutations at initial diagnosis [9].
Tyrosine kinase inhibitors have been recommended as standard therapy for asymptomatic NSCLC patients with EGFR mutations with BMs [12]. However, resistance to the first targeted therapy usually occurs in 9–13 months [13]. Previous studies have shown the different mechanisms of acquired EGFR TKI resistance [14–16], and 50–60% of the cases were associated with T790M-resistant mutations [17,18].
Although previous study had demonstrated that osimertinib, as a third-generation EGFR-TKI, not only improved median progression-free survival (PFS) in NSCLC patients by overcoming T790m-mediated resistance [19] but also was more effective than other EGFR-TKI as a first-line treatment for metastatic NSCLC patients [20], this patient in our case with BMs from lung adenocarcinoma with EGFR L858R mutation also had a very good survival with well-toleration following sequential osimertinib treatment after gefitinib failure. For patients with BMs from lung adenocarcinoma, continued administration of osimertinib should still be an important option after the first-generation EGFR-TKI failure, when T790M mutation has been confirmed by biopsy. The regimen in our report of gefitinib as first-line treatment followed by osimertinib after gefitinib resistance resulted in a PFS of 58 months even longer than the reported overall survival of osimertinib as first-line treatment, which was less than 54 months [20].
If osimertinib was selected as the first-line treatment, it would be more difficult after drug resistance, because there was no ready-made drug choice. For example, in our case, after osimertinib resistance, we needed to choose invasive brain radiotherapy which required higher technical conditions. Compared with drug treatment, this kind of radiotherapy was obviously affected by the availability of local radiotherapy conditions, which would increase the patient’s body and economic burden.
Metastases to bones were frequent events in a variety of cancers including breast cancer, prostate cancer, etc., especially lung cancer which had been increasing in some areas over the years, and were associated with poor prognosis in lung cancer patients [1,21,22]. Previous studies have shown that metastatic bone diseases, especially metastatic tumors that disproportionately affected the axial bone [21], often developed bone-related events in patients, and spinal metastases were more likely to cause pain, instability, and vertebral collapse, making them spinal surgical emergencies with significant public health and economic consequences [23], greatly influencing on the quality of life of patients [24]. For the treatment of bone metastases, chemotherapy combined with radiotherapy, supplemented by bisphosphonates and nuclides, had always been emphasized on the basis of palliating symptoms [25], and bone-targeted drugs have also been mentioned [24]. In our case, bone metastasis was reduced and improved after targeted therapy combined with bisphosphonate therapy for primary lesion control.
4 Conclusion
In conclusion, multiple metastases, especially BMs, are still important threats to lung cancer patients. Sequential administration of osimertinib after gefitinib resistance remains one of the primary options in patients with lung adenocarcinoma with brain and bone metastases with EGFR exon 21 mutation. The treatments are not only very effective in disease control but also have little impact on patients’ quality of life.
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Funding information: The authors received no financial support for the research, authorship, and/or publication of this article.
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Conflict of interest: The authors have declared no conflict of interests.
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Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
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- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Artikel in diesem Heft
- Research Articles
- Identification of ZG16B as a prognostic biomarker in breast cancer
- Behçet’s disease with latent Mycobacterium tuberculosis infection
- Erratum
- Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
- Research Articles
- GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
- Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
- Additional baricitinib loading dose improves clinical outcome in COVID-19
- The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
- SLC12A8 plays a key role in bladder cancer progression and EMT
- LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
- Case Report
- Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
- Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
- Research Articles
- TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
- CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
- LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
- Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
- Rapid Communication
- COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
- Case Report
- Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
- An infertile female delivered a baby after removal of primary renal carcinoid tumor
- Research Articles
- Hypertension, BMI, and cardiovascular and cerebrovascular diseases
- Case Report
- Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
- Research Articles
- Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
- Review Articles
- Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
- Research Articles
- Thermography in the diagnosis of carpal tunnel syndrome
- Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
- Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
- The influence of smoking in minimally invasive spinal fusion surgery
- Impact of body mass index on left atrial dimension in HOCM patients
- Expression and clinical significance of CMTM1 in hepatocellular carcinoma
- miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
- Comparison of multiple flatfoot indicators in 5–8-year-old children
- Early MRI imaging and follow-up study in cerebral amyloid angiopathy
- Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
- miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
- Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
- Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
- Review Articles
- The ambiguous role of mannose-binding lectin (MBL) in human immunity
- Case Report
- Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
- Fertility problems in males carrying an inversion of chromosome 10
- Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
- Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
- Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
- Skull hemophilia pseudotumor: A case report
- Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
- Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
- Clinicopathologic features of Good’s syndrome: Two cases and literature review
- Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
- Research Articles
- Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
- Significance of nucleic acid positive anal swab in COVID-19 patients
- circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
- Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
- Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
- Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
- Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
- Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
- FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
- Platelet-rich fibrin: Basics of biological actions and protocol modifications
- Accurate diagnosis of prostate cancer using logistic regression
- miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
- Prognostic significance of TRIM28 expression in patients with breast carcinoma
- Integrative bioinformatics analysis of KPNA2 in six major human cancers
- Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
- A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
- Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
- Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
- Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
- COVID-19 severity in relation to sociodemographics and vitamin D use
- Clinical analysis of 11 cases of nocardiosis
- Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
- Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
- Relation between IL-8 level and obstructive sleep apnea syndrome
- circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
- Nomogram prediction model for renal anaemia in IgA nephropathy patients
- Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
- NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
- A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
- Clinical and prognostic features of MMP-2 and VEGF in AEG patients
- The value of miR-510 in the prognosis and development of colon cancer
- Functional implications of PABPC1 in the development of ovarian cancer
- Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
- Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
- Prediction of improvement after anterior cruciate ligament reconstruction
- Effluent Osteopontin levels reflect the peritoneal solute transport rate
- circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
- Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
- Association between hair cortisol concentration and metabolic syndrome
- Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
- Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
- Knee alterations in rheumatoid arthritis: Comparison of US and MRI
- Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
- lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
- Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
- Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
- Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
- Travelers’ vaccines and their adverse events in Nara, Japan
- Association between Tfh and PGA in children with Henoch–Schönlein purpura
- Can exchange transfusion be replaced by double-LED phototherapy?
- circ_0005962 functions as an oncogene to aggravate NSCLC progression
- Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
- Serum intact fibroblast growth factor 23 in healthy paediatric population
- Algorithm of rational approach to reconstruction in Fournier’s disease
- A meta-analysis of exosome in the treatment of spinal cord injury
- Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
- Dexmedetomidine may decrease the bupivacaine toxicity to heart
- Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
- Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
- External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
- miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
- HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
- Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
- Cell population data in identifying active tuberculosis and community-acquired pneumonia
- Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
- Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
- 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
- Association of gene polymorphisms with women urinary incontinence
- Influence of COVID-19 pandemic on stress levels of urologic patients
- miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
- miR-519d downregulates LEP expression to inhibit preeclampsia development
- Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
- Fluorescent light energy modulates healing in skin grafted mouse model
- Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
- Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
- Severe postoperative hyperbilirubinemia in congenital heart disease
- Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
- Clinical factors predicting ureteral stent failure in patients with external ureteral compression
- Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
- Triple-Endobutton and clavicular hook: A propensity score matching analysis
- Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
- Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
- miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
- Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
- The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
- Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
- circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
- Educational program for orthopedic surgeons’ influences for osteoporosis
- Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
- lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
- Anticoagulation is the answer in treating noncritical COVID-19 patients
- Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
- Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
- VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
- Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
- Treatment of osteoporosis with teriparatide: The Slovenian experience
- New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
- Superenhancer–transcription factor regulatory network in malignant tumors
- β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
- Clinical features of atypical tuberculosis mimicking bacterial pneumonia
- Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
- Effect of electromagnetic field on abortion: A systematic review and meta-analysis
- miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
- MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
- Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
- miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
- Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
- MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
- Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
- circATP2A2 promotes osteosarcoma progression by upregulating MYH9
- Prognostic role of oxytocin receptor in colon adenocarcinoma
- Review Articles
- The function of non-coding RNAs in idiopathic pulmonary fibrosis
- Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
- Role of cesarean section in the development of neonatal gut microbiota: A systematic review
- Small cell lung cancer transformation during antitumor therapies: A systematic review
- Research progress of gut microbiota and frailty syndrome
- Recommendations for outpatient activity in COVID-19 pandemic
- Rapid Communication
- Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
- Use of microspheres in embolization for unruptured renal angiomyolipomas
- COVID-19 cases with delayed absorption of lung lesion
- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning