Background:Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins)-mutant non-small cell lung cancer (NSCLC) is characterized by limited sensitivity to standard-dose EGFR tyrosine kinase inhibitors (EGFR-TKIs) and historically poor clinical outcomes. Although agents such as amivantamab and other targeted therapies have expanded treatment options, access barriers and marked variant-specific heterogeneity remain major challenges. Emerging evidence suggests that dose-escalated third-generation EGFR-TKIs may provide clinical benefit in selected ex20ins subtypes, yet real-world data are scarce. Case presentation:We describe a 56-year-old never-smoking female with metastatic lung adenocarcinoma harboring an EGFR A767_V769dup exon 20 insertion and co-mutations in TP53, SETD2, SMAD4, and ETV6, with low PD-L1 expression. In the setting of limited access to amivantamab at diagnosis and preliminary evidence supporting intensified EGFR inhibition in certain "near-loop" ex20ins variants, the patient received off-label high-dose osimertinib 160 mg once daily as first-line therapy. She achieved a durable partial response with manageable Grade 1 skin and nail toxicities and no dose reductions. Following disease progression, and after multidisciplinary discussion and informed consent, she was switched to off-label furmonertinib 240 mg once daily, resulting in additional disease control. Sequential high-dose osimertinib followed by high-dose furmonertinib yielded an overall survival of approximately 37 months. Literature and trend overview:To contextualize this case, we conducted a targeted narrative review and a descriptive bibliometric overview using CiteSpace (2000-2023) based on Web of Science Core Collection records. This analysis demonstrated a growing global research focus on third-generation EGFR-TKIs and variant-specific treatment strategies for EGFR ex20ins-mutant NSCLC, supporting the rationale underpinning the therapeutic approach adopted in this report. Conclusion:Sequential high-dose third-generation EGFR-TKIs may offer clinically meaningful benefit in selected EGFR ex20ins cases; however, this strategy remains non-standard and should be regarded as hypothesis-generating, warranting further prospective evaluation.

Primary gastric melanoma is a rare clinical finding. Its diagnosis can be challenging due to the complex tissue structure of the stomach and the diverse morphology of melanoma cells, which contribute to the increased likelihood of misdiagnosis. Here we report a 69-year-old female patient with primary gastric melanoma, initially misdiagnosed as “gastric adenocarcinoma”. The patient initially received two cycles of neoadjuvant therapy with Tegeo in combination with oxaliplatin (SOX). Unfortunately, the response was not satisfactory. In order to guide further treatment decisions, immunohistochemistry (IHC) and next-generation sequencing (NGS) were conducted. Immunohistochemistry: CK (-), CK8/18 (-), Vimentin (+), CD56 (-), CgA (-), Syn (-), ALK (-), CD30 (-), S-100 (+), INI1 (expression), CD43 (-), CD3 (-), CD20 (-), Brg-1 (expression), CD117 (-), DOG-1 (-), CD34 (-), HMB-45 (+), melan-A (+), Her-2 (-). NGS showed no significant abnormalities in HER-2 and wild type in the range of BRAF gene detection. Through a Multidisciplinary Team (MDT) consultation, she was finally diagnosed with “primary gastric malignant melanoma”. Despite the disease progressing after first-line chemotherapy with temozolomide, cisplatin, and bevacizumab, a second-line treatment with albumin paclitaxel, carboplatin, and bevacizumab resulted in a sustained partial remission (PR). The patient’s condition was stable during the follow-up period. As far as we know, this is a rare case of primary gastric malignant melanoma which received persistent PR after second-line treatment. Combined with the pathological manifestations of MM and recent clinical studies, the pathological features and treatment of primary gastric malignant melanoma were discussed.

BackgroundSmall cell lung cancer (SCLC) is highly aggressive, and durable disease control after multiple treatment lines is uncommon. Anti-angiogenic therapy combined with PD-1 blockade may provide complementary antitumor effects through vascular and immune microenvironment remodeling.Case presentationWe report a 64-year-old never-smoking woman diagnosed with limited-stage SCLC in September 2017. She achieved a partial response after concurrent chemoradiotherapy but developed recurrence in November 2018 and subsequently progressed after irinotecan-based and pemetrexed-based chemotherapy. Anlotinib was initiated in August 2019 and achieved radiologic tumor regression. In May 2020, biopsy of a right submandibular lymph node confirmed extrathoracic metastatic SCLC. Sintilimab was added to ongoing anlotinib in June 2020, and a partial response was achieved after three cycles. Grade 2 immune-related hypothyroidism developed during combination therapy, and sintilimab was discontinued. Anlotinib monotherapy was subsequently continued as maintenance treatment. At the latest follow-up in July 2026, the patient remained alive with stable disease, with an overall survival of 106 months from initial diagnosis.ConclusionsThis case highlights exceptionally durable disease control in multiply relapsed SCLC following sequential anlotinib and short-course sintilimab. The sustained activity of anlotinib, reactivation of antitumor immunity by PD-1 blockade, and potential vascular–immune interaction may have jointly contributed to the prolonged outcome. However, because anlotinib had demonstrated activity before immunotherapy and was continued after sintilimab discontinuation, the relative contribution of each treatment cannot be determined. Further prospective studies with biomarker analyses are warranted.

Background:Type 2 diabetes mellitus (T2DM) is a major public health challenge. This study aimed to explore the molecular mechanisms underlying the effects of semaglutide on lipid metabolism in visceral white adipose tissue in a mouse model of T2DM.Methods:Male C57BL/6J mice were given a normal diet, a high-fat diet with streptozotocin, or a high-fat diet with semaglutide. Blood samples, liver tissue, and adipose tissue were collected for analysis. Serum adipokines, inflammatory cytokines, liver function, and lipid profiles were assessed. White adipose tissue and liver sections were processed for hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC) staining for the macrophage marker F4/80. High-throughput targeted lipidomic analysis of epididymal white adipose tissue from these animals was performed using liquid chromatography-tandem mass spectrometry to characterize changes in lipid composition and function. Furthermore, the expression of genes related to adipokines, inflammation, and lipid metabolism in epididymal adipose tissue was determined by reverse transcription-quantitative PCR (RT-qPCR).Results:Semaglutide significantly improved systemic metabolism in mice with T2DM, as demonstrated by reductions in body weight, blood glucose, serum lipid levels, and insulin resistance indices homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (Adipo-IR). Serum Leptin, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were downregulated, while Adiponectin levels were elevated. Histological analysis revealed that semaglutide effectively reduced adipocyte size, suppressed macrophage infiltration in adipose tissue, and decreased liver lipid accumulation. Targeted lipidomic profiling identified 24 lipid subclasses, of which 50 lipid molecules were significantly changed after semaglutide treatment. Enrichment analysis identified 15 metabolic pathways, with glycerophospholipid metabolism being the most prominently affected. RT-qPCR results confirmed that semaglutide altered the expression of key genes involved in glycerolipid, glycerophospholipid, fatty acid, and cholesterol metabolism.Conclusions:These results shed light on the comprehensive remodeling of semaglutide in improving lipid metabolism in epididymal white adipose tissue mice with T2DM.

Background:Solid pseudopapillary neoplasm of the pancreas (SPN), also known as Frantz's tumor is a peculiar pancreatic neoplasm with an unclear pathogenesis. Early surgery often results in a curative effect; however, rare postoperative metastasis can occur. Currently, no standard systemic treatment strategy has been established for metastatic SPN. In this article, we report an older woman with SPN who developed postoperative multiple liver metastases and experienced rapid progression despite sequential systemic therapies. Case Description:A 68-year-old woman who underwent surgical resection of a SPN (approximately 44 months earlier) presented with multiple liver lesions despite having no obvious clinical findings. After laparoscopic distal pancreatectomy and splenectomy, multiple postoperative liver metastases were diagnosed by ultrasound-guided percutaneous liver biopsy, and a CTNNB1 gene mutation was detected. The patient received sequential palliative systemic therapies, however, the disease continued to progress, and she ultimately died 8 months later. Conclusions:SPN is an extremely rare tumor with a relatively good prognosis. Complete surgical resection remains the mainstay of treatment; however, evidence for systemic therapy in unresectable or metastatic SPN remains limited. We report the case of a SPN patient with rare postoperative metastases and a poor prognosis, and describe the treatment course and systemic therapeutic strategy, which may serve as a reference for the management of similar cases.

OBJECTIVE:To evaluate the potential of brain-tumor interface (BTI) radiomics for predicting the Ki-67 proliferation index in meningiomas and to construct and validate a nomogram integrating radiomics with clinical features for this purpose. MATERIALS AND METHODS:This multicenter retrospective study enrolled 300 patients from two distinct centers. Patients diagnosed with meningioma were stratified into low (<5%) and high (≥5%) Ki-67 expression groups based on immunohistochemistry. Clinical data were collected, and independent predictors were identified via univariate and multivariate logistic regression analyses. Radiomics features from the tumor parenchyma and the 4 mm BTI region were extracted from T1-CE and T2WI images to construct single-region and combined-region radiomics models. A nomogram integrating the radiomics scores (Radscore) from the optimal radiomics model and clinical predictors was developed and validated. RESULTS:In the internal validation cohort, the tumor radiomics model achieved an AUC of 0.754, the BTI radiomics model achieved an AUC of 0.702, and the combined Radiomics model performed better with an AUC of 0.780, significantly outperforming both single-region models.In the external test cohort, corresponding AUCs were 0.681 for the tumor radiomics model, 0.682 for the BTI radiomics model, and 0.709 for the combined Radiomics model, again showing the combined model's superiority. Univariate and multivariate analyses identified tumor volume and maximum diameter as independent clinical predictors of Ki-67 proliferation status. The clinical model incorporating these features reached an AUC of 0.741 in the internal validation cohort and 0.688 in the external test cohort. The nomogram integrating radiomics scores with clinical predictors achieved the highest diagnostic performance (AUC of 0.846 in the internal validation cohort, 0.752 in external test cohort), significantly outperforming all other evaluated models. CONCLUSIONS:The BTI region shows the potential for predicting meningioma Ki-67 proliferation. The nomogram developed in this study provides an effective tool for this prediction, supporting personalized treatment strategies.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.

目的 筛选熊去氧胆酸(ursodeoxycholic acid,UDCA)应答不佳原发性胆汁性胆管炎(primary biliary cholangitis,PBC)女性患者肝组织长链非编码RNA(long noncoding ribonucleic acid,lncRNA)、mRNA差异表达基因,并进行生物信息学分析.探讨其在PBC应答不佳中的作用及潜在功能.方法 收集2016年7月至2017年7月首都医科大学附属北京地坛医院6例女性PBC患者的肝组织穿刺标本,其中3例对UDCA应答好(对照组),另外3例对UDCA应答不佳(试验组).通过RNA提取、纯化、扩增及芯片实验,以差异倍数(fold change,FC)≥1.5倍,P＜0.05作为筛选条件,利用Illumina高通量测序技术检测6例PBC患者肝组织中lncRNA、mRNA的表达水平,筛选差异表达的lncRNA和mRNA.对差异表达的LncRNA、mRNA进行基因本体(gene ontology,GO)功能分析、信号转导通路富集分析(kyoto encylopaedia of genes and genomes,KEGG分析)及蛋白互作网络分析,寻找与PBC应答不佳相关的lncRNA.结果 共检测到差异表达的mRNA 599个(312个上调,287个下调)、lncRNA 1167个(685个上调,482个下调).GO与KEGG分析发现,差异表达的mRNA与甘油三酯、长链脂肪酸代谢、胆固醇排出、糖原异生及正向调节血管生成等相关.而这些mRNA与核受体过氧化物酶体增殖激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路、转化生长因子β(transforming growth factor beta,TGF-β)信号通路、脂肪酸降解通路、细胞因子受体相互作用信号通路等相关.差异表达lncRNA的靶基因与磷代谢、磷酸盐代谢、能量代谢、细胞活化、免疫效应调节、抗原加工和提呈相关.这些靶基因与病毒感染通路、泛素介导的蛋白降解通路、线粒体自噬通路、细胞因子受体相关通路、Wnt信号通路相关.结论 本研究是PBC应答不佳相关lncRNA谱的补充,研究发现了一定数量差异表达的lncRNA,并预测其功能靶向基因及涉及信号通路,有望为PBC应答不佳研究提供新的参考依据.

Rationale: Signet-ring cell carcinoma, which is an infrequent type of colorectal cancer. Abdominal pain is the primary presenting complaint of patients with acute appendicitis. It is difficult to diagnose patients with appendiceal carcinomas accompanying with symptoms of acute appendicitis. Patient Concerns: A 33-year-old female patient was admitted to our hospital, with chief complaints of “bilateral pelvic space-occupying lesions for 1 month, aggravated abdominal distension, and she accompanied with diarrhea for 3 days.” Diagnosis: The patient was with primary signet ring cell carcinoma of the appendix, presented with acute appendicitis, as well as bilateral ovarian metastasis and peritoneal implantation metastasis. Interventions: She was then treated with irinotecan, oxaliplatin, calcium folinate, 5-FU combined with bevacizumab, surgical treatment, and postoperative adjuvant treatment with oxaliplatin, capecitabine regimen to consolidate the efficacy. Outcomes: The patient is in good conditions, and postoperative adjuvant chemotherapy is in progress as well. Conclusion: The outcomes highlighted the importance of strict histopathologic assessment for appendiceal adenocarcinoma, and provided new ideas for the diagnosis and treatment of advanced-stage signet ring cell carcinoma of the appendix.

Objective Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case-control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Objective:To analyze the clinical characteristics of re-positive patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta strain.Methods:The clinical data of four patients readmitted for SARS-CoV-2 delta variant strain infection in Beijing Ditan Hospital, Capital Medical University from May 2021 to October 2021 were analyzed, retrospectively.Results:Total of 2 male and 2 female were collected, with the median age as (36.75 ± 21.55) years old (11-63 years old). First hospitalization: 2 cases were general type, 1 case was mild type, and 1 case was asymptomatic infected. All the re-positive specimens were nasopharyngeal swabs. Clinical symptoms were mild when patients were re-positive of SARS-CoV-2 nucleic acid, only one patient with transient chest distress; no obvious clinical symptoms of fever, cough, pharyngalgia and gustation occurred. Most laboratory indicators of re-positive patients (blood routine examination, liver and renal function, inflammatory indicators) after re-admission were roughly normal. There was no change in chest CT of re-positive inpatients compared with mild type and asymptomatic infected inpatients, and the general type infected patients with pulmonary infection showed absorption and improvement compared with those before re-positive chest CT. The duration of re-hospitalization was shorter than that of the first hospitalization [(11.5 ± 4.95) d vs. (29.75 ± 2.12) d], with significant difference (t = 6.949, P < 0.001).Conclusions:The condition of patients with re-positive SARS-CoV-2 nucleic acid delta strain continues to improve, but as a nucleic acid detection phenomenon, it has no significant clinical significance, but the cause of re-positive SARS-CoV-2 nucleic acid still needs further discuss.

目的 检索、评价和整合急性缺血性脑卒中静脉溶栓院内全程管理的最佳证据,为制定急性缺血性脑卒中静脉溶栓院内全程管理方案提供依据.方法 计算机检索2011年1月—2021年12月发表于UpToDate、BMJ Best Practice、国际指南协作网(Guidelines International Network,GIN)、苏格兰院际指南网(Scottish Intercollegiate Guidelines Network,SIGN)、英国国家卫生与临床优化研究所(National Institute for Health and Care Excellence,NICE)、美国国立指南库(National Guideline Clearinghouse,NGC)、Cochrane Library、JBI、Embase、PubMed、OVID、医脉通、中国知网、万方数据库的相关证据,类型包括临床决策、指南、证据总结、推荐实践、系统评价、专家共识/立场声明.由2名研究者对符合纳入标准的文献进行质量评价、证据提取和证据综合.结果 共纳入13篇文献,包括指南5篇、系统评价3篇、证据总结1篇、专家共识/立场声明4篇,总结成急性缺血性脑卒中静脉溶栓预检分诊、病情评估、急性期护理、溶栓治疗、溶栓监护、并发症护理、质量管理7个维度43条证据.结论 急性缺血性脑卒中静脉溶栓院内全程管理的证据总结可为临床提供循证实践依据,在证据转化时,应结合医院环境、临床实际及患者意愿等选择性应用证据,改善患者结局.

Dysregulation of circular RNAs (circRNAs) executes important regulatory roles in carcinogenesis. Nonetheless, few studies focused on the mechanisms of circRNAs in cholangiocarcinoma (CCA). qRT-PCR was applied to verify the dysregulated circRNAs in CCA. Fisher's exact test, Kaplan-Meier analysis and Cox regression model were utilized to investigate the clinical implications of circ-LAMP1 in the patients with CCA. The viability, apoptosis, migration and invasion of CCA cells were detected after silencing/overexpression of circ-LAMP1. Xenograft and lung metastasis assays were performed to verify the in vitro results. The regulatory networks of circ-LAMP1 were unveiled by bioinformatic analysis, RNA immunoprecipitation (RIP), RNA pulldown and luciferase reporter assays. Up-regulation of circ-LAMP1 was found in CCA tissue samples and cell lines. Enhanced level of circ-LAMP1 was linked to clinical severity, high post-operative recurrence and poor prognosis for the patients with CCA. Gain/loss-of-function assays confirmed the oncogenic role of circ-LAMP1 in mediating cell growth, apoptosis, migration and invasion. Nevertheless, the level of circ-LAMP1 had no effect on normal biliary epithelium proliferation and apoptosis. Animal study further verified the in vitro data. Mechanistically, circ-LAMP1 directly sponged miR-556-5p and miR-567, thereby releasing their suppression on YY1 at post-transcriptional level. Rescue assay indicated that the oncogenic role of circ-LAMP1 is partially dependent on its modulation of YY1 in CCA. In summary, this study suggested that circ-LAMP1 might be used as a promising biomarker/therapeutic target for CCA.

Since online publication of this article, the authors noticed that there was an error in Figs. 2 and 4. In Fig. 2c the samples were mislabelled, the correct labelling order is 'Control, HG, HG + NPS R568, HG + Calhex231'. In Fig. 4c, an incorrect image was used to compile the HG + NPS R568 group, meaning the control was accidentally duplicated. The corrected images are provided below. The authors confirm that these errors did not influence the reported data, discussion, or conclusion. The authors apologise for any inconvenience to readers arising from this error.

Objective: To observe the protective effects of exogenous spermine on renal fibrosis induced by diabetic nephropathy (DN) and to explore its mechanism.Methods: Twenty-four male C57 mice were randomly divided into control group, type 1 diabetes group (TID) and spermine pretreatment group (TID+Sp, n=8 in each group). TID mice were induced by STZ (60 mg/kg), and TID+Sp mice were pretreated with spermine (5 mg/(kg·d)) for 2 weeks before STZ injection. The mice were killed at the 12th week. The renal function was determined by serum creatinine and urea nitrogen. HE, PAS and Masson staining were used to evaluate renal tissue injury and fibrosis. The expressions of matrix metalloproteinase (MMP-2, MMP-9) and collagen IV (Coll-IV) in the kidney of mice were detected by Western blot. Results: Compared with the control group, the blood glucose (5.67±0.22 vs 28.40±0.57 mmol/L), creatinine (14.33±1.22 vs 30.67±4.73 μmol/L) and urea nitrogen (6.93±4.94 vs 22.00±1.04 mmol/L) in the T1D group were increased significantly (P＜0.05), the glomerular basement membrane was thickened, the collagen was significantly increased, the expressions of MMP-2, MMP-9 and Coll-IV protein were increased (0.57±0.07 vs 1.06±0.20, 47.00±0.04 vs 1.29±0.09 and 0.42±0.16 vs 0.95±0.18,P＜0.05). Exogenous spermine significantly alleviates the above-mentioned changes. Conclusion: Exogenous spermine pretreatment could significantly alleviate renal fibrosis in diabetic mice by regulating the balance between MMPs and collagen.

Epidemiologic, clinical and imaging data were collected from 14 children with confirmed coronavirus disease 2019 (COVID-19) admitted in Beijing Ditan Hospital from January 27, 2020 to February 12, 2020. There were 6 boys and 8 girls with a median age of 3.5 years (6 months-9.4 years). Four patients had a history of travel to Wuhan City or Hubei Province and 2 patients had contacted with people from Wuhan; 13 patients were familial cluster of infection. The incubation period was 4 to 16 days. The clinical manifestations were fever in 8 cases, cough in 5 cases, diarrhea in 1 case; and 2 cases were asymptomatic. Four patients had abnormal peripheral blood routine, including 1 had lymphocytosis, 3 had lymphocytopenia; 3 patients had a slightly elevated CRP, and 3 patients had hepatic dysfunction. Thirteen patients underwent chest CT; and 1 case showed bilateral lung glass exudation, 1 case showed multiple patchy high density shadows of bilateral lung. One patient underwent chest X-ray examination, which was showed no abnormal findings. The pediatric patients with COVID-19 in this series generally have a traceable epidemiological history. The clinical manifestations are fever, cough and diarrhea. Peripheral white blood cell counts were most normal. Chest CT reveals less severe changes than those in adults, most child patients show no manifestation of pneumonia.

Circular RNAs play an imperative role in cancer development and metastasis by regulating oncogenic and tumor‐suppressive pathways. However, the role and mechanism of circ_0074027 in non–small‐cell lung cancer (NSCLC) have not been elucidated. The expression levels of circ_0074027 were detected by qRT‐PCR. The link between circ_0074027 expression and clinicopathologic parameters was analyzed by Fisher's exact test. The prognostic role of circ_0074027 was investigated by Kaplan‐Meier and Cox regression analysis. Cell counting kit‐8 and flow cytometric assays were utilized to evaluate NSCLC cell proliferation and apoptosis, respectively. Wound scratch and Transwell tests were applied to detect cell migratory and invasive capacities. The interaction potential of circ_0074027 and miR‐185‐3p was analyzed by the circBank database, and verified by dual‐luciferase reporter assay. The downstream gene of miR‐185‐3p was also investigated. Circ_0074027 was elevated in NSCLC specimens and cell lines. Overexpressed circ_0074027 was related to more advanced TNM stages, poorer differentiation grade, and worse overall survival. Upregulated circ_0074027 increased the proliferation of H1299 cells by inhibiting cell apoptosis. Cell migration and invasion were enhanced after circ_0074027 overexpression. Silenced circ_0074027 caused the opposite effects in the A549 cell line. For mechanism investigation, circ_0074027 directly sponges miR‐185‐3p to enhance bromodomain‐containing protein 4 (BRD4) and MAPK‐activating death domain‐containing protein (MADD) expression levels at the posttranscriptional level. Furthermore, we found the oncogenic function of circ_0074027 is attributed to its modulation of BRD4 and MADD. Collectively, upregulated circ_0074027 in NSCLC accelerates cell progression via miR‐185‐3p/BRD4/MADD pathway as a competing endogenous RNA.

糖尿病肾病(DKD)是1型和2型糖尿病常见的严重微血管并发症之一.我国约有20％～ 40％的糖尿病患者合并DKD,其已成为慢性肾脏病(CKD)和终末期肾病(ESRD)的主要原因,也是糖尿病肾病患者生存期缩短的主要原因之一[1].早期诊断有助于对高危患者进行有针对性的预防性治疗,从而延缓病情进展,提高患者的生存质量[2].尿白蛋白/肌酐(UACR)或尿白蛋白排泄率(UAER)是目前被广泛接受的DKD早期诊断指标,但白蛋白尿作为DKD诊断标志物的效能受到许多因素的限制[3],因此,迫切需要寻找一个比白蛋白尿灵敏性和特异性更高的生物标志物来早期预测和诊断DKD.近年来,随着人们对尿蛋白质组学研究的进一步深入,CKD生物标志物分类模型—CKD273作为早期诊断及预测DKD进展的生物标志物逐渐受到重视,其已被证实可以在多研究中心背景下诊断及预测DKD进展,并在微量白蛋白尿发生前数年即可作为DKD的诊断标志物.本文主要对CKD273在DKD的诊断及预后中的作用进行综述.

Gilbert综合征是一种常染色体显性遗传疾病,是由UGT1A1基因突变引起的肝脏胆红素代谢障碍,从而导致间接胆红素水平升高.Gilbert综合征最常见的基因型是UGT1A1基因启动子上的纯合多态性A(TA)7TAA,即TA插入UGT1A1*28的启动子上.Gilbert综合征的诊断一般为排除诊断,目前可进行分子遗传学检测.现报道1例首诊原发性胆汁性胆管炎,最终确诊为Gilbert综合征患者的临床资料并回顾相关文献进行分析.