MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.     

Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27−32.91; 95% CI 3.64−6.22) and 14.70 (range, 0.27−32.91; 95% CI 0.27−43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, p<0.05) and mOS (24.03 vs. 6.07 months, p<0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand-and-foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash, and palpitation. In conclusion, apatinib exhibited high activity and good tolerance for NSCLC patients with brain metastasis, and it might become a potential choice for metastatic brain tumors in NSCLC patients.     

Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study

Abstract

Background

Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19.     

eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

外周血miR-150-5p、SOCS1 mRNA对类风湿关节炎“病”“证”诊断意义的初步探讨＊

目的 探讨类风湿关节炎患者外周血miR-150-5p、细胞因子信号抑制因子1（suppressor of cytokine signaling 1，SOCS1）mRNA的表达及对类风湿关节炎（Rheumatoid Arthritis，RA）疾病诊断、中医证型判断的意义。方法 纳入符合诊断标准的RA患者57例及健康对照组19例，根据《22个专业95个病种中医诊疗方案》有关RA的中医证候诊断标准，判断RA的中医证型。qPCR检测RA患者及健康对照组miR-150-5p、SOCS1mRNA的相对表达水平，同时检测血常规、肝功能、肾功能等常规指标。双荧光素酶分析方法判断两者是否存在靶向关系。统计分析miR-150-5p、SOCS1 mRNA对RA疾病的诊断意义及其与中医证型的相关性。结果 RA患者外周血miR-150-5p的相对表达水平下调，低于正常人群（t = -19.019，P < 0.05）；其表达水平随疾病活动度升高，有下降趋势；患者外周血SOCS1 mRNA的相对表达水平上调，低于正常人群（t = 5.333，P < 0.05）；其表达水平随疾病活动度升高，有上升趋势。MiR-150-5p与SOCS1 mRNA有靶向结合关系（P < 0.05）。通过AUC曲线比较，miR-150-5p的相对表达水平区分RA的敏感性及特异性分别为98.1%、92.1%（AUC = 0.972，P < 0.05）；SOCS1 mRNA的相对表达水平无法区分RA（AUC = 0.472，P > 0.05）。RA患者中miR-150-5p的相对表达水平低于3.06，RA患者风湿痹阻证、寒湿痹阻证的相对风险分别为8.33、250.00（P < 0.05）。结论 miR-150-5p、SOCS1 mRNA在RA患者中有差异性表达，且有靶向结合关系。miR-150-5p可能是RA的疾病诊断及中医风湿痹阻证、寒湿痹阻证证型诊断的潜在生物标志物。     

自血穴位注射疗法联合马来酸茚达特罗治疗老年稳定期慢性阻塞性肺疾病的临床分析

目的探讨自血穴位注射疗法联合马来酸茚达特罗治疗老年稳定期慢性阻塞性肺疾病(COPD)的临床疗效及其对患者炎性因子、免疫功能及肺功能的影响。 方法将2015年5月至2016年5月我院收治的86例老年缓解期COPD患者分为观察组与对照组。对照组给予马来酸茚达特罗治疗，观察组在对照组治疗基础上另给予自血穴位注射疗法。治疗12周后，评价2组临床疗效。治疗前及治疗12周后，分别检测2组患者肺功能指标(FEV₁、FVC与PEF)，炎性因子(IL-8、α1-AT、IL-6及TNF-α)，免疫功能指标(IgG、IgA、CD3^＋及CD4^＋)水平。治疗期间，对2组患者的不良反应进行密切观察。 结果治疗后二组患者各项检测指标均优于治疗前。治疗12周后，观察组总有效率为90.7%，明显高于对照组的72.1%(P<0.05)。治疗12周后，观察组FEV₁、FVC与PEF等肺功能指标，IgG、IgA、CD3^＋及CD4^＋等免疫功能指标水平均明显高于对照组(P<0.05)，而IL-8、α1-AT、IL-6及TNF-α含量分别为(23.23±3.87)ng/L、(3.43±0.41)g/L、(52.25±5.38)ng/L及(43.12±3.98)ng/L，改善程度均明显优于对照组(P<0.05)。治疗期间，2组患者均未出现严重不良反应。 结论自血穴位注射疗法联合马来酸茚达特罗治疗老年稳定期COPD疗效确切，可有效改善患者炎症水平，值得进行深入研究。     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

尿干化学法和离心沉渣镜检法检测穿刺羊水母体细胞污染的应用

目的　探讨一种快速简便鉴别羊水母血污染的方案。方法　选取30 例2019 年6~10 月羊水穿刺样本, 检测 羊水及母血DNA，将母血DNA 污染量换算对应体积全血量建立羊水母血DNA 污染梯度模型，运用尿干化学法及离 心沉渣镜检法检测母血污染情况。结果　羊水母血DNA 污染率为5%，10%，20% 和30%，尿干化学法检出率分别为 16.67%，60%，100% 和100%；离心沉渣镜检法检出率分别为60%，100%，100% 和100%。结论　尿干化学法及离心 沉渣镜检法联合检测可更简便快捷地进行羊水母血污染鉴定，检出率与母血DNA 污染率呈正比关系。     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.