ObjectiveBy observing the effect of Qianyang Yuyin granules on the phenotype of renal tubule epithelial cells， the intervention of Qianyang Yuyin granule on renal interstitial fibrosis was investigated. MethodThe renal tubular epithelial cells （HK-2） were treated with different concentrations of transforming growth factor （TGF）-β₁ （5， 10， 15， 20， 25 μg·L^-1） for 24 hours， and cell morphology and growth state were observed with an inverted phase contrast microscope. The 20 μg·L^-1 was selected as the most appropriate concentration of TGF-β₁ according to Western blot results for subsequent experiments. HK-2 cells were divided into six groups： blank group， TGF-β₁ group （concentration of 20 μg·L^-1）， low， medium， and high dose Qianyang Yuyin granule groups （concentration of 0.5， 1， 2 g·L^-1）， and valsartan group （1 × 10^-5 mol·L^-1）. The cell activity was measured by cell proliferation and cell counting kit-8 （CCK-8）. The cell migration ability was detected by scratch test. The Transwell method was used to detect the invasiveness of cells. Western blot was used to detect levels of fibronectin （FN）， E-cadherin， α-smooth muscle activator （α-SMA）， Vimentin， collagen type Ⅰ（Col Ⅰ）， collagen type Ⅳ（Col Ⅳ）， and other related proteins. ResultTGF-β₁ stimulating epithelial-mesenchymal transition （EMT） in renal tubular epithelial cells was time- and concentration-dependent. Compared with the blank group， higher concentration in the TGF-β₁ group indicates longer intervention time and more obvious long spindle change of cells， and the migration and invasion ability of the cells was significantly enhanced. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ increased significantly （P<0.05， P<0.01）， while the expression level of E-cadherin protein decreased （P<0.05）. Compared with the TGF-β₁ group， Qianyang Yuyin granule groups could maintain normal cell morphology， and the migration and invasion ability of the cells was inhibited. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ decreased （P<0.05， P<0.01）， and the expression of E-cadherin protein was significantly restored （P<0.05）. ConclusionQianyang Yuyin granule can reverse TGF-β₁-induced interstitial transformation of renal tubular epithelial cells by reducing the phenotypic expression of mesenchymal cells and increasing the phenotypic expression of epithelial cells.

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Apoptosis/genetics* ; Autophagy/genetics* ; bcl-2-Associated X Protein ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Reactive Oxygen Species ; Rats ; Animals ; Myocytes, Cardiac/drug effects* ; Homocysteine/adverse effects* ; Hyperhomocysteinemia

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

In order to construct the online teaching mode of clinical clerkship course and improve the online clerkship teaching system of clinical medicine in China, based on the "3P" model, a complete set of online clinical clerkship mode has been constructed from three links of teaching, pre-class preparation, classroom teaching and after-class evaluation, and applied to clinical teaching practice of Internal Medicine. The practice suggests that students are highly satisfied and the teaching effect is good, which provides a new idea for the reform of online clerkship teaching of clinical medicine.

Objective:To construct the online teaching model of clinical clerkship teaching and improve the online teaching system of clinical medicine in China.Methods:Based on "3P" teaching model, a complete online clinical clerkship teaching model was constructed from three links: pre-class preparation, classroom teaching and after class evaluation. It was applied to practical teaching in 101 students in 2017 batch of clinical medicine "5+3" class, 2017 batch of five-year pediatrics class and 2017 batch of basic medicine class. After practice, all students were surveyed and the results were analyzed.Results:Through the analysis of questionnaire, 89.5% of the students were satisfied with the online course design, 81.61% of the students thought that the online design was scientific and reasonable, 86.6% of the students thought that the clerkship teaching process was attractive and could stimulate students' interest in learning, and 90.72% of the students thought that the goal of clerkship teaching was clear and the key problems and difficulties were clear.Conclusion:The online teaching mode of clinical clerkship has high student satisfaction and good teaching effect, which provides a new way for online clerkship model.

Family physicians contracted service is an important choice to deepen the reform of China′s healthcare reform and achieve the strategic goal of " health for all" . In order to effectively promote the contracted service, the central government has successively issued a number of policy documents, which are echoed by the localities in their proactive explorations, achieving remarkable results. But there are also multiple roadblocks hindering the contracted service to progress. This article referred to the three-circle theory and studied policy implementation from the three dimensions of policy value, policy resources, and policy impetus. A thorough analysis of the problems in the implementation process revealed such main problems as insufficient family physicians, inadequacy of supporting policies and low level of policy acceptance among the young healthy age groups. The follow-up work will promote the long-term implementation of the family physicians contracted service policy by enriching the family physicians team, enriching supporting policies, and focusing on promotions to key age groups.

Objective:To evaluate the heterogeneity in pediatric ETV6-RUNX1 acute lymphoblastic leukemia (ALL) by gene expression profile and to study clinical characteristics in different clusters.Methods:An improved advanced fragment analysis (iAFA) technique was developed to detect 57 marker genes in 264 pediatric ALL patients treated in Beijing Children’s Hospital from August 2016 to June 2019. The 56 ALL patients with ETV6-RUNX1 positive were evaluated by clinical characteristics in gene expression profile, immunophenotype and early response of chemotherapy in different clusters.Results:The 56 ETV6-RUNX1-positive patients were clustered into 2 groups of E/R-1 (45, 80.4%) and E/R-2 (11, 19.6%) . Spearman coefficient was 0.788 and 0.901 in E/R-2 and E/R-1, respectively. The median of initial platelet counts was 104 (27-644) and 50 (8-390) ( P<0.01) in E/R-2 and E/R-1, respectively. The median of proportion of initial bone marrow immature cells was 0.830 (0.270-0.975) and 0.935 (0.445-0.990) ( P<0.05) in E/R-2 and E/R-1, respectively. The most specific immunophenotype at initial diagnosis, CD22 +CD34 +CD20 -CD117 -CD56 -, mainly gathered in E/R-2 ( P<0.001) . Patients negative of minimal residual disease detected by flow cytometry (MRD-FCM) at day 33 were 5 (55.6%) and 32 (88.9%) in E/R-2 and E/R-1, respectively. There was no significant difference in the original analysis ( P=0.064) but difference in sensitivity analysis ( P=0.035) . Nevertheless, patients negative of MRD detected by polymerase chain reaction (MRD-PCR) at day 33 were 7 (77.8%) and 36 (100%) in E/R-2 and E/R-1, respectively, with significant difference ( P=0.047) . Conclusion:Gene expression profile shows heterogeneous in ETV6-RUNX1 ALL, and the E/R-2 profile indicates that these patients may have a less tendency to thrombocytopenia at the initial diagnosis but have poorer response to induction chemotherapy and may influence further outcome.

Objective: To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods: From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay. Results: The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1. Conclusion miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.

Objective To investigate the role of microRNA?96?5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA?96?5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para?cancerous tissues were quantified by quantitative real?time PCR (qRT?PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA?96?5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA?96?5p in gastric cancer tissue and adjacent normal tissue were detected by qRT?PCR. miRNA?96?5p mimics was transfected to BGC?823 gastric cancer cells. The effects of miRNA?96?5p on cell proliferation and invasion were detected by cell counting kit?8 (CCK?8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E?cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA?96?5p expressed in BGC?823 cells was detected by dual?luciferase reporter assay. Results The median expression of miRNA?96?5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para?cancerous tissues (P＜0.05).The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para?cancerous tissues ( P＜0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA?96?5p (r＝－0.613, P＝0.006). The expression of miRNA?96?5p in gastric cancer cell BGC?823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84± 0.15, P＜0.05). The results of CCK?8 assay and Transwell assay showed that overexpression of miRNA?96?5p significantly reduced the proliferation and invasion abilities of gastric cancer cells ( P＜ 0.05 ). Overexpression of miRNA?96?5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E?cadherin and downregulated the expression of vimentin. The result of dual?luciferase?3′?UTR reporter assay confirmed that miRNA?96?5p binds to the 3′UTR of FoxQ1. Conclusion miRNA?96?5p may suppress the proliferation, migration and epithelial?mesenchymal transition (EMT) of gastric cancer cell by down?regulation of FoxQ1.

Objective To investigate the role of microRNA?96?5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA?96?5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para?cancerous tissues were quantified by quantitative real?time PCR (qRT?PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA?96?5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA?96?5p in gastric cancer tissue and adjacent normal tissue were detected by qRT?PCR. miRNA?96?5p mimics was transfected to BGC?823 gastric cancer cells. The effects of miRNA?96?5p on cell proliferation and invasion were detected by cell counting kit?8 (CCK?8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E?cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA?96?5p expressed in BGC?823 cells was detected by dual?luciferase reporter assay. Results The median expression of miRNA?96?5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para?cancerous tissues (P＜0.05).The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para?cancerous tissues ( P＜0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA?96?5p (r＝－0.613, P＝0.006). The expression of miRNA?96?5p in gastric cancer cell BGC?823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84± 0.15, P＜0.05). The results of CCK?8 assay and Transwell assay showed that overexpression of miRNA?96?5p significantly reduced the proliferation and invasion abilities of gastric cancer cells ( P＜ 0.05 ). Overexpression of miRNA?96?5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E?cadherin and downregulated the expression of vimentin. The result of dual?luciferase?3′?UTR reporter assay confirmed that miRNA?96?5p binds to the 3′UTR of FoxQ1. Conclusion miRNA?96?5p may suppress the proliferation, migration and epithelial?mesenchymal transition (EMT) of gastric cancer cell by down?regulation of FoxQ1.