Objective To investigate the potential therapeutic effects,targets,and pathways of wogonoside in hypertension-induced renal injury using the Gene Expression Omnibus(GEO)database and network pharmacology,and to validate the effects of wogonoside intervention on the renal tissues of spontaneously hypertensive rats(SHR),angiotensin Ⅱ(Ang Ⅱ)-stimulated NRK-52E cell apoptosis,and the regulation of relevant pathways through in vivo and in vitro experiments.Methods GEO dataset and network pharmacology analyses were performed to investigate the key therapeutic targets of wogonoside for hypertensive nephropathy.The STRING database was used to analyze protein-protein interactions.Biological functions were annotated via Gene Ontology(GO),and the potential signaling pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).SHR were randomly divided into groups and given low,medium,or high doses of wogonoside(0.075,0.75,and 7.5 mg/kg)via gastric gavage for 10 weeks.Morphological changes in the kidney tissue were assessed by hematoxylin-eosin(HE)staining.Serum levels of inflammatory cytokines,including tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,and IL-6,were measured using ELISA.Apoptosis rates were evaluated by TUNEL staining,and Western blot was performed to determine the expression of Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the expression of phosphorylated and total extracellular signal-regulated kinases(ERK)and p38 mitogen-activated protein kinase(MAPK)proteins.An in vitro model of Ang Ⅱ-stimulated NRK-52E cells was constructed and was treated with wogonoside at different concentrations(25,50,or 100 μmol/L)for 24 h.The apoptosis rates were then assessed by Annexin V staining,and Western blot was performed to validate the expression of apoptosis-related and pathway-associated proteins.Results Analysis of dataset GSE41453 revealed 11673 upregulated and 5902 downregulated genes in the renal tissues of SHR compared to the Wistar Kyoto(WKY)rats,or the WKY control group.Through the analysis of multiple databases,371 potential targets of wogonoside were identified,resulting in 98 overlapping targets.From these,45 core therapeutic targets were identified through further analysis,including TNF,CASP3,etc.GO analysis significantly enriched processes such as the negative regulation of apoptosis.KEGG pathway enrichment analysis highlighted the apoptosis pathway,IL-17 signaling pathway,and MAPK signaling pathway as being significantly enriched.Wogonoside treatment effectively mitigated pathological damage in SHR kidney tissues and significantly inhibited the expression of inflammatory cytokines,including TNF-α,IL-1 β,and IL-6(P＜0.05).It also decreased cell apoptosis rates in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells,downregulated the expression of Bax and cleaved caspase-3,and upregulated Bcl-2 expression(P＜0.05).Furthermore,wogonoside treatment inhibited the phosphorylation of ERK and p38 MAPK in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells(P＜0.05).Conclusion Wogonoside may exert its protective effects against hypertension-induced renal injury by suppressing the inflammatory response and cell apoptosis,potentially through the regulation of the MAPK signaling pathway.

Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.

Objective:To investigate the efficacy of clinical pathway teaching method in standardized training of general practitioners in gastroenterology.Methods:From 2018 to 2019, 40 residents who participated in the standardized training of general practitioners in the Department of Gastroenterology, Zhongshan Hospital Qingpu Branch, Fudan University Medical College were randomized into the experimental group and the control group. The residents of the experimental group were trained by clinical pathway teaching method, while the control group were trained by traditional methods. After 6 weeks' teaching, theoretical examination, operation skills and case analysis test were assessed and satisfaction surveys were conducted.Results:The operation skills and case analysis scores of the experimental group were significantly better than those of the control group [operation test (91.50±2.77) vs. (89.80±3.74), P<0.01; case analysis (92.10±1.98) vs. (86.40±2.87), P<0.01]. The teaching satisfaction of the experimental group was significantly higher than that of the control group, and the difference was statistically significant ( P<0.01). Conclusion:The teaching model of clinical pathway can improve the teaching quality of the residents in the department of gastroenterology, improve the satisfaction of the doctors in the training, and broaden clinical thinking, which is worthy of promotion in clinical teaching.

Obsjective To analyze the inflammation characteristics and changes of small airway function in patients with eosinophil and neutrophil asthma, and provide evidence for individualized treatment of asthma. Methods:Using a cross-sectional study, 46 patients with eosinophilic asthma and 42 patients with neutrophilic asthma confirmed by cytology of induced sputum were recruited from July 1, 2017 to June 30, 2019 at the respiratory Department of Respiratory Medicine,Jinshan Branch of the Sixth People's Hospital of Shanghai. Patients were divided by asthma category into eosinophilic asthma group and neutrophilic asthma group.The severity of acute attack, the score of asthma control test (ACT) and the concentration of serum C-reactive protein (CRP) were compared between the two groups The fraction of exhaled nitric oxide (FeNO), related cytokines(interleukin-4(IL-4), interleukin-5(IL-5), interleukin-13(IL-13), interleukin-17(IL-17) and interferon γ(IFN-γ)) in peripheral blood and induced sputum supernatant and lung function indicators (forced exhalation volume in one second (FEV1)% percent predicted (%pred), maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow (FEF) 75% pred, forced expiratory flow at 50% of FVC exhaled (FEF50%) pred were detected. Independent sample t-test was used for the comparison between measurement data groups comforming to normal distritution, rank sum test was used for the comparison between measurement data groups not conforming to normal distribution, and χ 2 test was used for the comparison of counting data. Results:There were no significant differences in the general data and ACT scores between the two groups (all P>0.05). The ratio of severe and critical degree (52.38%(22/42)), uncontrolled and partially controlled patients (59.52%(25/42)), CRP level (24.6(7.1, 35.0) mg/L) in neutrophil asthma group were higher than those in eosinophilic asthma group(30.43% (14/46), 36.96% (17/46), and 8.5 (2.0, 12.0) mg/L, respectively) (χ 2=4.37, χ 2=4.48, Z=4.76; P=0.036, P=0.034, P<0.001). The concentration of FeNO was higher in eosinophilic asthma group (76(54,93) ppb) than that in neutrophil asthma group(27(15,41) ppb),and the differences was statistically significant ( Z=6.52, P<0.001). The values of FEV1% pred ((56.13±21.51)%), MMEF% pred ((62.03±23.97)%), FEF75% pred ((54.42±20.49)%), FEF50% pred ((66.89±26.47)%) in neutrophil asthma group were lower than those in eosinophilic asthma group ((68.53±29.81)%, (72.16±23.05)%, (65.38±25.46)% and (79.86±27.61)%), and the difference between the two groups was statistically significant( t values were 2.25, 2.02, 2.21, 2.24; P values were 0.027, 0.046, 0.030, 0.027). The concentrations of serum IL-4((49.42±24.46) ng/L), IL-5((104.89±43.91) ng/L) and IL-4((44.49±19.12) ng/L), IL-5((95.45±28.58) ng/L) in induced sputum supernatant were higher than neutrophilic asthma group((32.29±14.19), (50.35±22.30), (33.33±15.08), (55.61±26.41) ng/L). The difference between the two groups was statistically significant ( t values were 4.06, 7.44, 3.02, 6.77, P values were <0.001, <0.001, 0.003, <0.001). In eosinophilic asthma group, the concentrations of serum IL-13 ((76.18±20.62) ng/L), IL-17 ((31.32±9.32) ng/L), IFN-γ ((18.27±5.56) ng/L) and IL-13((71.08±20.08) ng/L), IL-17((26.29±6.70) ng/L), and IFN-γ((17.61±5.94) ng/L) in induced sputum supernatant were lower than those in neutrophilic asthma group((153.83±44.53 ) ng/L, (55.27±18.89) ng/L, (26.46±10.08) ng/L, (120.32±28.41) ng/L, (44.99±12.66) ng/L, (23.91±7.66) ng/L). The difference between the two groups was statistically significant ( t values were 10.33, 7.43, 4.66,9.31,8.54,4.33, respectively; all P<0.001). Conclusion:Eosinophilic asthma and neutrophil asthma have different inflammation, small airway function characteristics and different response to treatment. The small airway function changes in early stage of neutrophil asthma are more obvious.

Preoperative neoadjuvant chemoradiotherapy NCR) combined with total mesorectal excision (TME) is the standard treatment mode for locally advanced rectal cancer.Compared with postoperative NCR,preoperative NCR increases the tumor down-staging,sphincter-preserving rate and local control rate.Patients who attain pathological complete response (pCR) after preoperative NCR have better prognosis compared with their counterparts.This article reviews the research progress on preoperative NCR in recent years.

Objective This study examined the value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)in serum and exhaled ventilator condensate (EVC)in early diagnosis and prognosis of ventilator-associated pneumonia (VAP). Methods A total of 37 adult patients undergoing mechanical ventilation were evaluated after treatment,including 24 patients with infection,13 without infection.Of the 24 patients with infection,10 patients were assigned to ineffective subgroup and 14 to effective subgroup.Levels of sTREM-1 in serum and EVC were measured on days 1,3,5,and 7 for all patients.sTREM-1 in serum and EVC were determined in patients by double antibody sandwich enzyme-linked immunosorbant assay (DAS-ELISA).The early diagnostic and prognostic value was assessed by receiver operating characteristic (ROC)curve analysis.Re-sults On Day 1,the sTREM-1 levels in serum and EVC did not show significant difference between the three groups (P>0.05).On Day 3 and Day 5,the level of sTREM-1 in the infection group was higher than that in the non-infection group (P <0.01).On Day 7,the sTREM-1 levels of serum and EVC in ineffective subgroup were higher than those in the effective subgroup and non-infection group (P <0.01). There were no difference between the non-infection group and effective subgroup (P >0.05).For ROC analysis,area under the curve (AUC)of serum sTREM-1 was 0.897,and AUC of EVC sTREM-1 was 0.909 on Day 3.When the cut-off value of EVC sTREM-1 was set at 4.70 ng/mL on Day 3,the sensitivity was 85.8%,specificity was 92.3%.Conclusions The results suggest that the levels of sTREM-1 in serum and EVC are conducive to the early diagnosis of VAP.The levels of sTREM-1 in serum and EVC on Day 7 are helpful for estimating the prognosis.EVC sample is easier to collect than serum.

Objective To explore the most suitable equation in accessing renal function for the elderly type 2 diabetic patients, and its clinical utility in combination with hypersensitive C-reactive protein (hsCRP). Methods The new Cystatin C-based equations for estimated glomerular filtration rate (Cys-eGFR) and conventional predictive equations were compared with isotopic GFR (iGFR) by linear regression analysis, paired t-test, Bland and Altman procedures and non-parametric receiver operating characteristic (ROC) curves. The new Cys-eGFR equation and hsCRP were also incorporated for detecting renal disease in this population. Results The new Cys-eGFR equation had a better relativity with iGFR (r= 0.767, P＜0.001), a less bias (bias: 0.0007, P＞0.05), a higher conformance (2SD: 21.56), higher sensitivity (90.7%) and specificity (88.6%) for diagnosing moderate decrease in renal function. There was a negative relationship between the new Cys-eGFR and hsCRP (r=-0.655, P＜0.01). When the new Cys-eGFR was 67.06 ml· min-1 ·1.73 m-2 and hsCRP was 5.65 mg/L, the combination of Cys-eGFR and hsCRP was better than the combination of serum creatinine and urine albumin/creatinine ratio in screening stage 3 chronic kidney disease (95%vs.46%). Conclusions The combination of new Cys-eGFR equation and hsCRP may screen an early decrease of moderate GFR.