This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

OBJECTIVE To investigate the mechanism of cordycepin in delaying the transformation from acute kidney injury （AKI） to chronic kidney disease （CKD） （short for “AKI-CKD”）. METHODS Network pharmacology and bioinformatics were used to analyze and predict the signaling pathways of cordycepin in delaying AKI-CKD progression and its relationship with the ferroptosis pathway. Cell experiments were performed to verify the predicted results. Human renal tubular epithelial HK-2 cells were divided into blank group， cordycepin group， model group， and H 2 O 2 +cordycepin group. Except for the blank group and cordycepin group， all other groups were treated with 150 μmol/L H 2 O 2 for 72 h to induce persistent oxidative stress injury in cells. After 72 h of cordycepin （40 μmol/L） intervention， the protein and mRNA expression levels of glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4），nuclear factor-erythroid 2-related factor 2（Nrf2）， and heme oxygenase-1 （HO-1） in cells were detected. Furthermore， the Nrf2 inhibitor ML385 was added on the basis of H 2 O 2 +cordycepin to verify the role of the Nrf2/HO-1 pathway. RESULTS Network pharmacology and bioinformatics analysis showed that there were 42 overlapping genes related to AKI-CKD and ferroptosis that interact with cordycepin ferroptosis， among which 38 were annotated as ferroptosis-related genes. HO-1 and Nrf2 might be important targets for cordycepin to inhibit ferroptosis. The binding energies of cordycepin with Nrf2 and HO-1 proteins were －8.5 and －6.7 kcal/mol， respectively. Cell experiments showed that compared with the model group， the protein and mRNA expression levels of GPX4， Nrf2 and HO-1 were significantly increased （ P ＜0.05），while the protein and mRNA expression levels of ACSL4 were significantly decrease d （ P ＜0.05） in the H 2 O 2 +cordycepin group. After the addition of the Nrf2 inhibitor ML385， the effects of cordycepin on the above proteins and mRNA were significantly reversed （ P ＜0.05）. CONCLUSIONS Cordycepin can inhibit ferroptosis by activating the Nrf2/HO-1 pathway， reduce persistent oxidative stress injury of renal tubular epithelial cells， and delay the progression of AKI-CKD.

Objective To explore the effect and mechanism of keratin 17(KRT17)on proliferation of human esophageal squamous cell line KYSE-150.Methods The correlation of KRT17 expression with the disease stage and survival of patients with esophageal squamous cell carcinoma was analyzed by GEPIA2 website.Human esophageal squamous cell line KYSE-150 was divided into control group,si-NC group,si-KRT17 group and activator group.Small interfering RNA of si-NC and si-KRT17 were transfected into cells of si-NC group and si-KRT17 group,re-spectively.Cells in the activator group were transfected with si-KRT17 and treated with 740 Y-P(PI3K/AKT/mTOR pathway activator)with a final concentration of 30 μmol/L in the medium.The cell proliferation was detec-ted by CCK-8 assay.The clonal formation was detected by clonal formation experiment.The apoptosis was detected by TUNEL staining.The cell cycle was detected by flow cytometry.The cell migration and invasion were detected by Transwell assay.The contents of glucose,lactic acid and pyruvate in cell supernatant were detected by commercially available kits.The expression of KRT17 mRNA was detected by qRT-PCR.And the expression of KRT17,GLUT1,PDK1 and LDHA,p-PI3K,PI3K,p-AKT,AKT,p-mTOR and mTOR protein were detected by Western blot.Results The expression level of KRT17 in esophageal squamous cell carcinoma tissues was significantly higher than that in normal tissues(P＜0.05).There was a statistically significant correlation between the expression level of KRT17 and the stage of esophageal squamous cell carcinoma(P＜0.05).The survival prognosis of patients with low KRT17 expression was better than that of patients with high KRT17 expression(P＜0.05).Compared with control group or si-NC group,the mRNA and protein expression of KRT17 in si-KRT17 group were decreased(P＜0.05),and the cell proliferation activity,number of clone formation,migration and invasion cells were de-creased(P＜0.05).And the lactic acid content,protein expression levels of GLUT1,PDK1 and LDHA were de-creased(P＜0.05),values of p-PI3K/PI3K,p-Akt/AKT and p-mTOR/mTOR were decreased(P＜0.05).The proportion of cells in G0/G1 phase,TUNEL positive rate,and contents of glucose and pyruvate were increased(P＜0.05).Compared with si-KRT17 group,the mRNA and protein expression levels of KRT17 in activator group were increased(P＜0.05),and the cell proliferation activity,number of clone formation,migration and in-vasion cells were increased(P＜0.05).And the lactic acid content,protein expression levels of GLUT1,PDK1 and LDHA were increased(P＜0.05),the values of p-PI3K/PI3K,p-Akt/AKT and p-mTOR/mTOR were in-creased(P＜0.05).The proportion of cells in G0/G1 phase,TUNEL positive rate,and contents of glucose and pyruvate were decreased(P＜0.05).Conclusions KRT17 is highly expressed in esophageal squamous cell car-cinoma tissues and cells.Silencing KRT17 inhibits proliferation,migration and invasion of human esophageal squamous cell line KYSE-150,and promotes apoptosis and cell cycle arrest.

Objective To investigate the effect of growth differentiation factor 15(GDF15)on apoptosis and insulin secretion of MIN6 cells under high glucose conditions.Methods The mouse pancreatic islet β cell line(MIN6 cells)were divided into four groups:NG group,NG+rGDF15 group,HG group,and HG+rGDF15 group.The cell morphology among groups were observed,the apoptosis rate,the protein expression levels of Bcl-2 and Bax and the insulin level was detected.Results HG group exhibited significant cellular damage,characterized by upregulated apoptosis-promoting protein Bax and downregulated apoptosis-suppressing protein Bcl-2 expression,accompanied by a marked increase in apoptosis rate and a substantial decrease in insulin secretion(P＜0.01).Administration of recombinant GDF15 protein improved MIN6 cell morphology,significantly reduced Bax protein relative expression,elevated Bcl-2 protein relative expression,markedly decreased apoptosis rate,and enhanced insulin secretion(P＜0.01).Conclusion GDF15 can mitigate high glucose-induced MIN6 cell damage.

BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Objective To develop a Treatment Burden Scale for patients with chronic heart failure(CHF)and evaluate its reliability and validity,aiming to provide an effective tool for assessing treatment burden levels in this population.Methods According to Cumulative Complexity Model,the study was conducted in 2 phases.A preliminary item pool was established through literature review and semi-structured interviews,from August 2022 to March 2023,followed by expert consultation to finalize the initial scale.A convenience sample of CHF patients from 4 tertiary A hospitals in Hunan and Hubei provinces was conducted to refine scale items and assess psychometric properties,from June 2023 to April 2024.Results The final scale contained 26 items.Exploratory factor analysis revealed 6 domains,including family financial support burden,healthcare utilization burden,the challenges patients face in acquiring knowledge about proper medication use and water/sodium dietary management,the behavioral burden associated with tracking daily water/sodium intake and symptom patterns,psychological burden,and medication management burden,cumulatively explaining 68.661％of variance.Confirmatory factor analysis demonstrated satisfactory model fit;the x2/df was 2.076;the root mean square error of approximation was 0.070;the normed fit index was 0.912;the content validity score was 0.974.The total Cronbach's α coefficient of the scale was 0.903;the split-half reliability was 0.785;the test-retest reliability was 0.936.Conclusion The Treatment Burden Scale for CHF patients developed in this study has good reliability and validity psychometric properties,and it can be used to evaluate treatment burden levels and influencing factors in clinical practice.

Objective To evaluate the safety and efficacy of transcatheter mitral valve-in-valve replacement(ViV-TMVR)in the treatment of bioprosthetic mitral valve failure.Methods Seventeen patients with bioprosthetic mitral valve failure who required ViV-TMVR were selected.Preoperative data including age,gender,body mass index(BMI),usage time of bioprosthetic mitral valve,comorbidities(hypertension,coronary heart disease,old cerebral infarction,atrial fibrillation and diabetes)and New York Heart Association(NYHA)functional class were recorded,and left ventricular end-diastolic diameter(LVEDD),right atrial diameter(RA),pulmonary artery systolic pressure(PASP),left ventricular ejection fraction(LVEF),type of bioprosthetic mitral valve failure,degree of bioprosthetic mitral valve regurgitation and stenosis,peak velocity and mean transvalvular pressure gradient of the bioprosthetic mitral valve,and Society of Thoracic Surgeons(STS)score were also collected.Intraoperative data included puncture route,valve type,intraoperative complications,operation time and immediate postoperative transesophageal echocardiography(TEE)assessment(peak velocity and mean transvalvular pressure gradient of the valve-in-valve,valve-in-valve regurgitation or paravalvular regurgitation)were collected.Postoperative data included time in the intensive care unit(ICU)/cardiovascular intensive care unit(CCU),total postoperative hospital stay and 30-day postoperative echocardiographic results and NYHA functional class were recorded.Patients were divided into the domestic NewMed valve group(10 cases)and the imported Edwards valve group(7 cases)based on the type of valve used.The safety and efficacy of ViV-TMVR were analyzed,and the efficacy of domestic valves and imported valves was compared.Results All 17 patients successfully underwent ViV-TMVR via the transseptal approach without serious complications,and the 30-day readmission rate was 0%.There were no significant differences in operation time of domestic valves and imported valves,mild paravalvular regurgitation of the valve-in-valve,peak velocity and mean transvalvular pressure gradient of the valve-in-valve immediately after surgery and at 30-day postoperatively,time in ICU/CCU,total postoperative hospital stay and the proportion of patients with NYHA functional class Ⅲ-Ⅳ at 30-day postoperatively between the domestic valve group and the imported valve group.During the 30-day follow-up,one patient died of cerebral hemorrhage,and one patient had major adverse cardiovascular events(MACE,cerebral hemorrhage).Compared with before the operation,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve,LVEF,and PASP decreased immediately after surgery and at 30 days after surgery.Compared with immediately after surgery,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve increased at 30 days postoperatively(P＜0.01),while there were no significant differences in LVEF and PASP.Conclusion Transseptal ViV-TMVR is safe and effective in the short term for patients with bioprosthetic mitral valve failure who are at high risk of re-thoracotomy,and the efficacy of domestic valves is comparable to that of imported valves.

Objective To explore the effectiveness of the OKR method in improving the efficiency of the whole process of critical value management,and to provide new ideas for the implementation of medical quality improvement in other medical insti-tutions.Methods A hospital in Tianjin was selected as the study object,which used the OKR method to reform the management of critical value since January 2024.The core goal of"improving the effectiveness of critical value management"was set,and the goal was broken down into quantitative key results such as"the rate of receiving the critical value system is over 95％"and"the rate of completing the standardised writing of medical records is up to 85％".Results After the reform,several quantitative key results,such as the completion rate of critical care medical record writing,the rate of standardised medical record writing,and the rate of overtime acceptance,were all better than before.Conclusion Through the OKR method to unify the whole hospital's strategic objectives,and the dynamic adjustment of the program based on data review,the hospital's critical value management efficiency has been significantly improved,effectively guaranteeing the safety of patients,and providing new perspectives and methods for the management of critical value in other medical institutions.