OBJECTIVE To evaluate the clinical comprehensive value of four Chinese patent medicines （Xuezhikang， Zhibitai， Zhibituo， Jiangzhiling） in the treatment of hyperlipidemia， and provide a reference for rational clinical drug use. METHODS A clinical comprehensive evaluation index system was established in accordance with the Evidence and Value： Impact on Decision-Making （EVIDEM） framework and Technical Guideline for Clinical Comprehensive Evaluation of Cardiovascular Drugs （2022 edition， trial implementation）. CNKI， Wanfang data， VIP， PubMed， ScienceDirect， Embase and official websites were retrieved to collect the literature such as drug instructions， guidelines and consensus statements， and systematic reviews/meta-analyses for the four Chinese patent medicines. A comprehensive evaluation was conducted from seven dimensions： effectiveness， safety， economy， suitability， accessibility， innovation and characteristics of traditional Chinese medicine. RESULTS This evaluation index system included 7 first-level indicators， 15 second-level indicators and 30 third-level indicators. Xuezhikang achieved the highest comprehensive evaluation score of 81.4 points， and was classified as class Ⅰ recommendation. Zhibitai with 76.0 points and Zhibituo with 60.9 points were both classified as class Ⅱ recommendation. Jiangzhiling with 48.8 points was classified as class Ⅳ recommendation. CONCLUSIONS Xuezhikang demonstrates the optimal clinical comprehensive value for treating hyperlipidemia. Zhibitai exhibits certain advantages in terms of safety and characteristics of traditional Chinese medicine； Zhibituo shows a moderate performance in all aspects； Jiangzhiling has a relatively low score. Appropriate medicines can be selected clinically according to actual conditions and patients’ characteristics.

BACKGROUND: China has made significant progress in medical accessibility and quality over the past decades, and quality improvements in gastroenterology and digestive endoscopy have been consistent. The study aimed to describe the status quo of gastroenterology and digestive endoscopy in the Chinese mainland based on the data from the National Clinical Improvement System (NCIS) and the Hospital Quality Monitoring System (HQMS). METHODS: Data were extracted from the NCIS and the HQMS. Data analysis included general information from the Department of Gastroenterology and Endoscopy centers, management of inpatients and outpatients, and annual volume and quality indicators of digestive endoscopy. Acute pancreatitis, gastrointestinal bleeding, inflammatory bowel disease, and cirrhosis were identified as priority diseases and were subjected to detailed analysis. RESULTS: Data from 4620 and 7074 hospitals were extracted from the NCIS and HQMS, respectively. In 2023, 9.6 gastroenterologists, 6.7 endoscopists, and 37.3 gastroenterology beds per hospital nationwide were observed, achieving 19,252.4 outpatient visits, 1615.2 hospitalizations (97.0 for acute pancreatitis, 146.1 for gastrointestinal bleeding, 40.2 for inflammatory bowel disease, and 111.4 for cirrhosis), and 9432.7 digestive endoscopic procedures per hospital. Overall, the quality of practice improved significantly. The proportion of early cancer among gastrointestinal cancers increased from 11.1% in 2015 to 23.4% in 2023, and the adenoma detection rate during colonoscopy increased from 19.3% in 2019 to 26.9% in 2023. Regarding priority diseases, hospitalizations increased, and 31-day unplanned readmission rates decreased between 2019 and 2023. The median hospitalization costs and median proportion of medication costs decreased for acute pancreatitis, gastrointestinal bleeding, and cirrhosis. However, it increased for inflammatory bowel disease. CONCLUSION This report evaluates the status quo and development of gastroenterology and digestive endoscopy in the Chinese mainland, providing guidance for future quality improvements.
Humans ; China ; Gastroenterology/statistics & numerical data* ; Gastrointestinal Hemorrhage ; Endoscopy, Gastrointestinal/statistics & numerical data* ; Endoscopy, Digestive System/statistics & numerical data*

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective To analyze the influence of clinical indicators and PPARD gene polymorphism on the hypoglycemic efficacy of dapagliflozin(DAPA)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 102 patients with T2DM who visited the Affiliated Hospital of Jiangnan University and the Affiliated Hospital of Xuzhou Medical University from June 2021 to December 2023 were selected as the study subjects,an observational cohort of T2DM patients treated with DAPA was established,and DAPA tablets of 10 mg were administered orally once a day for 12 weeks,the venous blood and clinical data of the patients were col-lected.PPARD gene polymorphism typing was performed by using the Snapshot method.The differences in clinical indicators among patients with different genotypes were compared and the influencing factors of DA-PA in improving insulin resistance index(HOMA-IR)were analyzed.Results Eighty-two patients completed the 12-week follow-up.Before DAPA treatment,the differences in the clinical indicators of patients with dif-ferent PPARD rs3777744 genotypes were not statistically significant(P＞0.05).After 12 weeks of DAPA treatment,compared with patients with AA genotype,patients carried of G allele(GG+AG genotype)had lower levels of fasting blood glucose(FPG),HOMA-IR and its decrease,and the differences were statistically significant(P＜0.05).The results of multiple linear regression analysis showed that the genotype of PPARD rs3777744 locus and baseline HOMA-IR were correlated with the improvement of HOMA-IR after 12 weeks of DAPA treatment,and the improvement of HOMA-IR in G allele carriers was not as significant as that in AA genotype patients,and the higher the baseline HOMA-IR,the more significant the improvement of HO-MA-IR.Conclusion Different genotypes of PPARD rs3777744,baseline HOMA-IR are important influencing factors for DAPA to improve insulin resistance of T2DM patients.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective To systematically evaluate the efficacy and safety of finerenone in treating the pa-tients with heart failure.Methods The databases of Pubmed,Embase,Cochrane Library,Web of Science and Scopus were retrieved.The retrieval time was from the establishment of the database to April 21,2024.The data of randomized controlled trials(RCTs)on finerenone in treating heart failure were collected.After screening the literatures and extracting the data,the Jadad scale and Cochrane bias risk assessment tool were used to evaluate the quality of included literatures.The RevMan5.4 software was adopted to conduct the meta analysis.Results Five RCTs involving in a total of 2 518 patients with heart failure were finally included.In the aspect of effectiveness outcome indicators,there was no statistical difference in improving NT-proBNP lev-els and cardiovascular mortality risk between finerenone and eplerenone(P＞0.05).Compared with placebo,finerenone could reduce the ris k of first hospitalization due to heart failure(RR=0.68,95％CI:0.49-0.94,P=0.02)and the risk of cardiovascular composite endpoint event(RR=0.79,95％CI:0.64-0.98,P=0.03).In the aspects of safe outcome indicators,the occurrence risk of adverse events of finerenone was slight-ly lower than that of placebo(RR=0.95,95％CI:0.90-1.01),the risk of finerenone induced hyperkalemia was slightly lower than that of eplerenone(RR=0.90,95％CI:0.46-1.76),but the difference was not statis-tically significant(P＞0.05).Finerenone had a higher risk for causing hyperkalemia than placebo(RR=2.07,95％CI:1.46-2.95,P＜0.01).Conclusion Finerenone could reduce the NT-proBNP level,risk of first time HHF and the cardiovascular composite endpoint event,moreover its safe and tolerance are good.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Sodium-glucose linked transporter 2 inhibitors（SGLT2i） are novel oral hypoglycaemic agents and are widely used for hypoglycemic therapy in patients with type 2 diabetes mellitus， but differences in the genetic backgrounds of patients often lead to variable responsiveness to drug therapy. By summarizing the pharmacogenomic studies of SGLT2i， the article found that the genetic variants of UGT1A9， UGT2B4， SLC5A2， ABCB1， PNPLA3 and WFS1 may influence the pharmacokinetics of SGLT2i and the external hypoglycemic effects of SGLT2i in improving non-alcoholic fatty liver disease， weight loss and so on， but there is no clinical evidence that genetic polymorphisms affect the hypoglycemic efficacy of SGLT2i.