Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective To investigate the effects and mechanism of Linggui Qihua Prescription against myocardial inflammation and fibrosis in heart failure with preserved ejection fraction(HFpEF).Methods Totally 40 spontaneously hypertensive rats(SHR)were equally divided into model group,Entresto group(18 mg/kg)and Linggui Qihua Prescription low-and high-dosage groups(3.87,7.74 g/kg),the HFpEF model was induced using a 16-week high fat-salt-sugar diet and 8-week streptozotocin intraperitoneal injection.Ten WKY rats(WKY group)and 10 SHR(SHR group)served as control.After successful modeling,the groups were subjected to a 6-week corresponding intervention.Left ventricular end diastolic diameter(LVEDD),left ventricular end-diastolic volume(LVEDV),relative ventricular wall thickness(RWT),left ventricular fractional shortening(LVFS),isovolumic relaxation time(IVRT),mitral annular early and late diastolic velocities of motion(e? and a?),global longitudinal strain(GLS)and global longitudinal strain rate(GLSr)were measured by echocardiography;serum tumor necrosis factor-α(TNF-α)and soluble growth stimulation expressed gene 2 protein(sST2)contents were detected by ELISA;the morphology of myocardial tissue was observed by HE staining;myocardial fibrosis was assessed by Masson staining;the mRNA and protein expressions of myocardial tissue vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),growth differentiation factor-15(GDF-15)and sST2 were detected by qPCR and Western blot.Results Compared with the WKY group and SHR group,the model group exhibited significant increase in LVEDV,RWT,IVRT,along with significant decrease in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly increased(P<0.01);there was pronounced myocardial inflammatory infiltration and collagen fiber deposition,while the mRNA and protein expression of VCAM-1,ICAM-1,GDF-15 and sST2 significantly increased(P<0.05,P<0.01).Compared with the model group,Entresto group and Linggui Qihua Prescription low-and high-dosage groups demonstrated significant decrease in LVEDV,RWT,IVRT,along with significant increases in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly decreased(P<0.01);myocardial inflammatory infiltration and collagen fiber deposition were reduced,the mRNA and protein expressions of ICAM-1,GDF-15 and sST2 decreased in Linggui Qihua Prescription high-dosage group(P<0.01).Conclusion Linggui Qihua Prescription may inhibit chronic inflammation and fibrosis of the myocardium in HFpEF rats by regulating the expressions of ICAM-1,VCAM-1,GDF-15 and sST2,improving cardiac remodeling and functional impairment.

Objective To investigate the efficacy and safety of Linggui Qihua No.2 Prescription(LGQH2)in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 60 HFpEF patients were randomly divided into experimental group and control group according to random number table method,with 30 patients in each group.On the basis of standardized treatment for heart failure,the experimental group was given LGQH2 granules,13 g/time,twice a day,orally;the control group was given placebo granules of LGQH2,with the same administration method as the experimental group.The treatment course for both groups was 4 weeks.6-minute walking distance(6MWD),Kansas City Cardiomyopathy Questionnaire(KCCQ)score,TCM syndrome score and serum NT-proBNP levels.Echocardiography was used to detect the ratio of early diastolic blood flow velocity(E)at the mitral valve to early diastolic myocardial motion velocity(e')at the mitral annulus,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and interventricular septal thickness(IVST).Adverse reactions and events were also recorded.Results Compared with before treatment,both groups showed significant improvement in 6MWD,KCCQ score,TCM syndrome score,serum NT proBNP,and E/e'after treatment(P<0.05),and there was no statistical significance in LAD,LVEDD and IVST between the two groups(P>0.05);after treatment,the experimental group showed better improvement in 6MWD,KCCQ score,TCM syndrome score and E/e'compared to the control group(P<0.05).During the research process,neither group of patients experienced any adverse reactions or events.Conclusion LGQH2 Prescription can effectively enhance exercise tolerance and cardiac function of HFpEF patients,alleviate symptoms,improve quality of life,and inhibit diastolic dysfunction of the heart,without notable adverse reactions.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Objective:To establish a quality and safety evaluation index system for the daytime chemotherapy in the Day Medical Management Quality Control Center of Fujian Province, providing references for objectively evaluating the quality of day chemotherapy.Methods:From December 2023 to August 2024, this study screened the initial indexes of the quality and safety evaluation index system for daytime chemotherapy through literature search and expert discussions. An index system and its weights were determined by using two rounds of Delphi method and precedence chart method. The quality of daytime chemotherapy services in 8 hospitals was evaluated by using a thousand point scale checklist based on this index system.Results:The expert motivation of both rounds of Delphi method was 100%, and the expert authority coefficient was 0.92. The quality and safety evaluation index system for daytime chemotherapy included 3 first-level indicators, 13 second-level indicators, and 54 third-level indicators; Among them, the weights of the first-level indicator included structure quality, process quality, and result quality were 0.334, 0.556, and 0.110, respectively. The quality and safety scores of daytime chemotherapy in 8 hospitals ranged from 812 to 980 points, with an average of 933 points.Conclusions:The quality and safety evaluation index system for daytime chemotherapy could objectively and comprehensively evaluate the quality and safety of hospital daytime chemotherapy.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective To investigate the effects and mechanism of Linggui Qihua Prescription against myocardial inflammation and fibrosis in heart failure with preserved ejection fraction(HFpEF).Methods Totally 40 spontaneously hypertensive rats(SHR)were equally divided into model group,Entresto group(18 mg/kg)and Linggui Qihua Prescription low-and high-dosage groups(3.87,7.74 g/kg),the HFpEF model was induced using a 16-week high fat-salt-sugar diet and 8-week streptozotocin intraperitoneal injection.Ten WKY rats(WKY group)and 10 SHR(SHR group)served as control.After successful modeling,the groups were subjected to a 6-week corresponding intervention.Left ventricular end diastolic diameter(LVEDD),left ventricular end-diastolic volume(LVEDV),relative ventricular wall thickness(RWT),left ventricular fractional shortening(LVFS),isovolumic relaxation time(IVRT),mitral annular early and late diastolic velocities of motion(e? and a?),global longitudinal strain(GLS)and global longitudinal strain rate(GLSr)were measured by echocardiography;serum tumor necrosis factor-α(TNF-α)and soluble growth stimulation expressed gene 2 protein(sST2)contents were detected by ELISA;the morphology of myocardial tissue was observed by HE staining;myocardial fibrosis was assessed by Masson staining;the mRNA and protein expressions of myocardial tissue vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),growth differentiation factor-15(GDF-15)and sST2 were detected by qPCR and Western blot.Results Compared with the WKY group and SHR group,the model group exhibited significant increase in LVEDV,RWT,IVRT,along with significant decrease in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly increased(P<0.01);there was pronounced myocardial inflammatory infiltration and collagen fiber deposition,while the mRNA and protein expression of VCAM-1,ICAM-1,GDF-15 and sST2 significantly increased(P<0.05,P<0.01).Compared with the model group,Entresto group and Linggui Qihua Prescription low-and high-dosage groups demonstrated significant decrease in LVEDV,RWT,IVRT,along with significant increases in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly decreased(P<0.01);myocardial inflammatory infiltration and collagen fiber deposition were reduced,the mRNA and protein expressions of ICAM-1,GDF-15 and sST2 decreased in Linggui Qihua Prescription high-dosage group(P<0.01).Conclusion Linggui Qihua Prescription may inhibit chronic inflammation and fibrosis of the myocardium in HFpEF rats by regulating the expressions of ICAM-1,VCAM-1,GDF-15 and sST2,improving cardiac remodeling and functional impairment.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.