OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus （T2DM） patients led by clinical pharmacists. METHODS Based on literature research， a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process （AHP） method was used to determine the weight values of items at all levels， and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%， respectively， and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084， respectively， and the P values from the χ 2 tests were all less than 0.05； the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items （pharmacy service pathway for T2DM patients during hospitalization， pharmacy management pathway for hypoglycemia in T2DM inpatients， and the pharmacy follow-up pathway for T2DM discharged patients， with weights of 0.098， 0.568 and 0.334， respectively）， twelve secondary-level items （e.g. pharmaceutical care during hospitalization for 1 to 2 days， admission assessment and education， with weights ranging from 0.143 to 0.333） and thirty-seven tertiary-level items （e.g. assessment of medication compliance， verification of the medication plan for discharge， with weights ranging from 0.068 to 0.750）. Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762， 0.879， 0.928 and 0.951， respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808， respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully， demonstrating high scientificity and reliability.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 （T2DM） and long-term weight management， and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase， PubMed， the Cochrane Library， CNKI and health technology assessment （HTA） official website from their inception to October 1st 2024 to collect HTA report， systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation， descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included， including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies， and no HTA report was retrieved. In terms of efficacy， most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 （GLP-1） receptor agonists in reducing glycosylated hemoglobin， body weight， and waist circumference （P＜0.05）. In terms of safety， compared with other GLP-1 receptor agonists， tirzepatide did not increase the incidence of gastrointestinal-related adverse events （AE）， the incidence of AE of grade ≥3， or the incidence of severe hypoglycemia （P＞0.05）. However， tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions （P＜ 0.05）. In terms of cost-effectiveness， based on the background of foreign pharmacoeconomic studies， tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However， when using the 15 mg dose of tirzepatide， close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results， tirzepatide exhibits economic advantages.

Objective:To preliminarily establish a sample clot warning model for coagulation screening tests using 5 machine learning methods.Methods:This cross-sectional study collected 7 401 routine screening test samples from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, from January 1st, 2015, to August 18th, 2024, including 4 786 clotted (positive) and 2 615 qualified (negative) samples for model development. The dataset was divided into Dataset 1 and Dataset 2 based on a reagent change for APTT in December 2018, with separate models developed for each. An additional 2 493 samples (October 31st to November 8th, 2024) were used to evaluate consistency between the model and manual assessment, while 23 200 samples (October 17th to December 31st, 2024) were used for assessing real-world predictive performance. Five machine learning algorithms were employed to develop the clot prediction model: logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), naive bayes (NB), and artificial neural network (ANN), with the ANN model constructed using two different hidden layer and neuron parameter settings. Model selection was based on AUC, accuracy, sensitivity, specificity, F1-score, PPV, and NPV, with the optimal model integrated into the LIS for validation.Results:Among the six models using 5 machine learning algorithms, XGBoost demonstrated the highest performance (AUC=0.961, sensitivity=0.945, F1-score=0.934) and robustness to reagent changes ( Z=-1.333, P=0.113). When deployed, the differences between the model's predictions and manual pre-judgment were statistically significant ( Z=-5.289 to 8.933, all P<0.01). The predictive efficacy indices AUC (95% CI), sensitivity, specificity, and accuracy of the XGBoost model deployed in real-world operation of the LIS were 0.939 (0.918—0.960), 0.958, 0.921, and 0.921 respectively. Conclusion:In this study, a clot warning model for coagulation screening samples was established based on the XGBoost algorithm, and its prediction efficacy is good, providing a foundation for intelligent pre-analytical quality control for coagulation screening tests.

Objective:To preliminarily establish a sample clot warning model for coagulation screening tests using 5 machine learning methods.Methods:This cross-sectional study collected 7 401 routine screening test samples from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, from January 1st, 2015, to August 18th, 2024, including 4 786 clotted (positive) and 2 615 qualified (negative) samples for model development. The dataset was divided into Dataset 1 and Dataset 2 based on a reagent change for APTT in December 2018, with separate models developed for each. An additional 2 493 samples (October 31st to November 8th, 2024) were used to evaluate consistency between the model and manual assessment, while 23 200 samples (October 17th to December 31st, 2024) were used for assessing real-world predictive performance. Five machine learning algorithms were employed to develop the clot prediction model: logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), naive bayes (NB), and artificial neural network (ANN), with the ANN model constructed using two different hidden layer and neuron parameter settings. Model selection was based on AUC, accuracy, sensitivity, specificity, F1-score, PPV, and NPV, with the optimal model integrated into the LIS for validation.Results:Among the six models using 5 machine learning algorithms, XGBoost demonstrated the highest performance (AUC=0.961, sensitivity=0.945, F1-score=0.934) and robustness to reagent changes ( Z=-1.333, P=0.113). When deployed, the differences between the model's predictions and manual pre-judgment were statistically significant ( Z=-5.289 to 8.933, all P<0.01). The predictive efficacy indices AUC (95% CI), sensitivity, specificity, and accuracy of the XGBoost model deployed in real-world operation of the LIS were 0.939 (0.918—0.960), 0.958, 0.921, and 0.921 respectively. Conclusion:In this study, a clot warning model for coagulation screening samples was established based on the XGBoost algorithm, and its prediction efficacy is good, providing a foundation for intelligent pre-analytical quality control for coagulation screening tests.

OBJECTIVE To identify and analyze adverse drug event(ADE)signals associated with tirzepatide based on the FDA Adverse Event Reporting System(FAERS)database,providing a reference for clinical medication safety.METHODS ADE reports from January 1,2022,to June 30,2024,with tirzepatide as the primary suspected drug,were extracted from the FAERS database.Medical Dictionary for Regulatory Activities was used to systematically categorize the selected system organ class(SOC)and preferred term of ADE.Signal mining and analysis were performed using the reporting odds ratio method and the proportional reporting ratio method.RESULTS A total of 39 229 ADE reports related to tirzepatide were obtained,including 3 934 severe ADE reports(10.03%).The majority of severe ADE reports were related to hospitalization or prolonged hospitalization(3.82%),involving 131 positive ADE signals.Among the reports with documented patient gender and age,26 195 were female(66.77%),7 869 were male(20.06%),and the majority of patients were aged 18-64 years(54.26%).The top three most frequently reported ADE were injection site pain,nausea,and injection site hemorrhage.Strong ADE signals not mentioned in the tirzepatide instruction included injection site coldness,starvation ketoacidosis,injection site hemorrhage,hunger,elevated adrenaline,injection site skin cracking,binge eating,skin laxity,intestinal sepsis,lack of satiety,and dysesthesia.Subgroup analysis for patient's gender and age showed differences in the proportion of ADE reports across different SOC.Male patients or those aged≥65 years had a higher risk of gastrointestinal system disorders compared to female patients or those aged＜65 years.CONCLUSIONS In clinical use of tirzepatide,in addition to monitoring ADE listed in the instruction,attention should also be paid to ADE not mentioned in the instruction,such as injection site coldness,starvation ketoacidosis,injection site hemorrhage,elevated adrenaline,and intestinal sepsis,to ensure patient safety.

Objective:To observe and analyze the influence of deoxycholic acid (DCA) on intestinal microbiota and bile acid metabolism during the process of enteritis induced by DCA in mice.Methods:Twenty C57BL/6J mice were randomly and equally divided into DCA group and control group. The mice in DCA group were developed by feeding the feed with 0.2% DCA and the mice in control group were developed with routine feed for 24 weeks. The degree of intestinal tissue inflammation was evaluated by HE staining and scored, the change of intestinal microbiota was analyzed by pyrosequencing, bile acid levels of all grades in faeces were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) , the expressions of bile acid-related genes were detected by quantitive real-time PCR.Results:The intestinal histology scores in DCA group was significantly higher than that of the control group (both P<0.05) . The diversity of fecal microbiota in the DCA group was significantly reduced, the percentage of Firmicutes at the phylum level and the percentage of Clostridium XIVa at the genus level were significantly decreased (both P<0.05) . The total bile acid, secondary bile acid, unconjugated bile acid and tauro-α-muricholic acid (T-α-MCA) of mice faeces in DCA group were significant higher than those in control group (all P<0.05) . The expression of biliary acid transporter gene organic solute transporter β ( Ost- β) , farnesoid X receptor ( FXR) and fibroblast growth factor 15 ( FGF15) in DCA group decreased significantly (all P<0.05) , while the expressions of liver bile synthesis rate-limiting enzymes Cyp7a1, Cyp7b1 and Cyp27a1 increased obviously (all P<0.05) . Conclusions:DCA can induce the progress of enteritis, which may be related to its destruction of intestinal microbiota in mice and the promotion of liver bile acid synthesis through FXR-FGF15 signaling pathway.

Objective:To observe and analyze the influence of deoxycholic acid (DCA) on intestinal microbiota and bile acid metabolism during the process of enteritis induced by DCA in mice.Methods:Twenty C57BL/6J mice were randomly and equally divided into DCA group and control group. The mice in DCA group were developed by feeding the feed with 0.2% DCA and the mice in control group were developed with routine feed for 24 weeks. The degree of intestinal tissue inflammation was evaluated by HE staining and scored, the change of intestinal microbiota was analyzed by pyrosequencing, bile acid levels of all grades in faeces were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) , the expressions of bile acid-related genes were detected by quantitive real-time PCR.Results:The intestinal histology scores in DCA group was significantly higher than that of the control group (both P<0.05) . The diversity of fecal microbiota in the DCA group was significantly reduced, the percentage of Firmicutes at the phylum level and the percentage of Clostridium XIVa at the genus level were significantly decreased (both P<0.05) . The total bile acid, secondary bile acid, unconjugated bile acid and tauro-α-muricholic acid (T-α-MCA) of mice faeces in DCA group were significant higher than those in control group (all P<0.05) . The expression of biliary acid transporter gene organic solute transporter β ( Ost- β) , farnesoid X receptor ( FXR) and fibroblast growth factor 15 ( FGF15) in DCA group decreased significantly (all P<0.05) , while the expressions of liver bile synthesis rate-limiting enzymes Cyp7a1, Cyp7b1 and Cyp27a1 increased obviously (all P<0.05) . Conclusions:DCA can induce the progress of enteritis, which may be related to its destruction of intestinal microbiota in mice and the promotion of liver bile acid synthesis through FXR-FGF15 signaling pathway.

Objective To validate the performance of 4 domestic chemiluminescence immunoassay (CLIA) systems on 8 tumor markers quantitative assay kits. Methods Four domestic CLIA systems were randomly marked as A, B, C, D and 8 tumor markers, including carbohydrate antigen (CA)125, CA15-3, CA19-9, ferritin (Fer), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific an-tigen (PSA) and free PSA (fPSA) were determined. According to the standard of Clinical and Laboratory Standards Institute (CLSI), the precision, methodological comparison and analytical measure range of 4 systems were validated. Clinical serum samples were obtained from patients in Suzhou Hospital. According to the CLSI EP9-A3 protocol, imported equipment was used as the reference system. The biases of medical de-cision points were assumed, and Pearson correlation analysis and Spearman correlation analysis were used to analyze the data. Results The precision verification of CA125 and PSA on A, CA125 and AFP on B, CA125, CEA, AFP and PSA on C, and all 8 tumor markers on D could meet the laboratory quality control requirements. The correlations of the test results between A-D and the imported equipment were significant (all P<0.05) with the correlation coefficients 0.79-0.99, 0.47-0.99, 0.90-0.98 and 0.78-1.00, respec-tively, and the number of acceptable tests at the level of medical decision was 5, 2, 5, 4. All tests were certified to meet the analytical measure range validation. Conclusions The detection performance of 4 do-mestic CLIA systems for all 8 tumor markers are different. The performance of domestic CLIA systems should be tested when choosing one that can meet laboratory quality control requirements.

Objective To assess long-term outcomes of coronary artery (CA) Z scores in children with Kawasaki disease (KD) with echocardiography.Methods Echocardiographic data of 100 KD children during 7-14 years interval follow-up were analyzed retrospectively.The children were divided into dilatation group (n =54,CA dilated) and non-dilatation group (n=46,CA not dilated) at the acute phase.Fifty one children were selected simultaneously as the controls (control group).Diameters and Z scores of left main coronary artery (LMCA),left anterior descending (LAD) and proximal right coronary artery (pRCA) were compared,and factors affecting CA diameter during the recovery phase were analyzed.Results CA diameters in dilatation group were larger than those in non-dilatation group and control group (all P＜0.05),whereas no statistical difference of CA diameter was found between non-dilatation group and control group (all P＞0.05).In dilatation group,Z score of LMCA,LAD and pRCA was 0.569 5 ± 1.061 6,0.420 (-0.029,1.078) and 0.640(0.283,1.250),while in non dilatation group,Z score of LMCA,LAD and pRCA was-0.0313±0.8467,-0.0662±0.6612 and 0.1887±0.5935,respectively.In control group,Z score of LMCA,LAD and pRCA was-0.1246±1.0167,-0.2558±1.0848 and 0.1943±0.6101,respectively.Z scores in dilatation group were larger than those in non-dilatation group and control group (all P＜0.05),while no statistical differences of Z scores was found between nondilatation group and control group (all P＞0.05).Dilation degree of CA at the acute phase was the factor affecting longterm CA dilation (odds ratio=39.146,P＜0.001).Conclusion During 7-14 years of follow-up,CA diameters and Z scores kept to increase in KD children with CA dilatation at the acute phase.The dilation degree of CA at the acute phase in KD children affects the long-term CA dilation.

Objective To study the changes and characteristics of TPO -Ab and TG-Ab in type 2 diaetic patients and provide new ideas for the diagnosis of diabetes.Methods From January 2014 to January 2017,160 samples in General Hospital of Taiyuan Iron&Steel (Group) Co.Ltd were selected,80 healthy people and 80 patients with type 2 diabetes,fasting venous 5 mL blood was obtained in the morning ,then electrochemical luminescence method was used to test TPO-Ab and TG-Ab contents.The diabetic patients were divided into four groups :TPO-Ab normal group,TPO-Ab elevation group,TG-Ab normal group,TG-Ab elevation group.The blood glucose,age and gender of the four groups were compared.Results Compared with the control group ,the proportions of increased TPO -Ab and TG-Ab in diabetic patients were 11.25%and 2.5%respectively,the difference was statistically significant (χ2＝4.86,P＜0.05).In type 2 diabetic patients,the blood glucose value of the normal TPO -Ab group was (6.67 ± 1.53)mmol/L,which in the TPO -Ab elevation group was (7.87 ±1.24) mmol/L,the difference was statistically significant (t＝2.94,P＜0.05).The blood glucose of the normal TG -Ab group was (6.75 ±1.34)mmol/L,which in the TG-Ab elevation group was (7.04 ±1.25)mmol/L,the difference was statistically significant (t＝2.82,P＜0.05).TPO-Ab and TG-Ab elevation had no obvious relation with age ,gender.The age of the normal TPO -Ab group was (62.1 ±6.3)years,which in the TPO-Ab elevation group was (63.0 ±4.9)years,there was no statisti- cally significant difference (t＝1.37,P＞0.05).The age of the normal TG -Ab group was (62.8 ±7.1)years,which in the TG-Ab elevation group was (61.6 ±2.7)years,the difference was not statistically significant (t＝1.27,P＞0.05).In male patients,TPO-Ab normal accounted for 84.09%,TPO-Ab rise accounted for 15.91%.In female patients,TPO-Ab normal accounted for 86.11%,TPO-Ab rise accounted for 13.89%,there was no statistically significant difference (χ2＝1.20,P＞0.05).In male patients,TG-Ab normal accounted for 97.73%,TG-Ab rise accounted for 2.27%, in female patients, TG -Ab normal accounted for 97.22%, TG -Ab rise accounted for 2.78%,there was no statistically significant difference (χ2＝0.97,P＞0.05).Conclusion TPO-Ab and TG-Ab in type 2 diabetes patients are higher than healthy people.The increase of TPO -Ab and TG -Ab is positively correlated with blood glucose level.The increase of TPO-Ab and TG-Ab is not correlated with age and gender.