Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective To evaluate the effectiveness of screening-intervention management program for high risk population of stroke in community.Methods Participants aged≥60 years old in Tairi Community,Fengxian District,Shanghai from May 2019 to July 2022 were selected as screening and intervention objects.The first round of stroke high-risk group screening was conducted in 2019 and 2020 in two years respectively,and the second round of stroke high-risk group screening(re-screening)was conducted in 2021 and 2022 respectively for the 2019 and 2020 screening groups,and the groups who had received stroke high-risk screening in both rounds of screening(overlapping groups)were selected as the observation objects of this study.The cerebrovascular function score was used to screen the high-risk individuals of stroke,75-100 was classified as non-high-risk,＜75 were classified as high risk,among which 50-74,25-49,0-24 were light,medium and severe risk,in turn.Baseline and follow-up data were collected for all screening groups,including systolic blood pressure,diastolic blood pressure,overweight or obesity,fasting blood glucose,glycated hemoglobin,triglyceride,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,and blood uric acid.After the completion of screening,the test report interpretation and first diagnosis intervention were carried out on the screening site,and the screening results were recorded into the health examination file.The first intervention includes lifestyle intervention,risk factor intervention and therapeutic intervention for high-risk individuals.Lifestyle intervention and risk factor intervention were conducted through the distribution of popular science handbook for stroke prevention and individualized face-to-face guidance.Therapeutic intervention for high-risk individuals was guided by anti-platelet aggregation drug therapy,statin therapy,and further examination and treatment of cerebral vessels according to stroke risk assessment results and the incidence of related chronic diseases.Prior to the implementation of the project,the incidence of stroke in the community in 2018 was retrospectively investigated to compare annual changes in stroke screening-intervention.In the process of implementation of intervention management,stroke incidence monitoring of the whole community registered population was carried out,and the monitoring method was to conduct stroke incidence registration once a year,and cooperate with the disease control and community police station to obtain the community stroke incidence monitoring data and death registration information provided by the police station from 2018 to 2022.Results A total of 5 188 subjects who completed both the initial screening and the follow-up screening and met the inclusion and exclusion criteria were identified,of whom 2 269 were male and 2 923 were female.The age of participants ranged from 60 to 93 years at the time of the first round of screening,with a mean age of(68±6)years.The proportions of subjects in the age groups of 60-64,65-69,70-74,and≥75 years were 30.3％,34.7％,21.1％,and 14.0％,respectively.(1)After screening and intervention,the proportion of individuals with increased systolic blood pressure,diastolic blood pressure,fasting blood glucose,triglyceride,and low-density lipoprotein cholesterol all decreased(respectively 49.4％vs.57.3％,26.6％vs.28.7％,9.6％vs.10.9％,14.7％vs.17.0％,2.4％vs.3.3％;all P＜0.05),but the proportion of individuals with hyperuricemia increased(15.8％vs.13.1％,P＜0.01),with statistically significant differences.(2)Before the implementation of the screening-intervention program in 2018,the stroke incidence rate in the community was 332.1/100 000.The stroke incidence rates in the community during the period from 2019 to 2022 after the implementation of the screening-intervention program were 335.0/100 000,270.8/100 000,235.0/100 000,and 193.6/100 000,respectively.The incidence rates of ischemic stroke(x2trend=8.350,P=0.004)and stroke(x2trend=9.910,P=0.002)decreased during the period from 2019 to 2022,while the incidence rate of hemorrhagic stroke did not show a decreasing trend(x2trend=1.636,P=0.201).(3)The median baseline and follow-up cerebrovascular function scores for the 5 188 elderly individuals undergoing residual stroke risk screening were 82.50(52.50,98.75)and 88.5(59.00,100.00),respectively,with stroke risk rates of 39.8％and 35.6％before and after intervention,respectively.After intervention,the follow-up cerebrovascular function scores increased compared to the baseline,and the stroke risk rate decreased.The distribution of stroke risk levels before and after screening-intervention had statistically significant differences(P＜0.01).Conclusion Implementing a stroke high-risk population screening-intervention management program for the elderly in the community,combined with health examinations and family doctor team services,can significantly reduce the incidence,high-risk rate,and exposure level of risk factors for stroke in the community.

Objective:To explore the effect of heterozygous deletion of histone methyltransferase Kmt2c gene on the hematological system of mice.Methods:CRISPR/Cas9 technology was used to construct mice model of Kmt2c heterozygous deletion(Kmt2c+/-)and the changes of whole blood cell count in mice were continuously monitored by blood routine test.The clonal expansion ability of bone marrow cells was explored by colony formation assay in vitro and the proportion of primitive hematopoietic cells,including long-term hematopoietic stem cell(LT-HSC),short-term hematopoietic stem cell(ST-HSC),and multipotent progenitor cell in mutant mice was analyzed by flow cytometry.Results:Kmt2c+/-mice model was successfully constructed,and the mRNA expression level of Kmt2c was 28％of that of C57BL/6J mice.The colony formation ability of bone marrow cells of Kmt2c+/-mice in vitro increased with the passage times,and the colony number in the fourth generation was significantly higher than that of control group(P＜0.05).The proportions of LT-HSC and ST-HSC in the primitive hematopoietic cell population of Kmt2c+/-mice was 19.6％±3.3％and 28.9％±4.9％,respectively,which showed an increasing trend compared with 16.9％±2.6％and 18.9％±2.5％in control group,but the difference was not statistically significant(P＞0.05).The white blood cell count of Kmt2c+/-mice gradually increased after 12 weeks of monitoring and reached(9.8±1.0)×109/L at the 14th week,which was significantly higher than(7.3±1.4)× 109/L of control group(P＜0.05).Conclusion:The bone marrow cells of Kmt2c+/-mice have potential of clonal expansion.

Objectives:To compare the diagnostic efficacy of non-ST-segment elevation myocardial infarction (NSTEMI) and the predictive value for major adverse cardiovascular events (MACE) of the 0/3-hour algorithm for high-sensitivity cardiac troponin (hs-cTn) recommended by the 2015 European Society of Cardiology (ESC) guidelines for the management of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the 2021 "Chinese Expert Consensus on Laboratory Testing and Clinical Application of Cardiac Troponin" in suspected acute coronary syndrome (ACS) patients in the Chinese population. Methods:This is a multicenter prospective observational study,including 1527 patients with suspected ACS from three clinical centers from January 2017 to September 2020.Plasma hs-cTnI levels were measured using the ARCHITECT assay at the time of presentation and 3 hours later in patients with suspected ACS (test determination).Clinical judgment (independent clinical judgment by cardiac experts,independent of the test results) was used as the gold standard to compare the sensitivity,specificity,and consistency of the two diagnostic algorithms,and to analyze their predictive value for MACE at 30 days and 180 days.MACE in this study was defined as a composite event of cardiovascular death,myocardial infarction,and unplanned coronary revascularization. Results:According to clinical judgment,there were 400 patients with NSTEMI and 1127 patients without NSTEMI.The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus showed higher sensitivity in diagnosing NSTEMI than the 2015 ESC guidelines (91.50％[95％ CI:88.32％-94.04％]vs.87.75％[95％ CI:84.13％-90.80％]),but slightly lower specificity (93.88％[95％ CI:92.32％-95.21％]vs.95.56％[95％ CI:94.19％-96.69％]),with both differences being statistically significant (both P<0.001).In the follow-up at 30 days and 180 days,the incidence of MACE in patients diagnosed with NSTEMI by both algorithms was higher than in those without NSTEMI (P<0.001).The incidence of MACE at 30 days and 180 days for the group excluded from the diagnosis of NSTEMI by 2015 ESC guidelines was 0.19％ and 1.120％,respectively,and for the NSTEMI group was 2.89％ and 3.68％,respectively;for the group excluded from NSTEMI by the 2021 Chinese Expert Consensus,the incidence was 0.096％ and 0.770％,respectively,and for the NSTEMI group was 2.91％ and 4.36％,respectively.Cox analysis showed that the HR ratio for MACE at 180 days in the NSTEMI group diagnosed by both algorithms was 3.418 and 5.892,respectively,significantly higher than the group excluded from NSTEMI. Conclusions:The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus has superior diagnostic sensitivity compared to the 2015 ESC NSTE-ACS guidelines,at the cost of slightly lower specificity.Both algorithms can effectively predict MACE within 180 days,but based on the data from this study,the algorithm recommended by the 2021 Chinese Expert Consensus is more sensitive in predicting the risk of MACE,and patients excluded from the diagnosis of NSTEMI by this method have a lower incidence of MACE,suggesting that its application in clinical practice may be more helpful in terms of long-term safe management of patients.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.