Objective: To evaluate the effect of community comprehensive management model intervention among patients with dyslipidemia, so as to provide the reference for optimizing community management strategies and improving the target achievement rate for blood lipids among this population. Methods: From May to June 2023, a multi-stage stratified random sampling method was employed to select patients with dyslipidemia from primary healthcare institutions in Jiaxing City, Zhejiang Province. Eligible participants were randomly assigned to either a control group or an intervention group. The control group received routine management, while the intervention group was subjected to a community comprehensive management model in addition to the routine care. Both groups were followed up for 24 months. Data on demographic characteristics, lifestyle behaviors, physical examination indices, and blood biochemical indicators were collected at baseline and after the intervention through questionnaires, physical examinations, and laboratory tests. Changes in obesity rate, central obesity rate, target achievement rates for blood lipids, blood pressure, and blood glucose, as well as lifestyle modifications, were analyzed. Differences between the two groups before and after the intervention were assessed using generalized estimating equations (GEE). Results: The control group consisted of 560 patients, including 303 females (54.11%) and 430 individuals aged ≥65 years (76.79%). The intervention group also included 560 patients, with 300 females (53.57%) and 431 individuals aged ≥65 years (76.96%). Before the intervention, no statistically significant differences were observed between the two groups in terms of gender, age, educational level, history of chronic diseases, and atherosclerotic cardiovascular disease risk stratification (all P>0.05). After 24 months of intervention, interaction effects between group and time were observed for obesity rate, central obesity rate, target achievement rate for blood lipids, target achievement rate for blood glucose, composite target achievement rate, physical activity rate, and medication adherence (all P<0.05). Specifically, the intervention group demonstrated lower rates of obesity and central obesity, and higher target achievement rate of blood lipids, target achievement rate of blood glucose, composite target achievement rate, physical activity rate, and medication adherence compared to the control group. Conclusion The community comprehensive management model contributed to improvements in multiple metabolic parameters (including body weight, waist circumference, blood lipids, and blood glucose) among patients with dyslipidemia, and was associated with increased physical activity rate and medication adherence.

ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

Objective: To investigate the current status and influencing factors of overweight and obesity among adults in Jiaxing City, Zhejiang Province, so as to provide a basis for developing targeted weight management measures. Methods: In 2024, a multistage stratified random cluster sampling method was employed to recruit permanent residents aged ≥18 years from Jiaxing City for questionnaire surveys. Data on basic information, lifestyle behaviors, and history of chronic diseases were collected. Height and body weight were measured, and overweight and obesity were determined based on body mass index (BMI). The influencing factors of overweight and obesity among adults were analyzed by a multivariable logistic regression model. Results: Totally 10 509 questionnaires were allocated, and 9 802 valid questionnaires were recovered, with an effective recovery rate of 93.27%. Among the respondents, 4 808 (49.05%) were males and 4 994 (50.95%) were females, with a mean age of (51.27±17.26) years. A total of 4 884 overweight and obesity individuals were identified, with a detection rate of 49.83%. Multivariable logistic regression analysis showed that gender (male, OR=1.719, 95%CI: 1.578-1.873), age (≥60 years, OR=0.802, 95%CI: 0.652-0.986), educational level (bachelor and above, OR=0.640, 95%CI: 0.518-0.791), marital status (being married/cohabiting, OR=1.224, 95%CI: 1.009-1.486), adequate nut intake (OR=0.910, 95%CI: 0.832-0.995), hypertension (OR=2.462, 95%CI: 2.219-2.732), and dyslipidemia (OR=1.629, 95%CI: 1.444-1.837) were statistically associated with overweight and obesity among adults. Conclusion The detected rate of overweight and obesity among adults in Jiaxing City was relatively high, and was mainly associated with gender, age, education level, marital status, nut intake, hypertension, and dyslipidemia.

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Objective: To investigate the trend in mortality of injury in Jiaxing City, Zhejiang Province, from 2010 to 2022, so as to provide the evidence for developing injury prevention and intervention strategies. Methods: Data on injury mortality in Jiaxing City from 2010 to 2022 were obtained from the Jiaxing Chronic Disease Monitoring Information Management System. Crude mortality was calculated, and standardized mortality was computed using data of the Sixth National Population Census in 2010. Descriptive analysis of injury mortality and cause of injury death was conducted by gender and age. The average annual percent change (AAPC) was used to analyze the trend in mortality of injury from 2010 to 2022. Results: From 2010 to 2022, the crude injury mortality in Jiaxing City was 79.24/100 000, and the standardized mortality was 47.08/105. The crude injury mortality was higher in males than in females (80.51/100 000 vs. 78.01/100 000, P<0.05). The standardized injury mortality for the total population, males, and females showed significant declining trends (AAPC=-2.011%, -2.373% and -1.542%, all P<0.05). The crude injury mortality increased with age (P<0.05), peaking in the age group of ≥85 years (1 806.46/100 000). Decreasing trends were observed in the age groups of 0-<15 years, 15-<45 years, and 45-<65 years (AAPC=-7.794%, -4.698% and -4.521%, all P<0.05), while no significant trend was found in the age group of ≥65 years. The top five causes of injury death were falls (29.96/100 000), motor vehicle traffic accidents (17.81/100 000), drowning (6.50/100 000), suicide (5.40/100 000), and poisoning (0.69/100 000). Drowning was the leading cause of injury death in the age group of 0-<15 years, while falls were the primary cause in the age group of ≥65 years. Motor vehicle traffic accidents were the top cause of injury death in age groups of 15-<45 years and 45-<65 years. From 2010 to 2022, the standardized mortality of falls showed an upward trend (AAPC=1.094%, P<0.05), while the standardized mortality of motor vehicle traffic accidents, drowning, and suicide demonstrated downward trends (AAPC=-7.576%, -2.745% and -2.786%, all P<0.05). Conclusions The standardized injury mortality in Jiaxing City showed an overall downward trend from 2010 to 2022. Falls were the leading cause of injury death, and particular attention should be paid to the prevention and control of falls among the elderly aged ≥65 years.

Point-of-care testing(POCT)is a new model of medical testing development,which develops rapidly in recent years.POCT has the characteristics of rapid detection,convenient operation,and can be car-ried out at the patient's bedside.It can provide favorable conditions for early diagnosis of patients with critical illnesses in the emergency department and can significantly reduce their consultation time,alleviate the over-crowding of the emergency department,which is appropriate to the needs of the development of emergency medicine.This paper mainly introduces the specific application and research progress of POCT in emergency medicine,analyzes the advantages and challenges of POCT technology,and discusses the new technology and development prospect of POCT.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To evaluate the association between short-term exposure to air pollutants of end-stage renal disease(ESRD)patients on maintenance hemodialysis and the number of daily hospital admissions.Methods The data on hospitalizations were obtained from the database of the municipal Urban Employees'Basic Medical Insurance and Urban Residents'Basic Medical Insurance of a city in Southwest China.Single and multiple pollutant generalized additive models were utilized to estimate the effect of air pollutants(CO,NO2,O3,PM10,PM25,and SO2)on patient admissions after the lag time of different numbers of days.In addition,subgroup analyses stratified by sex,age,PM25 and PM10 concentration thresholds,seasonality,and comorbidity status for cardiovascular diseases and hypertension were conducted.Results In the single pollutant models,the pollutants significantly associated with patient admissions and the corresponding lag time of the strongest association were as follows,every time CO increased by 0.1 mg/m3,there was a 2.39％increase(95％confidence interval[CI]:0.96％-3.83％)in patient admissions after 7 days of lag time;every time NO2,O3,PM2.5,PM10,and SO2 increased by 10 μg/m3,patient admissions increased by 4.02％(95％CI:1.21％-6.91％)after 7 days of lag time,3.57％(95％CI:0.78％-6.44％)after 0-4 days of lag time,2.00％(95％CI:1.07％-2.93％)after 6 days of lag time,1.19％(95％CI:0.51％-1.88％)after 7 days of lag time,and 8.37％(95％CI:3.08％-13.93％)after 7 days of lag time,respectively.In the multiple pollutant model,every time O3 and PM2.5 increased by 10 μg/m3,there was an increase of 3.18％(95％CI:0.34％-6.09％)in daily patient admissions after 0-4 days of lag time and an increase of 1.85％(95％CI:0.44％-3.28％)after 7 days of lag time.Furthermore,subgroup analyses showed that seasonality,the severity of air pollution,and patients'comorbidities might be the effect modifiers for the association between ambient air pollution and hospital admissions in ESRD patients receiving maintenance hemodialysis.Conclusion Air pollution is closely associated with hospital admissions in ESRD patients undergoing maintenance hemodialysis and the strength of this association varies according to seasonality,the severity of air pollution,and patients'status of comorbidities.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective:To investigate the efficacy of dapagliflozin combined with tirofiban in patients with type 2 diabetes mellitus complicated with coronary heart disease.Methods:A total of 120 patients with type 2 diabetes mellitus and coronary heart disease treated in Fuyang People′s Hospital from January to August 2022 were prospectively selected as subjects. According to different treatment methods, they were divided into control group and experimental group. The control group was treated with tirofiban, and the experimental group was treated with dapagliflozin combined with tirofiban. The efficacy and safety of treatments between the two groups were compared.Results:After 3 months of treatment, fasting plasma glucose (FPG), 2 h postprandional blood glucose (2 h PG), glycated hemoglobin (HbA 1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), D-dimer (D-D) and fibrinogen (FIB) levels in 2 groups were decreased compared with before treatment:experimental group: (7.33 ± 1.77) mmol/L vs. (9.45 ± 2.05) mmol/L, (10.33 ± 2.07) mmol/L vs. (13.57 ± 2.88) mmol/L, (7.22 ± 1.28) % vs. (9.25 ± 1.78) %, (1.98 ± 0.29) mmol/L vs. (6.05 ± 1.24) mmol/L, (2.95 ± 0.37) mmol/L vs. (4.35 ± 0.76) mmol/L, (0.78 ± 0.23) mg/L vs. (1.85 ± 0.79) mg/L, (2.57 ± 0.37) g/L vs. (7.15 ± 1.36) g/L, control group: (8.21 ± 1.85) mmol/L vs. (9.68 ± 2.17) mmol/L, (11.78 ± 2.26) mmol/L vs. (13.89 ± 3.02) mmol/L, (8.25 ± 1.36) % vs. (9.37 ± 1.86) %, (2.77 ± 0.42) mmol/L vs. (6.08 ± 1.22) mmol/L, (3.84 ± 0.44) mmol/L vs. (4.27 ± 0.72) mmol/L, (1.34 ± 0.52) mg/L vs. (1.81 ± 0.72) mg/L, (5.25 ± 0.84 ) g/L vs. (7.11 ± 1.28) g/L, the differences were statistically significant ( P< 0.05). The levels of FPG, 2 h PG, HbA 1c, TC, LDL-C, D-D and FIB between the two groups were statistically significant ( P<0.05). High density lipoprotein cholesterol (HDL-C) level, left ventricular ejection fraction (LVEF), cardiac blood transfusion volume (CO), stroke output (SV), thrombin time (TT) and partially activated prothrombin time (APTT) were all increased: experimental group: (1.76 ± 0.30) mmol/L vs. (1.07 ± 0.28) mmol/L, (68.64 ± 12.91) % vs. (45.05 ± 12.24) %, (4.88 ± 0.91) L/min vs. (3.95 ± 1.12) L/min, (53.66 ± 5.43) ml/min vs. (43.27 ± 4.88) ml/min, (31.83 ± 4.39) s vs. (23.25 ± 3.44) s, (13.85 ± 2.17) s vs. (10.75 ± 1.56) s, control group: (1.43 ± 0.26) mmol/L vs. (1.06 ± 0.24) mmol/L, (60.37 ± 11.86) % vs. (45.42 ± 12.41) %, (4.37 ± 0.84) L/min vs. (4.17 ± 1.16) L/min, (47.86 ± 5.27) ml/min vs. (43.36 ± 4.94) ml/min, (27.24 ± 3.91) s vs. (23.78 ± 3.62) s, (12.74 ± 1.94) s vs. (10.89 ± 1.78) s, the differences were statistically significant ( P<0.05). There were significant differences in HDL-C, LVEF, CO, SV, TT and APTT between the two groups ( P<0.05). The incidence of adverse reactions in experimental group was lower than that in control group during treatment: 5.00% (3/60) vs. 16.67% (10/60), and the difference was statistically significant ( P<0.05). Conclusions:Dapagliflozin combined with tirofiban in the treatment of patients with type 2 diabetes mellitus complicated with coronary heart disease has obvious curative effect, and can improve blood glucose and blood lipid levels, coagulation function and cardiac function, with high safety.