ObjectiveTo analyze the epidemiological status, serotypes, and drug resistance characteristics of Vibrio parahaemolyticus in foodborne disease surveillance in Wenzhou from 2016 to 2024, and to provide scientific evidence and data support for the prevention and control of Vibrio parahaemolyticus infections. MethodsA total of 45 980 stool or anal swab samples were collected from patients with vomiting and diarrhea as the main symptoms and a history of consuming suspicious food at medical institutions at all levels in Wenzhou from 2016 to 2024. Isolation, identification, and drug susceptibility testing were performed. Case information was collected through the National Foodborne Disease Surveillance Reporting System. The Cochran-Mantel-Haenszel (CMH) chi-square test was used to analyze the detection rates among groups. ResultsAmong the 45 980 suspected samples, 2 821 were positive for Vibrio parahaemolyticus, with an overall detection rate of 6.14%. A comparison of detection rates across different population groups revealed that the highest rates were found among adults aged 20‒39 (8.57%,1 603/18 697) and among farmers and workers (7.93%, 994/12 537). A comparison of detection rates across different seasons revealed that the detection rates were higher from June to October (5.12%, 9.04%, 15.04%, 14.68%, and 7.80%, respectively), peaking in August. Analyses of the sampling results for suspect foodstuffs revealed that aquatic products and their derivatives accounted for the highest proportion (42.86%). Regarding the setting of food consumption, the household accounted for 44.53% (1 257/2 821). From 2016 to 2020, the predominant serotype was O3:K6 (28.82%, 813/2 821), followed by O10:K4 (28.25%, 797/2 821) and O4:KUT (23.61%, 666/2 821). In terms of drug resistance, the resistance rate to cefazolin was the highest at 84.15% (393/467), and the multi-drug resistance rate was 6.21% (29/467). ConclusionFrom 2016 to 2024, patients with suspected foodborne illnesses in Wenzhou City experienced a peak in Vibrio parahaemolyticus infections during the summer and autumn months (June to October). Young adults aged 20‒39, as well as farmers and manual workers, were the key target groups for the prevention and control of Vibrio parahaemolyticus infections. The predominant serotype of Vibrio parahaemolyticus shifted from O3:K6 to O10:K4. Vibrio parahaemolyticus exhibited a high level of resistance to cefazolin. It is essential to strengthen surveillance of the epidemiological trends of the predominant serotype, monitor changes in the antibiotic resistance of Vibrio parahaemolyticus, enhance health education for key populations, and intensify regulatory inspections of high-risk foods such as aquatic products and their derivatives.

In the context of global climate change, the impact of ambient temperature change on cardiovascular health has become increasingly significant. Epidemiological studies have shown that both high and low temperature can lead to the occurrence of adverse cardiovascular outcomes. For example, exposure to low temperature and high temperature, and diurnal temperature difference can increase the risk of cardiovascular diseases (CVD) mortality. Exposure to cold and heat, heatwaves and cold spells may induce myocardial infarction. Low temperature, high temperature and variations in temperature can increase the risk of heart failure. There are complex interactions among the effects of temperature and humidity, wind speed, radiation, precipitation and air pollution on adverse cardiovascular outcomes. Valnerable groups such as the elderly, patients with chronic diseases, and outdoor workers are particularly susceptible to temperature-related CVD risks. The mechanisms by which temperature affects adverse cardiovascular outcomes involves hemodynamic changes, autonomic nervous system dysregulation, blood rheology alterations, as well as inflammation and metabolic abnormalities, but many research gaps remain. Future studies should conduct in-depth research on mechanisms, individual differences, climate change impacts, and public health interventions to provide more effective policies and interventions to reduce the burden of CVD.

Objective To investigate the relationship between serum levels of plasminogen activator inhibi-tor-1(PAI-1)and annexin A2(ANXA2)and the carotid atherosclerosis stability(CAS)plaque in patients with transient ischemic attack(TIA).Methods A total of 131 patients with TIA admitted to the hospital from January 2021 to January 2023 were selected as the TIA group,and 46 healthy people in the same period were selected as the control group.According to the CAS plaque stability of TIA patients,they were divided into unstable plaque group(64 cases)and stable plaque/no plaque group(67 cases).The serum levels of PAI-1 and ANXA2 were detected by enzyme-linked immunosorbent assay and chemiluminescence immunoassay,respectively.Multivariate Logistic regression analysis was used to analyze the factors of CAS plaque stability in TIA patients.Receiver operating characteristic curve was used to analyze the predictive value of serum PAI-1 and ANXA2 levels for CAS instability in TIA patients.Results Compared with the control group,the levels of PAI-1 and ANXA2 in TIA group were significantly increased(P<0.05).Compared with the stable plaque/no plaque group,the unstable plaque group was significant increaseed in the serum levels of PAI-1 and ANXA2(P<0.05).Smoking,high risk of TIA,elevated PAI-1 and ANXA2 were independent risk factors for CAS plaque stability in patients with TIA(P<0.05).The area under the curve predicted by serum PAI-1 and ANXA2 levels combined was 0.879,which was larger than 0.788 and 0.783 predicted by serum PAI-1 and ANXA2 levels alone(P<0.05).Conclusion The increased levels of serum PAI-1 and ANXA2 are closely re-lated to CAS plaque instability in patients with TIA.The combination of serum PAI-1 and ANXA2 levels has a higher value in predicting CAS plaque instability in patients with TIA.

Objective To evaluate the clinical efficacy of stellate ganglion block(SGB)combined with intranasal dexmedetomidine for the treatment of insomnia.Methods A total of 64 patients aged 18 to 75 with insom-nia were randomly assigned to either the experimental group(DS group)or the control group(S group).The S group received SGB treatment for 14 consecutive days,whereas the DS group received an additional intranasal dexmedeto-midine spray at a dose of 100 μg,administered 30 minutes before bedtime on days 1 through 6,in conjunction with SGB.We measured and recorded the Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS)scores,and Psychomotor Vigilance Test(PVT)results for both groups at three time points:baseline(T1),the day after treatment(T2),and one month after treatment(T3).Results Intra-group Com-parison:In both the DS and S groups,PSQI scores and dimensionspecific scores at T2 and T3 were significantly lower compared to T1(P<0.05).SAS and SDS scores in both groups showed a significant reduction at T3 compared to T1 and T2(P<0.05),while PVT results exhibited no significant changes(P>0.05).Inter-group Comparison:The PSQI scores and dimensionspecific scores in the DS group at T2(8.44±2.99)and T3(8.22±2.60)were significantly lower than those in the S group at T2(10.88±2.56)and T3(10.88±2.84)(P<0.05).However,no significant differences were observed in SDS and SAS scores between the DS and S groups at T2 and T3(P>0.05).Conclusion Compared to standalone SGB,the combination of SGB with intranasal dexmedetomidine significantly enhances sleep quality in patients with insomnia,while not impacting their levels of anxiety,depression,or alertness.

Objective:To investigate the association between dopamine D2 receptor ( DRD2) promoter methylation levels and melancholic depression (MD), and its correlation with psychosocial factors and depression severity. Method:A total of 30 patients with melancholic depression (MD group) and 30 with non-melancholic depression (NMD group) were recruited from the First Affiliated Hospital of Xinjiang Medical University between October 2023 and October 2024, along with 30 healthy controls. Participants were assessed by the Hamilton depression rating scale (HAMD-24), dimensional anhedonia rating scale (DARS), childhood trauma questionnaire (CTQ), life event scale (LES), and social support rating scale (SSRS). DRD2 methylation levels in peripheral blood were measured by MassArray technology. Data were analyzed in SPSS 29.0 software using ANOVA, non-parametric tests, and t-tests to compare methylation levels among groups, and Logistic regression, Pearson correlation, and multiple linear regression to examine associations between DRD2 methylation and psychosocial factors and depression severity. Results:(1) There were statistically significant differences among the three groups in years of education ( F=9.873, P=0.007), HAMD-24 total scores ( H=76.669, P<0.001), DARS total scores ( H=60.617, P<0.001), SSRS total scores ( F=3.592, P=0.032), LES negative stimulus scores ( H=43.461, P<0.001), and CTQ total scores ( H=10.751, P=0.005). The MD group had a longer course of illness ( Z=-1.980, P=0.048), more episodes ( Z=-2.027, P=0.043), and a higher rate of suicide attempts in the past year ( χ2= 9.643, P=0.002) compared with the NMD group. The MD group had higher HAMD-24 total scores (31.00 (28.00, 32.25)) than the NMD group (23.00 (21.00, 25.00)), and lower DARS total scores (17.00 (9.75, 22.00)) compared with the NMD group(36.50 (33.75, 43.00)) (both P<0.05). (2) No statistically significant difference was found in DRD2 gene methylation levels among the three groups ( F=0.081, all P>0.05). Logistic regression showed that DRD2 gene methylation level was not an influencing factor for the onset of MD ( P>0.05). (3)The correlation analysis and multiple linear regression analysis showed that childhood trauma (CTQ total score) was negatively correlated with DRD2 gene methylation levels in MD patients ( r=-0.416, P=0.025) and MDD patients. DRD2 gene methylation level was not correlated with depression severity ( r=0.136, P>0.05) or anhedonia severity (both P>0.05). Social support (SSRS total score) was positively correlated with DARS total scores in MD patients( r=0.427, P=0.019), and years of education had a positive association with DARS total scores in MDD patients ( B=1.527, P=0.030), suggesting that both are negatively correlated with the degree of anhedonia. Conclusion:DRD2 methylation may be influenced by early-life trauma, but its role in the pathogenesis of MD and its association with depression severity require further investigation.

Objective:To investigate the biological role of miR-1224-5p in the proliferation,migration and apoptosis of prostate cancer cells,as well as its regulatory mechanism of expression.Methods:Human prostate cancer cells(PC3,DU145,LNCaP,22Rv1)and normal prostate epithelial RWPE-1 cells were selected for this study.The expression of miR-1224-5p in prostate cancer cells was detected by qPCR.miR-1224-5p mimic,inhibitor and corresponding negative control(NC)plasmids were transfected into PC3 and DU145 cells by liposome transfection technology,respectively.The transfection efficiency was verified by qPCR.The effects of miR-1224-5p mimic and inhibitor on cell proliferation,migration and apoptosis were detected by CCK-8 assay,plate clone formation assay,scratch healing assay and flow cytometry.The potential N6-methyladenosine(m6A)modification sites in the pri-miR-1224-5p sequence were predicted using SRAMP website,and the prediction results were verified using methylated RNA immunoprecipitation(MeRIP).The expression of methyltransferase 3(METTL3),a key methyltransferase involved in m6A modification,in prostate cancer cells was detected by qPCR.CCK-8 assay and Transwell assay were used to detect the effect of METTL3 siRNA transfection on the proliferation and migration of PC3 and DU145 cells.The regulatory effect of METTL3-mediated m6A modification on the expression of miR-1224-5p was detected by qPCR and MeRIP.Results:miR-1224-5p was upregulated in prostate cancer cells(all P<0.01).Transfection with miR-1224-5p mimic promoted the proliferation,migration and inhibited the apoptosis of PC3 and DU145 cells(P<0.05 or P<0.01).Conversely,miR-1224-5p inhibitor suppressed the proliferation,migration and induced apoptosis of PC3 and DU145 cells(P<0.05 or P<0.01).pri-miR-1224-5p contained m6A modification sites.METTL3 was highly expressed in prostate cancer cells(all P<0.01).Transfection of METTL3 siRNA inhibited the proliferation and migration of PC3 and DU145 cells(all P<0.01).METTL3-mediated m6A modification regulated the expression of miR-1224-5p.Conclusion:miR-1224-5p is upregulated in prostate cancer cells through METTL3-mediated m6A modification.Down-regulation of miR-1224-5p can inhibit the proliferation,migration and induce apoptosis of prostate cancer cells.

Objective To evaluate the clinical efficacy of stellate ganglion block(SGB)combined with intranasal dexmedetomidine for the treatment of insomnia.Methods A total of 64 patients aged 18 to 75 with insom-nia were randomly assigned to either the experimental group(DS group)or the control group(S group).The S group received SGB treatment for 14 consecutive days,whereas the DS group received an additional intranasal dexmedeto-midine spray at a dose of 100 μg,administered 30 minutes before bedtime on days 1 through 6,in conjunction with SGB.We measured and recorded the Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS)scores,and Psychomotor Vigilance Test(PVT)results for both groups at three time points:baseline(T1),the day after treatment(T2),and one month after treatment(T3).Results Intra-group Com-parison:In both the DS and S groups,PSQI scores and dimensionspecific scores at T2 and T3 were significantly lower compared to T1(P<0.05).SAS and SDS scores in both groups showed a significant reduction at T3 compared to T1 and T2(P<0.05),while PVT results exhibited no significant changes(P>0.05).Inter-group Comparison:The PSQI scores and dimensionspecific scores in the DS group at T2(8.44±2.99)and T3(8.22±2.60)were significantly lower than those in the S group at T2(10.88±2.56)and T3(10.88±2.84)(P<0.05).However,no significant differences were observed in SDS and SAS scores between the DS and S groups at T2 and T3(P>0.05).Conclusion Compared to standalone SGB,the combination of SGB with intranasal dexmedetomidine significantly enhances sleep quality in patients with insomnia,while not impacting their levels of anxiety,depression,or alertness.

Objective:To investigate the association between dopamine D2 receptor ( DRD2) promoter methylation levels and melancholic depression (MD), and its correlation with psychosocial factors and depression severity. Method:A total of 30 patients with melancholic depression (MD group) and 30 with non-melancholic depression (NMD group) were recruited from the First Affiliated Hospital of Xinjiang Medical University between October 2023 and October 2024, along with 30 healthy controls. Participants were assessed by the Hamilton depression rating scale (HAMD-24), dimensional anhedonia rating scale (DARS), childhood trauma questionnaire (CTQ), life event scale (LES), and social support rating scale (SSRS). DRD2 methylation levels in peripheral blood were measured by MassArray technology. Data were analyzed in SPSS 29.0 software using ANOVA, non-parametric tests, and t-tests to compare methylation levels among groups, and Logistic regression, Pearson correlation, and multiple linear regression to examine associations between DRD2 methylation and psychosocial factors and depression severity. Results:(1) There were statistically significant differences among the three groups in years of education ( F=9.873, P=0.007), HAMD-24 total scores ( H=76.669, P<0.001), DARS total scores ( H=60.617, P<0.001), SSRS total scores ( F=3.592, P=0.032), LES negative stimulus scores ( H=43.461, P<0.001), and CTQ total scores ( H=10.751, P=0.005). The MD group had a longer course of illness ( Z=-1.980, P=0.048), more episodes ( Z=-2.027, P=0.043), and a higher rate of suicide attempts in the past year ( χ2= 9.643, P=0.002) compared with the NMD group. The MD group had higher HAMD-24 total scores (31.00 (28.00, 32.25)) than the NMD group (23.00 (21.00, 25.00)), and lower DARS total scores (17.00 (9.75, 22.00)) compared with the NMD group(36.50 (33.75, 43.00)) (both P<0.05). (2) No statistically significant difference was found in DRD2 gene methylation levels among the three groups ( F=0.081, all P>0.05). Logistic regression showed that DRD2 gene methylation level was not an influencing factor for the onset of MD ( P>0.05). (3)The correlation analysis and multiple linear regression analysis showed that childhood trauma (CTQ total score) was negatively correlated with DRD2 gene methylation levels in MD patients ( r=-0.416, P=0.025) and MDD patients. DRD2 gene methylation level was not correlated with depression severity ( r=0.136, P>0.05) or anhedonia severity (both P>0.05). Social support (SSRS total score) was positively correlated with DARS total scores in MD patients( r=0.427, P=0.019), and years of education had a positive association with DARS total scores in MDD patients ( B=1.527, P=0.030), suggesting that both are negatively correlated with the degree of anhedonia. Conclusion:DRD2 methylation may be influenced by early-life trauma, but its role in the pathogenesis of MD and its association with depression severity require further investigation.

Animal experiments are widely used in biomedical research for safety assessment,toxicological analysis,efficacy evaluation,and mechanism exploration.In recent years,the ethical review system has become more stringent,and awareness of animal welfare has continuously increased.To promote more efficient and cost-effective drug research and development,the United States passed the Food and Drug Administration(FDA)Modernization Act 2.0 in September 2022,which removed the federal mandate requiring animal testing in preclinical drug research.In April 2025,the FDA further proposed to adopt a series of"new alternative methods"in the research and development of drugs such as monoclonal antibodies,which included artificial intelligence computing models,organoid toxicity tests,and 3D micro-physiological systems,thereby gradually phasing out traditional animal experiment models.Among these cutting-edge technologies,3D bioprinting models are a significant alternative and complement to animal models,owing to their high biomimetic properties,reproducibility,and scalability.This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research.It starts by detailing the essential elements of 3D bioprinting,including the selection and functional design of biomaterials,along with an explanation of the principles and characteristics of various printing strategies,highlighting the advantages in constructing complex multicellular spatial structures,regulating microenvironments,and guiding cell fate.It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors,infectious diseases,and rare diseases,as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart.Additionally,the review examines the role of 3D bioprinting in tissue engineering,discussing its contributions to the construction of functional tissues such as bone,cartilage,skin,and blood vessels,as well as the latest progress in regeneration and replacement.Furthermore,this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression,drug mechanisms,precision medicine,drug development,and tissue regeneration,and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance.In conclusion,as a cutting-edge in vitro modeling and manufacturing technology,3D bioprinting is gradually establishing a comprehensive application system covering disease modeling,drug screening,toxicity prediction,and tissue regeneration.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.