Objective To evaluate the causal relationship between serum uric acid(SUA)level and cerebrovascular disease(CVD)by a two-sample bidirectional Mendelian randomization(MR)study.Methods Single nucleotide polymorphisms(SNPs)from Genome-Wide Association Studies(GWAS)were obtained as instrumental variables for both samples.Inverse-variance weighted(IVW)method was primarily adopted,with weighted median method,weighted mode method,and MR-Egger regression serving as supplementary approaches for sensitivity analyses to verify the robust-ness of the results.Results The forward IVW analysis results showed that increased SUA was a risk factor for stroke(OR=1.183,95％CI,1.081 to 1.295,P=2.51× 10-4),ischemic stroke(OR=1.196,95％CI,1.084 to 1.320,P=3.81 ×10-4),and large artery atherosclerotic stroke(OR=1.466,95％CI,1.134 to 1.897,P=0.004),and also a protective factor for vascular dementia(OR=0.451,95％CI,0.273 to 0.745,P=0.002)and multi-infarct dementia(OR=0.372,95％CI,0.144 to 0.959,P=0.041).The reverse IVW analysis results did not support a causal effect of genetically predicted CVD risk on SUA level.All significant results were corrected by Bonfer-roni with P value less than 0.005.Sensitivity analyses further confirmed the reliability of the study find-ings.Conclusion The MR analysis reveals positive correlations between increased SUA level and the risk of stroke,ischemic stroke and large artery atherosclerotic stroke,and negative correlations of SUA level with the risk of vascular dementia and multi-infarct dementia.

Objective:To investigate the correlation between rectal colonization of carbapenem resistant Klebsiella pneumoniae（CRKP）and bloodstream infections（BSI）using molecular epidemiological analysis. Methods:Patients admitted to the Intensive Care Unit（ICU），Hematology Department，and Neurosurgery Department of the First Hospital of Jiaxing from January 2022 to December 2024，were enrolled. Rectal CRKP colonization screening was performed for all participants，with concurrent monitoring for BSI.Whole genome sequencing of CRKP strains in the intestine and blood flow of patients with CRKP rectal colonization and CRKP-BSI was performed using the Illumina NovaSeq PE150 sequencing platform，and samples were genotyped based on the PubMLST database. MLST 2.0 was applied for multi site sequence typing，VFDB online database was used to analyze virulence genes，ResFinder was used to analyze resistance genes，and whole genome sequences were imported into BioNumerics software for core genome multi site sequence typing and clustering analysis. Using the BacWGSTdb database to construct a phylogenetic tree based on genomic SNPs，and the homology between CRKP rectal fixed plants and corresponding BSI-CRKP infected plants were analyzed.Results:A total of 772 patients were included，including 78 cases with positive results in rectal CRKP colonization screening（10.1%）and 694 cases without rectal CRKP colonization（89.9%）. The CRKP-BSI rate in rectal CRKP colonization patients was significantly higher than that in non-CRKP colonization patients［19.2%（15/78） vs. 5.5%（38/694）， χ2=20.749， P<0.001］. Analysis of CRKP rectal colonization strains and bloodstream infection strains in 15 patients with CRKP rectal implantation and CRKP-BSI revealed that ST11 type was the main strain（ n=10），followed by ST37 type（ n=3），with all carrying multiple β-lactam and carbapenem producing enzyme resistance genes.The distribution of virulence genes showed that CRKP strains carried multiple virulence genes，with iroE being ubiquitous，followed by iucA/ B/ C/ D， rmpA2，rmpA，and iroN. All ST11-type CRKP strains exhibited hypervirulent characteristics. Capsular serotyping analysis showed that the predominant type of CRKP colonization and infection strains was KL64. The results of cgMLST and SNP clustering analysis showed that CRKP rectal fixed plants exhibited homology with blood flow infected plants. Moreover，two clusters of CRKP rectal colonization strains with significant homology were found to cluster together among 15 patients. Conclusions:Rectal colonization of CRKP is an important risk factor for the occurrence of BSI-CRKP in hospitals，and ST11 hypervirulent CRKP is the main type. It is recommended to screen high-risk patients for CRKP to reduce the risk of BSI-CRKP.

Objective To investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P＞0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)％ versus(0.54±0.27)％,total dip-loidy rate(0.25±0.27)％ versus(0.05±0.05)％,and disomy rate of chromosome 18(0.77±1.15)％ versus(0.18±0.21)％,sex chromosomes(2.79±2.38)％ versus(0.78±0.52)％,chromosome 13(0.79±0.99)％ versus(0.21±0.22)％,and chromosome 21(1.24±1.68)％ versus(0.22±0.19)％ were significantly higher than those in the control group(P＜0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18％,35.29％,41.18％,55.88％,and 47.06％,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.

Objective To investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P＞0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)％ versus(0.54±0.27)％,total dip-loidy rate(0.25±0.27)％ versus(0.05±0.05)％,and disomy rate of chromosome 18(0.77±1.15)％ versus(0.18±0.21)％,sex chromosomes(2.79±2.38)％ versus(0.78±0.52)％,chromosome 13(0.79±0.99)％ versus(0.21±0.22)％,and chromosome 21(1.24±1.68)％ versus(0.22±0.19)％ were significantly higher than those in the control group(P＜0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18％,35.29％,41.18％,55.88％,and 47.06％,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.

Objective:To investigate the correlation between rectal colonization of carbapenem resistant Klebsiella pneumoniae（CRKP）and bloodstream infections（BSI）using molecular epidemiological analysis. Methods:Patients admitted to the Intensive Care Unit（ICU），Hematology Department，and Neurosurgery Department of the First Hospital of Jiaxing from January 2022 to December 2024，were enrolled. Rectal CRKP colonization screening was performed for all participants，with concurrent monitoring for BSI.Whole genome sequencing of CRKP strains in the intestine and blood flow of patients with CRKP rectal colonization and CRKP-BSI was performed using the Illumina NovaSeq PE150 sequencing platform，and samples were genotyped based on the PubMLST database. MLST 2.0 was applied for multi site sequence typing，VFDB online database was used to analyze virulence genes，ResFinder was used to analyze resistance genes，and whole genome sequences were imported into BioNumerics software for core genome multi site sequence typing and clustering analysis. Using the BacWGSTdb database to construct a phylogenetic tree based on genomic SNPs，and the homology between CRKP rectal fixed plants and corresponding BSI-CRKP infected plants were analyzed.Results:A total of 772 patients were included，including 78 cases with positive results in rectal CRKP colonization screening（10.1%）and 694 cases without rectal CRKP colonization（89.9%）. The CRKP-BSI rate in rectal CRKP colonization patients was significantly higher than that in non-CRKP colonization patients［19.2%（15/78） vs. 5.5%（38/694）， χ2=20.749， P<0.001］. Analysis of CRKP rectal colonization strains and bloodstream infection strains in 15 patients with CRKP rectal implantation and CRKP-BSI revealed that ST11 type was the main strain（ n=10），followed by ST37 type（ n=3），with all carrying multiple β-lactam and carbapenem producing enzyme resistance genes.The distribution of virulence genes showed that CRKP strains carried multiple virulence genes，with iroE being ubiquitous，followed by iucA/ B/ C/ D， rmpA2，rmpA，and iroN. All ST11-type CRKP strains exhibited hypervirulent characteristics. Capsular serotyping analysis showed that the predominant type of CRKP colonization and infection strains was KL64. The results of cgMLST and SNP clustering analysis showed that CRKP rectal fixed plants exhibited homology with blood flow infected plants. Moreover，two clusters of CRKP rectal colonization strains with significant homology were found to cluster together among 15 patients. Conclusions:Rectal colonization of CRKP is an important risk factor for the occurrence of BSI-CRKP in hospitals，and ST11 hypervirulent CRKP is the main type. It is recommended to screen high-risk patients for CRKP to reduce the risk of BSI-CRKP.

An increasing number of studies have shown that neuroimaging techniques, including CT- and MRI-related imaging biomarkers, are associated with the clinical outcome after intravenous thrombolysis in patients with acute ischemic stroke. Therefore, as a necessary diagnostic item for acute ischemic stroke, imaging examinations and related biomarkers have important value in predicting the outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Objective To explore the influencing factors hindering compliance of discharged patients with coronary heart disease on enhanced external counterpulsation(EECP),and to provide basis for formulating corresponding intervention strategies.Methods A semi-structured interview method was used to conduct in-depth interviews on 19 patients with coronary heart disease who received EECP treatment during hospitalization in Gansu Provincial Hospital from March 2020 to August 2021 but withdrew from the EECP treatment program after discharge.According to phenomenological theory,the Colaizzi 7-step analysis method was applied to analyze the interview data.Results Cognitive factors(insufficient understanding of the disease and EECP treatment),objective factors(distance,transportation,economy,time,epidemic impact)and psychological factors were all influencing factors that hinder the compliance of patients discharged from coronary heart disease with EECP treatment.Conclusion In order to improve the enthusiasm and compliance of discharged patients with coronary heart disease to participate in EECP treatment,the medical staff should formulate intervention measures according to the influencing factors of the lack of EECP treatment compliance of discharged patients with coronary heart disease from the cognitive factors,objective factors and psychological factors of patients.

Objective To observe the ultrasonic manifestations and possible etiology of fetal tricuspid regurgitation(TR).Methods Totally 717 fetuses diagnosed with TR by prenatal ultrasound were retrospectively enrolled,and the prenatal ultrasonic findings were observed.Based on postpartum follow-up data,the fetuses were divided into physiological TR group(n=468)and pathological TR group(n=249),and those in the latter were further divided into right heart preload increase subgroup(n=76),right heart afterload increase subgroup(n=127)and tricuspid valve structure abnormality subgroup(n=46)according to the possible etiology,and the ultrasonic manifestations were comparatively analyzed.Results In physiological TR group,mild and moderate TR was found in 441(441/468,94.23％)and 27 fetuses(27/468,5.77％),respectively,while no severe TR was noticed.In pathological TR group,significant difference of TR degrees was found among 3 subgroups(x2=37.244,P＜0.001).Mild TR was more common in right heart preload increase subgroup,while moderate and severe TR were more common in the other 2 subgroups.In right heart preload increase subgroup,fetuses with persistent left superior vena cava were more likely to develop mild TR,while those with intact interventricular septum and pulmonary artery occlusion were more likely to develop severe TR in right heart afterload increase subgroup(both P＜0.05).No significant difference of TR degree was found among fetuses with different possible etiology in right heart preload increase subgroup nor right heart afterload increase subgroup(both P＞0.05).In tricuspid valve structure abnormality subgroup,significant differences of TR degrees were found among fetuses with different possible etiologies(P＜0.05),and fetuses with underdeveloped tricuspid valve were more prone to severe reflux(P＜0.05).There were significant differences of reflux velocity of moderate and severe TR among 3 subgroups(F=6.945,P=0.002).Conclusion Fetal TR was mostly physiological.The possible etiologies of pathological TR were variable,including pulmonary valve stenosis,persistent left superior vena cava and tricuspid valve hypoplasia,with different prenatal ultrasonic manifestations.

Intraventricular hemorrhage (IVH) accounts for about 3%-5% of all intracerebral hemorrhage, which can be divided into primary and secondary IVH. Primary IVH is mostly caused by choroid plexus vascular or subependymal artery rupture, and secondary IVH refers to spontaneous intracerebral hemorrhage that breaks into the ventricle and the prognosis was poor. This article reviews the pathophysiological mechanism, severity assessment, and treatment progress of secondary IVH.

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.