Objective:To investigate the role of mRNA expression in the pathogenesis of gout by analyzing the difference of gene expression in peripheral blood mononuclear cells(PBMCs)among acute gouty(AG),intermittent gouty(IG)and health con-trols(HC).Methods:AG patients,IG patients and HC were enrolled in this study.RNA-seq and bioinformatics techniques were used to observe the differences of mRNA expression in PBMCs of different groups,and to explore the genes and signaling pathways as-sociated with gout attack.GO and KEGG databases were used to investigate the biological functions of differentially expressed genes and the relationship between genes and signaling pathways.Genes involved in the KEGG enriched PPAR signaling pathway(CYP27A1,ACSL1,CD36,PPARG,ANGPTL4,PLIN2)were validated in PBMCs from 35 patients with AG,35 patients with IG,and 35 normal healthy subjects using real-time PCR.Results:Compared with HC group,there were 222 significant differential genes in AG group,including 193 up-regulated genes and 29 down-regulated genes.GO analysis showed that the genes differentially ex-pressed in AG group were mainly enriched in the regulation of multicellular biological processes such as inflammation,trauma,and stress response and immune response regulation compared with HC group.However,KEGG analysis showed that the up-regulated genes in AG group were enriched in"Toll-like receptor signaling pathway""complement and coagulation cascades""PPAR signaling pathway""lipid and atherosclerosis""osteoclast differentiation""cytokine-cytokine receptor interaction""chemokine signaling path-way""IL-17 signaling pathway",and"cholesterol metabolism"compared with HC group.The results of PCR validation of related genes in the PPAR signaling pathway showed that the expression levels of ACSL1,CD36,PPARG,and PLIN2 in the AG group were higher than those in the control group(P<0.05),and the expression levels of CYP27A1 and ANGPTL4 in the AG group were not dif-ferent from those in the HC group(P>0.05).Conclusion:PPAR signaling pathway may be involved in the pathogenesis of AG,of which ACSL1,CD36,PPARG,and PLIN2 may be used as potential therapeutic targets for acute gouty arthritis;CYP27A1 and ANG-PTL4 may not be associated with the pathogenesis of AG.

Objective:To determine the epidemic characteristics of polymyxin resistance ( mcr) genes of Enterobacteriales colonized in patients admitted to hospitals in Zhejiang, Henan, Gansu and Shandong provinces in China in 2023. Methods:A comprehensive collection of 667 fecal specimens from patients admitted to five medical facilities across the provinces of Zhejiang, Henan, Gansu, and Shandong in 2023 was collected. Epidemiological characteristics of Enterobacteriales bacteria positive for the mcr gene were examined, employing techniques such as microbial culturing, using agarose gel electrophoresis, PCR, whole-genome sequencing, bioinformatics analysis, and the induction of antimicrobial resistance. Statistical analysis was subsequently applied to the gathered data. Results:Among 667 fecal samples from admitted patients, five samples were positive for mcr gene, with a carrier rate of 0.75%(5/667), and from two of the samples, two different strains carrying the mcr gene were isolated, respectively. A total of seven strains of Enterobacteriales carrying the mcr gene were detected, of which four strains carried mcr-1 gene and three strains carried mcr-9 gene. The positive isolates included three strains of Escherichia coli, one strain of Citrobacter braakii, Citrobacter freundii, one strain of Klebsiella pneumoniae, and one strain of Enterobacter hormaechei. The seven mcr positive strains were isolated from two distinct geographical locations within China, with four from Zhejiang Province and three from Henan Province. After whole-genome sequencing, it was found that the 16S rRNA sequences of the three strains of mcr-1 positive Escherichia coli had high homology. The three isolates of mcr-9 positive strains preserved a significant degree of homology within the mcr-9 and wbuC regions. Following polymyxin exposure, there was a marked difference in the growth kinetics of the ZJ-307, HN-11-1, and HN-135 strains post-induction compared to their pre-induction growth rates, and their motility capacity was reduced. Conclusions:The prevalence of Enterobacteriales harboring the mcr gene is minimal among hospitalized patients. However, it is noteworthy that these genes are prone to horizontal transfer. They can move into drug-resistant strains, which may have elevate minimum inhibitory concentration(MIC). Resistance to polymyxin can alter the bacterial growth rate and motility, potentially impacting the MIC of other antibiotics, thereby complicating clinical management. Consequently, it is imperative to focus on the proactive screening of susceptible populations to prevent the further dissemination of plasmid-mediated polymyxin resistance among clinically significant gram-negative bacterial pathogens.

Objective:To investigate the role of mRNA expression in the pathogenesis of gout by analyzing the difference of gene expression in peripheral blood mononuclear cells(PBMCs)among acute gouty(AG),intermittent gouty(IG)and health con-trols(HC).Methods:AG patients,IG patients and HC were enrolled in this study.RNA-seq and bioinformatics techniques were used to observe the differences of mRNA expression in PBMCs of different groups,and to explore the genes and signaling pathways as-sociated with gout attack.GO and KEGG databases were used to investigate the biological functions of differentially expressed genes and the relationship between genes and signaling pathways.Genes involved in the KEGG enriched PPAR signaling pathway(CYP27A1,ACSL1,CD36,PPARG,ANGPTL4,PLIN2)were validated in PBMCs from 35 patients with AG,35 patients with IG,and 35 normal healthy subjects using real-time PCR.Results:Compared with HC group,there were 222 significant differential genes in AG group,including 193 up-regulated genes and 29 down-regulated genes.GO analysis showed that the genes differentially ex-pressed in AG group were mainly enriched in the regulation of multicellular biological processes such as inflammation,trauma,and stress response and immune response regulation compared with HC group.However,KEGG analysis showed that the up-regulated genes in AG group were enriched in"Toll-like receptor signaling pathway""complement and coagulation cascades""PPAR signaling pathway""lipid and atherosclerosis""osteoclast differentiation""cytokine-cytokine receptor interaction""chemokine signaling path-way""IL-17 signaling pathway",and"cholesterol metabolism"compared with HC group.The results of PCR validation of related genes in the PPAR signaling pathway showed that the expression levels of ACSL1,CD36,PPARG,and PLIN2 in the AG group were higher than those in the control group(P<0.05),and the expression levels of CYP27A1 and ANGPTL4 in the AG group were not dif-ferent from those in the HC group(P>0.05).Conclusion:PPAR signaling pathway may be involved in the pathogenesis of AG,of which ACSL1,CD36,PPARG,and PLIN2 may be used as potential therapeutic targets for acute gouty arthritis;CYP27A1 and ANG-PTL4 may not be associated with the pathogenesis of AG.

Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability.The biome-chanical microenvironment,consisting of fluid shear force,plaque structural stress,and matrix stiffness,serves as signifi-cant factors in mediating plaque angiogenesis.Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms.This review provides an overview of the mecha-nisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the pre-vention and treatment of atherosclerosis.

Objective:To determine the epidemic characteristics of polymyxin resistance ( mcr) genes of Enterobacteriales colonized in patients admitted to hospitals in Zhejiang, Henan, Gansu and Shandong provinces in China in 2023. Methods:A comprehensive collection of 667 fecal specimens from patients admitted to five medical facilities across the provinces of Zhejiang, Henan, Gansu, and Shandong in 2023 was collected. Epidemiological characteristics of Enterobacteriales bacteria positive for the mcr gene were examined, employing techniques such as microbial culturing, using agarose gel electrophoresis, PCR, whole-genome sequencing, bioinformatics analysis, and the induction of antimicrobial resistance. Statistical analysis was subsequently applied to the gathered data. Results:Among 667 fecal samples from admitted patients, five samples were positive for mcr gene, with a carrier rate of 0.75%(5/667), and from two of the samples, two different strains carrying the mcr gene were isolated, respectively. A total of seven strains of Enterobacteriales carrying the mcr gene were detected, of which four strains carried mcr-1 gene and three strains carried mcr-9 gene. The positive isolates included three strains of Escherichia coli, one strain of Citrobacter braakii, Citrobacter freundii, one strain of Klebsiella pneumoniae, and one strain of Enterobacter hormaechei. The seven mcr positive strains were isolated from two distinct geographical locations within China, with four from Zhejiang Province and three from Henan Province. After whole-genome sequencing, it was found that the 16S rRNA sequences of the three strains of mcr-1 positive Escherichia coli had high homology. The three isolates of mcr-9 positive strains preserved a significant degree of homology within the mcr-9 and wbuC regions. Following polymyxin exposure, there was a marked difference in the growth kinetics of the ZJ-307, HN-11-1, and HN-135 strains post-induction compared to their pre-induction growth rates, and their motility capacity was reduced. Conclusions:The prevalence of Enterobacteriales harboring the mcr gene is minimal among hospitalized patients. However, it is noteworthy that these genes are prone to horizontal transfer. They can move into drug-resistant strains, which may have elevate minimum inhibitory concentration(MIC). Resistance to polymyxin can alter the bacterial growth rate and motility, potentially impacting the MIC of other antibiotics, thereby complicating clinical management. Consequently, it is imperative to focus on the proactive screening of susceptible populations to prevent the further dissemination of plasmid-mediated polymyxin resistance among clinically significant gram-negative bacterial pathogens.

Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability.The biome-chanical microenvironment,consisting of fluid shear force,plaque structural stress,and matrix stiffness,serves as signifi-cant factors in mediating plaque angiogenesis.Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms.This review provides an overview of the mecha-nisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the pre-vention and treatment of atherosclerosis.

Abstract: Objective　To evaluate the value of bronchoalveolar lavage fluid Aspergillus-specific fluorescent PCR assay combined with galactomannan (GM) assay in the diagnosis of patients with non-neutropenic invasive pulmonary aspergillosis (IPA). Methods From March 2022 to December 2023, 113 hospitalized patients with clinically suspected IPA were selected from the Zibo First Hospital of Zibo City, Shandong Province. Bronchoalveolar lavage fluid samples from each patient were simultaneously subjected to potassium hydroxide microscopy, fungal culture, GM assay, and Aspergillus-specific fluorescence PCR assay. According to the diagnostic criteria of IPA, patients were divided into clinically diagnosed IPA and non-IPA groups. The values of these four methods for the diagnosis of IPA were compared. Results According to the diagnostic criteria for IPA, 37 out of the 113 suspected patients were clinically diagnosed as IPA. The proportion of diabetic patients was significantly higher in the IPA group compared to the non-IPA group (χ2=7.494, P=0.006); similarly, the proportion of patients using glucocorticoids was significantly higher in the IPA group (χ2=6.981, P=0.008). Patients in the IPA group more frequently showed cavitation within consolidation areas on imaging, which was statistically significant (χ2=15.603, P<0.001). There were significant differences in the sensitivity of the four fungal detection methods in the diagnosis of IPA (χ2=45.803, P<0.001), with Aspergillus-specific PCR assay showing the highest sensitivity at 94.59%. Specificity also varied significantly across the four methods (χ2=31.511, P<0.001), with the highest specificity being seen in potassium hydroxide microscopy and fungal culture at 100.00%. There were significant differences in the clinical coincidence rate of the four methods in the diagnosis of IPA (χ2=11.768, P=0.008), with Aspergillus-specific fluorescence PCR assay having the highest coincidence rate at 90.27%. The AUC of the ROC curve of Aspergillus-specific fluorescent PCR assay combined with the GM assay was 0.976 7, higher than 0.913 8 by Aspergillus-specific fluorescent PCR assay merely. Conclusions The combination of Aspergillus-specific fluorescent PCR assay and GM assay using bronchoalveolar lavage fluid could significantly improve the accuracy of IPA diagnosis in patients without neutropenia.

OBJECTIVE: To retrospectively analyze the results of chromosomal microarray analysis (CMA) and parental origins of unbalanced translocations among 17 patients, so as to provide reference for their genetic counseling. METHODS: The results of CMA for 7 001 samples tested in Chengdu Women and Children's Central Hospital from January 2019 to January 2022 were retrospectively reviewed. Unbalanced reciprocal translocation was defined as two non-homologous chromosomes with lost and gained segments respectively or both with gained segments, and their parental origins were identified by parental chromosomal karyotyping and/or fluorescence in situ hybridization (FISH). RESULTS: In total 17 unbalanced translocations were identified. In three cases, two non-homologous chromosomes both had gained segments, which constituted a derivative chromosome, with the total number of chromosomes being 47. In the remaining 14 cases, there was a terminal deletion on one chromosome and a terminal duplication on the other, 10 of which were confirmed by karyotyping, with the total number of chromosomes being 46. In the derivative chromosome, the lost segment was replaced by a gained segment from another chromosome. Among 15 cases undergoing parental origin analysis, 12 had paternal or maternal chromosomal abnormalities, including 11 balanced translocations and 1 unbalanced translocation. The unbalanced gametes therefore may form through meiosis. In 3 cases, the parental chromosomes were normal, indicating a de novo origin. CONCLUSION Discovery of terminal duplication and deletion or gained segments on two non-homologous chromosomes by CMA is suggestive of parental balanced translocation, which can facilitate genetic counseling and assessment the recurrence risk for subsequent pregnancies.
Child ; Pregnancy ; Humans ; Female ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Translocation, Genetic ; Microarray Analysis ; Chromosomes

Objective To investigate the correlations of serum prealbumin and albumin with the shortterm outcome in patients with acute cerebral infarction in different age groups.Methods Patients with acute ischemic stroke admitted to hospital with 48 h were prospectively enrolled in the study.The modified Rankin Scale was used to assess the functional outcomes at 14 d after onset,0-2 was defined as a good outcome.According to the age of the patients,they were divided into either a young and middle-aged group (＜ 60 years) or an elderly group (≥60 years).The demography,baseline clinical data and laboratory findings of the patients were compared in the overall patients and the different age groups between the good outcome group and the poor outcome group.Multivariate logistic regression analysis was used to determine the independent influencing factors of short-term outcomes.Results A total of 622 patients with acute ischemic stroke were enrolled,including 402 (64.6％) males and 220 (35.4％) females;206 (33.1％) were in the young and middle-aged group,and 416 (66.9％) were in the elderly group;310 (49.8％) had good outcomes and 312 (50.2％) had poor outcomes.There were significant differences in the proportions of patients in male,old people,hyperlipidemia,diabetes mellitus,history of previous stroke or transient ischemic attack (TIA),as well as age,body mass index,levels of prealbumin,albumin,triglyceride,high-density lipoprotein cholesterol low-density lipoprotein cholesterol total bilirubin,direct bilirubin,indirect bilirubin,urea nitrogen,and uric acid between the good outcome group and the poor outcome group (all P ＜0.05).Multivariate logistic regression analysis showed that the female (odds ratio [OR] 1.522,95％ confidence interval [CI] 1.023-2.266;P =0.038),diabetes (OR 1.789,95％ CI 1.171-2.735;P =0.007) and higher low-density lipoprotein cholesterol (OR 1.251,95％ CI 1.017-1.539;P =0.034),total bilirubin (OR 1.054,95％ CI 1.029-1.081;P＜0.001),urea nitrogen (OR 1.245,95％ CI 1.100-1.409;P=0.001),and baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 2.854,95％ CI 1.027-3.628;P =0.019) were the independent risk factors for poor outcomes,and higher prealbumin (OR 0.798 95％ CI 0.633-0.979;P =0.034) and albumin (OR 0.741,95％ CI 0.693-0.988;P =0.020) were the independent predictors of good outcomes.In the young and middle-aged patients,there were significant differences in the proportions of patients with small artery occlusion as well as age,triglyceride,and high-density lipoprotein cholesterol levels between the good outcome group and the poor outcome group (all P ＜0.05);multivariate logistic regression analysis showed that diabetes (OR 2.343 95％ CI 1.127-4.871;P=0.023) and higher baseline NIHSS scores (OR 2.041,95％ CI 1.304-4.125;P =0.027) were the independent risk factors for poor outcome,and higher high-density lipoprotein cholesterol (OR 0.742 95％ CI 0.639-0.937;P =0.044)was an independent predictor for good outcome.In the elderly patients,there were significant differences in the proportions of patients in male,previous stroke or TIA,and cardiogenic embolism,as well as prealbumin,low-density lipoprotein cholesterol,total bilirubin,direct bilirubin,indirect bilirubin,and uric acid levels between the good outcome group and the poor outcome group (all P ＜ 0.05);multivariate logistic regression the analysis showed that diabetes (OR 2.797,95％ CI 1.153-4.756;P =0.039),higher baseline NIHSS score (OR 2.586,95％ CI 1.033-3.435;P =0.035) and higher low-density lipoprotein cholesterol (OR 1.304,95％ CI 1.027-1.656;P =0.029) were the independent risk factors for poor outcome,and higher prealbumin was an independent predictor for good outcome (OR 0.795,95％ CI 0.691-0.998;P =0.002).Conclusions Prealbumin and albumin are the independent predictors for short-term good outcome in patients with acute ischemic stroke.The protective effect of serum prealbumin is more obvious in the elderly population (≥60 years).

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of the low molecular weight polypeptide (LMP) gene with chronic hepatitis C virus (HCV) infection among ethnic Han population from Yunnan.

METHODSA total of 427 patients with chronic HCV infection and 412 healthy controls were recruited. SNPs rs1351383, rs17587 and rs2127675 from the promoter region of the LMP2 gene and rs2071543 from the promoter region of the LPM7 gene were genotyped using a TaqMan probe. The haplotypes were constructed. Frequencies of various alleles, genotypes and haplotypes of the selected SNPs were calculated, and their association with chronic HCV infection was analyzed.

RESULTSThe frequencies of rs1351383 and rs2127675 alleles of the LMP2 gene, as well as the A-G-A and C-G-G haplotypes of the rs1351383/rs17587/rs2127675 loci, had differed significantly between the two groups (P<0.05).

CONCLUSIONThe C allele of the rs1351383 locus and G allele of the rs2217675 locus of the LMP2 gene may be susceptible factors for chronic HCV infection among ethnic Han people from Yunnan. The A-G-A haplotype of the rs1351383/rs17587/rs2127675 loci may confer a protective effect, while the C-G-G haplotype may be a susceptible factor for chronic HCV infection in this population.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Hepatitis C ; genetics ; Humans ; Male ; Peptides ; genetics ; Polymorphism, Single Nucleotide ; genetics