BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To prepare in-house coagulation factor Ⅷ(F Ⅷ)inhibitor-positive control material and evaluate its perform-ance.Methods Frozen plasma samples from hemophilia A patients with positive factor Ⅷ inhibitors were pooled,and diluted with Owren's Veronal Buffer(OVB)to 1 BU/mL of the inhibitor concentration in the mixture,then aliquoted and freeze-stored.The homo-geneity and stability of the in-house quality control material were verified,and its suitability was further assessed through intra-laborato-ry reproducibility among different technologists and inter-laboratory comparisons.Results Twenty-one aliquots were randomly tested for homogeneity assessment,yielding an average of 1.05 BU/mL(range 0.9-1.15 BU/mL),with a standard deviation(SD)of 0.083 and coefficient of variation(CV)of 7.90％.The freshly prepared inhibitor-positive control samples contained a concentration of 1.03 BU/mL.After storage at-80℃ for 24 hours,1 week,1 month,2 months,3 months,4 months,5 months,6 months,7 months,8 months,and 9 months,thawed the samples showed relative deviations of 9％,0％,10％,9％,14％,15％,6％,0％,-10％,-5％,and 2％,respectively.The intra-laboratory CV value from different technologists at this center was 7.28％,and the inter-labora-tory CV across different centers was 18.75％.Conclusion The prepared in-house positive control material of Factor Ⅷ inhibitor ex-hibited adequate uniformity and stability.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

OBJECTIVE To analyze the characteristics of imported malaria cases in West China Hospital of Sichuan University in recent years and to provide reference for the prevention and control of imported infectious diseases.METHOD A retrospective analysis of 62 cases of imported malaria from abroad reported in West China Hospital of Sichuan University from 2012 to 2023 were retrospectively analyzed.RESULTS From 2012 to 2023,62 cases of imported malaria were reported,including 49 cases(79.03％)of falciparum malaria,10 cases(16.13％)of vivax malaria,and 3 cases(4.84％)of ovale malaria.Among the imported malaria cases,9 cases were severe malaria,with 8(16.33％,8/49)severe cases caused by falciparum malaria,of which 6 cases(75.00％,6/8)were cere-bral malaria.The cases were mainly Chinese citizens and young-to-middle-aged adults,with the highest concentra-tion in the 40-49 age group(37.10％,23/62).There were more males than females,with a male-to-female sex ratio of 11.4∶1;the predominant occupation was worker(38.71％,24/62).The primary region of importation was Africa(90.32％,56/62).There was importation throughout the year,with no distinct seasonal distribution pattern.Two of the admitted cases died(severe cases of falciparum malaria,which developed into cerebral malari-a),while the rest were improved and discharged from the hospital after standardized treatment.CONCLUSIONS Cases of imported malaria from abroad are characterized by Chinese nationality,males,young adults and workers.The type of malaria is mainly falciparum malaria,and the prognosis for most cases is relatively good.It is necessary to strengthen the construction of joint prevention and control systems and other long-term mechanisms,and to continuously and scientifically implement various strategies and measures to prevent the re-emergence of malaria through imported ca-ses,in order to avoid the occurrence of secondary cases resulting from imported infections.

OBJECTIVE To observe the influence of carbapenem-resistant Klebsiella pneumoniae(CRKP)infec-tion/colonization on mortality risk of the intensive care unit(ICU)patients.METHODS The patients who were hospitalized in ICUs of West China Hospital of Sichuan University from Jan.1,2016 to Dec.31,2018 were recrui-ted as the research subjects.By means of retrospective cohort study,the enrolled patients were divided into the CRKP infection/colonization group and the non-CRKP infection/colonization group according to the status of isola-tion of CRKP strains from the clinical specimens of the ICU patients.The 30-day mortality risk of the CRKP in-fection/colonization group and the non-CRKP infection/colonization group was analyzed by Kaplan-Meier.The in-fluencing factors for the 30-day mortality risk of the ICU patients were analyzed by means of Cox proportional haz-ard model.RESULTS A total of 2229 patients were enrolled in the study,of which 89 were assigned as the CRKP infection/colonization group,and 2140 were assigned as the non-CRKP infection/colonization group.The sputum was the major specimen source from the patients with CRKP infection/colonization,and the lower respira-tory tract was the major infection site.The 30-day survival rate was 66.49％in the CRKP infection/colonization group,78.49％in the non-CRKP infection/colonization group,and there was significant difference(x2=7.200,P=0.007).The Cox proportional hazard model analysis showed that the CRKP infection/colonization could in-crease the 30-day mortality risk of the ICU patients(HR=1.839,95％CI:1.126 to 3.002,P=0.015);the age(HR=1.014,95％CI:1.006 to 1.022,P＜0.001),APACHE Ⅱ(HR=1.035,95％CI:1.018 to 1.053,P＜0.001),use of caspofungin(HR=1.398,95％CI:1.038 to 1.882,P=0.028),central venous catheter indwelling(HR=3.752,95％CI:1.808 to 7.790,P＜0.001)and blood purification(HR=2.061,95％CI:1.518 to 2.797,P＜0.001)may also increase the 30-day mortality risk of the ICU patients.CONCLUSIONS The CRKP infection/colonization patients are at higher 30-day mortality risk than the non-CRKP infection/colonization patients.It is necessary to formulate and implement the prevention and control measures to reduce the incidence of CRKP infection/colonization and take measures to reduce the mortality rate of the patients so as to improve the prognosis.

Objective To conduct bibliometrics and visual analysis of local benign paroxysmal positional verti-go(BPPV)research in the past 20 years for further basic and clinical research in the future.Methods We collected the journal articles on BPPV published between January 1,2004 and December 31,2023 from the databases of CNKI,Wanfang,VIP and Web of Science Core Collection.Multidimensional measurement and visual analysis were carried out using bibliometrics software to identify the research hotspots and new trends in this field,and to deter-mine the cooperation and influence among authors,institutions and journals.Results A total of 717 Chinese papers and 212 SCI papers were utilized for the analysis.The literature in this field gradually increased at an average annual growth rate of 12.8％,among which the Journal of Clinical Otolaryngology Head and Neck Surgery published the most articles(n=167),followed by the Chinese Journal of Otology(n=94)and the Journal of Audiology and Speech Pathology(n=76).The journal with the largest number of SCI publications is Frontiers in Neurology(n=44).In terms of authors and institutions,Zhuang Jianhua published the most Chinese papers,Yang Xu published the most SCI papers,and Shanghai Jiaotong University published the earliest and most SCI papers in this field(n=21).The main research keywords in this realm in recent years involve video head pulse test,vestibular migraine,re-sidual symptoms,residual dizziness and anxiety.The keywords retaining burst intensity to 2023 include video head pulse test,residual dizziness,children,anxiety,and residual symptoms.Conclusion Video head impulse test,re-sidual dizziness,children,anxiety and other aspects are critical areas of ongoing research in BPPV.