Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Work serves as a critical means of obtaining resources, facilitating personal growth, realizing self-worth, and engaging in social interactions. However, work-related diseases pose significant threats to workers’ health and productivity, and impose considerable economic burdens. This article categorized work-related diseases into six major types, including musculoskeletal disorders, mental and behavioral disorders, cardiovascular and metabolic diseases, digestive system diseases, reproductive system diseases, and non-specific respiratory diseases, and summarized their risk factors, assessment methods, policy regulation, and prevention and control measures. Current research in this field predominantly relies on cross-sectional studies, which present limitations in causal inference and potential risks of bias. Future studies should expand sample sizes, optimize research designs, and establish multidimensional evaluation systems to comprehensively assess the health and economic impacts of work-related diseases. It is recommended to enhance the translation of research findings into practice, thereby providing a scientific basis for the occupational health protection system and promoting the well-being and sustainable development of the working population.

OBJECTIVE To investigate the regulatory effect of vitamin D3(VD3)-mediated TIPE2 on macrophage function and phenotype in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS Peripheral blood samples were collected from 100 CRSwNP patients and 100 patients with simple nasal septum deviation.RT-qPCR and Western blot were used to measure the expression of TIPE2 and Arg-1,and chemiluminescence was used to measure VD3 concentration.In the J774A.1 macrophage cell line,TIPE2 was silenced,and in CRSwNP model mice,TIPE2 was overexpressed,followed by treatment with overexpressed TIPE2 combined with VD3.Western blot was used to measure the expression of TIPE2 and Arg-1,and ELISA was used to measure the expression of IL-4 and IL-13.RESULTS In the CRSwNP group,VD3 levels decreased,while TIPE2 and Arg-1 levels increased(all P<0.05).Arg-1 and TIPE2 were positively correlated(r2=0.994,P<0.05),and both were negatively correlated with VD3 levels(r2=0.652,P<0.05;r2=0.745,P<0.05).Silencing TIPE2 in J774A.1 cells led to a decrease in Arg-1,IL-4,and IL-13 levels(all P<0.05).In CRSwNP mice,overexpression of TIPE2 resulted in decreased VD3 and increased Arg-1,IL-4,and IL-13 levels,which were reversed by VD3 treatment(all P<0.05).CONCLUSION VD3 inhibits the expression of Arg-1,IL-4,and IL-13 in CRSwNP by downregulating TIPE2 expression.

Objective : To explore the role and mechanism of 25-hydroxycholesterol (25-HC) in inflammatory bow- el disease (IBD) in mice． Methods : All mice were divided into three groups : the control group was fed normally ; the DSS model group was fed with 2. 5% dextran sulfate sodium (DSS) solution ; the DSS + 25-HC experimental group was fed with 2. 5% DSS solution and he mice in the experimental group were intraperitoneally injected with 25-HC．The symptom changes of the mice were evaluated by assessing the disease activity index(DAI) ，and the tis- sue changes were judged by histological scoring．The expression of interleukin-17 and its signaling pathways in the mice were detected by Western blot，qRT-PCR, immunohistochemistry /fluorescence，and flow cytometry．Combined with the detection of tight junction proteins in the intestinal epithelium of the mice，the mechanism by which 25-HC affects IBD in mice was explored． Results : In comparison to the DSS control group，The DSS + 25-HC experimen- tal group mice exhibited a reduction in body weight ( F = 30. 1，P ＜0. 000 1) ，a shortened colon ( F = 63. 8，P < 0. 05) ，and elevated DAI(F = 774. 5，P＜0. 000 1) and histopathological scores(F = 141. 5，P＜0. 05) ．Addition- ally，the expression of tight junction-associated proteins(ZO-2，Occludin，JAM and Claudin-4) was found to be sig- nificantly reduced．The level of IL-17 significantly decreased，and its expression level was positively correlated with tight junction proteins． Conclusion 25-HC inhibited IL-17 production by colonic γδ T cells through the RORγt pathway，aggravated mucosal injury，and promoted the development of DSS-induced acute colitis in mice．

AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

Constructing an efficient and easy-to-operate multigene expression system is currently a crucial part of plant genetic engineering. In this study, a fragment carrying three independent gene expression cassettes and the expression unit of the gene-silencing suppressor protein(RNA silencing suppressor 19 kDa protein, P19) simultaneously was designed and constructed. This fragment was cloned into the commonly used plant expression vector pCAMBIA300, and the plasmid pC1300-TP2-P19 was obtained. Each gene expression cassette consists of different promoters, fusion tags, and terminators. The target gene can be flexibly inserted into the corresponding site through enzymatic digestion and ligation or recombination and fused with different protein tags, which provides great convenience for subsequent detection. The enhanced green fluorescent protein(eGFP) reporter gene was individually constructed into each expression cassette to verify the feasibility of this vector system. The results of tobacco transient expression and laser-confocal microscopy showed that each expression cassette presented independent and normal expression. Meanwhile, the three key enzyme genes in the betanin synthesis pathway, BvCYP76AD, BvDODA1, and DbDOPA5GT, were constructed into the three expression cassettes. The results of tobacco transient expression phenotype, protein immunoblotting(Western blot), and chemical detection of product demonstrated that the three exogenous genes were highly expressed, and the target compound betanin was successfully produced. The above results indicated that the constructed multigene expression system for plants in this study was efficient and reliable and can achieve the co-transformation of multiple plant genes. It can provide a reliable vector platform for the analysis of plant natural product synthesis pathways, functional verification, and plant metabolic engineering.
Nicotiana/metabolism* ; Genetic Vectors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Genetic Engineering/methods* ; Green Fluorescent Proteins/metabolism* ; Gene Expression

Objective To analyze the changes in myocardial injury markers and cardiac function in patients with hypertrophic obstructive cardiomyopathy (HOCM) after Liwen surgery. Methods A retrospective analysis was conducted on the clinical data of HOCM patients who underwent Liwen surgery at the Department of Cardiac Surgery, Wuhan Asia Heart Hospital from December 2019 to April 2023, mainly including preoperative and postoperative dynamic follow-up laboratory test results and echocardiograms. Results A total of 42 patients were included, with 25 males and 17 females, aged (44.76±17.72) years, and a postoperative follow-up time of (15.02±6.97) months. The myocardial troponin level of the patients decreased from preoperative 0.03 (0.02, 0.06) ng/mL to postoperative 0.02 (0.01, 0.05) ng/mL (P=0.006), and the N-terminal pro-brain natriuretic peptide level decreased from preoperative 748.95 (337.40, 1600.75) ng/L to postoperative 367.15 (126.93, 1030.25) ng/L (P<0.001). After surgery, the left atrial diameter of the patients decreased from preoperative (4.18±0.57) cm to postoperative (3.93±0.55) cm (P=0.004), the end-diastolic interventricular septum thickness decreased from preoperative 2.25 (1.90, 2.75) cm to postoperative 1.70 (1.50, 1.90) cm (P<0.001), the left ventricular mass index decreased from preoperative 211.73 (172.28, 261.54) g/m2 to postoperative 156.78 (132.34, 191.36) g/m2 (P<0.001), the left ventricular weight decreased from preoperative 368.89 (292.34, 477.72) g to postoperative 266.62 (224.57, 326.04) g (P<0.001), the end-diastolic posterior wall thickness of the left ventricle decreased from preoperative 1.30 (1.20, 1.60) cm to postoperative 1.20 (1.18, 1.40) cm (P<0.001), the relative wall thickness decreased from preoperative 0.78 (0.78, 1.02) to postoperative 0.63 (0.56, 0.72) (P<0.001), the end-systolic inner diameter of the left ventricle increased from preoperative (2.91±0.50) cm to postoperative (3.19±0.53) cm (P=0.001), and the end-diastolic inner diameter of the left ventricle increased from preoperative (4.41±0.48) cm to postoperative (4.66±0.52) cm (P=0.005). The left ventricular outflow diameter increased from preoperative (1.28±0.46) cm to postoperative (1.57±0.32) cm (P=0.001), the left ventricular outflow pressure gradient decreased from preoperative 58.50 (40.75, 92.50) mm Hg to postoperative 11.50 (7.75, 20.50) mm Hg (P<0.001), the left ventricular ejection fraction increased from preoperative 60.00% (56.75%, 65.00%) to postoperative 63.00% (62.00%, 66.00%) (P=0.024), and the degree of systolic anterior motion of the mitral valve leaflets decreased (P＜0.001). Conclusion The cardiac function of patients with HOCM is improved after Liwen surgery, myocardial injury marker levels are decreased, cardiac reverse remodeling occurres, and the surgical outcome is good.

Objective To investigate the effect of the small molecule inhibitor C42 of kallikrein-related peptidase 7(KLK7)on ovarian cancer with elevated expression of KLK7 and evaluate the feasibility of C42 as a new therapeutic strategy for ovarian cancer.Methods The CCK-8 assay,flow cytometry,cell scratch assay,Transwell assay,and Western blotting were employed to assess the effects of C42 on the proliferation,migration,and invasion of the ovarian cancer cell line SKOV3,which was characterized by high KLK7 expression.Additionally,a subcutaneous xenograft model of ovarian cancer was established with SKOV3 cells in nude mice to evaluate the effects of C42 on the tumor growth and metastasis.The expression levels of proteins associated with tumor metastasis and invasion in the tumor tissue were examined by immunohistochemical techniques.Results The cellular experiment showed that C42 suppressed the proliferation,migration,and invasion(all P<0.001)of SKOV3 cells,compared with the control group.The animal experiment showed that compared with the control group,the 10.2 mg/kg C42 group exhibited a decreased tumor weight(P=0.009) and attenuated liver metastases.Immunohistochemical staining revealed that the 10.2 mg/kg C42 group demonstrated down-regulated expression of the tumor proliferation marker Ki-67(P=0.002)and the tumor metastasis and invasion-associated proteins such as matrix metalloproteinase-9(P=0.027)and Vimentin(P=0.039).Conclusion The small molecule inhibitor C42 of KLK7 effectively suppresses the proliferation,migration,and invasion of ovarian cancer SKOV3 cells.
Female ; Humans ; Ovarian Neoplasms/drug therapy* ; Kallikreins/antagonists & inhibitors* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C