ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

Objective:To explore the effects and potential mechanisms of chemokine-like factor-like MARVEL transmembrane domain-containing Protein 3 (CMTM3) on the proliferation and migration of glioblastoma (GBM) cells.Methods:Using CMTM3 expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we analyzed the differential expression of CMTM3 in GBM tissues and its impact on the prognosis of GBM patients. Immunohistochemical staining and protein content determination of CMTM3 was performed on GBM and adjacent non-cancerous tissue samples from 11 GBM patients who underwent surgical treatment at the Affiliated Hospital of Guizhou Medical University between November 3, 2022 and March 15, 2023. Additionally, the expression of CMTM3 was validated in GBM cell lines U87, U251, LN229, and the human astrocyte (NHA) cell line using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Stable cell lines with silenced and overexpressed CMTM3 (sh-CMTM3 group and OE-CMTM3 group) were constructed using U251 cells. The effect of CMTM3 expression on cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to examine the impact of CMTM3 expression on the cell cycle. Transwell assays were conducted to evaluate the influence of CMTM3 expression on cell migration. Bioinformatics analysis, Western blotting, NF-κB activation-nuclear translocation assays, and the NF-κB pathway inhibitor pyrrolidine dithiocarbamate ammonium (PDTC) were used to validate the effect of CMTM3 on the NF-κB pathway. Finally, a subcutaneous tumorigenesis assay in nude mice was performed to observe the impact of CMTM3 expression on the in vivo growth of U251 cells. Results:Bioinformatics analysis revealed that CMTM3 is highly expressed in GBM tissues. Patients with a high CMTM3 expression had lower overall survival (OS) and disease-free survival (DFS) rates compared with those with a low CMTM3 expression (with P values of 0.010 and 0.032, respectively). Among the 11 GBM pathological specimens, 10 samples exhibited higher CMTM3 protein expression levels in the cancerous tissue compared with the adjacent non-cancerous tissue. The average CMTM3 protein expression in these samples was 0.44±0.09, significantly higher than that in the adjacent non-cancerous tissues (0.12±0.02, P＜0.001). In one sample, the difference in CMTM3 protein expression between the cancerous and adjacent non-cancerous tissues was not statistically significant ( P=0.750).The RT-qPCR results showed that the mRNA expression level of CMTM3 in NHA cells was 1.0±0.1, whereas in GBM cells U87, LN229, and U251, the levels were 2.1±0.3, 3.4±0.5, and 3.7±0.8, respectively, all significantly higher than that in NHA cells (all P＜0.01). Western blot results demonstrated that the protein expression levels of CMTM3 in GBM cells U87, LN229, and U251 were 1.5±0.2, 1.8±0.2, and 1.9±0.1, respectively, also higher than that in NHA cells (0.7±0.2, all P＜0.01), with the highest level observed in U251 cells. The CCK-8 assay, Flow cytometry, and Transwell migration experiments indicated that cell viability was inhibited in the sh-CMTM3 group, with an increase in the proportion of cells in the G 0/G 1 phase ( P＜0.01) and a decrease in the S phase ( P＜0.01), and the number of migrated cells was 233.6±35.5, lower than that in the sh-NC group ( P＜0.001). Conversely, the OE-CMTM3 group showed enhanced cell viability, a reduction in the proportion of cells in the G 0/G 1 phase ( P＜0.01), and an increase in the S phase ( P＜0.01), and the number of migrated cells was 1212.0±20.8, higher than that in the OE-NC group ( P＜0.001). However, in the OE-CMTM3+PDTC group, cell viability, cell cycle distribution (G 1, S, and G 2 phases), and cell migration numbers showed no significant changes (all P＞0.05). Western blot analysis and NF-κB activation-nuclear translocation assay results indicated that in the sh-CMTM3 group, the p-p65/p65 ratio was 0.51±0.04 and the p-IκBα/IκBα ratio was 0.39±0.03, both lower than those in the sh-NC group (both P＜0.01). The cytoplasmic staining rate was (49.29±1.98)%, higher than that in the sh-NC group ( P＜0.01). In the OE-CMTM3 group, the p-p65/p65 ratio was 2.27±0.10 and the p-IκBα/IκBα ratio was 2.14±0.15, both higher than those in the OE-NC group (both P＜0.01). The cytoplasmic staining rate was (18.96±1.44)%, lower than that in the OE-NC group ( P＜0.01). In the OE-CMTM3+PDTC group, there were no significant differences in the p-p65/p65 ratio, p-IκBα/IκBα ratio, and cytoplasmic staining rate compared with the OE-NC group (all P＞0.05). The subcutaneous tumorigenesis assay in nude mice showed that the tumor volume in the sh-CMTM3 group was (408.9±96.2) mm3, smaller than that in the sh-NC group ( P=0.003). The tumor volume in the OE-CMTM3 group was (1 514.5±251.5) mm3, larger than that in the OE-NC group ( P=0.005). Conclusions:In GBM, CMTM3 is highly expressed and negatively correlated with both OS and DFS of patients. CMTM3 regulates the proliferation and migration abilities of U251 cells through the NF-κB signaling pathway.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

INTRODUCTION: The primary objective of this guideline is to establish evidence-based recommendations for the clinical use of parenteral nutrition (PN) in adult patients within the acute hospital setting in Singapore. METHOD: An expert workgroup, consisting of healthcare practitioners actively involved in clinical nutrition support across all public health institutions, systematically evaluated existing evidence and addressed clinical questions relating to PN therapy. RESULTS: This clinical practice guideline developed 30 recommendations for PN therapy, which cover these key aspects related to PN use: indications, patient assess-ment, titration and formulation of PN bags, access routes and devices, and monitoring and management of PN-related complications. CONCLUSION This guideline provides recommendations to ensure appropriate and safe clinical practice of PN therapy in adult patients within the acute hospital setting.
Humans ; Singapore ; Parenteral Nutrition/adverse effects* ; Adult