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Risk of Pediatric Bipolar Disorder After General Anesthesia in Infants and Toddlers: A Propensity Score-Matched Population-Based Cohort Study.

The potential role of anesthesia as an independent risk factor for childhood bipolar disorder (BD) remains unclear. To address this, we conducted a population-based cohort study employing propensity score matching to compare BD incidence between pediatric patients undergoing surgery with and without general anesthesia. Our study included patients aged 0-3 years who received at least 1 episode of general anesthesia and were hospitalized for over 1 day in Taiwan between January 2004 and December 2014. They were matched 1:1 with a population not receiving general anesthesia to assess pediatric BD incidence. The study cohort comprised 15 070 patients, equally distributed between the general anesthesia and nongeneral anesthesia groups (7535 each). Multivariate Cox regression analysis revealed adjusted hazard ratios (aHRs; 95% CIs) for pediatric BD in the general anesthesia group as 1.26 (1.04-1.54; P = .021) compared to the nongeneral anesthesia group. Moreover, the incidence rate ratio (95% CI) for the general anesthesia group was 1.26 (1.03-1.53) compared to the nongeneral anesthesia group. Early childhood exposure to general anesthesia is significantly associated with an increased risk of pediatric BD. This expands understanding of pediatric BD's complex development, informing preventive strategies, and enhancing mental health outcomes for vulnerable young patients and global pediatric healthcare.

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Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial

BackgroundA recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy.MethodsThis is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years.ResultsNo significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493).ConclusionsAmong patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

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Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases. A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90. Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km. In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.

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Causal relationship between narcolepsy and anxiety: A two-sample Mendelian randomization study

BackgroundThe aim of this study was to assess the causal relationship between narcolepsy and anxiety using Mendelian randomization (MR) methodology. MethodsOur research applied a bidirectional two-sample Mendelian Randomization strategy to explore the linkage between narcolepsy and anxiety. Utilizing summary data from GWAS on both conditions, we primarily employed the inverse-variance weighted technique for our analysis. To evaluate heterogeneity and horizontal pleiotropy, we utilized tools such as the MR Egger method, the weighted median method, Cochran's Q statistic, and the MR Egger intercept. ResultsThe analysis using the inverse variance-weighted method showed a clear positive link between narcolepsy and anxiety, with an odds ratio of 1.381 (95% CI: 1.161–1.642, p < 0.001). Tests for heterogeneity and horizontal pleiotropy, including MR Egger and IVW methods, indicated no significant findings (p-values 0.616 and 0.637, respectively, for heterogeneity; p = 0.463 for pleiotropy). Furthermore, no reverse causation was observed between anxiety and narcolepsy (odds ratio 1.034, 95% CI: 0.992–1.078, p = 0.111), with consistent findings across various analytical approaches. ConclusionThis research suggests a possible causal link between narcolepsy and anxiety disorders. The results illuminate this connection and advocate additional studies to elucidate the mechanisms involved and to identify effective interventions.

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The effect of budesonide-formoterol powder inhalation on cough and lung function following thoracoscopic pulmonary surgery: a retrospective cohort study.

To explore whether portable budesonide-formoterol powder inhalation can ameliorate cough symptoms and improve pulmonary function recovery in patients who underwent thoracoscopic lung surgery. Clinical data of patients who underwent thoracoscopic pulmonary resection at Henan Provincial People's Hospital between December 2022 and May 2023 were extracted. To evaluate the impact of continuous post-operative use of portable budesonide-formoterol powder inhalation, patients were divided into two groups: the control group and the case group. Next, we compared the Leicester cough score and pulmonary function indexes of the patients before surgery, one month and six month after the operation. A total of 188 cases were included, and the baseline demographic characteristics of both groups were well-balanced. The internal consistency of the LCQ-MC scale, as indicated by Cronbach's α coefficients, were all greater than 0.8, and there was no significant difference in LCQ-MC scores between the two groups before the operation (Z=-1.173, P=0.241). Postoperatively, the LCQ-MC score in the case group was significantly higher than that in the control group (18.66 vs. 16.79, P<0.01), with a notable statistically significant difference in the reduction of LCQ-MC scores between the two groups (1.32 vs. 3.30, P<0.01). Analysis of lung function revealed that patients in the case group exhibited significant improvements in FEV1/FVC, FVC, FEV1, PEF, MMEF75/25, MVV, DLCO and the RV/TLC indexes compared to the control group (P<0.01). Portable budesonide-formoterol powder inhalation can alleviate cough symptoms and promote pulmonary function recovery in patients following thoracoscopic lung surgery.

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Assessing public health service capability of primary healthcare personnel: a large-scale survey in Henan Province, China

BackgroundThe public health service capability of primary healthcare personnel directly affects the utilization and delivery of health services, and is influenced by various factors. This study aimed to examine the status, factors, and urban-rural differences of public health service capability among primary healthcare personnel, and provided suggestions for improvement.MethodsWe used cluster sampling to survey 11,925 primary healthcare personnel in 18 regions of Henan Province from 20th to March 31, 2023. Data encompassing demographics and public health service capabilities, including health lifestyle guidance, chronic disease management, health management of special populations, and vaccination services. Multivariable regression analysis was employed to investigate influencing factors. Propensity Score Matching (PSM) quantified urban-rural differences.ResultsThe total score of public health service capability was 80.17 points. Chronic disease management capability scored the lowest, only 19.60. Gender, education level, average monthly salary, professional title, health status, employment form, work unit type, category of practicing (assistant) physician significantly influenced the public health service capability (all P < 0.05). PSM analysis revealed rural primary healthcare personnel had higher public health service capability scores than urban ones.ConclusionsThe public health service capability of primary healthcare personnel in Henan Province was relatively high, but chronic disease management required improvement. Additionally, implementing effective training methods for different subgroups, and improving the service capability of primary medical and health institutions were positive measures.

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Prognostic implications of tumor mutation burden in postoperative patients with colorectal cancer who received capecitabine-based adjuvant chemotherapy: a retrospective exploratory study

Abstract Background: This study aimed to investigate the prognostic implications of tumor mutation burden (TMB) in patients with colorectal cancer (CRC) who underwent surgical resection and capecitabine-based adjuvant chemotherapy. Methods: A total of 82 patients with CRC who underwent surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Tumor tissue specimens were collected for DNA extraction after surgical resection. Somatic mutation detection and TMB analysis were performed using next-generation sequencing (NGS) of tumor-related genes. The recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and the long-term survival data of patients were obtained by telephone follow-up. The univariate analysis between TMB status and prognosis was carried out by Kaplan-Meier survival analysis and adjusted by multivariate Cox regression analysis subsequently. Results: The median follow-up period of this study was 5.3 years (range: 0.25-9.6 years). The median disease-free survival (DFS) of the 82 patients was 4.5 years, the median overall survival (OS) was 5.7 years. The results of NGS analysis demonstrated that the most common mutated somatic genes among the 82 patients were TP53, APC, RAS, PIK3CA and EGFR, and the prevalence was 62.2%, 58.5%, 47.6%, 34.1% and 30.4%, respectively. Other somatic mutant genes were of relatively low frequency (&lt;30%). Regarding the TMB analysis, the overall somatic mutation burden of the 82 patients was comparatively low [median: 3.9/Mb (range: 1.6-48.6/Mb)]. TMB status was divided into TMB-L (≤3.9/Mb) and TMB-H (&gt;3.9/Mb) according to the median TMB threshold. And the patients with TMB-L and TMB-H were observed in 42 cases and 40 cases, respectively. Prognostic analysis according to TMB status demonstrated that the median OS of patients with TMB-L and TMB-H was 6.5 and 4.5 years, respectively (P=0.009). Additionally, in order to adjust the confounding factors that might influence OS, a multivariate Cox regression analysis was introduced and the results exhibited that TMB status was an independent factor for OS (HR=0.71, P=0.011). Conclusion: TMB might be considered as a potential biomarker for predicting the prognosis of patients with CRC who underwent surgical resection and capecitabine-based adjuvant chemotherapy. Results of this study should be elucidated in large-scale prospective clinical trial subsequently.

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SLAMF8 as a potential biomarker for rheumatoid arthritis identified by comparing peripheral blood mononuclear cells, fibroblast‐like synoviocytes, and synovial tissue using bioinformatics analysis

AbstractBackgroundRheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Its pathogenesis is not fully understood, and early diagnosis is challenging owing to the lack of effective biomarkers. This study aimed to analyze different samples to identify potential biomarkers and therapeutic targets.MethodsMicroarray datasets of RA, osteoarthritis (OA), and healthy control (HC) were downloaded from the Gene Expression Omnibus database. R software was used to identify differentially expressed genes (DEGs), which were visualized using volcano and heat maps. Venn diagrams, principal component analysis, gene set enrichment analysis, gene ontology, and Kyoto Encyclopedia of genes and genomes were used to analyze the data. A protein–protein interaction network was constructed, and synovial tissues from patients with RA and OA were collected for verification using the collagen‐induced arthritis mouse model.ResultsMore DEGs were found in synovial tissues than in peripheral blood mononuclear cells or fibroblast‐like synoviocytes. Principal component analysis revealed significant differences between the RA and OA samples, highlighting the unique advantages of synovial tissue. Enrichment analysis revealed that metabolic and cytokine signaling pathways play crucial roles in the development of RA. Further analysis of the four synovial datasets identified 54 DEGs, of which signaling lymphocytic activation molecule family (SLAMF) 8 was identified as the key molecule. SLAMF8 levels were increased in the synovial tissue of patients with RA compared to those of patients with OA (0.38 ± 0.19 vs. 12.40 ± 1.66), and SLAMF8 levels were similarly elevated in collagen‐induced arthritis model mice compared with those in the healthy mice (1.13 ± 0.47 vs. 9.05 ± 2.52).ConclusionsThis study established the unique advantages of synovial tissue for RA research and identified metabolic and cytokine signaling pathways as important for RA development. Thus, SLAMF8 may be a potential therapeutic target for RA.

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Gut Microbiome and Immune Dysregulation in Childhood Atopic Dermatitis with Food Allergy

Background: This study aims to investigate whether immune dysregulation and gut microbiome alteration are exacerbated in atopic dermatitis (AD) with food allergy (ADFA) and potential treatment strategies. Methods: Total 159 children with AD (tAD) were divided into two groups: AD without-food allergy (ADNFA) and with food allergy (ADFA); 100 children without AD were included as control. Eosinophil counts and total serum IgE levels were measured by routine methods, serum food-specific IgE levels by quantitative fluorescence immunoassay, and serum cytokine levels by multi-microsphere flow immunofluorescence. The intestinal microbiota was evaluated in fecal specimens using metagenomic sequencing. A novel ADFA mouse model was generated to evaluate whether probiotic candidates identified from human fecal samples contributed to the improvement in ADFA pathology. Results: The levels of eosinophils, IgE, IL-2, TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, IL-12P70 and IFN-α were elevated in tAD compared to normal controls. Compared with ADNFA, the levels of eosinophils, IgE and IL-5 were persistently increased, while IFN-γ was decreased, the species of Lactococcus lactis (L. lactis) was reduced in ADFA. Compared with AD, the ADFA model had more severe skin lesions on the back and significantly higher serum OVA-specific IgE, IL-4 and IL-5. Following oral administration of L. lactis ( L. lactis 1.1936+1.3992), skin lesions in ADFA mice was significantly improved. The levels of OVA-specific IgE, IL-4 and IL-5 decreased in a dose-dependent manner. Conclusions: Food allergy aggravates immune dysregulation and gut microbiome dysbiosis in children with AD. L. lactis could be a candidate probiotic for the treatment of ADFA.

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