Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.

Objective To investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.

Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P＜0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P＜0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P＞0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P＞0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.