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: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Objective To identify potential ergonomic risk factors of works and quickly assess their risks of developing work-related musculoskeletal disorders (WMSDs) in the medical staff. Methods A total of 188 medical staff were selected as the research objects using a two-stage random sampling method. The method for the identification of musculoskeletal stress factors (PLIBEL) was used to analyze the adverse ergonomic factors in the work process, and the rapid entire body assessment (REBA) was used to quickly assess the whole-body posture load. Results The PLIBEL assessment results showed that various adverse ergonomic factors affected different parts of the body during the work process of medical staff. Specifically, 18 adverse ergonomic factors were identified in the neck, shoulders, and upper back, while 10 adverse ergonomic factors were identified in the elbow, forearm, hand, and lower back. Rehabilitation therapists and nurses engaged in patient handling in general wards and medication preparation and blood collection were exposed to ≥35 adverse ergonomic factors. The REBA assessment showed that the REBA score was 3-12 points for medical staff during their work process. Rehabilitation therapists were classified as having an extremely high ergonomic risk. High-risk occupations included ward housekeeping nurses, surgery assistant nurses, operating-room instrument nurses, and surgeons. Medium-risk occupations included general ward nurses (medication preparation and blood collection, venipuncture/infusion, and patient handling), intensive care unit (ICU) nurses, internal medicine residents, and dentists. Low-risk occupations included administrative front-desk nurses, outpatient internal medicine physicians, and technicians/physicians in ultrasonography, laboratory medicine, physical examination, and occupational health departments. Conclusion Adverse ergonomic factors of medical staff predominantly affect the neck, shoulders, upper back, elbows, forearms, hands, and the lower back during the work process. Rehabilitation therapists, ward housekeeping nurses, ICU nurses, operating-room instrument nurses, and surgeons are high-risk groups for WMSDs. Attention should be paid to the management and control of adverse ergonomic factors for medical staff to prevent the occurrence of WMSDs.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Inhalation therapy,as a drug delivery method directly targeting the respiratory tract and lungs,has been widely used in the treatment of respiratory diseases due to its characteristics of efficient drug delivery,rapid onset,and low systemic side effects.However,traditional inhalation particles still have some limitations in drug stability,release control,and pulmonary delivery efficiency.In recent years,with the continuous development of biochemical materials,the performance of new inhaled particles has been significantly improved,which can provide better drug-loading capacity,more precise release control,and more efficient pulmonary delivery,showing great potential in improving drug efficacy and reducing side effects.This review comprehensively summarizes the classification,preparation techniques,and applications of inhalable particles.It further explores their prospects in precise therapy,personalized medication,and the next-generation drug delivery systems,aiming to promote research and technological innovation in inhalation therapy,ultimately advancing therapeutic solutions for respiratory diseases.

Objective:This study aims to analyze the weight management policy practices in Japan,South Korea,and Singapore to provide international references for improving China's weight health management and metabolic disease prevention system.Methods:Based on the Innovative Care for Chronic Conditions Framework(ICCC),we conducted a literature review and policy analysis methods of domestic and international policies and publications on weight management,systematically analyzing and summarizing relevant strategies and practices to extract key insights in Japan,South Korea,and Singapore.Results:All three countries have established a multi-level collaborative governance system:at the macro level,they built institutional foundations through legislation,cross-sectoral collaboration,and diversified financing;at the meso level,they enhanced management efficiency via comprehensive medical services,multidisciplinary coordination,and smart information systems,while community-level initiatives fostered supportive environments through health education and environmental modifications;at the micro level,they emphasized personalized interventions and family involvement to strengthen self-management capabilities.Conclusion:China can learn from these neighboring countries'experiences to develop a multi-tiered prevention system,strengthen primary care capacity,improve medical security mechanisms,and facilitate a shift from disease treatment to health management,ultimately constructing a weight management solution with Chinese characteristics.

Objective:Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion.Methods:This study combined retrospective and prospective registry approaches. Data were sourced from the case database of Henan province "Multicenter Clinical Observation Study of Variant Angina Pectoris". A total of 507 patients with variant angina pectoris who had complete records from June 1980 to December 2022 were consecutively enrolled. Select patients among them who experienced syncope, and analyze the target vessel sites of coronary artery spasm, arrhythmias during variant angina pectoris attacks, and the degree of stenosis in coronary artery lesions.Results:Among 507 variant angina pectoris patients, 88 experienced syncope. Age was (53.9±9.7) years and 66 patients (75.0%) were male. Forty patients (45.5%, 40/88) were aged 50-59 years. The incidence of syncope in variant angina pectoris caused by left anterior descending artery (LAD) spasm, right coronary artery (RCA) spasm, and multivessel coronary artery spasm was 7.4% (15/202), 22.7% (42/185), and 23.6% (25/106), respectively. The latter two were significantly higher than those in the LAD group ( P all<0.05). Among 77 patients with variant angina pectoris syncope, definitive electrocardiogram recordings were available during syncope episodes. All patients exhibited arrhythmias during syncope: 34 cases involved tachyarrhythmias and 43 cases involved bradyarrhythmias. The incidence of rapid arrhythmias in patients with LAD, RCA, and multi-vessel spasm syncope was 72.7% (8/11), 24.3% (9/37), and 54.2% (13/24), respectively, with P<0.05 for the first two. Bradyarrhythmias occurred in 27.3% (3/11) of LAD, 75.7% (28/37) of RCA, and 45.8% (11/24) of multivessel coronary artery spasm syncope cases, with the first two showing P<0.05. Coronary angiography analysis of 56 syncope patients revealed target vessel locations and stenosis severity: 12 patients had LAD lesions and 41 had RCA lesions, stenosis ≥50% occurred in 66.7% (8/12) and 43.9% (18/41) of these lesions, respectively ( P>0.05). Conclusions:Variant angina pectoris syncope predominantly affects middle-aged males. Bradyarrhythmias triggered by RCA spasm are a common cause, while the incidence of syncope shows no significant correlation with the degree of coronary artery stenostic lesion, whether in the LAD or the RCA.