ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

To evaluate the clinical value of nebulized indocyanine green(ICG) combined with near-infrared fluorescence imaging for intraoperative detection of air leaks during pulmonary resection.

Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each corresponding to a specific peripheral immune response pattern. Elucidating these peripheral immune response patterns may facilitate the objective quantification of the degree of vital qi deficiency, prediction of future metastasis risk, and providing an important reference for the individualized clinical implementation of Fuzheng Juandu therapy.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.

Objective:To investigate the feasibility and clinical effects of ultra early enteral nutrition (≤24 h) in critically ill children supported by extracorporeal membrane oxygenation (ECMO).Methods:A retrospective cohort study was conducted. Clinical data of 43 critically ill children who received ECMO support in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2016 to December 2023 were collected, including general information, nutritional support modalities, and enteral nutrition tolerance. Based on the timing of enteral nutrition initiation, patients were divided into the within 24 h enteral nutrition group and the after 24 h enteral nutrition group. Nutritive indicators, nutritional intake, duration of ECMO support, duration of mechanical ventilation duration, and mortality rates were compared between the 2 groups using the two independent sample t test, Mann-Whitney U test, χ2 test and Fisher′s exact test. Results:Among the 43 children, 25 were male and 18 were female, with an age of 47 (18, 97) months. There were no statistically significant differences between the within 24 h enteral nutrition group (21 cases) and the after 24 h enteral nutrition group (22 cases) in terms of age, body mass index Z score, total protein, albumin, hemoglobin levels before ECMO support, duration of ECMO support, duration of mechanical ventilation, length of PICU stay, number of enteral nutrition intolerance events, number of enteral nutrition interruption, or mortality rate (all P>0.05). The protein intake adequacy rate during ECMO support was higher in the within 24 h enteral nutrition group than in the after 24 h enteral nutrition group (0 (0, 21%) vs. 0 (0, 0), U=175.00, P<0.05). Conclusions:Ultra early enteral nutrition is safe for children supported by ECMO. Initiating enteral nutrition within 24 h can increase the proportion of days with adequate protein intake in ECMO children without increasing the occurance of enteral nutrition intolerance or interruptions.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Transmembrane proteins (TMEM) are a type of membrane protein. Most proteins in this family are located in the phospholipid bilayer of the cell membrane, while a smaller portion is found in the membranes of cellular organelles. Transmembrane protein 43 (TMEM43) is a member of the TMEM protein family and is encoded by the TMEM43 gene. This protein consists of 400 amino acids and has 4 transmembrane domains and 1 membrane-associated domain. TMEM43 is localized to various biological membranes within the cell, such as the cell membrane and nuclear membrane, where it forms transmembrane channels for various ions. Additionally, TMEM43 is expressed in many species, showing high genetic similarity, especially with the four transmembrane domains being highly conserved. Current studies on the TMEM43 gene are still in its early stages, mainly focusing on its association with arrhythmogenic right ventricular cardiomyopathy (ARVC) and cancer. However, recent studies suggest that pathogenic mutations in TMEM43 may cause auditory neuropathy spectrum disorder (ANSD). Patients with TMEM43 p.Ser372Ter exhibited late-onset progressive ANSD. Impact of TMEM43 pathogenic mutations on individual hearing was likely mediated through effects on gap junction (GJ) structures on glia-like supporting cells (GLS), cell membranes. The TMEM43 p.Arg372Ter pathogenic mutation primarily affected the structure and function of TMEM43 protein, leading to premature termination of protein translation and the production of a truncated protein. Abnormal TMEM43 protein significantly reduced K⁺ influx in GLS cells, disrupting the endolymphatic K⁺ circulation and cochlear microenvironment homeostasis. When K⁺ circulation was obstructed, the endocochlear potential (EP) became abnormal, impairing the physiological function of hair cells and potentially leading to hearing impairment. However, it is important to note that studies on the mechanism is limited, and more experimental evidence is needed to confirm this hypothesis. Currently, there is a significant gap in research on TMEM43 and hearing loss, with many issues remaining unresolved. While TMEM43 has been studied in relation to hearing loss in humans, zebrafish, mice, and rats, the research is still preliminary. Detailed investigations into the molecular pathogenic mechanisms, the impact of mutations on hearing damage, and related therapeutic strategies are needed. Additionally, as a newly identified hearing loss-related gene, the mutation frequency and incidence of hearing disorders associated with TMEM43 have not been effectively quantified. For example, the ClinVar database listed 829 mutation sites for the TMEM43 gene, with only three mutations related to auditory neuropathy: c.605A>T (p.Asn202Ile), c.889T>A (p.Phe297Ile), and c.1114C>T (p.Arg372Ter). Aside from the aforementioned TMEM43 c.1114C>T (p.Arg372Ter) mutation observed in patients, the other two mutations were experimentally induced and have not been found in patients. Consequently, these mutations have been classified as unknown significance. We reviewed the current understanding of TMEM43 and hearing loss, analyzed its role in ear development and sound conduction, and explored the impact of TMEM43 gene variations on hearing loss, aiming to provide new insights for future research and precision medicine related to TMEM43.