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.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B （CHB） complicated by metabolic dysfunction-associated fatty liver disease （MAFLD） and explore the correlations between these syndrome types and clinical indicators， as well as ocular manifestation characteristics， thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data， information from the four diagnostic methods of traditional Chinese medicine， clinical indicators， and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis， principal component analysis， and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators， as well as ocular manifestation characteristics， were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation （51.58%）， liver depression with spleen deficiency （31.62%）， blood stasis obstructing collaterals （8.89%）， and Qi-Yin deficiency （7.91%）. No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However， patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， liver stiffness measurement （LSM）， controlled attenuation parameter （CAP）， and alpha-fetoprotein （AFP）， along with lower levels of high-density lipoprotein cholesterol （HDL-C）， compared with those with other syndrome types. Regarding ocular manifestations， the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally， the incidence in scleral zone 3 （corresponding to the large intestine） was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD， commonly accompanied by spleen deficiency， liver depression， blood stasis， and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat， along with a mixture of deficiency and excess， is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them， patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury， whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.

ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

Under the current upsurge of cross-disciplinary research between artificial intelligence （AI） and traditional Chinese medicine （TCM）， the inheritance of academic thought in TCM is confronted with the deep-seated predicament of cognitive paradigm dislocation. The existing AI model is based on the classical reasoning mode of formal logic and statistical probability， which is difficult to adapt to the nonlinear and holistic cognitive logic of TCM with image-based thinking and syndrome-differentiated treatment as the core， resulting in systematic misreading and loss of the core essence in digital inheritance. Based on this， this paper proposes to construct a new cognitive model oriented towards the context of TCM. Its essence is not to have AI imitate the thinking of TCM， but to establish an auxiliary understanding framework based on semantic mapping and relational reasoning. It is advocated that the role of AI should be reconstructed from a knowledge substitute to a clinical interactor， and its application boundary in the inheritance of TCM wisdom should be clarified. By establishing the theoretical framework and practical path of human-computer collaboration， this paper aims to provide a scientific basis for realizing the deep integration of AI technology and the academic thought in TCM.

OBJECTIVE To construct and validate a prognostic prediction model for first-line immune checkpoint inhibitors （ICIs） therapy for advanced non-small cell lung cancer （NSCLC）.METHODS The clinicopathological data and peripheral blood parameters from 211 patients with advanced NSCLC who received first-line ICIs therapy at our hospital from January 2020 to December 2023 were retrospective collected. The patients were randomly divided into a training set （151 cases） and a validation set（60 cases） at a ratio of 7∶3. Using progression-free survival （PFS） as the outcome measure， LASSO regression was used to preliminarily screen predictive variables in the training set，and the preliminarily screened predictive variables were entered into a multivariable Cox regression model to construct Model 1. Meanwhile，restricted cubic splinec analysis was performed on the continuous variables preliminarily screened by LASSO regression. The variables with nonlinear relationships （ P ＜0.1） were analyzed by multivariable Cox regression in RCS form to construct Model 2. The concordance index，receiver operating characteristic curves，calibration curves，and decision curve analysis were used to compare the predictive performance of the two models； the optimal model was selected to construct a nomogram.Sensitivity analysis was performed by reconstructing the multivariable Cox regression model after excluding cases with unknown programmed death-ligand 1（PD-L1）status. Kaplan-Meier method was used to plot survival curves to analyze the survival differences among patients with different risk strata.RESULTS The variables used to construct Model 1 were sex， smoking history， PD-L1 expression status， bone metastasis， and carcinoembryonic antigen （CEA）；the variables used to construct Model 2 were sex， smoking history， PD-L1 expression status， bone metastasis， CEA， neutrophil（Neu）， and albumin（ALB）. The concordance indices of Model 2 were 0.710 in the training set and 0.672 in the validation set，both superior to those of Model 1 （0.649，0.634）. The areas under the curve （AUC） of Model 2 for 12， 18， and 24 months PFS were 0.737，0.782 and 0.788 in the training set，and 0.709，0.630 and 0.663 in the validation set，respectively，all outperforming Model 1 （0.653， 0.704， 0.697 in the training set；0.688， 0.605， 0.651 in the validation set）.The calibration curves of both models showed good consistency between the predicted probability and actual probability，and the clinical net benefit of Model 2 was higher than that of Model 1. Sensitivity analysis indicated that the prediction model was robust. The median PFS of patients in the low-risk group was significantly longer than that in the high-risk group（ P ＜0.05）.CONCLUSIONS Sex， smoking history， PD-L1 expression status， bone metastasis， Neu， ALB， and CEA were independent influencing factors for PFS in advanced NSCLC patients receiving first-line ICIs. The prediction model constructed based on the above factors has good predictive performance and can be used to predict the prognosis of advanced NSCLC patients.

Under the current upsurge of cross-disciplinary research between artificial intelligence （AI） and traditional Chinese medicine （TCM）， the inheritance of academic thought in TCM is confronted with the deep-seated predicament of cognitive paradigm dislocation. The existing AI model is based on the classical reasoning mode of formal logic and statistical probability， which is difficult to adapt to the nonlinear and holistic cognitive logic of TCM with image-based thinking and syndrome-differentiated treatment as the core， resulting in systematic misreading and loss of the core essence in digital inheritance. Based on this， this paper proposes to construct a new cognitive model oriented towards the context of TCM. Its essence is not to have AI imitate the thinking of TCM， but to establish an auxiliary understanding framework based on semantic mapping and relational reasoning. It is advocated that the role of AI should be reconstructed from a knowledge substitute to a clinical interactor， and its application boundary in the inheritance of TCM wisdom should be clarified. By establishing the theoretical framework and practical path of human-computer collaboration， this paper aims to provide a scientific basis for realizing the deep integration of AI technology and the academic thought in TCM.

Objective To revise Guidelines for Diagnosis and Treatment of Commom Diseases of Pediatrics in Traditional Chinese Medicine·Recurrent Respiratory Tract Infections in Children through the Delphi method-based expert questionnaire survey.Methods Bsaed on a comprehensive literature review,the expert questionnaire was developed for the 2024 Edition of the guidelines.Using the Delphi method,the questionnaire was distributed in three rounds to gather expert opinions.Statistical analyses were conducted on expert positivity coefficients and consensus levels,evaluated by expert familiarity,the concentration of expert opinions,and their degree of coordination.Results After three rounds of consultation,consensus was achieved among experts regarding the terminology and definitions,diagnosis,syndrome differentiation,treatment,prevention and health related to recurrent respiratory tract infections in children.This led to the formulation of a draft version of the 2024 Edition of the guidelines for further consultation.Conclusion The participating experts were geographically diverse,held senior titles,and possessed extensive clinical experience,ensuring the credibility of the findings.Their high level of engagement throughout the survey process indicates strong motivation.The content of the expert questionnaire of the Guidelines for the Diagnosis and Treatment of Traditional Chinese Medicine in Children with Recurrent Respiratory Tract Infections in Children(2024 Edition)objectively reflects the core perspectives of the experts,and the results are authentic and reliable,providing a solid foundation for the development of the guidelines.

Objective:To evaluate the efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in elderly women with locally advanced cervical cancer.Methods:A retrospective analysis was conducted among elderly patients with cervical cancer who received nimotuzumab combined with concurrent chemoradiotherapy in the gynecology department of Beijing Hospital from November 2018 to March 2023.Efficacy assessments included the objective response rate(ORR), recurrence rates after 1-3 years of follow-up, and comparisons of the levels of squamous cell carcinoma antigen(SCC), carcino-embryonic antigen(CEA), and carbohydrate antigen 125(CA125)before and after treatment.Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 5.0.Results:A total of 47 elderly patients aged 60 years and older with stage ⅠB3-Ⅳa cervical cancer were included, with ages ranging from 60 to 76 years[mean age: (65.8±4.3) years; median age: 65(62, 70) years].The patients were divided into three age groups: 60-64 years(21 cases), 65-69 years(14 cases), and ≥70 years(12 cases).After treatment, SCC and CEA levels significantly decreased compared to pre-treatment levels, with statistically significant differences ( W=5.281 and 2.607, respectively; both P<0.05).However, there was no significant difference in CA125 levels before and after treatment( W=1.591, P=0.112).Among the 47 patients, 3 did not undergo post-treatment imaging examinations.Efficacy evaluation results were collected from 44 patients, including 21 cases of complete response(CR)(47.7%), 21 cases of partial response(PR)(47.7%), 1 case of stable disease(SD)(2.3%), and 1 case of progressive disease(PD)(2.3%).The ORR was 95.5%(42/44), and the diseae control rate was 97.7%(43/44).There were statistically significant differences in efficacy among different age groups(Fisher's exact test P=0.015).During the treatment process, a total of 36 patients experienced grade 3 or higher adverse reactions during treatment.Among them, 14 cases(29.8%)with grade 3 or higher acute hematological adverse reactions, 11 cases(23.4%)with grade 3 or higher acute gastrointestinal reactions, and 6 cases(12.8%)with grade 3 or higher acute urinary symptoms.Additionally, 2 cases of radiation cystitis and 3 cases of radiation proctitis were reported.There was no statistically significant difference in recurrence rates among different age groups(Fisher's exact test P=0.292).The highest recurrence rate among elderly patients was observed at the 2-3 year follow-up. Conclusions:For elderly patients with good organ function status, standard concurrent chemoradiotherapy combined with nimotuzumab may be an effective treatment for locally advanced cervical cancer.

Alzheimer′s disease(AD), as a common cognitive impairment disorder in the elderly, has imposed a significant burden on the global public health system.The latest international diagnostic criteria emphasize defining AD from a biological perspective and viewing it as a continuous pathological and physiological change process.This article, guided by the principle of ′early diagnosis-precision intervention′, systematically elaborates on the current research status of AD regarding diagnostic criteria, biomarkers, new drug development, and the establishment of China-specific AD cohorts.It also provides an in-depth outlook on the future research directions and clinical application prospects of AD.