BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

ObjectiveTo enhance the genetic diagnostic yield for fetal short femur length （FL） and to evaluate the integration of whole exome sequencing （WES） with chromosomal abnormality detection in prenatal diagnosis. MethodsA total of 27 mid-to-late trimester fetuses diagnosed with short FL ［FL < 5th percentile for gestational age or < -2 SD （Standard Deviation）］ at the Prenatal Diagnosis And Medical Genetics Center，Shenshan Medical Center，Memorial Hospital of Sun Yat-Sen University between November 2023 and May 2025 were included. Amniotic fluid or umbilical cord blood samples were collected and subjected to chromosomal karyotyping （19cases）， chromosomal microarray analysis （CMA） or low-coverage whole genome copy number variation（CNV-Seq） （27 cases）， and trio-based whole exome sequencing （trio-WES） （27 cases）. The pathogenicity of genetic variants were interpreted according to the American College of Medical Genetics and Genomics （ACMG） guidelines. ResultsTwenty-six genomic variants were detected in 17 of the 26 fetuses， including numerical chromosomal abnormalities （mosaic type）， copy number variations （CNVs）， single nucleotide variants （SNVs） and insertions-deletions （INDELs）. Genomic variants detected in 11 cases could explain the short femur phenotype.The overall diagnostic rate was 11/27， with pathogenic/likely pathogenic variants explaining 9 cases and variants of uncertain significance （VUS） accounting for 1 cases. In addition Chromosomal karyotype analysis revealed chromosome mosaicism explaining 1 case. The diagnostic rate of CNV detection （CMA/CNV-seq） was 2/27， while WES achieved a diagnostic rate of 10/27， with an incremental yield of 8/27 in cases with negative or inconclusive CNV results. Pathogenic mutations involved genes such as FGFR3， SHOX， DUOX2， CLCN5， and HBA1/HBA2. ConclusionTrio-WES significantly improves the genetic diagnostic rate for fetal short femur length， particularly in cases where chromosomal analysis fails to identify a cause. Karyotyping remains valuable for detecting low-level mosaicism in large-scale chromosomal abnormalities， thereby complementing WES and CNV detection. A stepwise or parallel genetic testing strategy is recommended in prenatal diagnosis to optimize diagnostic efficiency and support clinical decision-making.

ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease （MAFLD） through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data， and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization （SMR）/heterogeneity in dependent instruments （HEIDI） test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups， and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression， and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed， 40 showed a causal relationship with MAFLD， among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD （FDR<0.05）. Nine proteins were supported by SMR/HEIDI （P_SMR<0.05， P_HEIDI>0.05）， and 14 showed a strong colocalization signal （PPH₄>0.9）. The transcriptomic analysis identified 5 differentially expressed proteins （all P<0.05）， i.e.， adenosine diphosphate-ribosylation factor-like GTPase 2， insulin-like growth factor binding protein 2， casein kinase 1 delta （CSNK1D）， leucine-rich repeat neuronal 1， and moesin （MSN）. In vitro validation showed upregulated expression levels of MSN （1.612±0.346 vs 0.569±0.077， P<0.05）， 14-3-3 protein theta （YWHAQ） （1.267±0.126 vs 0.313±0.029， P<0.05）， and CSNK1D （0.871±0.025 vs 0.431±0.080， P<0.05） and a downregulated expression level of histone deacetylase 8 （0.637±0.059 vs 1.097±0.260， P<0.05） in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation， YWHAQ modulated the Hippo pathway and lipid signal transduction， and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D， YWHAQ， and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets， providing new directions for research on disease mechanisms and the development of intervention strategies.

Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease， making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine （TCM） in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation， using standardized measurements of the overall TCM condition， multi-omics research of hematologic tumors， and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma， thereby establishing a risk warning system for virus-related lymphoma. At the same time， a TCM health management approach will be applied to manage and regulate virus-related lymphoma， interrupting its progression and forming a human-centered， comprehensive， continuous health service model. Based on this， a standardized， integrated clinical prevention and treatment decision-making model for virus-related lymphoma， recognized by both Chinese and western medicine， will be established to provide TCM solutions for primary prevention of major malignant tumors.

Objective: To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators. Methods: From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed. Results: Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05). Conclusion The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.

The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of genital herpes in China from 2010 to 2023 and provide evidence for the prevention and control of genital herpes.Methods:The reported data of genital herpes cases in 31 provinces (autonomous regions and municipalities) in China from 2010 to 2023 were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Software Joinpoint 5.2.0 was used to analyze the epidemiological characteristics of genital herpes, software ArcGIS 10.5 was used for spatial autocorrelation analysis, and software SaTScan 10.2.3 was used for spatiotemporal scanning analysis.Results:The reported incidence rate of genital herpes increased from 1.58/100 000 to 2.00/100 000 in China from 2010 to 2023, with an average annual percentage change of 0.90%. The upward trend of reported incidence rate was significant ( t=2.35, P=0.037). There was a positive spatial autocorrelation in the reported incidence of genital herpes with the global Moran's I ranging from 0.36 to 0.51 (all P<0.001). Local spatial autocorrelation analysis showed that the number of hotspots increased from 144 in 2010 to 232 in 2023, mainly distributed in provinces Zhejiang, Guangdong, Guangxi, Chongqing and Hunan. The number of hotspots in of Chongqing, Sichuan, Yunnan and Guizhou increased significantly from 7 to 57. A total of 67 spatiotemporal clusters were detected by spatiotemporal scanning analysis, mainly distributed in Guangdong from 2011 to 2015, in Zhejiang and Fujian from 2015 to 2019, and in Chongqing and Guizhou from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence of genital herpes in China showed an upward trend, and there was an obvious spatiotemporal clustering of genital herpes. The distribution of hotspots was basically consistent with the distribution of spatiotemporal clustering areas, mainly distributed in the southeastern coastal area and southwestern region, and the spatiotemporal clustering areas gradually changed from the southeast coastal area to the southwest region.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.