Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Autism spectrum disorder （ASD）， also known as autism， is a series of neurodevelopmental disorders characterized by social disorders and repetitive stereotyped behaviors/narrow interests. Its pathogenesis is complex， and there is a lack of effective treatment drugs， with some cases having adverse outcomes. Recent studies have consistently revealed that individuals with autism spectrum disorder （ASD） commonly exhibit characteristics such as gut microbiota dysbiosis （abnormal Bacteroidetes/Firmicutes ratio）， impaired intestinal barrier function （elevated serum levels of zonulin and LPS）， and intestinal immune dysregulation （increased pro-inflammatory cytokines including IL-6 and TNF-α）， suggesting that gastrointestinal abnormalities may influence central nervous system development through neuroendocrine， immunoregulatory， and metabolic pathways. Consequently， growing scholarly attention has focused on dietary interventions as potential approaches to alleviate clinical symptoms in children with ASD. This review systematically summarizes the role of gut microbiota and their metabolite alterations in ASD pathogenesis， along with recent advancements in understanding the microbiota-gut-brain axis mechanisms. Additionally， it elaborates on the therapeutic effects and underlying biological basis of restrictive diet therapy， modified diet therapy， and nutritional supplementation therapy in promoting the health of children with ASD. This systematic review reveals that children with ASD exhibit significant gut microbiota dysbiosis （e.g.， increased Clostridium， decreased Faecalibacterium） and abnormal metabolite profiles （e.g.， altered short-chain fatty acid spectra， elevated 4EPS levels）. These alterations exacerbate neuroinflammation and immune dysregulation through the microbiota-gut-brain axis， thereby impacting nervous system development and function. Furthermore， interventions such as ketogenic diets， camel milk， and specific nutritional supplements can alleviate certain ASD symptoms by modulating gut microbiota， restoring intestinal barrier function， and improving metabolic pathways. Future investigations should aim to create multi-omics evaluation systems for pinpointing potential beneficiaries， devise individualized intervention strategies rooted in microbiome characteristics， and verify their therapeutic value and safety in large-scale randomized controlled trials. These efforts are crucial to transitioning ASD treatment from symptomatic control to address disease etiology， thereby paving the way for improving prognoses.

Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

Objective To explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n＝75) and the non-sepsis group (n＝45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P＜0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P＜0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR＝1.12, 95% CI 1.07–1.17, P＜0.001). Survival analysis demonstrated that patients with E/e′ ＞10.9 had lower 28-day survival rates (P＝0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P＜0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.

This study identified the types and pathogen carrying status of fleas on the surface of sheep in some areas of southern Xinjiang,and analyzed the genetic evolution differences with respect to related pathogens.The aim was to provide a reference for the local prevention and control of fleas and insect borne infectious diseases.A total of 1 586 fleas were collected from agricultural and pas-toral areas of Tumushuke City and Hotan Prefecture.Flea species were identified on the basis of morphology and the Pulex irritans mi-tochondrial COII gene.Flea DNA was extracted,and PCR was conducted to amplify the Bartonella gltA gene;Arsenophonus,Ana-plasma,Ehrlichia,and Wolbachia 16S rRNA genes;RickettsiaOmpA,17kDa,16S rRNA genes,and Yersinia pestis 16S rDNA gene.The amplified products were sequenced,and the homology of the genes of the three detected pathogens(gltA gene of Bartonella,16S rRNA gene of Wolbachia,and Anaplasma phagocytophilum)with respect to known corresponding genes of the same pathogen in Gen-Bank was analyzed.Phylogenetic trees were constructed with the adjacency method in MEGA 11.0.According to morphological and mo-lecular biology identification results,all fleas collected in this study were Pulex irritans.PCR indicated that the target gene fragments had been added to the mitochondrial COII,BartonellagltA,Wolbachia,and autophagosomal 16S rRNA genes of human fleas,all of which were consistent with the expected fragment sizes.Target bands were not amplified from Ehrlichia,Arsenophonus,spotted fever group Rickettsia,and Yersinia pestis.According to homology and genetic evolution analysis of human flea mitochondrial COII and the corresponding genes of the above-described pathogens,the COX2 gene(ON455234.1)of human fleas in Tumushuke city and Iran ob-tained in this study showed the highest homology(99.84%).The COII gene(NC_063709.1)of human fleas in Hetan City and Hunan region showed the highest homology(100%).Our findings further confirmed that the flea species was Pulex irritans.The PCR amplifi-cation results indicated that the collected Pulex irritans carried multiple pathogens,among which Bartonella and Wolbachia had the highest infection rates,and the infection rate with Anaplasma phagocytophilum was relatively low.This study is the first to discover flea species on the surface of sheep in some areas of southern Xinjiang.Our findings preliminarily confirmed that Bartonella,Wolba-chia,and Anaplasma phagocytophilum are the main Pulex irritans pathogens.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Blood products are biological products derived from human plasma for use in clinical treatment.As such,they inherently carry the risk of blood-bome viral contamination,which has garnered significant attention from regulatory agencies worldwide regarding the viral safety of these products.This article compares and discusses the differences in domestic and international regulations on viral safety for blood products,focusing on aspects such as raw material selection and viral testing.Additionally,the article explores further impactful measures for viral safety control,namely,viral reduction during the manufacturing process and strategies to prevent cross-contamination.Moreover,we propose corresponding recommendations for China's regulatory framework to further enhance the viral safety of blood products in the country.

Background and Aims:Radical resection is the only potentially curative treatment for intrahepatic cholangiocarcinoma(ICC),yet the high recurrence rate results in poor prognosis.In recent years,"textbook outcome"(TO)has been proposed as a comprehensive quality metric,but its association with prognosis remains unclear.This study aimed to analyze the risk factors influencing the achievement of TO after radical resection of ICC and to explore the relationship between TO and survival.Methods:A retrospective analysis was conducted on the clinical data of 180 ICC patients who underwent radical resection at the 904th Hospital of the Joint Logistic Support Force of the PLA between February 2018 and February 2023.Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with TO,and survival analysis was carried out using the Kaplan-Meier method and Log-rank test.Results:Of the 180 patients,66 achieved TO.Multivariate Logistic regression analysis indicated that preoperative total bilirubin＞22 μmol/L,preoperative CA19-9＞35 U/mL,maximum tumor diameter＞5 cm,poor tumor differentiation,microvascular invasion(MVI),and lymph node metastasis were independent risk factors for failing to achieve TO(all P＜0.05).Survival analysis demonstrated that patients who achieved TO had a significantly longer median survival compared with those who did not(36 months vs.16 months,P＜0.001).Conclusion:Preoperative total bilirubin＞22 μmol/L,preoperative CA19-9＞35 U/mL,maximum tumor diameter＞5 cm,poor tumor differentiation,MVI,and lymph node metastasis are independent risk factors for not achieving TO after radical resection of ICC.Patients who achieved TO exhibited markedly longer survival,suggesting that TO not only reflects perioperative treatment quality but also serves as an important prognostic indicator.Greater attention to these risk factors and optimization of perioperative management may improve the likelihood of achieving TO and enhance long-term outcomes.

Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P＜0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P＜0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P＜0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.

Objective To investigate the predictive capacity of the Triglyceride-Glucose(TyG)index and the Triglyceride-Glucose-Body Mass Index(TyG-BMI)for the development of hyperuricemia(HUA)in a health examination population,and to identify suitable indicators as risk assessment tools for HUA.Methods This study ultimately included 12 004 participants from a health examination cohort.According to SUA levels,the partici-pants were categorized into a normal group(n=9 952)and a hyperuricemia(HUA)group(n=2 052).The TyG index and TyG-BMI index were calculated,and participants were further stratified into four groups(Q1—Q4)based on the quartiles of these indices.Binary logistic regression analysis was performed to assess the association between TyG,TyG-BMI,and HUA.The predictive value of TyG,TyG-BMI,and their combination for HUA was evaluated using Receiver Operating Characteristic(ROC)curves and the Area Under the Curve(AUC).Subgroup analyses were carried out by gender and age.Results The TyG and TyG-BMI indices were significantly elevated in the HUA group compared to the normal group.The prevalence of HUA was markedly higher in the TyG-Q4 and TyG-BMI-Q4 groups than in the other three corresponding quartile groups.Binary logistic regression analysis revealed a positive association between TyG,TyG-BMI levels,and the risk of HUA.The AUC values for predicting HUA using TyG,TyG-BMI,and their combination were 0.700,0.747,and 0.822,respectively.Specifically,for males,the AUC values were 0.641,0.674,and 0.709,respectively,whereas for females,they were 0.742,0.776,and 0.829,respectively.Among individuals younger than 60 years old,the AUC values were 0.716,0.759,and 0.835,respectively,while for those aged 60 years or older,the values were 0.614,0.645,and 0.731,respectively.Conclusions TyG and TyG-BMI are significantly associated with the risk of HUA.Specifically,TyG-BMI demon-strates superior predictive performance compared to TyG alone.Moreover,the combination of TyG and TyG-BMI further improves predictive accuracy,particularly among female and middle-aged or younger populations.