Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5％(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P＞0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P＜0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P＞0.05).Among 17 children infected with TTV,13(76.5％)had co-infections with other viruses,mainly including cytomegalovirus(58.8％,10/17),human polyomavirus(41.2％,7/17),and Epstein-Barr virus(17.6％,3/17).In children with TTV infection,the most common complications were sepsis(82.4％),graft-versus-host disease(GVHD)(70.6％),pulmonary infection(41.2％),and hemorrhagic cystitis(17.6％).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P＜0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

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.

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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

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.