OBJECTIVE To investigate the protective effects and potential mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice. METHODS Fifty male Kunming mice were divided into the blank group， model group， and alisol B 23-acetate low-， medium- and high-dose groups （10， 20， 40 mg/kg）， with 10 mice in each group. Each group was given relevant drug solution or normal saline intragastrically， once a day， for 2 consecutive weeks. On the 15th day， mice in the blank group were given normal saline intragastrically， while the other four groups were given 12 mL/kg white wine intragastrically， twice at six-hour intervals， to establish an acute alcoholic liver injury model. On the 16th day of the experiment， the liver indexes of mice in each group were calculated； the serum levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglycerides （TG）， malondialdehyde （MDA） and glutathione （GSH） were also determined. The histopathological morphology of their liver tissues was observed and scored. The protein expressions of cytochrome P450 2E1 （CYP2E1）， Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor erythroid 2-related factor 2 （Nrf2） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were measured in liver tissue. RESULTS Compared with model group， mice in each dosage group of alisol B 23-acetate showed varying degrees of recovery in body weight， along with improvements in pathological changes in liver tissues such as inflammatory cell infiltration and fatty vacu oles. Their liver indexes， histopathological scores of liver tissue， serum levels of ALT， AST， TC， TG and MDA， as well as the protein expressions of CYP2E1 and Keap1 in liver tissue， were all significantly decreased （ P ＜0.05 or P ＜0.01）. The serum GSH levels and the protein expressions of Nrf2 （except for the alisol B 23-acetate low-dose group） and NQO1 in liver tissue were significantly increased （ P ＜0.05 or P ＜0.01）， and the changes in the above quantitative indicators showed a dose-dependent pattern. CONCLUSIONS Alisol B 23-acetate can ameliorate acute alcoholic liver injury in mice， and its mechanism may be related to improving antioxidant capacity by regulating the Keap1/Nrf2/NQO1 signaling pathway while simultaneously improving liver lipid metabolism-related indexes.

Objective To understand the current status of blood pressure variability and dyslipidemia in young and middle-aged patients with ischemic stroke, and to explore their relationship with prognosis. Methods A total of 312 young and middle-aged patients with ischemic stroke who met the inclusion criteria in Beijing Pinggu District Hospital from January 2022 to January 2025 were selected. The prognosis status [modified Rankin scale (mRS)], blood pressure variability, and blood lipids [total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were analyzed. The correlation of blood pressure variability and blood lipids levels with prognosis was explored by logistic regression analysis. Results There were 206 patients with good prognosis and 106 patients with poor prognosis. The number of patients who received diversified health education in the good prognosis group was more than that in the poor prognosis group (P<0.05). The systolic blood pressure successive variation (SV) and average real variability (ARV), and diastolic blood pressure SV and ARV were lower in the good prognosis group than those in the poor prognosis group (P<0.05). Furthermore, compared with the poor prognosis group, the good prognosis group had lower levels of TC, TG and LDL-C, while the number of patients receiving diversified health education and the level of HDL-C were higher (P<0.05). After logistic regression analysis, it was found that the levels of TC, TG, LDL-C, systolic blood pressure SV and ARV, and diastolic blood pressure SV and ARV were risk factors for poor prognosis. Conversely, receiving diversified health education and HDL-C level were protective factors for poor prognosis (P<0.05). Conclusion High blood pressure fluctuation, dyslipidemia, and lack of health education will increase the risk of poor prognosis in young and middle-aged stroke patients.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

Objective: To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents. Methods: From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD). Results: The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05). Conclusion Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

Objective To explore the influencing factors of frailty among the health check-up elder-ly participants from our outpatient clinic.Methods A total of 710 elderly individuals(≥60 years old)who taking health check-up in our outpatient department between April and August 2022 were consecutively enrolled,and according to the results of Fried Frailty Phenotype Scale,they were divided into non-frailty group(422 cases),pre-frailty group(225 cases)and frailty group(63 cases).Their general clinical data,laboratory indicators and echocardiographic parameters were collected,and multivariate logistic regression analysis was applied to identify the independent in-fluencing factors for pre-frailty and frailty.Results The overall prevalence of pre-frailty and frail-ty was 31.7％and 8.9％,respectively.The pre-frailty and frailty groups had obviously larger left atrial anterior-posterior diameter and left ventricular end diastolic diameter and lower left ventric-ular ejection fraction when compared with the non-frailty group(P＜0.05).Multivariate logistic regression analysis showed that Hb was a protective factor for pre-frailty in the elderly partici-pants(OR=0.984,95％CI:0.966-0.992,P=0.048),while age(OR=1.064),CCI(OR=1.387)and LAAP(OR=1.059)were risk factors for pre-frailty in them(P＜0.05,P＜0.01).Serum albumin was a protective factor for frailty(OR=0.823,95％CI:0.728-0.931,P=0.002),but age(OR=1.081),CCI(OR=1.458),left atrial anterior-posterior diameter(OR=1.249)and NT-proBNP(OR=1.652)were independent risk factors for frailty(P＜0.05,P＜0.01).Conclusion There are differences in influencing factors for frailty of different severity,and the status of frailty is related to factors such as age,comorbidity,cardiac function and nutritional sta-tus.Therefore,comprehensive interventions should be implemented as early as possible for the elderly occurrence of pre-frailty so as to prevent and reverse frailty at the same time.

Objective:To investigate the expression of lysosome-associated membrane protein 3(LAMP3)and activating transcription factor 4(ATF4)in cervical cancer and their correlation with clinicopathological parameters.Methods:The expression of LAMP3 and ATF4 in normal cervical tissues,cervical intraepithelial lesions,and cervical cancer tissues was detected by SP immunohistochemistry.The relationships between the expression of these two proteins and patient clinicopathological parameters were analyzed,as well as the correlation between LAMP3 and ATF4 expression.Results:LAMP3 was negative or lowly expressed in both normal cervix tissues and high-grade squamous intraepithelial lesions,but highly expressed in cervical cancer tissues(38.3%),showing a statistically significant difference(χ2=14.113,P=0.001).ATF4 was highly expressed in 26.7%of the normal cervix tissues,10.0%of the high-grade squamous intraepithelial lesions,and 58.3%in the cervical cancer tissues,also showing a significant difference(χ2=11.078,P=0.004).In cervical cancer,LAMP3 expression was significantly associated with FIGO stage(χ2=10.139,P=0.006)and lymph node metastasis(χ2=8.475,P=0.004);ATF4 expression was significantly associated with tumor size(χ2=4.578,P=0.032),FIGO stage(χ2=8.971,P=0.009),and lymph node metastasis(χ2=7.881,P=0.005).There was a positive correlation between the expression of LAMP3 and ATF4 in cervical cancer tissues(r=0.388,P=0.002).Conclusion:LAMP3 and ATF4 are highly expressed in cervical cancer tissues and are positively correlated.Both of them play important roles in the development and progression of cervical cancer and could serve as potential therapeutic targets for cervical cancer treatment.

Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

OBJECTIVE To observe the current status and influencing factors for the water contamination of humid-ification tanks of ventilators of the patients undergoing invasive mechanical ventilation.METHODS Totally 139 hu-midified water samples were collected from the patients who received invasive mechanical ventilation in The First Medical Center of Chinese PLA General Hospital from Jul.2024 to Nov.2024.The humidified water samples were collected,cultured and identified on Day 1,3,5 and 7 after humidification tanks replacement.RESULTS Among the 139 samples,25 were tested positive for pathogens,with the positive test rate 17.99％;the positive test rate was highest(33.33％,8/24)in respiratory intensive care unit.The positive test rate was 12.90％on Day 1,18.42％on Day 3,15.00％on Day 5 and 26.67％on Day 7,showing an upward trend.The result of bacterial culture showed that the percentage of isolated Burkholderia cepacia was highest(36.00％).The result of analysis of the related factors for positive test of humidified water samples showed that the sample adding pattern was as-sociated with the isolation rate(P＜0.05).Only 1 case was diagnosed with ventilator-associated pneumonia(VAP)after the humidified water was detected with pathogens and varied in the pathogens.CONCLUSIONS There is an association between the status of water contamination of the ventilator humidification tanks and usage duration of humidification tank.It is necessary to attach great importance to the contamination of humidification tanks,carry out standard management,and implement the prevention and control measures in an all-round way.