Objective: To explore the relationship between serum homocysteine (Hcy), interleukin-5 (IL-5), folate and core symptoms in children with autism spectrum disorders, so as to provide potential biomarkers for early diagnosis and intervention of diseases. Methods: A total of 106 children with autism spectrum disorders and 106 healthy children with matched sex and age in Lu an People s Hospital were enrolled as autism group and healthy group between May 2020 to December 2023. On the day of admission, levels of serum Hcy, IL-5 and folate were detected. The core symptoms in autism group were evaluated by Autism Behavior Checklist (ABC), Wechsler Preschool and Primary Scale of Intelligence-fourth edition(WPPSI-IV), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). The levels of serum Hcy, IL-5 and folate in the two groups were compared by t- test. The relationship between serum Hcy, IL-5, folate and core symptoms in children with autism spectrum disorders was determined by Pearson correlation analysis. Results: The levels of serum Hcy and IL-5 in autism group were (7.48±0.32) μmol/L and (345.77±32.51) pg/mL, higher than those in healthy group [(6.11±0.54) μmol/L, (274.04±25.17) pg/mL], while folate level was lower than that in healthy group [(15.24±3.47) ng/mL, (22.51±4.69) ng/mL], the differences were statistically significant ( t =22.47, 17.96, 12.83, all P < 0.05 ). In autism group, levels of serum Hcy and IL-5 were positively correlated with scores of ABC, CARS and SRS ( r =0.29, 0.53 , 0.54; 0.45, 0.41, 0.50), while negatively correlated with WPPSI-IV score ( r =-0.28, -0.26)(all P <0.05). The folate level was negatively correlated with scores of ABC, CARS and SRS ( r =-0.55, -0.40, -0.25), while positively correlated with WPPSI-IV score ( r =0.41) (all P <0.05). Conclusion Children with ASD show elevated serum Hcy and IL-5 alongside decreased folate,and three markers correlate with core symptoms and intellectual level.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg^-1）， medium-dose group （4.86 g·kg^-1）， high-dose group （9.72 g·kg^-1）， and benazepril group （0.01 g·kg^-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.

ObjectiveTo analyze the epidemiological characteristics of latent tuberculosis infection (LTBI) among newly detained populations in eastern China, to identify high-risk groups, and to provide a scientific basis for formulating tuberculosis prevention and control strategies in the prison system. MethodsA cross-sectional study was conducted among the newly admitted detainees in two prisons in eastern China in 2022. Data on demographic characteristics, behavioral risk factors and previous disease history of the research subjects were collected through a structured questionnaire survey. The LTBI status of the detainees was determined using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. Lasso regression was used to screen variables, followed by multivariate logistic regression analysis to investigate the influencing factors of LTBI. ResultsA total of 305 detainees were included in the study. The median age of detainees was 35 (31, 43) years. The study population was predominantly male (67.21%), of Han ethnicity (95.41%), had a junior or senior high school education (59.34%), and was unemployed (31.80%). A history of smoking was reported by 52.79% of participants, while 57.70% reported no alcohol consumption. The majority had no history of hypertension (85.90%), diabetes mellitus (93.77%), human immunodeficiency virus (HIV) infection (97.38%), familial genetic diseases (95.08%), surgery or trauma (73.77%), drug use (92.79%), or hepatitis (93.77%). The LTBI rate was 14.75%. After comparing the demographic characteristics of LTBI and non-infected groups, it was found that smoking history (χ²=7.40, P=0.025), drug use history (χ²=5.49, P=0.019), and HIV infection (χ²=8.12, P=0.004) were statistically correlated with LTBI infection. The results of multivariate logistic regression analyses showed that smoking [adjusted odds ratio (aOR)=4.08, 95%CI: 1.60‒10.42, P=0.003], HIV infection (aOR=11.57, 95%CI: 2.50‒53.51, P=0.002) and drug use (aOR=3.04, 95%CI: 1.02‒9.09, P=0.046) were risk factors for LTBI. ConclusionThe LTBI rate among newly detainees in two prisons in eastern China is slightly lower than that among long-term detainees. Early screening and intervention should be implemented for newly detainees, with particular attention focused on high-risk groups such as those with a history of smoking, HIV infection, or drug use.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective:To investigate the clinical effect of arthroscopic combined fixation of acromioclavicular joint in the treatment of acute acromioclavicular dislocation.Methods:A retrospective controlled analysis was conducted on 40 patients with acute dislocation of the acromioclavicular joint were treated in Qinhuangdao First Hospital of Hebei Medical University from February 2021 to December 2023. There were 30 males and 10 females, aged from 22 to 54 years, with an average age of (40.55±7.75) years. The patients were divided into two groups based on the surgical method used. The observation group included 19 patients who were treated with Tightrope and suture to reconstruct the coracoclavicular ligament and acromioclavicular ligament, while the control group included 21 patients who were treated with Tightrope to reconstruct the coracoclavicular ligament only. All patients were followed up postoperatively, and their preoperative and postoperative data were recorded. The visual analogue scale (VAS) for pain, Constant score and coracoclavicular distance values of the two groups of patients before surgery and one year after surgery were recorded and compared. The changes of the internal fixation devices were observed. The measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups, skewed continuous data were presented as [ M( Q1, Q3)], and intergroup comparisons were performed using the Mann-Whitney U test; the count data were expressed as cases and percentages [ n(%)], and the chi-square test was used for comparison between groups. Results:There was no significant difference in the general information (gender, age, affected side, time from injury to operation) between the two groups ( P>0.05). The last follow-up showed that two patients in the control group had early failure of the implant, one of whom had an infection after surgery, and one of whom had obvious displacement of the Tightrope early on. All patients in the observation group were healed by first intention, without any postoperative early complications such as wound infection, early failure of internal fixation, etc. There was no statistically significant difference in the VAS score between the two groups ( P>0.05); the Constant score 85(84, 89) of the observation group was higher than that of the control group 82(80, 85), and the difference was statistically significant ( P<0.05); the VAS score and Constant score of both groups after surgery were significantly improved compared with those before surgery ( P<0.05). One year after operation the coracoclavicular distance was 8.5(8.0-8.8) mm in observation group, and 10.3(9.7, 10.6) mm in control group ( P<0.05). Conclusions:The method of reconstructing the coracoclavicular ligament and acromioclavicular ligament complex fixation with Tightrope and suture using arthroscopy is reliable and has fewer postoperative complications. It is a better method than using Tightrope alone to fix the coracoclavicular ligament for the treatment of acute Rockwood Ⅲ to Ⅴ type acromioclavicular dislocation.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.