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

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective: Scutellarin in Shuganning injection has potential allergenicity and is prone to causing anaphylactoid reactions. There is an urgent need to establish a simple and rapid chromatographic quantitative method to achieve the limit control of scutellarin in Shuganning injection.
Methods: For scutellarin, HPLC method was used in the quantitative analysis using a Shim-pack GIS C₁₈ (2.1 mm×150 mm, 5 μm) column. The mobile phase was a blend of 0.1% trifluoroacetic acid in water and acetonitrile, and gradient elution progress was applied for the whole process. The flow rate was 0.3 mL·min^-1 and the column temperature was maintained at 37 ℃. The detecting wavelength was 320 nm.
Results: The linear regression equation was y=51 456x-27 352, the correlation coefficient r=0.999 8, namely the calibration curve was linear in the range of 1.02-102.00 μg·mL^-1; the average recovery was 103.76%; the detection and quantification limit for determining scutellarin was 0.16 μg·mL^-1 and 0.57 μg·mL^-1, respectively; the injection sample was stable at room temperature for 48 h.
Conclusion: This method is easy to operate, reproducible and has high accuracy, thus can be used for quality control of Shuganning injection.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Salmonella,an important foodborne pathogen,is responsible for numerous diseases in both humans and animals.We conducted a genome-wide analysis of Salmonella isolates from diarrheal and foodborne infection cases in Gansu Province between 2021 and 2023.A total of 163 Salmonella strains were collected and subjected to biochemical identification,followed by serological typing,whole-genome sequencing,and bioinformatics characterization.The results revealed 27 distinct serotypes,among which Sal-monella typhimurium variant(S.4,[5],12∶1∶-),Salmonella enteritidis,and Salmonella enterica London were predominant.Notably,the serotype distribution exhibited significant variation across sample sources.Multilocus sequence typing(MLST)classified the iso-lates into 27 sequence types(STs),among which ST34,ST11,ST155,and ST19 had the highest prevalence.The MLST profiles dem-onstrated strong concordance with serological classifications.For Salmonella,we detected a total of 17 673 virulence genes in 374 cat-egories,carrying multiple virulence islands.Some strains carried virulence plasmid genes,among which 45 strains of Salmonella enter-itidis had higher types and numbers of virulence factors detected than other serotypes of Salmonella.Antimicrobial resistance profiling identified 69 resistance genes conferring resistance to 13 classes of antimicrobial agents,and multidrug resistance patterns were preva-lent among isolates.Plasmid characterization revealed 35 plasmid types,some containing antimicrobial resistance determinants.Addi-tionally,three disinfectant resistance genes were identified.This study highlights the extensive diversity of Salmonella serotypes and STs in Gansu Province and the complex repertoire of virulence and resistance genes.The emergence of disinfectant resistance genes un-derscores challenges in conventional disinfection protocols.These findings provide critical insights for refining Salmonella surveillance and control strategies in public health and food safety contexts.

To achieve efficient and rapid detection of duck astrovirus type 2(DAstV-2),RPA prim-ers and crRNA were designed and synthesized based on the conserved sequence of the ORF2 gene of DAstV-2.A detection method for DAstV-2 was constructed,integrating RPA nucleic acid ampli-fication,LwCas13a cleavage,and colloidal gold lateral flow dipstick visualization.The specificity,sensitivity,and concordance of this detection method were evaluated.The experimental results showed that the detection limit for the DAstV-2 recombinant plasmid standard was 1.2×101 cop-ies/μL,which is superior to the conventional RT-PCR method.The method can specifically detect DAstV-2 pathogenic nucleic acids without cross-reactivity with DAstV-1,DAstV-3,DAstV-4,duck plague virus(DEV),and duck tembusu virus(DTMUV).When testing liver tissue samples from ducks suspected of being infected with DAstV-2,the results obtained using this method were com-pletely consistent with those from real-time quantitative PCR,with a 100％concordance rate.How-ever,this method is simpler and faster to perform.The research indicates that the established RPA-CRISPR/Cas13a-LFD detection system has high sensitivity,strong specificity,and high accuracy,capable of completing rapid visual detection of DAstV-2 nucleic acids within 1 h at a constant tem-perature of 37 ℃,providing a new technical platform for the rapid diagnosis of DAstV-2.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

Objective To explore the clinical effect of applying an improved"outside-in"technique in hip arthroscopic surgery.Methods Totally 136 patients undergoing hip arthroscopic surgery between June 2021 and July 2023 were selected and studied retrospectively.According to their different surgi-cal approach,they were divided into a modified approach group(n=75,including 30 males and 45 fe-males,with an average age of 36±14)and a classic approach group(n=61,including 33 males and 28 females,with an average age of 31±11).Before as well as 4 weeks,3 months and 6 months after the surgery,both groups were evaluated using the visual analog scale(VAS)and Harris hip score,and observed their surgical complications.Moreover,the surgical outcomes and time of sur-gical approach establishment were compared between the two groups.Results There was no significant difference between the two groups in general information,preoperative VAS and Harris scores.More-over,no significant difference was found between the two groups in the Harris score after surgery.Compared with the classic approach group,the improved group had significantly less surgical time(49.0±16.9 min vs.66.0±13.3 min,P<0.05),without using the C-arm fluoroscopy during surgery.Moreover,in the modified approach group,the time for establishing the mid-anteriorapproach was sig-nificantly shortened(10.4±5.9 min vs.25.9±15.1 min,P<0.05),along with the traction time during surgery(66.0±13.3 min vs.49.0±16.9 min,P<0.05).Conclusion The modified"outside-in"hip ar-throscopy technique is a safe and effective surgical method,easier to operate,with shorter surgical time.

Objective:To analyze the prevalence and risk factors of blindness and moderate to severe visual impairment among Han and Kazakh residents aged 50 years and older in Tacheng City, Xinjiang Uygur Autonomous Region.Methods:This study is a cross-sectional survey conducted using cluster random sampling from October 2015 to June 2018 in Emin County, Tacheng City, Xinjiang Uygur Autonomous Region. The study included individuals aged 50 years and older to survey blindness and moderate to severe visual impairment. Ophthalmological examinations combined with questionnaires were conducted to gather basic information. The data collected from the questionnaires included general demographic information and health conditions. The results of the eye examinations were used to diagnose a total of 12 risk factors including cataracts, glaucoma, pterygium, suspected glaucoma, glaucoma, and refractive errors. These risk factors were analyzed in relation to blindness and moderate to severe visual impairment. Univariate analysis was conducted first, followed by logistic regression to identify the significant factors.Results:A total of 2 114 patients were included in the final analysis, among which the prevalence of moderate to severe visual impairment was 18.54% (392/2 114), and the prevalence of blindness was 2.74% (58/2 114). Univariate analysis showed that blindness and moderate to severe visual impairment were associated with age ( χ2 = 32.97, P < 0.05), hypertension ( χ2 = 3.48, P < 0.05), age-related cataract ( χ2 = 17.43, P < 0.05), glaucoma ( χ2 = 3.90, P < 0.05), macular degeneration ( χ2 = 16.04, P < 0.05), diabetes ( χ2 = 3.09, P < 0.05), pterygium ( χ2 = 2.57, P < 0.05), and fundus arteriosclerosis ( χ2 = 2.31, P < 0.05). Multivariate logistic regression analysis indicated that moderate to severe visual impairment was correlated with age (50 to < 60 years: OR = 2.91, 95% CI: 0.44-13.45; 60 to < 70 years: OR = 3.52, 95% CI: 0.73-8.77; 70 to < 80 years: OR = 4.31, 95% CI: 0.85-8.96), ethnicity ( OR = 4.45, 95% CI: 0.56-5.95), sex ( OR = 0.47, 95% CI: 0.34-0.64), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), glaucoma ( OR = 2.97, 95% CI: 1.67-5.30), and coronary heart disease ( OR = 2.56, P < 0.05). Blindness was correlated with age (70-79 years: OR = 1.54, 95% CI: 1.12-2.11), sex ( OR = 0.67, 95% CI: 0.34-0.64), glaucoma ( OR = 1.65, 95% CI: 0.42-6.49), diabetes ( OR = 2.05, 95% CI: 1.35-3.09), and coronary heart disease ( OR = 1.92, 95% CI: 1.07-3.43). Among these, age (70-79 years), glaucoma, diabetes, and coronary heart disease were identified as risk factors for blindness, while sex was observed as a protective factor against blindness in this region. Based on univariate and multivariate analyses as well as clinical practice, it was concluded that age (50 to < 60 years: OR = 4.42, 95% CI: 1.31-14.92; 60 to < 70 years: OR = 4.49, 95% CI: 1.70-11.84; 70 to < 80 years: OR = 3.19, 95% CI: 1.29-7.87), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), and glaucoma ( OR = 2.97, 95% CI: 1.67-5.30) were identified as significant risk factors for moderate to severe visual impairment. Glaucoma ( OR = 1.65, 95% CI: 0.42-6.49) and diabetes ( OR = 2.05, 95% CI: 1.35-3.09) were identified as the main risk factors for blindness in this region (both P < 0.05). Conclusions:In Tacheng City, Xinjiang Uygur Autonomous Region, the prevalence rates of moderate to severe visual impairment and blindness among Han and Kazakh residents are relatively high. Age-related cataracts and glaucoma are the primary causes, while age and diabetes are the main risk factors.