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

OBJECTIVE To investigate the effects and mechanism of Yigan huayu formula in alleviating liver fibrosis in mice. METHODS Mice were randomly divided into blank group （normal saline）， model group （normal saline）， Yigan huayu formula low- and high-dose groups （28.98， 57.96 g/kg， calculated by crude drug）， with 8 mice in each group. Except for the blank group， the liver fibrosis model was induced by intraperitoneal injection of 15%CCl 4 -olive oil solution. From the third week， the mice received the medicine/normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， liver indexes were calculated， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， as well as the hydroxyproline （HYP） content in liver tissue， were measured. Liver histopathology was evaluated. Differentially expressed proteins （DEPs） in liver tissue were analyzed based on proteomics， followed by bioinfo rmatics analysis. The expressions of core DEPs were validated using Western blot （WB） and immunohistochemistry （IHC） methods. RESULTS Compared with the blank group， the model group showed significantly elevated liver indexes， serum activities of ALT and AST， and hepatic HYP content （ P ＜0.05）， along with obvious pathological damage and collagen deposition. Compared with the model group， the above indexes of mice in the Yigan huayu formula high-dose group were decreased significantly （ P ＜0.05）， with marked improvement in liver pathological damage and collagen deposition. Proteomics identified 210 DEPs between the model group and Yigan huayu formula high-dose group. DEPs were significantly enriched in extracellular matrix （ECM）-receptor interaction and lipid metabolism pathways. WB and IHC confirmed that Yigan huayu formula could significantly inhibit the abnormally elevated expressions of collagen type Ⅳ alpha1 chain （COL4A1）， secreted protein acidic and rich in cysteine （SPARC）， vitronectin （VTN） and laminin subunit alpha5 （LAMA5） in liver tissue of mice （ P ＜0.05）. CONCLUSIONS Yigan huayu formula may exert anti-hepatic fibrosis effects by inhibiting the expressions of proteins such as COL4A1， LAMA5， SPARC， and VTN， thereby blocking the ECM-receptor interaction signaling pathway， and subsequently suppressing excessive ECM deposition and basement membrane remodeling.

Objective: To summarize the best evidence for the management of patients with gastrointestinal graft-versushost disease after hematopoietic stem cell transplantation, and provide evidence-based references for clinical nursing work. Methods: A systematic search was conducted for relevant evidence on the management of patients with gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation from domestic and foreign databases, as well as websites of blood and bone marrow transplantation related societies. The search period was from the establishment of the database until February 2026. Results: After screening, a total of 19 articles were included, encompassing 3 clinical decisions, 1 recommended practice, 4 guidelines, 7 expert consensuses, and 4 evidence summaries. Twenty-five pieces of best evidence were summarized across 8 aspects: multidisciplinary collaboration, influencing factors, assessment and monitoring, diagnostic differentiation, symptom management, dietary nutrition, medication guidance, and health education. Conclusion: Summarizing the relevant evidence on the management of patients with gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation can provide evidence-based support for clinical medical staff, and it is recommended to apply it in combination with clinical practice and patient wishes.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the pain intensity,location and relationship between pain and foot-ankle function in patients with functional ankle instability(FAI).Method:From September 2022 to July 2023,163 FAI patients were assessed at Beijing Tongren Hospital,with ankle pain location,pain intensity(visual analogue scale,VAS),and foot-ankle function(American or-thopedic foot and ankle society ankle and hindfoot score,AOFAS)scores recorded.The VAS and AOFAS of various pain locations and the number of pain locations was compared across groups.Multiple linear regression was used to examine the association between the number of pain locations,VAS,and AOFAS.Result:Out of 163 FAI patients,150 reported the pain.Among them,37.33％had pain in a single location,34％in two locations,and 28.67％in multiple locations(＞2).The most common pain locations were the sinus tarsi(32％)and the anterior talofibular ligament(31％).There were no significant differences in VAS and AO-FAS among different pain locations in FAI patients with the same number of pain locations(P＞0.05).The VAS of FAI patients with multi-location pain(＞2 regions)was higher than that of patients with single-loca-tion pain and 2-location pain(P＜0.01),whereas the AOFAS was lower(P＜0.05).The number of pain loca-tions and VAS were negatively correlated with AOFAS score(P＜0.05),which could predict 20.9％of the AO-FAS score.Conclusion:The majority of FAI patients experience pain,and the pain intensity and number of pain loca-tions impact foot and ankle function.When establishing and implementing rehabilitation strategies for FAI pa-tients,pain relief and minimizing the number of pain locations should be emphasized.Future research should investigate effective pain management measures to improve ankle function in patients with FAI at specific loca-tions with a high incidence(e.g.,tarsal sinus,anterior talofibular ligament).

Objective:To compare the differences in the rehabilitation effects of resistance training on elderly individuals with sarcopenia and those suffering from sarcopenia possibly.Method:A total of 64 elderly people aged 60 to 80 years old were selected,including 36 diagnosed sarcope-nia patients and 28 potential sarcopenia patients with decreased physical function.They underwent resistance muscle strength training for 4 weeks each.The effects of resistance training on body composition,muscle strength,balance function and fall risk,cardiopulmonary endurance,instrumental activities of daily living(IADL),and quality of life were analyzed.Result:After 4 weeks of training,both groups showed significant improvements in grip strength,30 second bending frequency,30 second sitting frequency,knee extension strength and single leg standing time,Berg balance scale(BBS),and timed up and go test(TUGT)(P<0.05 for all),but there was no significant change in body composition.The improvement in grip strength and six-minute walk test(6MWT)in the elderly possi-bly suffering from sarcopenia was more significant than that in the sarcopenia group(P<0.05).The sarcopenia group showed significant improvement in multiple dimensions of IADL and quality of life.There was no signif-icant difference in the changes in IADL and quality of life between the two groups.Conclusion:Compared with elderly people with sarcopenia,four weeks of early resistance training can more significantly improve muscle strength and cardiorespiratory endurance in potentially elderly people with sarcope-nia who have already experienced a decline in somatic function but have not yet met the diagnostic criteria for sarcopenia.

Objective:To investigate causal relationship between intestinal flora and risk of developing ankylosing spondylitis(AS)by a two-sample Mendelian randomization(MR)analysis.Methods:Genome-wide association study(GWAS)data on 211 types of intestinal flora and AS were obtained,and single nucleotide polymorphism(SNP)was used as an instrumental variable and sensi-tive SNPs were selected for analysis.Two-sample MR analyses were performed by inverse variance weighted(IVW)as well as MR-Eg-ger,Weighted median,to assess causal relationship between AS and intestinal flora by OR,and results were tested for heterogeneity and pleiotropy.Results:IVW analysis showed a significant causal relationship between 11 intestinal flora and AS risk.Among them,Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Akkermansia,Erysipelatoclostridium,Holdermannia,Holdemania,Bacillales and Verrucomicrobia had positive causal effect on AS risk,while Dialister,Howardella and Oscillospira had negative causal effect.Causal effect estimates obtained by different methods(MR-Egger,Weighted median)were consistent,and sensitivity tests did not reveal significant horizontal pleiotropy and heterogeneity.Conclusion:Intestinal flora plays an important role in pathogenesis of AS,while specific mechanism remains to be further investigated.

Objective To investigate the oral health status of second-grade primary school students in Suzhou,provide baseline data for evaluating Suzhou's"Bright Eyes and Healthy Teeth"public health project,and offer reference for formulating oral health policies for students in Suzhou.Methods A multi-stage,stratified,random sampling method was used to select 1 640 second-grade primary school students from 10 districts(county-level cities)across Suzhou.The oral health survey of primary school students in Suzhou was designedbased on WHO"Basic Methods for Oral Health Surveys"(5th edition).A survey on the students' oral health status was con-ducted.Results The caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate for primary teeth among second-grade students in Suzhou were 80.73％,4.25,and 24.48％,respectively.For permanent teeth,the caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate were 30.30％,0.62,and 16.96％,respectively.Specifically,the caries prevalence,mean DMFT,and filling rate for the first permanent molar were 29.88％,0.59,and 16.94％,respectively.The pit and fissure sealing rate for the first permanent molar was 13.74％.Additionally,the detection rate for gingival bleeding was 58.05％,and for dental calculus,49.15％.Conclusion The oral health status of second-grade primary school students in Suzhou is concerning.The caries prevalence rate for both primary and permanent teeth is high,while the filling rate is relatively low.Prior to the implementation of oral health programs,the pit and fissure sealing rate for the first permanent molars was low,with significant differ-ences observed between urban and rural areas,as well as among different districts(or county-level cities).

Objective:To investigate the changes of upper airway and adenoids in children with hypertrophic adenoid skeletal classⅠ and class Ⅲ anterior crossbite after orthodontic treatment.Methods:From January 2021 to January 2022,155 children with skeletal class Ⅲ anterior crossbite who were treated with anterior traction in Stomatological Hospital,Shanxi Medical University were selected.They were divided into class Ⅲ normal group(72 cases)and class Ⅲ hypertrophic group(83 cases)according to whether the adenoids were hypertrophic.A total of 122 children with class Ⅰ anterior counterocclusion were treated with"2×4"treatment,which were di-vided into Class Ⅰ normal group(60 cases)and class Ⅰ hypertrophy group(62 cases).The changes of upper airway and adenoid were compared between the two groups.Results:(1)After intervention,only the width of nasopharynx cavity increased(P＜0.05)in Class Ⅰ normal group and Class Ⅰ hypertrophic group,and there was no significant difference in other indicators(P＞0.05).(2)After intervention,the adenoid thickness and A/N ratio of children with skeletal class Ⅲ anterior crossbite decreased,and the width of na-sopharynx cavity,nasopharynx airway space,soft palate upper and rear airway space,uvula tip rear airway space,the minimum air-way space between soft palate and adenoid,and mandibular plane angle increased(P＜0.05).The A/N ratio of class Ⅲ hypertrophic group was lower than that of class Ⅲ normal group(P＜0.05).Conclusion:Orthodontic treatment can reduce the degree of adenoid hypertrophy and expand the airway in children with skeletal class Ⅲ anterior crossbite.Only the width of the nasopharynx cavity can be widened after the correction intervention for children with adenoid hypertrophy and skeletal class Ⅰ anterior crossbite.