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

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

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.

A retrospective analysis of clinical data of 8 patients with PICALM::MLLT10 (P/M) fusion gene-positive acute myeloid leukemia (AML) diagnosed by transcriptome sequencing (RNA-seq) at the First Affiliated Hospital of Soochow University from June 2017 to March 2023 was performed. Laboratory findings and treatment status were analyzed, and survival analysis was performed using the Kaplan-Meier method. The 8 patients included 5 males and 3 females, aged 16-35 years, with a median age of 27 years. The platelet count of patients was normal, and 3 patients had mild to moderate anemia. Extramedullary infiltration was present in all patients with clinical manifestations, including 5 patients with mediastinal masses, 2 patients with hepatosplenomegaly, 1 patient with central nervous system leukemia, and 1 patient with cervical lymph node enlargement. Karyotypical analysis revealed 7 patients with an abnormal karyotype, including 6 cases of complex karyotypes. Of these, 4 patients harbored the t(10;11) translocation. The complete remission rate of induction chemotherapy in the patients was 7/8, and 2 patients experienced early recurrence. All patients subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), The follow-up period ranged from 86 to 812 days, with a median of 330 days. Among the 8 patients, 3 survived and 5 died due to recurrence. Relapse and death only occurred in the P/M fusion gene-positive patients after transplantation. The overall survival rate at 1 year after transplantation was 37.5%. P/M +AML has the characteristics of young age at onset, normal platelet count, high incidence of extramedullary infiltration, and high proportion of complex karyotype. RNA-seq can significantly improve the detection rate of this disease type. Allo-HSCT can partially improve the prognosis of P/M +AML, and P/M positivity after transplantation can be a warning sign of recurrence, which is an important factor affecting survival.

Purpose To characterize the clinicopathological features of gastrointestinal mesenchymal tumors(GMTs)resected via endoscopic techniques.Methods A retrospective analysis was conducted on 495 cases of endo-scopically resected GMTs.Clinical information,histomorphological findings,immunohistochemical profiles,and mo-lecular characteristics were reviewed.Results The cohort included 495 patients aged 20-78 years(median:53 years).The majority of tumors were located in the stomach(58.8％)and esophagus(36.8％).Histologically,most tumors consisted of spindle cells,with a minority composed of epithelioid cells;fibrocollagenous or myxoid stroma was occasionally observed.Immunohistochemically,leiomyomas showed diffuse positivity for α-SMA(98.8％)and desmin(99.3％),gastrointestinal stromal tumors(GISTs)expressed CD117(99.4％),DOG1(97.6％),and CD34(97.0％),and schwannomas were positive for S-100(93.7％).The predominant tumor types were leiomyomas(54.1％)and GISTs(33.7％),while the remaining 12.2％comprised other rare types.Various endoscopic resection techniques were employed based on the tumors' anatomical depth,including endoscopic submucosal dissection(ESD,40.5％),submucosal tunneling endoscopic resection(STER,17.1％),endoscopic mucosal resection(EMR,16.5％),endoscopic full-thickness resection(EFTR,13.9％),and endoscopic submucosal excavation(ESE,12.0％).EMR and ESD were primarily used for superficial lesions,while deeper tumors with were more often treated with STER,EFTR,and ESE.The rate of negative resection margins was lower in GISTs(72.2％)and other tumors with indistinct margins,compared to leiomyomas(92.6％)and those with well-defined boundaries.Conclusion Leiomyomas and GISTs are the most common gastrointestinal mesenchymal tumors resected via endoscopy.A variety of resection techniques are applicable depending on tumor location and depth.Accurate pathological diagnosis should be based on HE morphology,supplemented by endoscopic findings,margin status,immunohistochemistry,and necessary molecular tests.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

Objective: To investigate the characteristics and trend of stroke incidence in Yixing City, Jiangsu Province from 2016 to 2023, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke case in Yixing City from 2016 to 2023 were collected from the National Health Information Platform of Yixing City, including sex, age, time of onset, and diagnostic subtypes. Crude incidence was standardized using the data from the 2010 Chinese National Population Census to analyze the characteristics of stroke incidence. The incidence trend of stroke was analyzed by average annual percent change (AAPC). Results: A total of 54 157 stroke cases were reported in Yixing City from 2016 to 2023, with a crude incidence of 629.52/100 000 and a standardized incidence of 299.50/100 000, showing an upward trend (AAPC=9.744% and 5.955%, both P<0.05). The crude and standardized incidence of stroke in males were significantly higher than those in females (695.30/100 000 vs. 565.79/100 000, 328.73/100 000 vs. 270.71/100 000, both P<0.05). Stroke incidence exhibited an age-dependent increase (P<0.05), peaking in the ≥60 years age group (1 820.43/100 000). The crude and standardized incidence of ischemic stroke (555.46/100 000 and 262.26/100 000) were significantly higher than those of hemorrhagic stroke (52.80/100 000 and 28.03/100 000, both P<0.05). From 2016 to 2023, the standardized incidences of stroke in males, females, the 0-<40 years age group, the 40-<60 years age group, the ≥60 years age group, and ischemic stroke all showed an upward trend (AAPC=6.692%, 4.925%, 5.607%, 5.777%, 5.698%, and 8.481%, respectively, all P<0.05). No significant temporal trend was observed for hemorrhagic stroke incidence (P>0.05). Conclusions The incidence of stroke among residents in Yixing City showed an upward trend from 2016 to 2023, with males and elderly individuals being high-risk populations. Ischemic stroke emerged as the predominant subtype, while a concerning trend of increasing stroke incidence among younger adults was observed.