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

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective To analyze the spatial distribution pattern of potential suitable habitats and the influencing factors of habitat spatial differentiation of Gastrodiae Rhizoma under current climate conditions.Methods Based on 137 distribution records of Gastrodiae Rhizoma sourced from the Global Biodiversity Information Facility and 104 environmental variables acquired from the WorldClim dataset,a predictive model for the potential suitable habitat of Gastrodiae Rhizoma was developed using the MaxEnt model.The geodetector was applied to quantitatively analyze the environmental factors influencing the spatial heterogeneity of the suitable habitats.Subsequently,an overlay analysis with land cover types was conducted to obtain the distribution characteristics of forest land and cultivated land in the potential suitable habitats.Results Under current climate conditions,key environmental factors affecting the distribution of Gastrodiae Rhizoma included precipitation in July,average temperature in the coldest quarter,precipitation in the warmest quarter,water vapor pressure in September,altitude,and solar radiation in December.The potential geographical distribution range of Gastrodiae Rhizoma was 1.64×106 km2.Considering land cover types,the actual potential suitable area for Gastrodiae Rhizoma was 1.33×106 km2,of which the forest land area was 8.56×105 km2 and the cultivated land area was 4.74×105 km2.The highly suitable forest areas were mainly located within the provinces of Guizhou,Sichuan,Shaanxi,Hubei,Hunan and Gansu.The cultivated land suitable areas are mainly located within the provinces of Guizhou,Sichuan,Yunnan,Shaanxi and Hubei.Conclusion The highly suitable habitats of Gastrodiae Rhizoma are mainly located in provinces such as Guizhou,Sichuan,Shaanxi and Hubei,and are affected by factors such as solar radiation,water vapor pressure,temperature and precipitation.The research results can provide reference for the protection of wild Gastrodiae Rhizoma resources,artificial nurturing and optimal selection of ecological planting areas.

Objective:To investigate the clinical application effects of free transplantation of lobulated inguinal flaps.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 34 patients with skin defect wounds whose wounds in one part met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 28 males and 6 females, aged 26 to 59 years. The wound area in the recipient area ranged from 3.0 cm×2.0 cm to 25.0 cm×20.0 cm. The lobulated inguinal flap pedicled with the branch of the superficial circumflex iliac artery were obtained in 19 patients, and the lobulated inguinal flap pedicled with the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery were obtained in 15 patients. The total area of the flaps ranged from 6.0 cm×2.2 cm to 27.0 cm×23.0 cm. The flaps were divided into 2 to 4 lobes, and the area of each lobe ranged from 2.0 cm×1.0 cm to 17.0 cm×12.0 cm. Each lobe of the flaps was reassembled, spliced, or directly transplanted onto the wounds, and the donor wounds were sutured in layers. The survival of each lobe of the flaps and wound healing in the recipient and donor areas were observed, and the wound recovery in the recipient and donor areas were followed up. At the last follow-up, the patient's satisfaction with the efficacy was assessed by 5-grade Likert scale.Results:A small amount of necrosis appeared in the tip of one lobe of the flaps in 4 patients after surgery, which healed after trimming. The flaps of the remaining 30 patients survived. The wounds in the recipient areas healed smoothly. There was a small amount of necrosis at the suture edge of the donor areas in 3 patients, which healed after local trimming and dressing change. The donor wounds healed well in the remaining 31 patients. During the follow-up of 6 to 42 months, all the recipient wounds were well repaired, and the shape of the donor areas was good. At the last follow-up, 15 patients were very satisfied with the efficacy, 15 were relatively satisfied, and 4 were generally satisfied.Conclusions:Through preoperative ultrasonic examination and positioning, the inguinal flap is designed according to the course of blood vessels and lobulated with the branch of the superficial circumflex iliac artery or the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery as the pedicles. The anatomical process is reliable and the blood flow of the flap after being lobulated is rich, which can meet the repair needs of various skin defect wounds. The repair effect is good, and the damage in the donor area is small, which is worthy of promotion.

Objective To analyze the spatial distribution pattern of the potential suitable habitats for Cordyceps under current climatic conditions in China based on space characteristics and biological traits;To explore the key environmental factors affecting the spatial differentiation of its habitats.Methods The Maximum Entropy model was utilized as a predictive tool to synthesize the distribution data of Cordyceps and its associated species Polygonum viviparum and Polygonum macrophyllum,along with environmental variable data.Factor detectors and interaction detectors of geographic detectors were used to conduct geographic exploration of spatial differentiation factors in the suitable habitats of Cordyceps.Furthermore,by overlaying the potential suitable habitats of Cordyceps with surface cover types and the suitable areas of Polygonum viviparum and Polygonum macrophyllum,the specific distribution range of the potential suitable habitats for Cordyceps was refined.Results Under the current climatic conditions,altitude,the precipitation amount of the warmest season,the highest temperature in February,and the precipitation in July are the key environmental factors influencing the distribution of Cordyceps.The potential suitable habitats for Cordyceps reaches 1.18×106 km2,and considering surface cover types,the actual potential suitable habitats for Cordyceps is 7.33×105 km2.Taking into account the associated relationships between species,the actual potential suitable habitats for Cordyceps is 7.27×105 km2.Conclusion The results of this study can reflect the ecological needs of Cordyceps,promote its sustainable utilization of resources,and provide reference for maintaining biodiversity and ecosystem integrity.

Neuraminidase(NA),a glycoprotein on the surface of the influenza virus,plays a crucial role in viral escape and serves as a stable target for drug candidates.Monoclonal antibodies targeting the NA active site can bind to multiple influenza virus subtypes and inhibit the spread of influenza virus through various mechanisms,such as neutralizing,mediating antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotox-icity.In vivo experiments have shown that human monoclonal antibodies targeting the influenza virus NA can ef-fectively exert preventive and therapeutic effects,rescuing mice infected with lethal doses and reducing viral ti-ters in lungs of mice.This article provides a review of the currently reported human monoclonal antibodies targe-ting NA of Influenza A and Influenza B viruses,providing new ideas and prospects for the subsequent development of anti-influenza drugs.

Objective To investigate the geographical distribution patterns and influencing factors of suitable habitats for the desert medicinal plant Cynomorium songaricum Rupr under current climatic conditions;To provide a basis for its resource conservation and sustainable utilization.Methods The MaxEnt model was used to analyze potential suitable habitats for Cynomorium songaricum Rupr.Geographical Detector model was used to identify key environmental factors affecting habitat suitability.Surface cover data were overlaid to assess the distribution of sandy and Gobi regions within suitable habitats,enabling a quantitative evaluation of actual potential suitable areas.Results Model predictions indicated a total suitable habitat area of approximately 2.98×106 km2,representing 30.99%of China's mainland area.Highly suitable habitats are concentrated in desert and Gobi regions of Gansu,Xinjiang,Inner Mongolia,Qinghai and Ningxia.Among climatic factors,precipitation of the coldest quarter(bio19),solar radiation in August(srad8),and mean temperature of the coldest quarter(bio11)significantly influence Cynomorium songaricum Rupr distribution.The interaction between temperature and solar radiation intensity exhibited the highest explanatory power for habitat distribution patterns(q=0.82).Overlay analysis with surface cover data estimated the actual potential suitable area at approximately 9.70×105 km2,with sandy regions comprising 5.73×105 km2 and Gobi regions 3.98×105 km2.Conclusion By integrating multi-source data and modeling approaches,this study delineates the potential suitable habitats for Cynomorium songaricum Rupr across China and evaluates the spatial distribution characteristics and influencing factors of suitable habitats in Cynomorium songaricum Rupr.These findings offer a foundation for conserving wild Cynomorium songaricum Rupr resources,optimizing ecological planting regions,and promoting sustainable industry development.

OBJECTIVE To investigate the current status of bloodborne occupational exposures among healthcare workers in a three-A specialized hospital of Shanghai so as to provide bases for formulating prevention measures for occupational exposures.METHODS A questionnaires titled'Survey of bloodborne occupational exposures among healthcare workers'were clinically distributed to Eye &ENT Hospital of Fudan University through'Wenjuanxing platform'from Feb.2024 to Apr.2024.The content of the questionnaire included four parts:the baseline data questionnaire,incidence of occupational exposures,awareness of knowledge about occupational exposures,and preventive behaviors regarding occupational exposures.RESULTS A total of 995 valid questionnaires were collect-ed in the survey,the result of the survey showed that the incidence of bloodborne occupational exposures was 10.65％.The clinicians and doctors engaging in advanced studies were at high risk of the occupational exposures especially when they were busy with work.The result of the survey indicated that the rate of missing report was 71.33％,the implementation rate of monitoring was only 48.11％after the exposures,of which the major cau-ses included the health care workers'insufficient attention to the exposure events,flaws in prevention and control of occupational exposures and some personnels'poor awareness of reporting process and requirements for monito-ring.Although the awareness rate of emergency processing exceeded 90％,the awareness rate of the knowledge a-bout prophylactic use of antibiotics and prevention of needlestick injuries,and the preparations before diagnosis and treatment,standardized operations and use of protective articles still needed to be improved.CONCLUSIONS The survey reveals that the health care workers pay less attention to the risk of infections,and the prevention of occupational exposure needs to be improved.It is of great importance to raise the awareness of prevention and en-hance the systematic training for occupational exposure.