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 evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

It is considered that "turbid pathogen damaging the clear， and the loss of clarity and harmony regulation" is the core pathogenesis of esophageal precancerous lesions， with turbid pathogen persisting throughout the disease course. Turbid pathogen encompasses qi turbidity， phlegm turbidity， stasis turbidity， and toxin turbidity， closely related to dietary indiscretion， emotional disharmony， spleen-stomach deficiency， and kidney deficiency failing to consolidate. Turbid pathogen undergoes a dynamic evolution process of qi constraint generating turbid→ phlegm-stasis transforming into toxin→turbidity toxin harming the healthy qi， corresponding to the pathological alterations of hypoxia， inflammation and immunosuppression within the tumor microenvironment. The overall therapeutic principle is to remove turbidity and restore clarity. In the early stage， targeting the hypoxic tumor microenvironment， the suggested treatment method is opening constraint and dispersing the block， regulating qi and remove turbidity， with emphasis on soothing liver and regulating stomach， raising the clear and directing the turbid downward. In the middle stage， targeting inflammatory microenvironment， the treatment aims to clear toxin and dissipate nodules， resolve stasis and eliminate turbid， emphasizing phlegm-stasis elimination， turbid-toxin resolution， and concurrent stomach qi protection. In the late stage， corresponding to immunosuppressive microenvironment， the method of boosting qi， nourishing yin， reinforcing healthy qi， and eliminating turbidity can be used， with focus on spleen-stomach tonification， kidney essence replenishment， and healthy qi reinforcement to expel pathogenic factors.

Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.