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

ObjectiveTo investigate the disease burden of non-alcoholic fatty liver disease （NAFLD） among young people in East Asian countries （including China， North Korea， Japan， Mongolia， and South Korea） in 1990—2023， and to provide a basis for formulating and adjusting the prevention and treatment strategies for NAFLD. MethodsRelated disease burden data of NAFLD among the young people in these five East Asian countries were collected from the Global Burden of Disease 2023 （GBD 2023） database， including incidence rate， prevalence rate， and disability-adjusted life years （DALY）， and the young people were divided into groups based on country， sex， and age. Estimated annual percentage change （EAPC） was used to comprehensively evaluate the changing trend of the disease burden of NAFLD among young people from 1990 to 2023， and the Autoregressive Integrated Moving Average model was used to predict the disease burden of NAFLD among the young people in China. ResultsIn 2023， the standardized incidence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 926.57/100 000， 805.83/100 000， 412.66/100 000， 747.66/100 000， and 534.08/100 000， respectively； the standardized prevalence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 16 817.94/100 000， 14 500.98/100 000， 8 534.40/100 000， 13 705.28/100 000， and 11 587.93/100 000， respectively； the standardized DALY rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 6.34/100 000， 10.18/100 000， 5.23/100 000， 47.93/100 000， and 6.76/100 000， respectively. From 1990 to 2023， there was a tendency of increase in the standardized incidence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.87%， 0.52%， 0.26%， 0.48%， and 0.87%， respectively； there was also a tendency of increase in the standardized prevalence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.99%， 0.49%， 0.24%， 0.59%， and 0.93%， respectively； conversely， there was a tendency of reduction in the standardized DALY rate of NAFLD among the young people in China， Japan， Mongolia， and South Korea， with an EAPC of -2.21%， -2.01%， -0.37%， and -4.62%， respectively， while the standardized DALY rate of NAFLD among the young people in North Korea remained relatively stable， with an EAPC of -0.01%. The subgroup analysis based on sex showed that there was a significant difference in the disease burden of NAFLD between the young people with different sexes in the five East Asian countries， and the subgroup analysis based on age showed that the incidence rate of NAFLD in young people decreased with the increase in age， while the prevalence rate and DALY rate of NAFLD increased with age. In addition， the standardized incidence rate and standardized prevalence rate of NAFLD among Chinese young people would further increase in the future， while there would be a reduction in standardized DALY rate in the future. ConclusionThere is a significant difference in the disease burden of NAFLD in young people across different countries， sexes， and age groups. In the future， targeted prevention and treatment measures should be developed based on the distribution characteristics of the disease burden of NAFLD， in order to effectively reduce the disease burden of NAFLD among young people.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Objective:To investigate the molecular characteristics of low-risk acute myeloid leukemia(AML)at recurrence,and analyze the factors affecting retreatment efficacy and prognosis.Methods:A retrospective analysis was conducted on the clinical and laboratory data of 31 patients with newly diagnosed low-risk AML who relapsed during consolidation treatment or follow-up after treatment in our hospital from April 2017 to January 2023.Gene mutations before and after relapse were compared,retreatment efficacy following relapse was evaluated,and univariate and multivariate analyses were performed to identify factors influencing treatment efficacy and prognosis.Results:Gene sequencing results after relapse showed that the most common newly acquired mutation was FLT3-ITD,while RAS mutation detected at initial diagnosis were predisposed to loss of expression during relapse.The median overall survival(OS)after relapse for the entire cohort was 349(170-528)days,with non-hematopoietic stem cell transplantation(HSCT)group and HSCT group demonstrating median survival times of 210(106-314)days and not reached,respectively(P=0.001).Multivariate analysis revealed that age ≥60 years was a significant risk factor for achieving remission after retreatment in initially diagnosed low-risk AML patients who experienced relapse(OR=18.222,95％CI:1.188-279.597,P=0.037).Additionally,DNMT3A mutation was identified as an independent risk factor for OS(HR=13.165,95％CI:2.018-85.877,P=0.007),while HSCT post-relapse demonstrated significant survival benefits(HR=0.133,95％CI:0.025-0.698,P=0.017)and served as an independent protective factor for OS.Conclusion:Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD.Age ≥ 60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival,respectively,while HSCT significantly improved patient outcomes.

Objective To explore the correlation between helicobacter pylori(Hp)infection and inflam-matory factors,as well as its association with the progression of liver fibrosis in patients with metabolically associ-ated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM).Methods A total of 300 patients diag-nosed with MAFLD and T2DM who were admitted to the Hepatology Department of Hebei Hospital of Traditional Chinese Medicine between April 2023 and March 2024 were recruited.Based on Hp infection status,these patients were classified into an Hp-positive group and an Hp-negative group.Subsequently,the clinical data,inflammatory factors,and liver fibrosis indices of the two groups were comprehensively compared.Furthermore,the patients in the Hp-positive group were randomly assigned to an intervention group and a control group.The intervention group received standard Hp eradication therapy,whereas the control group was administered placebo therapy.Pearson correlation analysis was employed to investigate the associations among Hp infection,inflammatory factors,and liver fibrosis indices.Binary logistic regression analysis was utilized to identify the independent risk factors influencing the progression of liver fibrosis.Results In both the Hp-positive and Hp-negative groups,parameters including age,fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),along with C-reactive protein(CRP)and liver stiffness measurement(LSM),were meticulously measured.Statistical analysis revealed that the differences in these parameters between the two groups were significant(P<0.05).Specifically,within the experimental setup,the levels of TNF-α,IL-6,CRP,and LSM in the intervention group were notably lower than those in the control group(P<0.05).Pearson correlation analysis was employed to explore the relation-ships among variables,and the results indicated a positive correlation between the Hp detection value(DPM)and the levels of TNF-α,IL-6,CRP,and LSM(P<0.05).Furthermore,binary logistic regression analysis was con-ducted to identify independent risk factors.The findings demonstrated that positive Hp infection,elevated TNF-α,elevated IL-6,and elevated CRP were independent risk factors for the progression of liver fibrosis(P<0.05).To evaluate the diagnostic performance,the receiver operating characteristic(ROC)curve analysis was carried out.The areas under the curve(AUC)for HP infection,TNF-α,IL-6,and CRP were 0.800,0.786,0.769,and 0.783,respectively.These values were significantly lower than the AUC of 0.896 obtained from the combined detection(P<0.05).Conclusions In MAFLD patients with T2DM,DPM is closely associated with inflammatory factors(such as TNF-α,IL-6,and CRP)and the advancement of liver fibrosis.The combined detection of these factors holds significant value in predicting the progression of liver fibrosis.It can offer a reliable foundation for the clinical assessment of the risk of liver fibrosis progression.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

Over the past four decades，China’s response to HIV/AIDS has undergone a profound transformation—from an initial state of nearly absence to a comprehensive，robust，and highly coordinated system. The implementation of the “Four Frees and One Care” policy，the widespread adoption of antiretroviral therapy，and the integration of the “test-and-treat” strategy have collectively shifted HIV/AIDS from a fatal condition to a manageable chronic disease，significantly improving both the quality of life and life expectancy of affected individuals. This article systematically reviews three critical stages in the development of HIV/AIDS prevention and control in China，with particular emphasis on the positive impact of medical advances. It further summarizes key progress in testing capacity，drug accessibility，and service delivery，while highlighting the challenges and directions that lie ahead. This review aims to provide scientific evidence to support the ultimate goal of ending the HIV/AIDS epidemic.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.

Removal of endogenic renal sinus tumors which are located at the renal hilum,is recognized as one of the most challenging surgeries in urology due to the complex anatomical structure.With the help of the high-definition field of vision and flexible robotic arms of the Da Vinci robot system,our team have carried out precision intra-sinus tumor enucleation based on preoperative interactive qualitative and Interactive Quantitative Quality Assurance for 3D Imaging(IQQA-3D)accurate reconstruction technology,as well as the clinical anatomical characteristics of patients with renal sinus tumors.During operation,the renal pedicle is fully dissected,the perihilar fat is cleared,and the tumor capsule is exposed.Subsequently,the blood supply to the kidney is blocked,and the tumor is precisely excised along the tumor capsule.The vascular stumps are sutured point-to-point,and the wound is closed and locked.After the blood supply restores,regional arterial occlusion is performed if necessary to ensure the safety of the surgery and maximize the preservation of renal function.This article discusses the definition of tumor boundaries during robot-assisted endogenic sinus tumor enucleation,the use of intraoperative cooling techniques,and the improvement of surgical safety.