Hepatitis D virus （HDV）， as a defective virus， relies on the envelope protein of hepatitis B virus （HBV） to complete replication and transmission. Chronic hepatitis B （CHB） patients comorbid with HDV infection may experience significant acceleration of liver disease progression and a significantly higher risk of serious complications such as liver cirrhosis and hepatocellular carcinoma （HCC） compared with the patients with CHB alone， which poses a serious threat to the life and health of patients. At present， the coverage rate of HDV screening needs to be improved， and some patients with HBV/HDV co-infection have not been found in time. Therefore， strengthening the understanding of HDV among clinicians， expanding the scope of HDV screening， identifying patients with infection in a timely manner， and performing standardized antiviral therapy and long-term follow-up management are of great significance for improving the prognosis of patients， reducing disease burden， improving the quality of life of patients， and achieving the global goal of “eliminating viral hepatitis as a public health threat by 2030”.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

Background Occupational disease diagnosis appraisal is an appeal procedure initiated when a party disagrees with the occupational disease diagnosis conclusion. It is a legal procedure to safeguard the health rights of employees and the legitimate rights and interests of employers. Objective To analyze the data of occupational disease diagnosis appraisal in Shanghai, identify existing problems, and provide suggestions for improving. Methods Statistical analysis was conducted on basic situation, characteristics of workers and employers, disease classification, and consistency between diagnosis and appraisal conclusions of all occupational disease diagnosis appraisal cases from 2012 to 2024. All diagnosis conclusions were named in accordance with the Classified Catalogue of Occupational Diseases included employers were classified according to the Measures for the Statistical Classification of Large, Medium, Small and Micro Enterprises" and the Notice on Adjusting the Provisions for Classifying Enterprise Registration Types; industry classification followed the Industrial Classification for National Economic Activities (GB/T 4754-2017). Results From 2012 to 2024, a total of 260 cases of occupational diseases diagnosis appraisal were closed. The main diagnosis were 138 cases of ear, nose, throat, and oral diseases (53.1%), chemical poisoning (18.8%), and pneumoconiosis and other respiratory diseases (16.2%). The proportion of ear, nose, throat, and oral diseases gradually increased (2022 excluded). The incidence of annual municipal and provincial cases decreased by 76.3% and 85.0% respectively (2024 vs 2012). The consistency rate of conclusions between appraisal and diagnosis gradually increased. The total consistency rates between final appraisals and diagnostic conclusions were 81.5%, and 79.7%, 87.8%, 100.0%, 85.0% for ear, nose, throat, and oral diseases, chemical poisoning, and pneumoconiosis and other respiratory system diseases, respectively. Specifically, the consistency rates were 80.1% and 80.0% for noise-induced deafness and chronic benzene poisoning. In terms of inconsistency reasons, "inconsistent interpretation of standards and excessive discretion in standard application" accounted for 43.8%, followed by "failure to correctly apply standards" (31.3%) and and "discrepancies in occupational exposure history recognition" (15.6%). Conclusion The revisions and improvements of the legal system for occupational disease diagnosis appraisal have played a positive role in improving the consistency of conclusions between appraisal and diagnosis of occupational diseases in Shanghai. It is suggested to further strengthening the publicity and training of occupational disease diagnosis standards to improve the quality of occupational disease diagnosis.

Objective To establish primary breast cancer cell lines from patient tissues and offer a new cancer cell model for basic research.Methods Breast cancer biopsy tissues were digested with typeⅡcollagenase and cultured in BCMI medium.When the cells proliferated rapidly,the medium was switched to DMEM.STR genotyping was per-formed to identify specific genetic markers of the four primary breast cancer cell lines.Colony expansion assays and sphere formation assays were conducted to analyze its tumorigenicity.Real-time PCR and Western blot experiments were used to analyze the expression of the epithelial-mesenchymal transition(EMT)molecule markers.Migration and invasion assays were performed to assess the metastatic potential of the primary breast cancer cells.Results We es?tablished four primary breast cancer cell lines:BC25#,BC51#,BC56#,and BC57#.These cell lines were cultured in DMEM medium,passaged multiple times and tagged with details about their clinical past.STR genotyping identified specific genetic markers for each of the four primary breast cancer cell lines.Clonogenic and sphere formation assays revealed that the four lines have a stronger tumor?forming capability compared to the classic breast cancer cell line T?47D.Real?time PCR and Western blot experiments showed that,compared to T?47D,the four primary breast cancer cell lines have decreased E?cadherin expression and increased vimentin expression.Migration and invasion assays indicated that BC25#had a higher metastatic potential than the traditional breast cancer cell line T?47D.Conclusions Four primary breast cancer cell lines,BC25#,BC51#,BC56#and BC57#are successfully estab?lished,which may act as new cancer cell model for laboratory research of breast cancer.

Objective To establish a backpack-based field emergency medical rescue equipment system to enhance emergency rescue efficiency.Methods A backpack-based field emergency medical rescue equipment system was preliminarily constructed with the concept of medical treatment in echelons and prolonged field care(PFC)and the method of capability-based equipment need analysis;with the Delphi method 15 experts from relevant fields were invited to execute two rounds of questionnaire consultations,and the final equipment system was determined after the equipment varieties and quantities were revised based on the expert opinions.Results The response rate for the two rounds of expert questionnaire surveys was 100%.The experts'authority coefficients were 0.8734 and 0.87,respectively;Kendall coefficients were 0.232 and 0.345(both P<0.001),indicating statistically significant results.Ultimately,a backpack-based field emer-gency medical rescue equipment system comprising 15 backpacks and 158 individual pieces of equipment was established.Conclusion The established system demonstrates a certain degree of specificity and practicability,providing references for the equipment allocation and utilization of emergency medical rescue teams.[Chinese Medical Equipment Journal,2025,46(10):17-22]

OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52％,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57％,the SVR12 of the GT3a type patients was 100.00％,the GT3b type patients 98.92％.The SVR12 of the patients with CHC,CC and DCC were 99.45％,100.00％and 100.00％,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47％,100.00％,100.00％and 100.00％,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors