Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

Animal models combining disease and syndrome are important research tools to explore the nature of traditional Chinese medicine (TCM) syndromes. At present, the construction and evaluation methods of animal models have preliminarily established the foundation for standardized development. Qi-yin deficiency syndrome is a common type of TCM syndrome in cardiovascular diseases. It is an important pathogenic factor causing the onset, pathological damage, and chronic nature of cardiovascular diseases, as well as triggering other illnesses. The establishment of an animal model of cardiovascular disease with the characteristics of Qi-yin deficiency, along with an objective and standardized evaluation system, has become an important part of modern cardiovascular disease research. In recent years, research on the construction and evaluation of animal models of heart Qi-yin deficiency syndrome has increased, but the construction methods and evaluation criteria vary. Compared with other animal models, the literature is limited, lacking statistics and overall analysis. Therefore, based on the scientific connotation of heart Qi-yin deficiency syndrome, this article systematically reviews the evaluation system of its animal model, covering multidimensional methods such as macroscopic characterization assessment, physicochemical indicators and objective evaluation, and syndrome differentiation based on prescriptions. The specific model construction strategies are described, including single-factor induction methods (sleep deprivation, chronic intermittent hypoxia, arterial occlusion, high-salt feeding) and the compound-factor induction methods (sleep deprivation combined with drug method, chronic intermittent hypoxia combined with drug method, exhaustive swimming combined with drug method). Meanwhile, application examples of each model in the research are listed, the existing problems in the current model construction and evaluation are analyzed, and optimization directions are proposed, such as promoting the compound factor induction strategy and improving the objectivity of the evaluation criteria. This article aims to provide theoretical references for constructing an animal model of heart Qi-yin deficiency syndrome that conforms to TCM characteristics, and thereby laying a scientific foundation for the prevention and treatment of cardiovascular diseases with TCM.

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 research hotspots and current trends in the field of general practitioner (GP) training in China through a visual analysis of relevant literature.Methods:Publications related to GP training were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, China Biology Medicine (CBM) Database, and Chinese Medical Association Journal Database from database inception to December 31, 2024. VOSviewer and CiteSpace were used to perform co-occurrence analysis of authors and institutions, as well as co-occurrence, clustering, and burst detection analysis of keywords, with corresponding visual maps generated.Results:A total of 4 131 publications were included, with the highest annual output occurring in 2019 (305 publications). There were 259 core authors (each with ≥7 publications). A total of 3 093 institutions participated in related research, with leading institutions including Capital Medical University (140 publications), Zhongshan Hospital Affiliated with Fudan University (108 publications), Guangzhou Medical University (65 publications), and Shanghai Jiao Tong University (53 publications). Keyword co-occurrence analysis identified 189 keywords with frequency ≥10; high-frequency terms included "general practice","general practitioners","education" and "community health services". Keyword clustering revealed current research hotspots mainly focus on training models, educational reform, and training outcome evaluation. Timeline and burst detection analyses indicate that medical education and post-placement training have long been key research themes, while recent emerging topics are closely aligned with national policy initiatives related to GP training.Conclusion:Publications in the field of GP training in China have shown fluctuations, with a concentration of authors and institutions. Reforms in educational systems and policy responsiveness remain core research focuses.

Castleman’s disease(CD) is a rare lymphoproliferative disorder that is classified based on the affected sites and pathological features. The pathogenesis of CD remains not fully understood and may be associated with viral infections, genetic abnormalities, and immunological factors. Clinically, CD is categorized into two types based on lymph node involvement: Unicentric Castleman Disease(UCD) and Multicentric Castleman Disease(MCD). Treatment options include surgery, chemotherapy, immunotherapy, and targeted therapy. This article summarizes recent advancements in the understanding of the pathogenesis, clinical characteristics, diagnosis, and treatment of CD, aiming to provide assistance for future clinical work.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with giant cell carcinoma of the lung (GCCL).Methods:A retrospective case series study was conducted. The clinical data and the survival related information of patients with GCCL in Surveillance, Epidemiology and End Results (SEER) database from the establishment of the databank to April 2019 were collected, and the clinicopathological characteristics of patients were summarized. Cox proportional hazards model was used for univariate and multivariate analysis of the overall survival (OS) and the independent influencing factors for poor OS were screened. Kaplan-Meier method was used to analyze the OS and cancer-specific survival (CSS) of the entire group and the patients stratified by the independent influencing factors. The log-rank test was used for inter-group comparisons.Results:A total of 248 GCCL cases were included. Among them, 64.9% (161 cases) were aged ≤70 years, 60.1% (149 cases) were male, and 57.7% (143 cases) were married. GCCL was more commonly found in the right lung [58.5% (145 cases)], and 64.1% (159 cases) were classified as TNM stage Ⅲ-Ⅳ. No high differentiation cases were observed, and there was only 1 case (0.4%) of moderate differentiation, while the remaining cases were poorly differentiated [56.0% (139 cases)] or undifferentiated [43.5% (108 cases)]. Lymph node metastasis was observed in 55.6% (138 cases), and distant metastasis occurred in 35.5% (88 cases). Regarding treatment, 50.4% (125 cases) underwent surgery, 18.5% (46 cases) received radiotherapy, and 39.1% (97 cases) underwent chemotherapy. Kaplan-Meier analysis showed that the 1-year and 5-year OS rates for all 248 cases were 38.8% and 21.3%, respectively, while the 1-year and 5-year CSS rates were 47.7% and 32.3%, respectively. Univariate and multivariate Cox regression analyses revealed that age (≥71 years vs. <70 years, HR = 1.526, 95% CI: 1.145-2.033, P = 0.004), marital status (married vs. others, HR = 0.755, 95% CI: 0.569-1.000, P = 0.049), N stage (all compared to N 0 stage; N 1 stage: HR = 1.876, 95% CI: 1.212-2.903, P = 0.005; N 2 stage: HR = 1.560, 95% CI: 1.074-2.265, P = 0.020; N 3 stage: HR = 1.902, 95% CI: 1.089-3.323, P = 0.024), M stage (M 1vs. M 0, HR = 2.122, 95% CI: 1.488-3.026, P < 0.001), and surgical treatment (surgery vs. no surgery, HR = 0.542, 95% CI: 0.361-0.813, P = 0.003) were independent risk factors for poor OS. Kaplan-Meier analysis demonstrated that patients aged >70 years, married, without lymph node metastasis, without distant metastasis, and those who underwent surgery had better OS, and the differences were statistically significant (all P < 0.05). Conclusions:GCCL is more common in elderly men and is more frequently found in the right lung. Most patients have lymph node metastasis and the patients with the distant metastasis are relatively common. The majority of cancer patients have an undifferentiated or poorly differentiated degree. Age, marital status, N stage, M stage, and whether surgery was performed are independent prognostic factors for GCCL.

Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.

Objective To analyze the prevalence of latent tuberculosis infection(LTBI)among relevant healthcare workers(HCWs)in designated tuberculosis medical institutions(MIs)in Yantai City,and explore its influencing factors.Methods The cluster random sampling method was adopted to select two county-and district-level desig-nated tuberculosis MIs.All HCWs underwent questionnaire survey and creation tuberculin skin test(C-TST)at the same time,and the influencing factors for LTBI were analyzed.Results A total of 215 HCWs from designated tu-berculosis MIs were included for analysis,37 were diagnosed with LTBI,with an infection rate of 17.21％(95％CI:12.42％-22.93％).Multivariate logistic regression analysis showed that clinicians(OR=3.19,95％CI:1.05-9.69),laboratory technician(OR=5.90,95％CI:1.21-28.77),working years≥10 years(OR=3.31,95％CI:1.39-7.90),and tuberculosis history of family members(OR=6.49,95％CI:1.01-41.46)were independent risk factors for LTBI.Conclusion The infection risk of clinicians and laboratory technicians who directly contact with tuberculosis patients or Mycobacterium tuberculosis is higher than that of other HCWs,and is related to the length of working years.It is suggested that healthcare-associated infection control measures should be streng-thened,and tuberculosis active screening should be carried out regularly for HCWs in key departments.

Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.

Objective To analyze the prevalence of latent tuberculosis infection(LTBI)among relevant healthcare workers(HCWs)in designated tuberculosis medical institutions(MIs)in Yantai City,and explore its influencing factors.Methods The cluster random sampling method was adopted to select two county-and district-level desig-nated tuberculosis MIs.All HCWs underwent questionnaire survey and creation tuberculin skin test(C-TST)at the same time,and the influencing factors for LTBI were analyzed.Results A total of 215 HCWs from designated tu-berculosis MIs were included for analysis,37 were diagnosed with LTBI,with an infection rate of 17.21％(95％CI:12.42％-22.93％).Multivariate logistic regression analysis showed that clinicians(OR=3.19,95％CI:1.05-9.69),laboratory technician(OR=5.90,95％CI:1.21-28.77),working years≥10 years(OR=3.31,95％CI:1.39-7.90),and tuberculosis history of family members(OR=6.49,95％CI:1.01-41.46)were independent risk factors for LTBI.Conclusion The infection risk of clinicians and laboratory technicians who directly contact with tuberculosis patients or Mycobacterium tuberculosis is higher than that of other HCWs,and is related to the length of working years.It is suggested that healthcare-associated infection control measures should be streng-thened,and tuberculosis active screening should be carried out regularly for HCWs in key departments.