OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

BackgroundMigrant children face many challenges in the process of social change and adaptation to a new environment， especially in school adaptation. Studies have shown that peer attachment plays a vital role in the social adaptation of children and adolescents， while psychological resilience and sense of security， as important psychological resources， also play a moderating and mediating role in individuals' coping with environmental changes. However， there is a lack of systematic research on how peer attachment affects the school adaptation of migrant children through psychological resilience and whether this process is moderated by sense of security. ObjectiveTo explore the relationship between peer attachment and school adaptation of migrant children and to examine the path of psychological resilience and sense of security in it， so as to provide references for improving the school adaptation of migrant children. MethodsUsing cluster sampling method， 695 migrant children in grades 4 to 6 of a primary school in an urban-rural fringe area of Sichuan Province were selected from April 1 to 30， 2022. Assessments were conducted using Revised Inventory for Parent and Peer Attachment （IPPA-R）， Resilience Scale for Chinese Adolescents （RSCA）， Scale of Sense of Security of Children Left Behind （SSSCLB） and Scale of School Adjustment of Student （SSAS）. Process 4.1 was used to examine the role of psychological resilience and sense of security. ResultsA total of 631 （90.79%） valid questionnaires were gathered. There were significant positive correlations among IPPA-R peer attachment subscale score， RSCA score， SSSCLB score and SSAS score （r=0.160~0.600， P<0.01）. Peer attachment had a significant positive predictive effect on the school adaptation （β=0.178， P<0.01） and psychological resilience （β=0.518， P<0.01） of migrant children. Psychological resilience had positive predictive effect on the school adaptation （β=0.467， P<0.01）. Psychological resilience played a partial mediating role in the relationship between peer attachment and school adaptation， with the mediating effect value was 0.242 （95% CI： 0.184~0.302）， accounting for 57.62% of the total effect. Moreover， the interaction term between psychological resilience and sense of security had a significant predictive effect on school adaptation （β=0.103， P<0.01）. ConclusionThe psychological resilience of migrant children plays a partial mediating role in the relationship between peer attachment and school adaptation， and the status of sense of security can moderate the relationship between psychological resilience and school adaptation of migrant children.

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.

Objective To explore and analyze the effects of different batches of fetal bovine serum(FBS) on the quality evaluation of human mesenchymal stem cells(hMSCs) products and provide reference for the development and quality control of hMSCs products.Methods Retrospective analysis was conducted on the immune-regulatory function data of standard cell line CCRC-hMSC-S1 cultured in medium supplemented with FBS from different batches, based on the quality review data of hMSCs products. The standard cell line CCRC-hMSC-S1 was co-cultured with allogeneic peripheral blood mononuclear cells(PBMCs) from 5-6 donors respectively, and five different batches of FBS(FBS-H, FBS-A, FBS-E1, FBS-E2 and FBS-E3)were added to the co-culture system to clarify the direct effects of different batches of FBS on the detection value of immuneregulatory function by CCRC-hMSC-S1. The hMSCs from eight different individuals were cultured respectively in five medium containing different batches of FBS for two weeks, and the immune-regulatory function and osteogenic differentiation capacity were evaluated to clarify the effects of long-term culture of different batches of FBS on the key quality attributes of hMSCs.Results In the co-culture system of hMSCs and PBMC, the detection value of regulatory T-cell(Treg) promotion rate in FBS-H culture system was significantly lower than that in FBS-A, FBS-E1, FBS-E2 and FBS-E3 culture systems(t = 3. 2,3. 0, 3. 2 and 2. 9, respectively, each P < 0. 05), and the detection value of T lymphocyte proliferation inhibition rate in FBSH culture system was significantly higher than that in FBS-A, FBS-E1, FBS-E2 and FBS-E3 culture systems(t = 3. 7, 3. 4,2. 8 and 3. 0, respectively, each P < 0. 05); the inhibitory ability of hMSCs long-term cultured in FBS-A on Th1 proliferation was significantly lower than that of hMSCs long-term cultured in FBS-H, FBS-E1, FBS-E2 and FBS-E3(t = 3. 0, 2. 4, 3. 7and 3. 3, respectively, each P < 0. 05); the suppressive effect of hMSCs long-term cultured in FBS-H on T lymphocyte proliferation was significantly higher than that of hMSCs long-term cultured in FBS-A, FBS-E1, FBS-E2 and FBS-E3(t = 4. 7,2. 6, 3. 4 and 3. 9, respectively, each P < 0. 05); the alizarin red S staining area of hMSCs long-term cultured in FBS-E3 after osteogenic differentiation was significantly lower than that of hMSCs long-term cultured in FBS-A, FBS-H and FBS-E1(t =4. 1, 5. 5 and 3. 9, respectively, each P < 0. 01).Conclusion In the research and development of hMSCs cell therapy products, it is necessary to pay close attention to the effects of FBS components on the quality evaluation of hMSCs, especially the immune-regulatory function and differentiation potential, and select suitable batches of FBS for the development and quality control of hMSCs products.

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 investigate the role of 24-dehydrocholesterol reductase(DHCR24)in doxorubicin-induced senescence-related dysfunction of vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were induced with 0.05 μM doxorubicin for 48 h to establish a stress-triggered premature senescence model.The lentiviral transfection method was employed to achieve DHCR24 overexpression in HUVECs.Cell senescence was evaluated by β-galactosidase staining and Western blot to detect the expression of the senescence-related molecules cyclin-dependent kinase inhibitor 1A(P21)and nicotinamide adenine dinucleotide dependent histone deacetylase 1(SIRT1).Western blot was performed to detect DHCR24 and endothelial nitric oxide synthase(eNOS)expression during endothelial senescence.DAF-FM DA(an NO fluorescent probe)was used to detect intracellular NO production.Results:In the stress-triggered premature senescence model of HUVECs induced by doxorubicin, the expression of the senescence marker P21 was up-regulated( t=19.44, P<0.01), SIRT1 was down-regulated( t=10.10, P<0.01, and the expression of DHCR24 was down-regulated( t=5.946, P<0.01), compared with the control group.Meanwhile, eNOS and NO expression was inhibited( t=11.26, P<0.01; t=10.83, P<0.01).After DHCR24 overexpression, compared with the control stimulation group, the overexpression stimulation group showed that DHCR24( F=72.10, P<0.01)was up-regulated.DHCR24 overexpression alleviated the doxorubicin-induced decrease in eNOS and NO( F=5.797, P<0.05; F=45.12, P<0.01), compared with the control group. Conclusions:DHCR24 may mitigate doxorubicin-induced senescence-related vascular endothelial dysfunction by modulating the eNOS/NO signaling pathway.

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable.Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the De-partment of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing U-niversity of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy + laparoscopic primary resection +hepatectomy)and a microwave ablation group(conversion therapy +laparoscopic primary re-section +microwave ablation).The surgical indicators(operation duration,time to first postoperative anal ex-haust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens.Results A total of 198 patients with potentially resectable color-ectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first post-operative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as inci-sion infection(P =0.740),anastomotic fistula(P =1.000),and anastomotic stenosis(P =1.000),the over-all survival period(P =0.191),and the disease-free survival period(P =0.934)showed no significant differ-ences between the two groups.Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection +surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outper-formed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Diabetic retinopathy(DR)is one of the most common fundus vascular diseases and a leading cause of blindness in adults of working age.The occurrence and development of DR involves a variety of pathophysiologic mecha-nisms,including metabolic dysregulation,oxidative stress,inflammation,and neurovascular unit hypofunction.Conven-tional clinical treatments,such as anti-vascular endothelial growth factor drugs and retinal laser photocoagulation,have long treatment cycles and variable outcomes in some patients and sometimes require vitrectomy in the later stages of the disease.With the in-depth research on the molecular level of the pathogenesis of DR,a number of biological therapeutic modalities,such as targeted therapy,gene therapy,immunotherapy and cell therapy,have received more and more atten-tion from researchers.This review summarizes the biologic therapeutic modalities currently available for DR and outlines the benefits and limitations of these approaches with a view to informing researchers.