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

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

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.

Objective:To investigate the efficacy of the nomogram model based on multiparametric MRI combined with clinical features for differential diagnosis of benign and malignant breast imaging reporting and data system (BI-RADS) 4 lesions.Methods:This study was a cross-sectional study. Clinical and imaging data of 56 patients (66 lesions) with pathologically confirmed BI-RADS 4 breast lesions from January 2020 to June 2022 at Second Affiliated Hospital of Shantou University Medical College were retrospectively analyzed. The patients were all females aged 42 (17, 71) years old. All patients underwent the breast MRI, including T 1WI, T 2WI, diffusion-weighted imaging, diffusion kurtosis imaging (DKI), and dynamic-enhanced MRI (DCE-MRI), and the patient clinical characteristics, imaging characteristics as well as relevant MRI quantitative parameters were recorded. Comparisons of the indicators of benign and malignant BI-RADS 4 lesions were performed by sample t-test , Mann-Whitney U, or χ 2 test. The least absolute shrinkage and selection operator regression was utilized to further select indicators with statistically significant differences in univariate analyses, and finally, nomogram models were constructed and reclassified all the lesions. Results:Of the 66 lesions in 56 patients, 24 lesions were found in 24 malignant patients and 42 lesions in 32 benign patients. The differences in age, body mass index, and menopausal status between benign and malignant patients were statistically significant (all P<0.05); the differences in tumor longest diameter, type of lesion enhancement, time-single intensity curve type, mean diffusivity and mean kurtosis (MK) between benign and malignant lesions were statistically significant (all P<0.05). After feature selection, MK ( OR=27.952, 95% CI 1.301-600.348, P=0.033), age ( OR=1.140, 95%CI 1.040-1.249, P=0.005), and the type of lesion enhancement ( OR=0.045, 95%CI 0.006-0.316, P=0.005) were the independent influences in predicting BI-RADS 4 malignant lesions. Using this to construct a nomogram model, its area under the curve for predicting BI-RADS 4 malignant lesions was 0.946, and the accuracy of reclassifying 66 BI-RADS 4 lesions as benign versus malignant was 86.36% (57/66). Conclusion:The nomogram model constructed with MK from DKI parameters, the type of lesion enhancement from DCE-MRI, and age is valuable in diagnosing the benign and malignant nature of BI-RADS 4 lesions.