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 levels of hypoxia-inducible factor 1α(HIF-1α)and lipopolysaccha-ride signal receptor(CD14)in gingival crevicular fluid of preschool children with dental caries and their clini-cal significance.Methods A total of 468 preschool children(aged 3-6 years)who underwent oral examina-tions in the hospital from April 2022 to May 2024 were selected as the research objects and were divided into the observation group(with dental caries,n=107)and the healthy group(without dental caries,n=361)based on the presence or absence of dental caries.The observation group was further divided into three sub-groups according to the degree of caries activity test(CAT)score:low activity group(n=29),moderate activ-ity group(n=46),and high activity group(n=32).The children in the observation group were followed up for 6 months,and then divided into the occurrence group(n=36)and the non-occurrence group(n=71)based on whether chronic apical periodontitis occurred during the follow-up period.The levels of HIF-1α and CD14 in gingival crevicular fluid in the research objects were detected.The relationship between the levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries and CAT score was ex-plored by Pearson correlation analysis.The predictive value of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was explored by receiver operating characteristic(ROC)curve.Results The levels of HIF-1α and CD14 in gingival crevicular fluid in the obser-vation group were higher than those in the healthy group(P＜0.05).With the increase of CAT score,the lev-els of HIF-1α and CD14 in gingival crevicular fluid gradually increased(high activity group＞moderate activi-ty group＞low activity group),and the differences were statistically significant(P＜0.05).The levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries were positively correlated with CAT score(r=0.526,0.634,P＜0.001).The levels of HIF-1α and CD14 in gingival crevicular fluid in the occurrence group were significantly higher than those in the non-occurrence group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of combined prediction of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was 0.902(95％CI:0.857-0.952),which was higher than 0.709(95％CI:0.664-0.759)and 0.825(95％CI:0.775-0.870)of individual prediction of HIF-1α and CD14 levels in gingival crevicular fluid.Conclusion HIF-1α and CD14 are highly expressed in gingival crevicular fluid of preschool children with dental caries,and their levels are related to the activity of dental caries and the occurrence of chronic apical periodontitis in preschool chil-dren with dental caries.The combined detection of the two can be used as effective indicators for predicting the occurrence of chronic apical periodontitis in preschool children with dental caries.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Objective To identify the effectiveness of physical therapy on neuromuscular control dysfunction of chronic ankle instability (CAI). Methods CAI physiotherapy-related systematic reviews, meta-analysis, randomized controlled studies and case-controlled studies were systematically searched in PubMed, Web of Science, Cochrane, PEDro, EBSCO and CNKI from October 1st, 2010 to October 1st, 2020. After quality assessment, the research evidence regarding certain intervention was then graded according to the Oxford Center for Evidence-based Medicine. Results A total of 20 articles were included. Intervention based on unstable plane exercise training could significantly improve lower limb balance control ability (Ⅰ A) and muscle strength (Ⅱ A) for CAI patients. The efficiency of exercise-based intervention could be further raised (Ⅱ C) with the aid of external equipment, but either the benefits in muscle reaction (Ⅲ C) or proprioception (Ⅱ D) was limited. Six sessions or more of manual therapy could be used to enhance the balance ability of the lower limbs (Ⅱ B), while taping failed to provide improvements in ankle proprioception in short period or immediately (Ⅰ A). Conclusion Unstable plane training-based therapeutic exercise and manual therapy could effectively enhance the neuromuscular control with high-quality evidence supporting, which can be primary interventions for CAI patients. Meanwhile, taping and other external devices could be used as adjunct methods to improve the efficiency of physiotherapy program, while there is currently no evidence to support the application of modality treatment in neuromuscular control of CAI.

Objective:To investigate the prognostic factors of renal function after nephron sparing surgery (NSS) in renal tumor patients.Methods:The data of 115 patients who underwent NSS in our hospital from December 2016 to December 2018 were retrospectively analyzed. There were 75 males and 40 females, aged (49.50±12.94) years. The body mass index was (24.59±3.59) kg/m 2. The maximum diameter of the tumor was (3.66±1.32) cm. The R. E.N.A.L. score was (6.43±1.60). Laparoscopic partial nephrectomy was performed in 61 cases and robot-assisted laparoscopic partial nephrectomy was performed in 54 cases, and all of which were successfully completed. Operative time, WIT and postoperative pathological results were recorded. Blood creatinine value, GFR of affected kidney, GFR of healthy kidney, total GFR, GFR preserving rate (the ratio of postoperative GFR to preoperative GFR), functioning parenchymal volume (FPV) of the affected kidneys, and FPV preserving rate of the affected kidneys (the ratio of postoperative FPV and preoperative FPV) were recorded 6 months after surgery. FPV was measured by the ellipsoid approximation on CT images before and after surgery. Paired sample t test was used to compare GFR and FPV before and after surgery. Spearman rank correlation analysis was used to evaluate the correlation between the study factors and GFR preserving rate of the affected kidneys. Multivariate linear regression models were used to analyze independent predictors of renal function of the affected kidneys. Independent sample t test was used for comparison between group of WIT≤25 min and group of WIT>25 min. Results:All of the 115 patients in this study underwent successfully operations, with the median operation time of 135(75-245) min, and WIT(24.57±5.51) min. Postoperative GFR of the affected kidneys(35.50±7.81)ml/(min·1.73 m 2) was significantly different from preoperative GFR( P<0.001). The FPV preserving rate of the affected kidneys was (84.28±4.37)%, which was significantly lower than that preoperative FPV of the affected kidneys ( P<0.001). Spearman rank correlation analysis showed that there was a strong positive correlation between the FPV preserving rate of the affected kidneys and the GFR preserving rate of the affected kidneys ( r=0.802), WIT was negatively correlated with the GFR preserving rate of the affected kidneys ( r=-0.503). Multiple linear regression analysis showed that preoperative GFR of the affected kidneys ( b=-0.150, P=0.008), WIT ( b=-0.443, P<0.001) and the FPV preserving rate of the affected kidneys ( b=1.638, P<0.001) were independent predictors of the GFR preserving rate of the affected kidneys. WIT>25 min group had a significantly lower GFR preserving rate of the affected kidneys than WIT≤25 min group [(68.77±10.88)% vs.(79.34±8.88)%, P<0.001]. Conclusions:In the case of short WIT (<30 min), the reservation of normal renal tissue is the most important variable prognostic factor of renal function after NSS, and short WIT plays a secondary role. Under the premise of complete tumor resection, normal renal tissue should be reserved as much as possible and WIT should be controlled within 25 min.

OBJECTIVE：To study the pr otective effect of schisandrin A （SA）on CCl 4-induced liver fibrosis model mice and its mechanism. METHODS ：Mice were randomly divided into blank control group ，model group ，silymarin group （positive control，100 mg/kg），SA low-dose and high-dose groups （20，40 mg/kg），with 10 mice in each group. Except for blank control group，other groups were given CCl 4 subcutaneously to induce liver fibrosis model. After successful modeling ，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 6 weeks；blank control group and model group were given constant volume of 0.5％sodium carboxymethyl cellulose solution intragastrically by the same way. HE staining was used to observe the pathological changes of liver tissue in mice. UV spectrophotometry and ELISA assay were adopted to detect the serum levels of liver injury indexes （ALT and AST ）and the contents of inflammatory factors （TNF-α，IL-1β，IL-6）. Western blotting assay was used to detect the expression of NOD like receptor protein 3（NLRP3）/NF-κB and TGF-β/Smad signaling pathway protein. RESULTS ：Compared with blank control group ，obvious pathological changes of liver fibrosis were observed in model group. The serum levels of liver injury indexes and contents of inflammatory factors were significantly increased （P＜0.01）. The expression of NLRP 3，apoptosis associated spot-like protein ，Caspase-1 and IL- 1β，TGF-β1 and ratios ofp-NF-κB p65/NF-κB p65，p-IκBα/IκBα，p-Samd3/Smad3 were increased significantly （P＜0.01）. Compared with model group ，SA could significantly relieve hepatic fibrosis in mice ，reduce serum levels of liver injury indexes and contents of inflammatory factors ，as well as the expression of NLRP 3/NF-κB and TGF-β/Smad signaling pathway protein and phosphorylation level（P＜0.01）. CONCLUSIONS ： SA can effectively relieve liver injury and inflammation of CCl 4-induced hepatic fibrosis model mice ，which may be through the regulation of NLRP 3/NF-κB and TGF-β/Smad3 signaling pathways ，thus inhibiting the process of liver fibrosis.

Fluoroquinolones are widely used in clinical practice, but their clinical application in juvenile patients has been controversial.The purpose of this study was to investigate the pharmacokinetic characteristics, indications and adverse reactions of Ciprofloxacin and Levofloxacin in minors.It is shown that the two drugs are effective for infectious diseases and no serious or persistent joint or skeletal muscle injury occurs in minors using the drugs.Hence, in the absence of alternatives, the benefits of Ciprofloxacin or Levofloxacin treatment for minors may outweigh the risks.