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 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 investigate the impact of preschool children s aquatic motor skill (AMS) acquisition on their fundamental motor skill (FMS) development and the correlation between AMS and FMS development, so ao to provide a scientific basis for early childhood education and physical education teaching. Methods: From April to June 2024, 60 children, recruited by random sampling from a kindergarten in Taiyuan, were stratified randomly divided into an experimental group ( n =30) and a control group ( n =30). The experimental group were further divided into five classes of six each. They received AMS practice interventions twice weekly, 40 minutes per session, over eight weeks (16 sessions total) at a designated swimming center. The control group maintained their usual routine. Children s FMS and AMS were assessed pre and post intervention using the Test of Gross Motor Development-3rd (TGMD3) and Actual Aquatic Skills Test (AAST), respectively. Before and after test comparisons within and between groups employed t-tests, Wilcoxon signedrank tests, ANCOVA (including ranktransformed ANCOVA), and Cohen s d effect sizes were calculated for standardized mean differences. Spearman rank correlation was used to analyze relationships between FMS and AMS. Results: After the aquatic learning, the experimental group scored significantly higher than the control group on locomotor skills ( F=20.47, P <0.01, η 2=0.26), FMS ( F=4.59, P =0.04, η 2=0.08), and AMS ( F=109.71, P<0.01, η 2=0.79). The experimental groups improvement in locomotor skills 5.0(3.8, 7.3) versus the control group (2.8±2.5) yielded a medium effect size (Cohen s d =0.71); AMS gains in the experimental group [26.0(20.8, 28.0)] versus controls [1.0(0, 2.3)] showed a very large effect size (Cohen s d =4.73) (both P <0.01). Among preschool children, AMS acquisition was positively correlated with locomotor skills ( r =0.39) and overall FMS ( r =0.43)(both P <0.05). Skill specific assessments revealed lower proficiency in headfirst entry (immersion), treading water, and sagittalplane rotation. Conclusion Preschool children s acquisition of AMS has a positive effect on their FMS, with mutual facilitation between the two, especially in locomotor abilities.

Flavonoids, the key active compounds in Epimedii Folium, have both protective and toxic effects on the liver. Their hepatoprotective effects are associated with reducing lipid accumulation and oxidative stress, which contribute to the management of various liver conditions. In contrast, the mechanisms driving Epimedii Folium-induced hepatotoxicity are less understood but likely involve oxidative stress and pyroptosis. Pharmacokinetic studies, especially on icaritin, indicate that it undergoes isopentenyl dehydrogenation, glycosylation, and glucuronidation in vivo, contributing to its pharmacological effects. However, intermediate metabolites of icaritin may interact with biomolecules, potentially leading to liver toxicity. This review offers a detailed examination of the dual effects of Epimedii Folium flavonoids on liver function, emphasizing recent discoveries in their hepatoprotective and hepatotoxic pathways. We also summarize and discuss the pharmacokinetics of these flavonoids, highlighting how their metabolism affects therapeutic efficacy and toxicity. Lastly, we propose strategies to mitigate liver injury, providing new perspectives on the safe use of Epimedii Folium.

Obesity is a well-established risk factor for thrombotic events such as venous thromboembolism， and the alterations in pharmacokinetics induced by obesity pose challenges for anticoagulation management. This article systematically reviews the advances of the use of various anticoagulants in obese patients， and finds that the dosage of low-molecular-weight heparin needs to be adjusted according to preventive or therapeutic goals in severely obese patients， the preventive dose may be increased to 40 mg， q12 h or 0.5 mg/（kg·d）， while the therapeutic dose is recommended to be reduced to 0.8 mg/（kg·d）， q12 h. Direct oral anticoagulant drugs are safe and effective for general obese patients； in severely obese patients， standard doses of rivaroxaban or apixaban may be used， warranting cautious application and consideration for therapeutic drug monitoring. In special clinical scenarios such as obesity combined with trauma， pregnancy， advanced age， or bariatric surgery， anticoagulation strategies should be individualized， with close attention to monitoring. Future research should focus on optimizing anticoagulant regimens for special populations and addressing anticoagulation management in obese patients with other embolic diseases.

Objective To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology,which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails'entry point,and to verify its clinical value through clinical tests.Methods After matching the locating module with the developing board,which are the two components of the locating device,they were placed on the skin surface of the proximal femur of the affected side.Anteroposterior fluoroscopy was performed.The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image,and then the yaw angle of the locating module was reset to zero.After resetting,the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire.The ideal direction of entry point was accurately located based on the angle guidance.By setting up an experimental group and a control group for clinical surgical operations,the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss with or without the locating device was recorded.Results Compared to the control group,the experimental group showed significant improvement in the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss,with a statistically significant difference(P<0.01).Conclusion The locating device can assist doctors in quickly locating the entry point of intramedullary nail,effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot,improving surgical efficiency,and possessing certain clinical value.

The inflammatory response runs through the entire process of the onset and progression of coronary atherosclerotic heart disease(CHD);various inflammatory cells and inflammatory factors are involved,and to a certain extent,determine the stability of coronary atherosclerotic plaques and the progression of the disease.Lipoprotein(a)[Lp(a)],C-reactive protein(CRP),neutrophils,platelets,and monocytes participate in the inflammatory response through various mechanisms such as inducing inflammatory factors,stimulating inflammatory cells,and secreting active substances,thus promoting the atherosclerosis.In contrast,the lymphocytes,as important immune cells,serve as the indicators of anti-inflammation.High-density lipoprotein cholesterol(HDL-C)exerts its anti-atherosclerotic effects by reversing cholesterol transport and inhibiting the aggregation of the inflammatory cells.In recent years,novel inflammatory markers composed of the aforementioned inflammation-related indicators have been closely related to the onset and progression of CHD and have significant guiding value in the diagnosis,treatment,and prognosis of CHD.Reducing inflammation remains a hotspot in current CHD research.The study analyzes the mechanism of promoting the CHD development by new inflammatory markers and reviews the therapeutic advancements targeting these relevant inflammatory markers,and provides the basis for the diagnosis and treatment of CHD.

Objective To investigate the correlation of human epididymis protein 4(HE4)with proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods A total of 147 T2DM patients from January 2020 to July 2023 in Jiujiang NO.l People's Hospital were enrolled in observation group.According to the severity of proteinuria,observation group was divided into three groups:Normal albuminuria group(101 cases),microalbuminuria group(25 cases),and massive albuminuria group(21 cases).50 healthy examinees with gender and age matching during the same period were selected as control group.HE4 levels and clinical indicators in each group were compared and analyzed.Correlation between HE4 and proteinuria was analyzed by using univariate and multivariate linear regression.Results The correlation network diagram reveals that HE4 functions was a pivotal node linking serum albumin,urinary microalbumin,urinary microalbumin-to-creatinine ratio(UACR),and renal function biomarkers.Compared to control group,HE4 levels significantly elevated in observation group(P＜0.01).Both univariate and multivariate linear regression analysis demonstrate a positive correlation between HE4 and UACR.Logistic regression analysis shew that after adjusting for confounding factors including age,gender,estimated glomerular filtration rate(eGFR),albumin(ALB),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),lactate dehydrogenase(LDH)etc.elevated HE4 levels was a risk factor for proteinuria(OR=1.110,95％CI:1.005-1.226).Conclusion Elevated HE4 levels in patients with T2DM is positivly correlated with UACR.Increase its level increases the risk of proteinuria in T2DM patients.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.