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.

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

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.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

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.

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.

Objective:To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns.Methods:This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing.Results:Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group ( Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups ( P>0.05). Conclusions:For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.

Objective The aim of this study is to analyze the prevalence of depression and anxiety symptoms and its relationship with the socio-economic position(SEP)among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Methods A multi-stage stratified random sampling method was used to conduct a questionnaire survey among 1409 people aged 60 and over in Dai rural areas of Jinggu County,Yunnan Province.The individual SEP index was constructed using the principal component analysis.Results The prevalence of anxiety symptoms,depression symptoms,and mixed anxiety-depressive disorder symptoms was 4.8%,52.0%,and 4.2% among them,2.6%,49.4%,and 2.3% among the males,and 6.8%,54.5%,and 6.0% among the females respectively.Females had the higher prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than males(P<0.05).Elderly people with the higher level of education,annual per capita household income and SEP had the lower prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than their counterparts(both P<0.05).The prevalence of depression symptoms increased with age(P<0.01).The difference in the prevelence of depression symptoms among the elderly people with the different numbers of chronic conditions was statistically significant(P<0.01).The results of multivariate logistic regression analysis showed that the elderly people with lower SEP were more likely to suffer from the anxiety symptoms(OR=0.707,95% CI:0.566～0.883),depression symptoms(OR=0.492,95% CI:0.438～0.552),and mixed anxiety-depressive disorder symptoms(OR=0.602,95% CI:0.469～0.773).Conclusion There are significant socio-economic differences in the prevalence of anxiety symptoms and depression symptoms among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Future mental health interventions should more focus on females,elderly people with advanced age,multiple chronic diseases and low SEP,so as to reduce the occurrence of depression symptoms and anxiety symptoms.