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 understand the situation of learning burnout and social support of medical laboratory technology undergraduates during their internship, analyze the correlation between them, and put forward countermeasures and suggestions for improvement.Methods:A total of 107 valid questionnaires were collected. Descriptive statistical analysis was used to present the total scores of the medical laboratory technology undergraduates' learning burnout and social support scales and the scores of various dimensions. Pearson correlation analysis was applied to test the correlation between learning burnout and social support scales. SPSS 23.0 was used for statistical analysis of the data, t test and F test were conducted to compare the scores of different demographic characteristics, and Pearson correlation analysis was used to test the correlation between college students' learning burnout and scores of all dimensions of the social support scale. Results:The detection rate of learning burnout of medical laboratory technology undergraduates was 67.29% (72/107), and the total scores of learning burnout and social support scale were (42.87±8.02) points and (57.22±16.94) points, respectively. Learning burnout was negatively correlated with the total score of the social support ( r=-0.43, P=0.001). Conclusions:During the internship, it is necessary to pay attention to the undergraduates' learning burnout, and effectively improve the level of relevant social support, especially the encouragement and support given by the teachers, which will help improve their internship initiative and internship effectiveness.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

A large number of non-specific immune cells, such as macrophages, neutrophils and natural killer cells, as well as specific immune cells, such as B cells and T cells, are presented in the atherosclerotic plaques and arterial blood. In addition, immune-related regulatory molecules such as interferon-γ, interleukin-17, and interleukin-1β highly express in atherosclerotic lesion tissues, which is similar to the tumor immune microenvironment and influence the atherosclerosis progression. In this paper, the research progress of immune cells and related factors involved in the immune microenvironment around cerebral atherosclerotic lesions is reviewed to provide idea and basis for its clinical diagnosis and treatment.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To define the definition and connotation of nursing shame by using Walker-Avant classical conceptual analysis.Methods:Literature was systematically searched from CNKI, Wanfang, VIP, PubMed, Web of Science, Wiley Online Library, ScienceDirect and CINAHL, and articles were screened according to inclusion and exclusion criteria. Based on Walker-Avant classical conceptual analysis, the concept of nursing shame was analyzed from the aspects of defining attribute, antecedent factors and post factors.Results:The three defining attributes of nursing shame included negative self-evaluation, avoidance and withdrawal and self-breakthrough. Antecedent factors included non-compliance with self-expectations and clinical bullying. Post-effects included physical and mental impairment and departure of nurses, increased patient burden and hindered expression. However, nursing shame could also be positive by cultivating shame resilience and become a psychological motivation for nurses to reflect and adjust themselves.Conclusions:The conceptual attribute of nursing shame is clarified through conceptual analysis, which lays a theoretical foundation for the future development or localization of targeted measurement tools to effectively identify and deal with nursing shame.

Objective:To explore the effect of "Internet +" combined with multidisciplinary out of hospital management in hospital-home transitional period management of patients after lumbar internal fixation.Methods:From October 2021 to September 2022, convenience sampling was used to select 176 patients who underwent lumbar internal fixation at the Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University. According to the admission time, patients enrolled from October 2021 to March 2022 were included in the control group, and patients enrolled from April to September 2022 were included in the observation group, with 88 cases in each group. The control group implemented routine out of hospital follow-up management, while the observation group implemented "Internet +" combined with multidisciplinary out of hospital management. After three months of intervention, the recovery of lumbar and back function [Oswestry Disability Index (ODI) and Macnab score], surgical efficacy (NaKa grading), nursing satisfaction, and readmission rate were compared between the two groups.Results:After three months, the ODI score of the observation group was lower than that of the control group, and the Macnab score was higher than that of the control group, the NaKa grading was better than that of the control group, with statistically significant differences ( P<0.05). In the observation group and control group, the total effective rate of surgery, nursing satisfaction, and readmission rate were 88.64% (78/88) vs. 67.05% (59/88), 94.32% (83/88) vs. 78.41% (69/88), 4.55% (4/88) vs. 17.05% (15/88), respectively. The total effective rate and nursing satisfaction of the observation group were higher than those of the control group, and the readmission rate was lower than that of the control group, with statistical differences ( P<0.05) . Conclusions:"Internet +" combined with multidisciplinary out of hospital management can effectively improve the recovery of lumbar function in hospital-home transitional period management of patients after lumbar internal fixation, enhance the surgical efficacy and nursing satisfaction, and reduce the readmission rate.

Objective To explore the role of MYC in lung cancer cell migration and reveal the mechanism affecting migration.Methods siRNA MYC or pRK5-MYC plasmid was transfected into lung cancer cells A549.Cell migra-tion was examined by wound healing assay.The mRNA expression of candidate genes AKR1C1 and AKR1C3 was detected by fluorescence quantitative PCR.Dual luciferase reporting assay and chromatin immunoprecipitation assay(ChIP)verified the transcriptional regulation of target genes by MYC.A549 cells were transfected with MYC and AKR1C1 siRNA or pRK5-MYC and pRK5-AKR1C1 at the same time.Wound healing assay and Transwell were used to examine cell migration and cell invasion respectively.Results Knockdown MYC in A549 cells promoted cell mi-gration,and over-expression of MYC inhibited cell migration.The level of protein and mRNA of AKR1C1 was sig-nificantly increased(P＜0.01)after knockdown MYC.The ChIP assay showed that MYC binded to the response ele-ment(RE)of AKR1C1.Compared with control plasmids,MYC induced the expression of luciferase in RE-containing plasmids.Decreased expression of AKR1C1 inhibited the invasion and migration of lung cancer cells(P＜0.05).AKR1C1 reduced cell invasion and migration caused by MYC loss(P＜0.05).Conclusions MYC might inhibit cancer cell migration by inhibiting AKR1C1 expression.

Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]％vs.[24.6±16.7]％,thrombus core:[35.7±19.6]％vs.[11.1±10.4]％,all P＜0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]％vs.[41.7±27.0]％,thrombus core:[12.1±8.5]％vs.[35.7±19.6]％,all P＜0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]％,[8.0±7.7]％,and[8.9±5.3]％;thrombus core:[12.1±8.5]％,[9.5±4.2]％,and[15.7±11.0]％),and the differences were not statistically significant(all P＞0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]％vs.[15.7±11.0]％,P＜0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]％vs.[11.4±8.7]％,P＜0.001;thrombus core:[24.5±9.8]％vs.[7.6±6.0]％,P＜0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]％vs.[22.1±11.3]％,P＜0.001;thrombus core:[9.2±4.3]％vs.[24.5±9.8]％,P＜0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]％vs.[9.2±4.3]％,P＜0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]％vs.[8.5±5.3]％,P＞0.05;thrombus core:[17.9±8.8]％vs.[14.4±10.0]％,P＞0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]％vs.[9.4±6.3]％,P＜0.001;12weeks after surgery:[14.4±10.0]％vs.[8.5±5.3]％,P＜0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.