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 basic situation of pre-analytical quality management in blood station laboratories in North China, and to provide baseline data for promoting the homogenization and standardization of these pre-analytical processes in each blood station laboratory. Methods: A cross-sectional status survey was designed based on the quality management regulations of blood stations, ISO15189 standards and relevant quality management requirements. This survey covering various aspects including laboratory general situation, sample collection and temporary storage, transportation, reception, and quality continuous improvement situations. Data analysis was performed on the survey results of each laboratory. Results: All the 38 blood station laboratories in North China had established a pre-analytical quality management system framework and implemented basic pre-analytical quality control activities; however, there were differences in implementation. 1) Among the 12 basic quality items, 3 items were monitored by all the investigated laboratories (100%), 6 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 60%). There were no significant differences in the monitoring index among the three regions and among different types of laboratories (P>0.05). 2) Among the total of 26 items in the three key processes before testing (sample collection and storage, transportation, reception and processing), 12 items were monitored by all laboratories (100%), 11 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 75%). There were no significant differences in monitoring index among different regions and types of laboratories (P>0.05). Conclusion: This survey provides a reference and basis for the gap analysis of the pre-analytical process quality management in 38 blood station laboratories across North China. It facilitates laboratories in identifying pre-analytical quality problems, resolving problems, preventing errors, and ensuring that the quality of blood samples before testing meets the established requirements. It lays a foundation for the homogenization of pre-analytical quality management in regional blood stations.

Objective: To investigate the assessment criteria and subsequent handling practices of hemolytic and lipemic blood samples before testing in blood screening laboratories in North China, and to provide data to support the standardization of their management in blood station laboratories. Methods: Data on the preanalytical management of hemolytic and lipemic samples from 38 laboratories were collected. The details of management on the criteria and verificatioon for assessment, the assessment methods, and subsequent handling procedures of hemolytic and lipemic samples in blood station laboratories were analyzed. Results: 1) All 38 blood station laboratories monitored serological and nucleic acid samples for hemolysis and lipemia in pre-analytical phase. 2) The criteria and methods for assessing hemolytic and lipemic samples varied among the laboratories of the 38 blood stations. 15 laboratories (39.47%) followed manufacturer's instructions, 9 laboratories (23.68%) formulated their own criteria, and 14 laboratories (36.84%) referred to the criteria of other laboratories. 16 laboratories (42.11%) verified the criteria for assessing hemolytic and lipemic samples, with significant variations in verification rate across laboratories from different regions (P<0.05). For the assessment methods, visual inspection was used by 28 laboratories (73.68%) for hemolytic samples and by 27 laboratories (71.05%) for lipemic samples; the colorimetric card method was used by 10 laboratories (26.32%) for assessing both hemolytic and lipemic samples; the instrumental method was used by 1 laboratory (2.63%) for assessing lipemic samples.3) The handling procedures for hemolytic and lipemic samples varied significantly and followed a gradient distribution pattern among 38 laboratories (including accepting samples for testing, accepting samples for concession testing, re-collecting samples, and rejecting samples and halting testing). With increasing severity of hemolysis and lipemia, more laboratories halted testing, and relatively fewer laboratories accepted samples for normal testing. 5 laboratories (13.16%) applied different handling procedures on serological and nucleic acid samples. Conclusion: This survey provides a reference and basis for analyzing gaps in the management of hemolytic and lipemic samples during the preanalyical phase in blood station laboratories in North China. It enables laboratories to identify the problems and deficiencies in the management of hemolytic and lipemic samples, to ensure preanalytical samples quality meets the established requirements, and to lay a foundation for promoting the homogenization and standardization of the regional sample quality management mode.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Objective:To assess the physical activity levels(PA)and patterns among older adults in rural areas, as well as to evaluate the association between PA levels and the conditions of sarcopenia and frailty.Methods:A cross-sectional survey was conducted involving 690 rural individuals aged 60 and above.Data on socio-demographic characteristics were collected, while Appendicular Skeletal Muscle Mass Index(ASMI)and grip strength were measured.The Physical Activity Scale for the Elderly(PASE)was employed to evaluate PA levels.Based on their PASE scores, participants were categorized into three groups: low PA level, medium PA level, and high PA level.Sarcopenia was defined according to the 2019 criteria established by the Asian Working Group for Sarcopenia(AWGS), and frailty status was assessed using the Frail Scale.Results:Among the study sample, 38.0% exhibited a low level of physical activity, 46.2% had a medium level, and 15.8% engaged in high levels of activity.As age increased, the level of physical activity among older adults significantly declined.Most of the physical activity reported by participants was attributed to household chores and farming-related activities.Participation in structured exercise among older adults was notably low, with only 1.3% engaging in muscle-strengthening exercises on a weekly basis.The majority(53.9%)reported walking as their preferred form of weekly exercise.After adjusting for confounding factors, the prevalence of sarcopenia was found to be 0.40(95% CI: 0.26-0.62)times lower in the medium physical activity group, and 0.56(95% CI: 0.31-1.01)times lower in the high physical activity group, compared to those with a low physical activity level.Similarly, regarding frailty as a negative outcome, the prevalence was 0.66(95% CI: 0.51-0.84)times lower in the medium physical activity group and 0.46(95% CI: 0.30-0.73)times lower in the high physical activity group, relative to the low physical activity group.When using PASE scores as a continuous variable, the results remained consistent. Conclusions:The physical activity levels of rural older adults are inadequate, and participation in multicomponent exercise programs is notably low.A lower level of physical activity is significantly associated with a higher prevalence of sarcopenia and frailty.Our findings indicate that it is essential to implement physical activity education and interventions to enhance exercise health literacy and to prevent sarcopenia and frailty among rural older adults.

To summarize experience in the diagnosis and treatment of adolescent non-freezing cold injury (NFCI).Methods:Retrospective case summary.The clinical data of 7 children with NFCI treated at the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were reviewed.Results:Among the 7 children, including 2 boys and 5 girls, the main clinical manifestations were persistent pain with stiffness in feet, involving metatarsophalangeal joint, interphalangeal joint, and plantar surface, with toe pain the severest, and the pain worsened at night.All 7 children had magnetic resonance imaging of the foot, and among them, 4 cases showed multiple patchy fat-suppressed high signals on talus, medial tarsal bone, metatarsal bone, and phalangeal bone, suggesting ischemia, and 3 cases showed long T1 long T2 fluid signals on ankle joint cavity, some tarsal joint space, and metatarsophalangeal joint space, suggesting bone marrow edema with joint effusion.Four children received intravenous infusion of 10 mg Hydroprednisone injection once a day for 5 consecutive days, with loss of pain and complete resolution of stiffness.Conclusions:NFCI is a rare cold injury but not frostbite disease.Pathogenic conditions and clinical manifestations are the main basis for its diagnosis, and low-dose hydroprednisone is effective for the treatment of this disease.

To summarize experience in the diagnosis and treatment of adolescent non-freezing cold injury (NFCI).Methods:Retrospective case summary.The clinical data of 7 children with NFCI treated at the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were reviewed.Results:Among the 7 children, including 2 boys and 5 girls, the main clinical manifestations were persistent pain with stiffness in feet, involving metatarsophalangeal joint, interphalangeal joint, and plantar surface, with toe pain the severest, and the pain worsened at night.All 7 children had magnetic resonance imaging of the foot, and among them, 4 cases showed multiple patchy fat-suppressed high signals on talus, medial tarsal bone, metatarsal bone, and phalangeal bone, suggesting ischemia, and 3 cases showed long T1 long T2 fluid signals on ankle joint cavity, some tarsal joint space, and metatarsophalangeal joint space, suggesting bone marrow edema with joint effusion.Four children received intravenous infusion of 10 mg Hydroprednisone injection once a day for 5 consecutive days, with loss of pain and complete resolution of stiffness.Conclusions:NFCI is a rare cold injury but not frostbite disease.Pathogenic conditions and clinical manifestations are the main basis for its diagnosis, and low-dose hydroprednisone is effective for the treatment of this disease.

Objective:To assess the physical activity levels(PA)and patterns among older adults in rural areas, as well as to evaluate the association between PA levels and the conditions of sarcopenia and frailty.Methods:A cross-sectional survey was conducted involving 690 rural individuals aged 60 and above.Data on socio-demographic characteristics were collected, while Appendicular Skeletal Muscle Mass Index(ASMI)and grip strength were measured.The Physical Activity Scale for the Elderly(PASE)was employed to evaluate PA levels.Based on their PASE scores, participants were categorized into three groups: low PA level, medium PA level, and high PA level.Sarcopenia was defined according to the 2019 criteria established by the Asian Working Group for Sarcopenia(AWGS), and frailty status was assessed using the Frail Scale.Results:Among the study sample, 38.0% exhibited a low level of physical activity, 46.2% had a medium level, and 15.8% engaged in high levels of activity.As age increased, the level of physical activity among older adults significantly declined.Most of the physical activity reported by participants was attributed to household chores and farming-related activities.Participation in structured exercise among older adults was notably low, with only 1.3% engaging in muscle-strengthening exercises on a weekly basis.The majority(53.9%)reported walking as their preferred form of weekly exercise.After adjusting for confounding factors, the prevalence of sarcopenia was found to be 0.40(95% CI: 0.26-0.62)times lower in the medium physical activity group, and 0.56(95% CI: 0.31-1.01)times lower in the high physical activity group, compared to those with a low physical activity level.Similarly, regarding frailty as a negative outcome, the prevalence was 0.66(95% CI: 0.51-0.84)times lower in the medium physical activity group and 0.46(95% CI: 0.30-0.73)times lower in the high physical activity group, relative to the low physical activity group.When using PASE scores as a continuous variable, the results remained consistent. Conclusions:The physical activity levels of rural older adults are inadequate, and participation in multicomponent exercise programs is notably low.A lower level of physical activity is significantly associated with a higher prevalence of sarcopenia and frailty.Our findings indicate that it is essential to implement physical activity education and interventions to enhance exercise health literacy and to prevent sarcopenia and frailty among rural older adults.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.