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

OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

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Objective To investigate the virulence and drug resistance characteristics of diarrheagenic Escherichia coli isolated from patients with infectious diarrhea in our hospital.Methods The preliminary identification of microbes was carried out by the VITEK-MS microbial mass spectrometry detection system and virulence genes were detected by the multiplex real-time PCR.Five types of diarrhea-genic Escherichia coli(DEC)clinically isolated from patients with infectious diarrhea in our hospital were identified.The drug resist-ance characteristics of DEC strains were detected by the microbroth dilution and E-test.The drug-resistant molecular characteristics were analyzed by the next-generation sequencing and bioinformatics.The Fisher exact probability method was used for statistical analy-sis.Results The detection rate of DEC in our hospital was 11.9%,with enteroaggregative E.coli(EAEC)accounting for 37.5%,a-typical enteropathogenic Escherichia coli(EPEC)accounting for 34.38%,enterotoxigenic E.coli(ETEC)accounting for 25.0%,and enteroinvasive E.coli(EIEC)accounting for 3.12%.None of enterohemorrhagic E.coli(EHEC)strain was detected.The resistance rates of 32 DEC strains to ampicillin,tetracycline,and trimethoprim/sulfamethoxazole were 53.12%,43.75%,and 37.5%,respec-tively.ESBLs(+)strains accounted for 18.75%,and the detection rate of multidrug-resistant strains was 83.83%,significantly higher than that of ESBLs(-)strains(P=0.042).A total of 25 ST genotypes were obtained from 32 DEC strains.The dominant genotypes were ST10(4 strains,12.5%),followed by ST28(2 strains,6.25%),ST31(2 strains,6.25%),ST3153(2 strains,6.25%),and the other 21 genotypes(1 strain,3.13%).One carbapenem resistant strain carrying the blaNDM-1 gene was detected in EAEC.Conclu-sion Four virulence genes such as aggR,pic,astA,and eae,are more common in the DEC of patients with infectious diarrhea in our hospital,with EAEC and EPEC as the main subtypes.The genotypes are highly polymorphic,and multidrug-resistant strains have been detected.

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.

Objective:To evaluate the knowledge of autism among child health care professionals in primary health care institutions.Methods:The study was a cross-sectional survey. An online questionnaire survey was conducted from February to March 2023 in primary health care institutions in Guangzhou to investigate the knowledge on autism among medical staff engaged in children′s health services and the influencing factors.Results:A total of 341 questionnaires were returned and 312 questionnaires were valid with a recovery rate of 91.5%. The age of 312 respondents was (35.9±7.9) years, of which 303 (97.1%) were female. One hundred and fifty-two (48.7%) child health care professionals in primary health care institutions had received specialist training in assessing the psychological and behavioral development of children, and only 139 (44.6%) reported that they were aware of the"five no"principle for early identification of autism. The questionnaire scores were 88.1% pass (275/312) and 53.2% excellent (166/312). The three questions with low accuracy were: autism can be cured with drugs, autism has a genetic basis and rehabilitation training has no effect, and the accuracy for these questions was 42.6% (133/312), 52.2% (163/312) and 70.2% (219/312), respectively. The passing of autism-related knowledge was positively associated with receiving relevant training ( OR=2.585, 95% CI:1.200-5.569), and the excellence was positively associated with the highest education ( OR=1.939, 95% CI:1.220-3.083) and receiving relevant training ( OR=2.016, 95% CI:1.247-3.260). Conclusions:There is a need for more professional training in autism knowledge among child health care professionals in primary health care institutions.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

ObjectiveTo observe the regulatory effect of Huangwu Ganfu ointment on transient receptor potential anchor protein 1 （TRPV1） receptor expression， macrophage polarization， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in synovial tissue of knee osteoarthritis （KOA） rats with yang deficiency and cold coagulation syndrome and explore the mechanism of relieving peripheral inflammatory hyperalgesia of KOA. MethodForty-eight male SD rats were randomly divided into blank group， model group， high-dose， middle-dose， and low-dose groups of Huangwu Ganfu ointment （9.3， 4.65， 2.325 g·kg^-1）， and celecoxib group （20.82 mg·kg^-1）. The KOA rat model of yang deficiency and cold coagulation syndrome was established through climate box and swimming for two weeks combined with an injection of sodium iodoacetate （MIA） in the articular cavity. After continuous administration for four weeks， the general condition of rats in each group was observed， and the pain withdrawal threshold （PWT） and joint diameter induced by mechanical stimulation were recorded. The expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） inflammatory factor were detected by enzyme-linked immunosorbent assay （ELISA）， and the histopathological changes of synovial tissue of the knee joint were observed by hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of TRPV1， p38 MAPK， and p-p38 MAPK in synovial tissue of the knee joint， and immunofluorescence （IF） was used to evaluate the polarization of M1/M2 macrophages. ResultCompared with that in the blank group， the overall mental state of the model group was worse， and the autonomous activity was decreased. The body mass was lower， and the joint diameter was increased. The X-ray showed that the osteophyte at the edge of the joint proliferated， and the articular surface was obviously rough. The articular cavity was significantly narrowed， and the PWT was significantly decreased （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in serum and synovium Krenn score increased significantly （P<0.01）. The protein expression of TRPV1 and p-p38 MAPK/p38 MAPK increased significantly （P<0.01）， and the proportion of M1 macrophages and M1/M2 increased （P<0.01）， while the proportion of M2 macrophages decreased （P<0.01）. Compared with model group， the body mass in the low， middle， and high dose groups of Huangwu Ganfu ointment increased to different degrees （P<0.05， P<0.01）. The diameter of the knee joint in the high dose group of Huangwu Ganfu ointment and celecoxib group decreased （P<0.01）. The recovery of PWT in the high and middle dose groups of Huangwu Ganfu ointment groups was more obvious （P<0.05）. The contents of IL-1β and CGRP in the serum of rats in each administration group were significantly decreased （P<0.01）， and the content of serum TNF-α in the celecoxib group and high dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）. The content of serum NGF in the middle dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）， and the synovium Krenn score decreased in the high dose group of Huangwu Ganfu ointment （P<0.05）. In addition， the protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in synovial tissue decreased significantly in all groups of Huangwu Ganfu ointment （P<0.01）. The proportion of M1 macrophages in synovial tissue in the celecoxib group and all groups of Huangwu Ganfu ointment decreased （P<0.01）， and the proportion of M2 macrophages in the high dose group of Huangwu Ganfu ointment increased （P<0.05）. The M1/M2 in the middle and high dose groups of Huangwu Ganfu ointment decreased （P<0.05）. ConclusionHuangwu Ganfu ointment can mediate the polarization of macrophages to reduce the inflammatory reaction of KOA， alleviate the release of inflammatory pain mediators， and lower the protein expression of TRPV1. The mechanism may be related to the p38 MAPK signaling pathway， so as to improve the peripheral hyperalgesia of KOA.

Objective:To establish a data middle platform for data assets of medical consumables,to provide open data sharing services for the management and application development of medical consumables,and to reduce the risk of data silos.Methods:Based on the data resource management model of data middle platform,data aggregation and big data development technology were adopted to realize data loading,integration and quality control between multi-business systems.A hierarchical data management system was established through data warehousing and object modeling methods.A data assets management system was built based on the data governance process to provide functions of data standards and data lineage maintenance,metadata management,data permission control,and data lifecycle management for medical consumables data resources.A microservice architecture was adopted to provide functions such as data service generation,registration,discovery and subscription for medical consumables management.The front-end data application development workload of business data and application operation time before and after the application of data middle platform service of medical consumables were compared in the South Campus of the Fifth Medical Center of PLA General Hospital from March to May 2020.Results:The medical consumables data middle platform realized the connection between the front-end application interface and the back-end data service,and provided synchronized data services for the front-end pages.The workload of front-end data application development for data middle platform data services decreased from 64 person-months of traditional data warehouses to 6 person-months,and the operation time for testing applications reduced from 430 minutes to 16 minutes.Conclusion:The data middle platform management mode is helpful to improve the information management capabilities and efficiency of medical consumables management,and provides reference for the digital transformation of medical consumable management.