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

Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

With the vigorous promotion of organ donation after citizen death in China, increased utilization of marginal livers, and continuous expansion of hepatocellular carcinoma indications for liver transplantation, innovations in techniques such as auxiliary liver transplantation, pediatric liver transplantation, laparoscopic liver transplantation, magnetic liver transplantation,and non-ischemic liver transplantation have significantly improved the number of liver transplantation surgery performed, patient survival rates, and graft survival rates in China, while complication rates have gradually decreased. As such,liver transplantation in China has reached leading or advanced levels internationally. In the new development context,Chinese liver transplantation faces new opportunities and challenges for development. Evolutions in basic diseases of transplant recipients and tumor classifications of will further broaden the population eligible for transplantation and introduce new demands for liver transplantation procedures. Emerging technologies including artificial organs, xenotransplantation,and artificial intelligence are bringing prospects for advancing liver transplantation. Looking ahead, the progression of liver transplantation will go beyond prioritizing patient survival rates and graft survival rates alone, instead emphasizing improved quality of life for transplant recipients post-surgery to an even greater extent.

With the vigorous promotion of organ donation after citizen death in China, increased utilization of marginal livers, and continuous expansion of hepatocellular carcinoma indications for liver transplantation, innovations in techniques such as auxiliary liver transplantation, pediatric liver transplantation, laparoscopic liver transplantation, magnetic liver transplantation,and non-ischemic liver transplantation have significantly improved the number of liver transplantation surgery performed, patient survival rates, and graft survival rates in China, while complication rates have gradually decreased. As such,liver transplantation in China has reached leading or advanced levels internationally. In the new development context,Chinese liver transplantation faces new opportunities and challenges for development. Evolutions in basic diseases of transplant recipients and tumor classifications of will further broaden the population eligible for transplantation and introduce new demands for liver transplantation procedures. Emerging technologies including artificial organs, xenotransplantation,and artificial intelligence are bringing prospects for advancing liver transplantation. Looking ahead, the progression of liver transplantation will go beyond prioritizing patient survival rates and graft survival rates alone, instead emphasizing improved quality of life for transplant recipients post-surgery to an even greater extent.

Objective:To evaluate the effect of berberine on acute kidney injury (AKI) in rats undergoing liver transplantation and the role of AMP-activated protein kinase (AMPK).Methods:Twenty-four SPF-grade adult male Sprague-Dawley rats, aged 12 weeks, weighing 210-230 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group (S group), AKI group, berberine group (BBR group), and berberine + AMPK inhibitor Compound C group (BBR-Comp C group). In BBR group, berberine 200 mg/kg was given by gavage starting from 2 weeks before surgery, once a day for 14 consecutive days. In BBR-Comp C group, Compound C 1 mg/kg was injected into the tail vein at 30 min before surgery. The rat AKI model was prepared by in situ liver transplantation in AKI group, BBR group and BBR-Comp C group. Blood specimens were taken from the inferior vena cava at 24 h postoperatively, and serum BUN and Cr concentrations were determined by enzyme-linked immunosorbent assay. Then the rats were sacrificed, and the kidney tissues were taken for microscopic examination of the pathological changes (with the light microscope after HE staining) and for determination of the expression of phosphorylated AMPK (p-AMPK), receptor-interacting protein kinase-1 (RIPK-1), receptor-interacting protein kinase-3 (RIPK-3) and mixed lineage kinase domain-like protein (MLKL) (by Western blot). Results:Compared with S group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, the expression of RIPK-1, RIPK-3 and MLKL was up-regulated ( P<0.05), and the pathological damage to renal tissues occurred in AKI group. Compared with AKI group, the serum BUN and Cr concentrations were significantly decreased, the p-AMPK expression was up-regulated, the expression of RIPK-1, RIPK-3 and MLKL was down-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in BBR group. Compared with BBR group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, and the expression of RIPK-1, RIPK-3 and MLKL was up-regulated in BBR-Comp C group ( P<0.05). Conclusions:Berberine can attenuate AKI in rats undergoing liver transplantation, and the mechanism may be related to the promotion of AMPK phosphorylation and inhibition of programmed necrosis.

Objective To investigate the relationship between serum L-carnitine and its related metabolites[trimethylamine(TMA)and trimethylamine N-oxide(TMAO)]levels and gestational diabetes mellitus(GDM)in the second trimester of pregnant women in Shanghai.Methods A case-control study was conducted in 280 pregnant women between 18 and 23 weeks of gestation from January 2018 to January 2021.Among them,134 cases of GDM were the case group(GDM),and 146 cases with normal blood glucose(BG)were the control group(Con).Serum L-carnitine,TMA and TMAO levels were quantified by ultra high performance liquid chromatography-mass spectrometry.Logistic regression analysis,stratified analysis and linear regression were used to explore the relationship between L-carnitine,TMA and TMAO levels and GDM and glucolipid metabolism.Results Serum L-carnitinelevelwas significantly lower in GDM group than that in Con group(P<0.01).After adjusting for confounders,logistic regression showed a 70%reduction in the risk of GDM in the group with highest tertile of L-carnitine compared with the group with lowest tertile(OR 0.30,95%CI 0.15～0.63).The risk of GDM decreased by 14%for each 1 μmol/L increase in serum L-carnitine(OR 0.86,95%CI 0.80～0.93).Serum L-carnitine was negatively correlated with 1 hPG(r=-0.21,P<0.01)and 2 hPG(r=-0.15,P<0.05),respectively,TMA was negatively correlated with 2 hPG(r=-0.21,P<0.01).Conclusions Higher serum L-carnitine level may be negatively associated with GDM.Serum L-carnitine and TMA levels were negatively correlated with blood glucose levels.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

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 investigate the influencing of high sodium donor liver transplan-tation from the death of a citizen′s organ donation (DCD) on the prognosis of recipients.Methods:The retrospective cohort study was constructed. The clinicopathological data of 125 pairs of donors and recipients who underwent DCD liver transplantation in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected. Of the 125 donors, there were 93 males and 32 females. Of the 125 recipients, there were 92 males and 33 females, aged 48(41,55)years. According to the last time of serum sodium level of donor liver in the 125 recipients, 9 donor livers with serum sodium level ≥170 mmol/L were divided into group 1 (extremely high sodium), 33 donor livers with serum sodium level ≥150 mmol/L and <170 mmol/L were divided into group 2 (moderate high sodium), and 83 donor livers with serum sodium level <150 mmol/L were divided into group 3 (normal sodium), respectively. Observation indicators: (1) postoperative recover situations; (2) follow-up and survival analysis. Measurement data with normal distribution were represented as Mean± SD. Repeated measures were analyzed by repeated measures ANOVA. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Kruskal-Wallis test. Count data were described as absolute numbers, and Pearson chi-square test or Fisher exact probability were used for data test. The Kaplan-Meier method was used to draw survival curves and Log-rank test was used for survival analysis. Results:(1) Postoperative recover situations. The changes of alanine transaminase (AlT), aspartate aminotransferases (AST), total bilirubin (TBil), alkaline phosphatase (ALP), prothrombin time (PT), international normalized ratio (INR), albumin (Alb) and creatinine (Cr) from the first day to the 14th day after operation were (736±972)IU/L to (75±46)IU/L, (1 290±1 651)IU/L to (38±20)IU/L, (102±98)μmol/L to (33±11)μmol/L, (66±34)IU/L to (104±54)IU/L, (19.9±3.3)seconds to (11.3±1.0)seconds, 1.76±0.31 to 1.00±0.08, (34±5)g/L to (38±3)g/L and (91±41)μmol/L to (76±19)μmol/L, respectively, in the recipients of group 1. The above indicators were (505±377)IU/L to (48±46)IU/L, (855±727)IU/L to (24±17)IU/L, (64±42)μmol/L to (32±22)μmol/L, (68±51)IU/L to (91±46)IU/L, (16.8±3.5)seconds to (11.9±1.2)seconds, 1.47±0.30 to 1.04±0.09, (33±4 g/L) to (40±5)g/L and (106±32)μmol/L to (97±27)μmol/L in the recipients of group 2 and (637±525)IU/L to (65±60)IU/L, (929±1 193)IU/L to (33±27)IU/L, (66±48)μmol/L to (33±36)μmol/L, (64±28)IU/L to (125±64)IU/L, (17.2±4.7)seconds to (13.3±12.8)seconds, 1.51±0.42 to 1.05±0.13, (35±6)g/L to (39±4)g/L, (105±44)μmol/L to (94±40)μmol/L in the recipients of groups. Results of overall effect showed there were significant differ-ences in the change trend of TBil (time effect, inter-group effect, interaction effect) in recipients among the three groups after liver transplantation ( Fgroup=5.42, Ftime=22.78, Finteraction=3.85, P<0.05). There were significant differences in the time effect of ALT, AST, ALP, PT, INR, Alb, Cr in recipients among the three groups after liver transplantation ( Ftime=50.17, 36.24, 19.24, 10.55, 59.61, 41.94, 10.82, P<0.05). (2) Follow-up and survival analysis. All recipients were followed up. Cases with early postoperative liver dysfunction, cases with donor liver failure 1 year after operation, cases with biliary complica-tions 1 year after operation, cases with vascular complications 1 year after operation, cases with rejection 1 year after operation were 2, 1, 0, 0, 0 in the recipients of group 1. The above indicators were 2, 1, 3, 0, 1 in the recipients of group 2 and 10, 8,20, 1, 6 in the recipients of group 3. There was no significant difference in the above indicators among the three groups ( χ2=1.58, 0.60, 5.19, 1.62, 0.97, P>0.05). The 1-year and 3-year cumulative survival rates of the donor liver were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 94.74% and 77.16% in the recipients of group 2 and 91.57% and 89.30% in the recipients of group 3. There was no significant difference in the cumulative survival rate of donor liver among the three groups ( χ2=2.69, P>0.05). The 1-year and 3-year cumulative survival rates were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 93.74% and 77.16% in the recipients of group 2 and 89.40% and 86.00% in the recipients of group 3. There was no significant difference in the cumulative survival rate among the three groups ( χ2=1.94, P>0.05). Conclusion:Donor livers with high serum sodium level can be used in the DCD liver transplantation.

Objective:To investigate the ultrasonic characteristics of eccrine spiradenoma (ES) and to analyze the diagnostic value.Methods:Nineteen ES patients with 24 lesions confirmed by pathology in 3 grade-A tertiary hospitals from October 2011 to October 2021 were enrolled as study group, and in the same time, 46 patients with 46 masses in the skin and muscular tissues with clinical features of automatic pain and/or tenderness were selected as control group. The ultrasonographic characteristics of the two groups were analyzed retrospectively, including anatomical location, shape, boundary, internal echogenicity, echogenic distribution, calcification, posterior acoustic effect, and vascularity. The ultrasonographic characteristics of the two groups were compared, and the risk sonographic characteristics of ES were obtained by multivariate logistic regression analysis. The sensitivity and specificity of ultrasound characteristics for the diagnosis of ES were calculated.Results:The ultrasonic characteristics of the two groups had significant differences in lobulated shape, boundary, internal echogenicity and posterior acoustic effect (χ 2=32.65, 15.65, 5.77, 13.63; all P<0.01). Multivariate logistic regression analysis showed that lobulated shape and posterior acoustic enhancement were the risk ultrasonic characteristics of ES. The sensitivity and specificity of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17%, 89.13%, 95.83% and 47.83%, respectively; and the sensitivity and specificity of the combination of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17% and 97.83%, respectively. Conclusions:The lobulated shape and posterior acoustic enhancement characteristics are important for the identification of ES, which have higher diagnostic efficacy for ES.