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

Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins,lipids,nucleic acids,and bioactive metabolites.They exhibit biological activities such as anti-inflammatory,antioxidant,and immunomodulatory effects.Owing to their unique advantages of low immunogenicity,excellent biocompatibility,stability,and natural targeting ability,milk-derived exosomes have emerged as promising natural nanocarriers,garnering significant attention in disease treatment and nutritional interventions.Sarcopenia,characterized by reduced skeletal muscle mass and diminished strength,is closely associated with aging,chronic inflammation,and oxidative stress.Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia.These exosomes can increase myotube diameter,enhance muscle mass and fiber cross-sectional area,and improve exercise performance metrics such as grip strength.Potential mechanisms may include promoting muscle anabolism,improving mitochondrial function through antioxidant mechanisms,and modulating the inflammatory microenvironments.However,challenges remain in their application for sarcopenia at present,such as the unclear mechanisms of key bioactive components[e.g.,microRNAs(miRNAs),L-ornithine,and milk fat globule-epidermal growth factor 8(MFG-E8)],and the targeting and stability of delivery systems need to be optimized.Future research should focus on the functional analysis of components in exosomes,optimization of delivery systems,and preclinical validation to promote their practical application in managing age-related muscle health.

Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins,lipids,nucleic acids,and bioactive metabolites.They exhibit biological activities such as anti-inflammatory,antioxidant,and immunomodulatory effects.Owing to their unique advantages of low immunogenicity,excellent biocompatibility,stability,and natural targeting ability,milk-derived exosomes have emerged as promising natural nanocarriers,garnering significant attention in disease treatment and nutritional interventions.Sarcopenia,characterized by reduced skeletal muscle mass and diminished strength,is closely associated with aging,chronic inflammation,and oxidative stress.Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia.These exosomes can increase myotube diameter,enhance muscle mass and fiber cross-sectional area,and improve exercise performance metrics such as grip strength.Potential mechanisms may include promoting muscle anabolism,improving mitochondrial function through antioxidant mechanisms,and modulating the inflammatory microenvironments.However,challenges remain in their application for sarcopenia at present,such as the unclear mechanisms of key bioactive components[e.g.,microRNAs(miRNAs),L-ornithine,and milk fat globule-epidermal growth factor 8(MFG-E8)],and the targeting and stability of delivery systems need to be optimized.Future research should focus on the functional analysis of components in exosomes,optimization of delivery systems,and preclinical validation to promote their practical application in managing age-related muscle health.

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3(GATA3)and forkhead protein P3(Foxp3)in peripheral blood.Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method.The control group was given conventional diet before operation,and the observation group was given enteral nutrition support before operation.The two groups were compared in terms of nutritional support.Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume(FEV1/FVC)(P<0.05),FVC(P<0.05),FEV1(P<0.05)and the levels of peripheral blood GATA3(P<0.05),Foxp3 mRNA(P<0.05)expression compared with those at admission(P<0.05),but no significant differences in pulmonary function(P>0.05),peripheral blood GATA3(P>0.05),and Foxp3 mRNA(P>0.05)expression between them at 1 week postoperatively.Both groups exhibited significantly lower levels of albumin,prealbumin,haemoglobin,transferrin,PNI and body mass and body mass index at admis-sion as compared to those at one week after surgery(P<0.05).The observation group showed significantly higher levels of albumin,prealbumin,haemoglobin,transferrin,and PNI at 1 week postoperatively(P<0.05),but no significant differences in ventilation time,defecation time,drain retention time,hospitalisation time,and compli-cation rate as compared to the control group(P>0.05).Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status,and ren-ders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression.

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.

Objective:To explore the risk factors of spontaneous rupture of hepatocellular carcinoma (HCC), and to analyze the prognosis of transcatheter arterial embolization (TAE) in the treatment of spontaneous rupture of HCC.Methods:From January 2008 to December 2018, at Tianjin Third Central Hospital, 126 patients diagnosed with spontaneous rupture of HCC (spontaneous rupture group) and in the same period 252 patients diagnosed as HCC without rupture (non-spontaneous rupture group) were retrospectively selected. Independent sample t test, Mann-Whitney U test and chi-square test were used to compare the general data, laboratory test results and imaging results between spontaneous rupture group and non-spontaneous rupture group. Multivariate logistic regression was used to analyze the independent risk factors of spontaneous rupture of HCC. Kaplan-Meier method and log-rank test were used for survival analysis of 92 patients treated with TAE and 31 patients treated with conservative treatment in patients with spontaneous rupture of HCC, and multivariate Cox proportional hazard regression was used to analyze the independent prognostic factors of patients treated with TAE. Results:The proportions of tumor maximum diameter ≥5 cm, tumors mainly located in segment Ⅱ, Ⅲ, Ⅳ and Ⅵ of the liver, tumors protruding height from the surface of liver ≥1 cm, liver cirrhosis and portal vein thrombosis (PVT) in spontaneous rupture group were all higher than those in non-spontaneous rupture group (46.8%, 59/126 vs. 35.7%, 90/252; 61.1%, 77/126 vs. 46.0%, 116/252; 73.0%, 92/126 vs. 18.7%, 47/252; 81.7%, 103/126 vs. 69.0%, 174/252; 20.6%, 26/126 vs. 11.5%, 29/252), and the level of fibrinogen is lower than that in non-spontaneous rupture group ((3.07 ±1.38) g/L vs. (3.92±1.13) g/L), and the differences were statistically significant ( χ2=4.343, 7.644, 106.780, 6.918 and 5.628, t=-3.276, all P<0.05). The results of multivariate logistic regression analysis showed that the location of tumors in segment Ⅱ, Ⅲ, Ⅳ, Ⅵ of the liver, the height of tumors protruding from the surface of liver ≥1 cm, liver cirrhosis and the fibrinogen was lower than the lower limit of the reference value were independent risk factors of spontaneous rupture of HCC (odds ratio ( OR)=1.354, 5.726, 1.152, 1.892; 95% confidence interval ( CI) 1.062 to 2.008, 1.049 to 19.575, 1.016 to 1.895, 1.267 to 3.346; all P<0.05). Among 92 patients with spontaneous rupture of HCC treated with TAE, the TAE technical success rate and clinical success rate were 100.0% (92/92) and 93.5% (86/92), respectively. Thirty-one patients received conservative treatment. The median survival time of the patients treated with TAE was 243 d (38 d, 377 d), which was about 10 times that of the patients who accepted conservative treatment (23 d (9 d, 51 d)). The 1-month, 3-month, 6-month, 1-year and 3-year survival rates of the patients treated with TAE were 72.8%, 50.8%, 46.0%, 31.1% and 13.6%, respectively, and those of patients who accepted conservative treatment were 25.8%, 17.2%, 11.5%, 5.7% and 0, respectively; and the differences in survival rates between the two groups were statistically significant ( χ2=34.606, P<0.01). Log-rank test analysis showed that initial hemoglobin <60 g/L, C grade of liver function, total bilirubin (TBil)≥50 μmol/L, complicated with portal vein tumor thrombus, hepatic lobe embolism during TAE, and tumor maximum diameter ≥10 cm were all correlated with poor survival rates of patients with spontaneous rupture of HCC after TAE ( χ2=3.752, 4.146, 22.318, 4.087, 5.685 and 7.893, all P<0.05). The results of multivariate Cox proportional hazard regression analysis showed that TBil ≥ 50 μmol/L, hepatic lobe embolism during TAE, and tumor maximum diameter ≥10 cm were independent factors of poor prognosis of spontaneous rupture of HCC treated with TAE ( OR=25.873, 8.415, 18.620; 95% CI 4.916 to 126.005, 1.136 to 27.319, 2.754 to 84.368; all P<0.05). Conclusions:In HCC patients with tumors located in segments Ⅱ, Ⅲ, Ⅳ and Ⅵ of the liver, the height of tumors protruding from the surface of liver ≥1 cm, liver cirrhosis or the fibrinogen is lower than the lower limit of the reference value, close attention should be paid to the risk of spontaneous tumor rupture. TAE is an effective treatment for acute spontaneous rupture of HCC, and the prognosis of patients treated with TAE is better than that of patients receiving conservative treatment. However, patients with TBil ≥50 μmol/L, hepatic lobe embolism during TAE and tumor maximum diameter ≥10 cm have a poor prognosis after TAE treatment.

Traumatic brain injury (TBI) is a kind of disease in which brain tissue injury and brain dysfunction are caused by external trauma. At present, the pathological mechanism of TBI is not fully clear, and there is no good clinical treatment plan. TBI can be preliminarily divided into primary injury and secondary injury according to the occurrence time. In recent years, a large number of researchers have begun to look for effective biological signaling molecules such as micro RNA (miRNA) to discover and intervene in secondary injury with strong response after TBI as early as possible. MiRNA, as a small non-coding RNA, can play a key role in the pathological process of central nervous system diseases, which is considered as an effective regulator of nerve function under pathophysiological conditions. In this paper, the effects of miRNA on the occurrence, development and recovery of TBI are summarized through the three major mechanisms of nerve cell apoptosis, inflammatory cytokine expression and blood-brain barrier repair, which lays the foundation for researching function of miRNA in TBI.

Objective To analyze the efficacy and complications of interventional treatment in hepatic hemangiomas with poor blood supply,and to explore the mode of treatment.Methods From May 2013 to October 2016,at Tianjin Third Central Hospital,82 patients with hepatic hemangiomas with poor blood supply were enrolled and divided into intervention group,puncture group and combination group.Conventional hepatic artery intubation was performed in intervention group,using a microcatheter to superselect to hemangioma and injecting pingyangmycin-lipiodol emulsion into the tumor of hemangioma.Patients of puncture group underwent the ultrasound-guided percutaneous liver puncture,and the pingyangmycin-lipiodol emulsion was injected into the tumor.The patients of combination group first received intervention treatment,and the pingyangmycin-lipiodol emulsion were injected again into the tumor area lacking of iodized oil deposition through percutaneous transhepatic puncture.After treatment,the complications and clinical efficacy of patients in three groups were evaluated and the reasons of patients lost to follow-up were analyzed.The analysis of variance,Chi-square test and Fisher's exact test were performed for statistical analysis.For patients lost to follow up,intention-to-treat (ITT) analysis and per protocol (PP) analysis were used.Results Among 82 patients with hepatic hemangiomas with poor blood supply,there were 27 in intervention group,24 in puncture group and 31 in combination group.Seven patients developed serious complications such as liver failure.At three months after the treatment,the overall efficacy of combination group (20.9％,9/31) was higher than that of intervention group (7.4％,2/27) and puncture group (4.2 ％,1/24),and the differences were statistically significant (x2 =6.296,P =0.014;x2 =5.622,P =0.031).At six months after the treatment,the overall efficacy of combination group (ITT analysis 70.3 ％,26/37;PP analysis 71.0 ％,22/31) was still higher than that of intervention group (40.9％,9/22) and puncture group (7/18),and the differences were statistically significant (ITT analysis x2 =4.929 and 4.969,PP analysis x2 =4.789 and 4.851;all P＜0.05).At twelve months after the treatment,a total of 41 patients of three group were lost.Among them,the patients with ineffective treatment by clinical effect evaluation accounted for 63.4％ (26/41),which was higher than those with significantly effective treatment (12.2 ％,5/41) and those with effective treatment (24.4 ％,10/41),and the differences were statistically significant (x2=22.873 and 12.676,both P＜0.01).Conclusions The efficacy of the interventional treatment alone for hepatic hemangiomas with poor blood supply is poor and the complications should be considered when selecting the appropriate treatment methods.

Objective To analyze the impact of the differences in blood supply to hepatic hemangiomas on interventional treatment effectiveness and complications.Methods A retrospective study was conducted on 322 patients with liver hemangiomas treated from January 2008 to December 2015 in Tianjin Third Central Hospital.The hemangiomas were diagnosed and classified into 3 groups according to the blood supply to the hemangioma:the rich blood supply group (n =128),the moderate blood supply group (n =104) and the poor blood supply group (n =90).The hemangiomas were embolized via the hepatic artery,and the therapeutic effect and complication were compared and analyzed among the 3 different groups.The mean follow-up was 12 months.Results The therapeutic effect of hepatic artery embolization was optimal for the rich blood supply group in the first 3-months of follow-up (the significant efficiency,effective rates were 18.8％ and 35.2％ respectively).There was no significant difference between the rich blood supply group and the moderate blood supply group at 12th month follow-up.The treatment effect on the poor blood supply group was significantly worse than the other two groups on follow-up.Complications after treatment occurred most commonly in the rich blood supply group and it was the least common in the poor blood supply group (the incidence rates were 43.8％,36.6％ and 8.9％ respectively).However,severe post-treatment complications were apparently more common in the poor blood supply group than the other two groups.Conclusions The therapeutic effects of transcatheter arterial embolization on hepatic hemangioma can differ because of the diversity in blood supply.In clinical practice,attention should be paid to the proper choice of treatment according to the blood supply to the lesion.Serious complications can occur after treatment.

Objective To compare the clinical efficacy and postoperative liver function in patients with primary hepatic carcinoma treated by transcatheter arterial chemoembolization(TACE) or TACE combined with portal vein chemoembolization.Methods 48 patients with primary hepatic carcinoma, randomly divided into 2 groups (hepatic artery group in 25 cases and dual interventional group in 23 cases),underwent interventional treatment.The hepatic artery group underwent conventional hepatic artery interventional therapy, while the dual interventional group underwent hepatic artery and portal vein interventional treatment.The postoperative clinical efficiency, liver volume and liver function between the two groups'' patients were compared.Results To the endpoint of observation,the clinical efficacy and tumor reduction degree of dual interventional group were better than that of hepatic artery group.Compared with hepatic artery group, the postoperative ALT, AST and TBIL of dual interventional group were higher on the first and third days.On the seventh and fourteenth days, the statistical difference was not significant.The volume of non-embolization part in dual interventional group was larger than that in preoperative volume to different degrees.The most obvious change of liver volume happened in the 4th weeks after treatment.There was no treatment-related death or severe adverse reaction in two groups.Conclusion The treatment of TACE combined with portal vein chemoembolization is a safe and effective method, which may effectively inhibit the growth and reduce the volume of tumor, and result in compensatory hypertrophy of non-embolization part.