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

To study the therapeutic effect and mechanisms of ethyl syringate(MD) on ulcerative colitis(UC), the MTT assay was used to detect the proliferation inhibition of RAW264.7 cells and HT-29 cells by different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)). UC cell models were constructed by inducing RAW264.7 cells and HT-29 cells with lipopolysaccharide(LPS) and tumor necrosis factor-α(TNF-α). An animal model was established by inducing mice with 2.5% dextran sulfate sodium(DSS) to verify the therapeutic effect of MD on UC. A control group, a model group(LPS or TNF-α), and groups treated with different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)) were set up in this study. Nitric oxide(NO) levels were measured using a NO detection kit. Intracellular reactive oxygen species(ROS) levels were assessed using a laser confocal microscope and ROS kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect changes in the levels of interleukin-6(IL-6), TNF-α, interferon-γ(INF-γ), interleukin-10(IL-10), and myeloperoxidase(MPO) in cells and animal tissues. Western blot was used to detect the expression levels of phosphorylated Janus kinase 2(p-JAK2), Janus kinase 2(JAK2), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), zonula occludens-1(ZO-1), occludin, and claudin-1 in cells and animal tissues. The results showed that MD can improve the inflammatory response by inhibiting the production of NO and ROS and regulating the expression of inflammatory factors. It significantly reduced the disease activity index(DAI) in mice, improved the shortening of the colon, and repaired intestinal epithelial damage by inhibiting the activation of the JAK2/STAT3 pathway, thereby exerting anti-UC activity.
Animals ; Colitis, Ulcerative/chemically induced* ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Mice ; Humans ; Signal Transduction/drug effects* ; Male ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism* ; Nitric Oxide/metabolism* ; HT29 Cells ; Salicylates/administration & dosage* ; Protective Agents/administration & dosage*

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective:To compare the efficacy and safety of Rotarex mechanical thrombectomy (Rotarex) combined with drug-coated balloon (DCB) versus percutaneous transluminal angioplasty (PTA) combined with DCB in the treatment of femoropopliteal artery in-stent restenosis (ISR).Methods:A multicenter, prospective, randomized controlled trial was conducted. 46 patients with femoropopliteal artery ISR admitted to five hospitals (Beijing Friendship Hospital, Capital Medical University; Beijing Chaoyang Hospital, Capital Medical University; Beijing Jishuitan Hospital, Capital Medical University; Xuanwu Hospital, Capital Medical University; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University) from July 2020 to June 2024 were enrolled. Patients were randomly divided into the Rotarex+ DCB group ( n=24) and the PTA+ DCB group ( n=22) using a random number table. The clinical data of the two groups were collected, including clinical characteristics, Fontaine classification, stent placement location, stent duration, and lesion length. The primary endpoint was the target blood vessel patency rate at 6 and 12 months postoperatively; the secondary endpoints included improvement in clinical symptoms (Fontaine classification), rate of reintervention, and safety indicators. Measurement data were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; count data were expressed as the number of cases and percentages, and intergroup comparisons were performed using the Chi-test or Fisher exact probability method. Results:At 12 months postoperatively, the target blood vessel patency rate in the Rotarex+ DCB group was significantly higher than that in the PTA+ DCB group (81.8% vs 45.5%, P=0.012), and the proportion of patients in Fontaine classification stage I was also higher (86.4% vs 45.5%, P=0.004). The results at the 6-month follow-up were consistent (target blood vessel patency rate: 87.0% vs 59.1%, P=0.035). In terms of safety, no severe complications such as arterial rupture, amputation, or procedure-related death occurred during the perioperative period in either group. During the postoperative follow-up, no amputation or procedure-related deaths occurred in either group. Conclusion:For the treatment of femoropopliteal artery ISR, Rotarex mechanical thrombectomy combined with DCB is significantly superior to PTA+ DCB in terms of 12-month target blood vessel patency rate and improvement of clinical symptoms, with comparable safety.

Traditional mass measurement methods are not applicable in microgravity environments,and the main challenge for in-orbit body mass measurement technology based on inertial principles is to address the random errors brought about by the weightless environment.These include additional torques due to shifts in the center of mass,nonlinear accelerations due to non-rigid human bodies,mechanical energy consumption due to organ vibrations,and random vibrations of the measurement device itself.To address the above difficulties,the project proposes a technical scheme based on the principle of linear acceleration,designs and constructs a ground-specific air-floating experimental and simulation platform,studies key data such as motion trajectory,acceleration change,and vibration frequency amplitude during the mass measurement process,and simulates the changes in the center of mass and random vibrations of the human body in a weightless environment.The project has designed an adjustable posture bracket to adapt to changes in the center of mass,enhance body restraint,and greatly reduce shaking;it has also developed an integrated four-bar linkage motion guidance mechanism,high-precision integrated photoelectric distance measurement,and modular motion constant force measurement device to ensure the accurate measurement of acceleration and constant force data.The product has undergone simulation calculations,ground human applicability tests,and in-orbit applicability verification in the space station.Ground test results show that the device achieves a body mass measurement accuracy better than 0.5%,and the dispersion is better than 0.38%;after flight mission verification and evaluation,the in-orbit body mass measurement dispersion is less than 0.4%,which is superior to the SLAMMD,a mass measurement device of the same principle on the International Space Station,and is at the forefront internationally,achieving accurate body mass measurement.

Aim To predict and verify the potential mechanism of the compatibility of"ginseng-astragalus-pueraria"in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TC-MSP,TCMIP,and BATMAN.The targets of type 2 dia-betes mellitus(T2DM)were obtained from three plat-forms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cy-toscape 3.9.1;GO and KEGG analysis were per-formed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results"Gin-seng-astragalus-pueraria"screened out 2 021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were i-dentified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experi-ments showed that the horn drug increased insulin binding rate and secretion index and reduced serum in-sulin level and insulin resistance index.These data benefited from"ginseng-astragalus-pueraria"reducing the expression of AGE-RAGE,activating PI3K-Akt,in-hibiting NF-κB,and reducing the expression of IL-6,IL-1β and TNF-α.Conclusion The study suggests that"ginseng-astragalus-pueraria"regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resist-ance.

Adenocarcinoma of the esophagogastric junction (AEG) has shown an increasing incidence in recent years. The treatment strategy for AEG differs from that of gastric and esophageal cancers due to its unique anatomical location and biological behavior. Surgical resection remains the cornerstone of AEG treatment, with the choice of surgical approach based on Siewert classification, esophageal invasion length, and individual patient factors. The extent of lymph node dissection is determined by tumor location, stage, and patterns of lymph node metastasis. Digestive tract reconstruction aims to maximize the preservation of digestive function and reduce postoperative complications while achieving radical tumor resection. In recent years, minimally invasive surgical techniques, including laparoscopic and robotic surgery, have been increasingly applied in AEG treatment, with preliminary validation of their safety and feasibility. Additionally, the application of neoadjuvant therapy, targeted therapy, and immunotherapy has brought new hope for AEG treatment. This article reviews the current status of surgical treatment for AEG, including surgical approaches, lymph node dissection, digestive tract reconstruction, and neoadjuvant therapy, and discusses future directions in AEG surgical treatment.

The da Vinci Surgical System provides surgeons with a three-dimensional image view with greater clarity, which improves surgical precision, particularly in confined surgical spaces. Compared to laparoscopic surgery, robotic surgery has a shorter learning curve and may be a better choice for surgeons. However, some surgeons are susceptible to laparoscopic experience when performing robotic surgery, which can diminish the advantages of the robotic system. We discussed some key issues such as indications, use of energy instruments, surgical approach, lymph node dissection, and digestive tract reconstruction, from the habit of laparoscopic surgery, in light of our team's experience with robotic radical gastric cancer surgery and the latest literature, in order to help beginners better understand the robotic surgical system.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.