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 effect of staphylococcal nuclease and tudor domain containing 1(SND1)on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating fer-roptosis in osteosarcoma cells via SLC7A11.Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small in-terfering RNA was employed to knock down the expression of SND1(si-SND1)in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11.Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Fer-rostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resul-ted in down-regulated SLC7A11 expression(all P<0.001)and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020).Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferrop-tosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

Objective:To examine the safety and feasibility of using fusion indocyanine green fluorescence imaging (FIGFI) technique for intraoperative evaluation of colorectal perfusion in the totally laparoscopic left colectomy.Methods:A retrospective cohort study was conducted to collect the clinical data of 58 patients with left colon cancer who underwent totally laparoscopic surgery at the Colorectal Surgery Department, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2019. There were 39 males and 19 females, aging (57.0±10.1)years(range:28 to 75 years). According to whether the FIGFI was used during the operation, they were divided into 36 cases in the study group and 22 cases in the control group. The clinical pathological characteristics, operative and postoperative recovery of the two groups were compared by t test, χ 2 test, and Fisher exact test. Results:All the 58 patients underwent R0 resection with totally laparoscopic surgery. In the study group, due to poor bowel blood flow after cutting the mesentery (Sherwinter score = 1), 1 patient had to be expanded the resection range until the blood flow was rich(Sherwinter score≥3), and 1 patient in the control group had the complication of postoperative anastomotic leakage of grade A. Compared with the control group, the operation time in the study group was shorter ((156.3±43.5) minutes vs. (180.4±41.3) minutes, t=-2.083, P=0.042). However, there were no significant differences in the amount of blood loss, postoperative hospital stay, postoperative time of anal exhaust, length of bowel resection, number of lymph nodes dissected, and in the incidence of postoperative complications between the two groups. Median follow-up period was 23 months (range: 18 to 37 months). There were no long-term postoperative complications such as ischemic enteritis and anastomotic stenosis in both groups. Conclusions:The FIGFI is safe and feasible to assess the blood supply of intestinal segment and anastomosis during totally laparoscopic left hemicolectomy, and is easy to operate. It is expected to reduce the incidence of anastomotic leakage.

Objective:To examine the safety and feasibility of using fusion indocyanine green fluorescence imaging (FIGFI) technique for intraoperative evaluation of colorectal perfusion in the totally laparoscopic left colectomy.Methods:A retrospective cohort study was conducted to collect the clinical data of 58 patients with left colon cancer who underwent totally laparoscopic surgery at the Colorectal Surgery Department, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2019. There were 39 males and 19 females, aging (57.0±10.1)years(range:28 to 75 years). According to whether the FIGFI was used during the operation, they were divided into 36 cases in the study group and 22 cases in the control group. The clinical pathological characteristics, operative and postoperative recovery of the two groups were compared by t test, χ 2 test, and Fisher exact test. Results:All the 58 patients underwent R0 resection with totally laparoscopic surgery. In the study group, due to poor bowel blood flow after cutting the mesentery (Sherwinter score = 1), 1 patient had to be expanded the resection range until the blood flow was rich(Sherwinter score≥3), and 1 patient in the control group had the complication of postoperative anastomotic leakage of grade A. Compared with the control group, the operation time in the study group was shorter ((156.3±43.5) minutes vs. (180.4±41.3) minutes, t=-2.083, P=0.042). However, there were no significant differences in the amount of blood loss, postoperative hospital stay, postoperative time of anal exhaust, length of bowel resection, number of lymph nodes dissected, and in the incidence of postoperative complications between the two groups. Median follow-up period was 23 months (range: 18 to 37 months). There were no long-term postoperative complications such as ischemic enteritis and anastomotic stenosis in both groups. Conclusions:The FIGFI is safe and feasible to assess the blood supply of intestinal segment and anastomosis during totally laparoscopic left hemicolectomy, and is easy to operate. It is expected to reduce the incidence of anastomotic leakage.

Objective To investigate the safety and efficacy of enhanced recovery after surgery (ERAS) used in laparoscopic colorectal cancer surgery.Methods We conducted a retrospective analysis of the medical records of 99 cases treated with ERAS programed laparoscopic colorectal cancer surgery (ERAS group) and 103 cases treated with traditional perioperative care and laparoscopic colorectal cancer surgery (controlled group) from Mar 2017 to Sep 2017 in our center.Results There was no significant difference in age,gender,BMI,ASA classification,tumor location,operation time,pathological stage and the incidence of postoperative complications between ERAS group and controlled group (all P ＞ 0.05).Compared to control group,ERAS had less blood loss,shorter time to pass first flatus,stool and start diet and shorter hospitalization day,with all the difference statistically significant [(60 ± 63)ml vs.(112 ± 245)ml,(3.0±0.8)dvs.(4.3 ±1.2)d,(3.5 ±1.0)dvs.(4.6±1.3)d,(4.1 ±1.2)dvs.(5.4± 2.0)d,(5.8±2.1)dvs.(7.8±2.5)d,t=-2.021、-9.216、-6.887、-5.252、-6.163,allP＜ 0.05].No patients in both groups suffered from readmission or death within 30 days after surgery.Conclusion Patients treated with ERAS programed laparoscopic colorectal cancer surgery is safe and effective,with rapid recovery and reduced hospital stay.

Objective To explore the mediating effect of anxiety in perimenopausal women between sleep disturbance and life quality. Methods A total of 516 perimenopmenopausal women in Shenyang,Lia-oning province and Jinzhou city were investigated using the Pittsburgh sleep quality index(PSQI),the self-rating anxiety scale(SAS) and the WHO quality of life( WHOQOL-BREF). Results The scores of sleep disorder,anxiety and quality of life were (14. 31±2. 75),(49. 94±9. 58) and (54. 02±4. 50) in perimeno-pausal women. There was a positive correlation between anxiety and sleep disorder (r=8. 32,P<0. 01),and a negative correlation between anxiety,sleep disorder and quality of life (r=-5. 37,-5. 62,P<0. 01). Anxiety had a mediating effect between sleep disorders and quality of life. The intermediate effect value was-0. 201, accounting for 32. 4%. Conclusion Anxiety has some mediating effects between sleep disorders and quality of life in perimenopausal women,and regulating anxiety can relieve sleep disorders and reduce their impact on quality of life.

Objective: To investigate the safety and feasibility of laparoscopic remedial surgery in patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. Methods: The clinical and follow-up data of 12 patients who didn′t reach the cure criterion of early colorectal cancer and then underwent endoscopic resection was collected. The clinicalpathological features and remedial indications were analyzed to evaluate the effects of laparoscopic remedial surgery. Results: The average number of lymph nodes in the lymph node dissection was 15 during remedial surgery, and 3 of them had lymph node metastasis. Among the 3 patients with residual cancer, two cases were poorly differentiated, 1 case was moderately differentiated, 1 case was positive for basal margin, and 1 case had vascular invasion. No lymph node metastasis occurred in the 9 patients who had no residual cancer. Among these, 8 cases were moderately differentiated, 1 case was poorly differentiated and 2 cases had positive basal margin. The average follow-up duration was 40 months and all 12 patients were in a state of survival at the last follow-up. During the follow-up of the 3 patients with residual cancer, 1 patient received adjuvant chemotherapy with unknown prognosis; 1 patient received postoperative adjuvant radiochemotherapy, and lung metastasis occurred; 1 patient did not receive any treatment after surgery and survived for 33 months. Conclusions Laparoscopic remedial surgery is a safe and feasible remedy for patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. However, the choice of remedial strategy for colorectal carcinoma needs further investigation for patients with no vascular invasion, high degree of differentiation, and negative basal margin.

Objective To investigate the feasibility of high resolution melting(HRM)curve analysis technique for detecting β-thalassemia gene mutations.Methods The HRM method was used to detect five kinds of common β-thalassemia mutations (-28, CD17,CD41-42,CD71-72 and IVS-2-654)in Guangdong province.Sixty specimens of the patients with suspectedβ-thalassemia were performed the HRM analysis.The results of HRM analysis were confirmed by the direct DNA sequencing.Results Among 60 specimens of the patients with suspectedβ-thalassemia,12 cases of heterozygosis mutant gene were detected,including 3 cases of-28,2 cases of CD17,5 cases of CD41-42,2 cases of CD71-72 and 2 cases of IVS-2-654 gene mutation;2 cases of homozygosis mu-tant gene were detected,including 1 case of-28 and 1 case of CD41-42 homozygous mutation (both were amniotic fluid specimens). The results of HRM analysis were consistent with the DNA sequencing results.Conclusion The HRM method can accurately de-tect five kinds of common β-thalassemia mutations in Guangdong province,has the advantages of simpleness,rapidness and high sensitivity and is expected to be a new method for screening β-thalassemia mutation in clinic.

Objective To study the clinical features of gallbladder small cell carcinoma (GSCC),to improve the diagnosis and treatment of GSCC.Methods We retrospectively analyzed the clinical data of GSCC patients at our hospital from January 2000 to January 2012,and made a collective review of the literature.Results In this series,there were four female cases,one male case,the age at the first diagnosis was between 42-67,with the median age of 57.The main complain was pain and dis-comfort on the up and right abdomen.Tumor located in the bottom of gallbladder in 3 cases,and in the body in 2.Cholelithiasis was complicated in 4 cases.2 patients received radical resection of GSCC,followed by adjuvant chemotherapy of VP-16 and cisplatin,radioactive therapy in one.Postoperatively,these two were followed up for 45 and 32 mons with tumor free survival.3 cases received palliative resection,followed by adjuvant chemoradioactive therapy or intervention treatment,these three were followed up to 8,11,30 months respectively to their death for tumor recurrence.Conclusions GSCC is a rare disease,the initial symptoms are not often specific and easily misdiagnosed.The prognosis of GSCC is poor.

Objective To summarize and analyze the clinical feature,therapeutic mnethods and prognosis of colorectal small cell carcinoma.Methods From January 2000 to January 2012,15 patients of colorectal small cell carcinoma were analyzed retrospectively.Results There were 12 male cases,3 females.The age at diagnosis was between 39-71 years,with median age of 60.SCC located in the rectum in 12 cases,in the colon in 3 cases.The time from the onset of symptoms to final diagnosis was from 1 to 12 months.The diameter of tumors varied from 2.5 to 8.0 cm.13 cases received up-front surgery,including radical tumor resection in 6 cases,palliative resection in 7 cases,and neoadjuvant-chemotherapy followed by palliative resection in one case.The initial Ⅰ,Ⅲ B,Ⅳ B stage were 1 case,6 cases and 8 cases,respectively.The overall median survival time is 11 months,1,2 year's survival rate is 40.0％ and 20.0％,respectively.Conclusions Colorectal SCC is less common and the prognosis is poor.Multimodality management,with radical surgical resection of the primary lesion followed by standard adjuvantchemotherapy,affords good local disease control and a fair survival.