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 impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

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 clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective: To understand the relationship between family environment and depressive symptoms among adolescent, and to provide a reference for adolescent mental health promotion and intervention. Methods: From September to December in 2021, a questionnaire survey on family environment and depressive symptoms was conducted among 8 102 middle school students by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Chi square test was used to compare the depression status of students in different family environments. Multivariate Logistic regression analysis was used to explore the relationship between family environment and depressive symptoms. Results: The detection rates of possible depression, likely depression and severe depression in adolescents were 11.2%, 5.9% and 8.4%, respectively. There were significant differences in the detection rate of depression by gender, academic period, urban and rural areas, family forms and only child statu( χ 2=87.60, 27.19, 6.65, 45.59, 4.78, P <0.05). Logistic regression analysis showed that adolescents in single parent families ( OR =1.45) and reorganized families( OR =1.69) were positively correlated with the occurrence of depressive symptoms compared with those in nuclear families( P <0.01). Conclusion Compared with nuclear families, the risks of adolescent depressive symptoms in single parent families and reorganized families are higher. Attention should be paid to the mental health education of teenagers from single parents and reorganized families to ensure the development of their physical and mental health.

Objective: To understand physical activity status and its relation with cardiopulmonary endurance among Chinese children and adolescents, so as to provide reference for cardiopulmonary endurance improvement and intervention of Chinese children and adolescents. Methods: During September to November 2018, a stratified cluster sampling method was used to select 4 269 children and adolescents aged 7-18 years in six major regions of China, 20 m shuttle run test and physical activity were assessed. Results: Average duration for daily lowintensity physical activity among boys was (31.49±30.01) min, for moderate to vigorous physical activity (68.37±46.50) min. Average duration for low intensity physical activity among girls was (34.02±31.58) min, for moderate to vigorous physical activity was (63.02±44.91) min. The number of 20 m shuttle run test for boys reached ( 36.17 ±21.94) times, and the maximal oxygen uptake per minute was (44.51±5.05) mL/kg; the number of 20 m shuttle run test for girls reached (26.59±12.56) times, and the maximal oxygen uptake per minute was (41.99±5.29) mL/kg. There were statistically significant differences in the number of 20 m shuttle run test and maximal oxygen uptake across age groups in boys ( F= 589.37 , 152.79, P <0.01), as well as that in girls ( F=305.21, 1 032.46, P <0.01). The proportion of boys and girls who met moderate to vigorous physical activity standard was 49.24% and 42.92%, respectively. Linear regression analysis showed that there was a significant positive correlation between the duration of moderate to vigorous physical activity and maximal oxygen uptake ( β=0.11, P ＜ 0.01). Conclusion There is a significant correlation between moderate to vigorous physical activity with cardiorespiratory endurance among Chinese children and adolescents. Higher level of moderate to vigorous physical activity is important to help improve cardiopulmonary endurance among children and adolescents.

Abstract In recent decades, there is a decreasing trend in physical activity, which might be associated with decline in physical and mental health among children and adolescents in China. The outbreak and spread of the COVID-19 further aggravated this trend. Under the background of normalized epidemic prevention and control, in order to deeply understand the relationship between physical activity and physical and mental health of children and adolescents, this study sorted out relevant domestic and foreign literatures, and analyzed the effects of physical activity on children and adolescents health and fitness. The positive effects of physical activity, cognition, and mental health were found to be significantly different in the type, intensity, and time of physical activity in the related health effects.

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

Objective:To explore the clinical value of introducing 68Ga PSMA PET / CT into the prostate cancer(PCa)screening clinic, and to analyze the incidence rate and biopsy of PCa in the screening clinic of our hospital. Methods:The data of the people who participated in PCa screening in the urology screening clinic of our hospital from March 2021 to November 2021 were retrospectively analyzed. Serum PSA was used as the screening index. The subjects with PSA≥4ng/ml were first examined by mpMRI to find suspicious nodules, and the positive ones were further examined by 68Ga-PSMA PET/CT to determine the lesions.The puncture target was outlined, and systematic+ targeted puncture was conducted under ultrasound guidance. The age, PSA distribution, puncture detection rate, Gleason score and clinical stage of patients with PCa were recorded. Results:A total of 1 079 subjects were included in the screening, with an average age of (63.9±9.9)(ranging 40-92) years old, and 249 patients (23.1%, 249/1 079) with PSA≥4ng/ml. Among them, 87 cases (87/249, 34.9%) received mpMRI, and 34 cases (34/249, 13.7%) had PI-RADS score ≥3 points. These 34 patients with suspected nodules on MRI were further scanned with 68Ga-PSMA PET/CT, and 11 cases (11/249, 4.4%) had abnormal uptake of PSMA nuclide. A total of 32 patients (12 patients with PSA abnormalities and 20 patients with positive imaging) finally received prostate biopsy, and 11 patients were diagnosed with PCa, with a positive detection rate of 34.4% (11/32), accounting for 1.0% (11/1 079) of the screening population. Among them, 20 patients with positive imaging (9 patients with only mpMRI positive and 11 patients with both mpMRI and 68Ga-PSMA PET/CT positive) underwent system + targeted fusion biopsy, and the positive rate was 45% (9/20). 12 patients (only PSA abnormal) underwent routine systematic puncture biopsy, and the positive detection rate was 16.7% (2/12). The difference between the two groups was statistically significant ( P<0.05). Among the patients with confirmed PCa, 27.3% (3/11) had Gleason score less than 7, and 72.7% (8/11) had Gleason score≥7. Localized PCa (≤T 2) accounted for 45.4% (5/11), local progression (T 3-T 4) accounted for 18.2% (2/11), and metastatic PCa suggested by 68Ga-PSMA PET/CT accounted for 36.4% (4/11), including 3 systemic multiple bone metastases and one bone metastasis with distant lymph node metastasis. Clinically significant PCa accounted for 90.9% (10/11) of the confirmed patients, and the proportion of high-risk patients in localized or locally advanced PCa was 71.4% (5/7). Conclusions:In PCa screening, if 68Ga-PSMA PET/CT is introduced on the basis of conventional mpMRI, the detection rate of clinically meaningful PCa can be improved. Combined with targeted puncture, tumor lesions can be found early and the screening efficiency of PCa can be improved. In this study, the detection rate of PCa in outpatient screening reached 1.0%. In confirmed cases, the proportion of high-risk patients and metastatic patients was higher.