Construction and validation of a prediction model for public acceptance of kidney xenotransplantation in China / 器官移植

Objective To explore the public attitude towards kidney xenotransplantation in China by constructing and validating the prediction model based on xenotransplantation questionnaire. Methods A convenient sampling survey was conducted among the public in China with the platform of Wenjuanxing to analyze public acceptance of kidney xenotransplantation and influencing factors. Using random distribution method, all included questionnaires (n=2 280) were divided into the training and validation sets according to a ratio of 7:3. A prediction model was constructed and validated. Results A total of 2 280 questionnaires were included. The public acceptance rate of xenotransplantation was 71.3%. Multivariate analysis showed that gender, marital status, resident area, medical insurance coverage, religious belief, vegetarianism, awareness of kidney xenotransplantation and whether on the waiting list for kidney transplantation were the independent influencing factors for public acceptance of kidney xenotransplantation (all P<0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) of the prediction model in the training set was 0.773, and 0.785 in the validation set. The calibration curves in the training and validation sets indicated that the prediction models yielded good prediction value. Decision curve analysis (DCA) suggested that the prediction efficiency of the model was high. Conclusions In China, public acceptance of kidney xenotransplantation is relatively high, whereas it remains to be significantly enhanced. The prediction model based on questionnaire survey has favorable prediction efficiency, which provides reference for subsequent research.

Research progress on the role of costimulatory signaling pathway in xenotransplantation / 器官移植

Organ shortage is a critical factor limiting the development of organ transplantation. Xenotransplantation is expected to resolve the problem of organ shortage, which has become a new research hotspot. Study of costimulatory signaling pathway related to T cell regulation is a hot topic in terms of immunity of xenotransplantation. Since the discovery of costimulatory molecule CD28, multiple costimulatory molecules have been identified, including costimulatory and coinhibitory receptors and their related ligands. Specific T cell activation of donors is the key factor leading to acute immune rejection. The expression and induction of costimulatory molecules on T cells differ during different immune stages, and these costimulatory molecules play a key role in maintaining T cell tolerance and the balance of T cell immune response. At present, increasing attention has been diverted to the role of costimulatory signaling pathway in organ transplantation. In this article, the latest research progress in costimulatory signaling pathway related to xenotransplantation immunity was reviewed, aiming to provide reference for the optimization of xenotransplantation immunosuppression regimen.

Application of total anatomical reconstruction during robot-assisted radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the effect of total anatomical reconstruction (TAR) during robot-assisted radical prostatectomy (RARP) .Methods:The clinical data of 99 patients with RARP performed by a single doctor in our hospital from January 2018 to January 2021 were analyzed retrospectively.There were 38 patients in the TAR+ vesicourethral anastomosis (VUA) group and 61 patients in the VUA group. There were no significant differences between the two groups in the age of patients [ 65.5 (60.8, 71.0) years vs. 66.0 (61.5, 69.0) years], body mass index[ (24.92±2.65) kg/m 2 vs. (25.51±2.80) kg/m 2], prostate volume [28.13 (25.21, 36.53) ml vs. 26.33 (19.75, 47.84) ml], PSA [15.67 (9.02, 31.49) ng/ml vs. 14.58 (9.23, 30.06) ng/ml], neoadjuvant therapy [50.0% (19/38) vs. 63.9% (39/61)], Gleason score (6/7/8/9-10 scores: 8/16/5/9 cases vs. 16/25/9/11 cases) and clinical T stage (T 1/T 2/T 3 stage: 4/29/5 cases vs. 3/53/5 cases)(all P>0.05). The TAR technique was performed as follows. ①The two layers of posterior reconstruction involved the residual Denonvilliers fascia, the striated sphincter and medial dorsal raphe (MDR), and the vesicoprostatic muscle (VPM), the fascia which was 1-2 cm from the cranial side of the bladder neck and MDR. ②The one layer of anterior reconstruction involved detrusor apron, tissues around the urethra and the visceral and parietal layers of the endoplevic fascia. The VUA technique was suturing the bladder neck and urethra consecutively. Perioperative indexes were compared between the two groups. Results:All 99 operations were successfully completed. There were no statistically significant differences between the TAR+ VUA and VUA groups in operation time [ (174.16±47.21) min vs. (188.70±45.39) min], blood loss [ 50 (50, 100) ml vs. 100 (50, 100) ml], incidence of postoperative complications [10.5% (4/38) vs. 14.8% (9/61)], phathological T stage [pT 2/pT 3~4 stage: 25/12 cases vs. 42/19 cases, P=0.895], and the time of indwelling catheter [ 21.0 (19.0, 21.0) d vs. 21.0 (21.0, 21.0) d] (all P>0.05). The difference in postoperative length of stay between the two groups was statistically significant[6.0 (5.0, 6.0) d vs. 7.0 (6.0, 7.5)d, P<0.001]. Follow-up was performed for 1 year after surgery. The recovery rate of urinary continence 3 months after surgery in TAR+ VUA and VUA groups were 86.8% (33/38) vs. 65.6% (40/61), which were statistically significant( P=0.019). There were no significant differences between TAR+ VUA and VUA groups in recovery rate of urinary continence 1 months after surgery [47.4% (18/38) vs. 45.9% (28/61)], 6 months after surgery [94.7% (36/38) vs. 85.2% (52/61)], and 12 months after surgery [94.7% (36/38) vs. 93.4% (57/61)] (all P>0.05). Conclusions:TAR technique has good surgical safety, and can promote recovery of early urinary continence after RARP.

Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation / 器官移植

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Clinical factors of positive surgical margin after robot-assisted laparoscopic radical prostatectomy in patients with high-risk prostate cancer / 中华泌尿外科杂志

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.

The clinical effect of thulium fiber laser lobes-enucleation of the prostate / 中华泌尿外科杂志

Objective:To investigate the technical points and clinical effect of thulium fiber laser lobes-enucleation of the prostate (ThuLLEP).Methods:A total of 90 patients underwent ThuLLEP and plasmakinetic enucleation of prostate (PKEP) in our hospital from November 2018 to December 2020 were collected. The age of patients in the two groups was (67.7±6.8) years and (65.7±7.1) years, the prostate volume was 56.0 (46.0-83.5) ml and 61.0 (53.5-79.5) ml, the serum PSA was 3.6 (2.2-6.0) ng/ml and 4.4 (1.8-7.3) ng/ml, the international prostate symptom score (IPSS) was 27 (22-31) and 28 (23-30), the quality of life score (QOL) was 5 (5-6) and 5 (5-6), the maximum urinary flow rate (Q max) was (8.5±5.7) ml/s and (7.8±3.8) ml/s, the post-void residual volume (PVR) was 127 (47-250) ml and 100 (27-209) ml. The differences had no statistical significance ( P>0.05). The glands were bluntly dissected to establish the surgical capsule plane on both sides of the verumontanum after the verumontanum being located. And then the middle lobe was removed. The glands formed grooves at 12 o'clock after vaporization, which served as anatomical marker. The left and right lobes were removed step by step. Finally, tissue crushing was performed. The PKEP group was enucleated by three lobes enucleation. Perioperative indicators were compared between the two groups. Results:All the operations were completed successfully. The median operative time in ThuLLEP and PKEP groups was 60 (50-73) minutes and 75 (60-100) minutes, the postoperative bladder irrigation time was 2.8 (2.3-3.6) d and 3.8 (2.6-4.7) d, the catheter indwelling time was 4.1 (3.7-4.9) d and 4.9 (4.7-6.0) d, the postoperative hospital stay was 5 (4-6) d and 6 (5-7) d. The decreased hemoglobin was 8.0 (1.5-14.5) g/L and 15.0 (6.5-21.0) g/L. The differences had statistical significance ( P<0.05). Follow-up was performed for 6 months after surgery. The median IPSS score of the two groups was 5 (2-11) and 6 (3-9), the QOL score was 1 (1-2) and 1 (1-2) respectively, which had statistical significance compared with the preoperative parameters ( P<0.05), but no statistical significance between the two groups ( P>0.05). The ThuLLEP group had 1 case of postoperative blood transfusion, 1 case of transient urinary incontinence and 2 cases of urethral stricture. The PKEP group had 1 case of fever and blood transfusion, 3 cases of transient urinary incontinence and 3 cases of urethral stricture. Conclusions:ThuLLEP has definite clinical effect because of less bleeding, quicker recovery and fewer complications. The relatively simple operation steps are beneficial for beginners to master.

Retroperitoneal laparoendoscopic single-site donor nephrectomy using home-made single-port device:report of 11 cases / 中华器官移植杂志

Objective To investigate the feasibility and safety of retroperitoneal laparoendoscopic single-site (LESS) donor nephrectomy using home-made single-port device.Methods From January 2011 to June 2012,11 consecutive LESS left donor nephrectomies using home-made single-port device with conventional laparoscopic instrument were performed through retroperitoneal access in our center.Results The procedures were completed and no complications occurred in all donors.Mean operative time was 149.5 min.Estimated blood loss was 30-350 ml.Warm ischemia time was 2-4 min.The urine output was prompt in all cases.Recipient graft function was normal within 2 weeks.Donor hospital stay was 5-6 days after operation.Conclusion LESS donor nephrectomy using home-made single-port device in our initial experience is feasible and safe.It is also cost-effective and minimally invasive with conventional laparoscopic donor nephrectomy.This technique is a good option for living donor nephrectomy.

A new understanding of the anatomic structure of posterior abdominal wall in retroperitoneal laparoscopic renal surgery / 中华泌尿外科杂志

Objective To provide reliable technical method by identifying referential anatomic landmarks for retroperitoneal laparoscopic renal surgery,with respect to the renal hilum and renal artery.Methods The regional anatomy of the posterior abdominal wall was studied in 35 cases of retroperitoneal laparoscopic renal surgery from January to August 2010.These included 27 cases of renal cancer,6 cases of renal pelvis cancer and 2 cases of renal tuberculosis.Distended the retroperitoneal space using balloon dilation along with sharp and dull dissection.We recorded the forms and positions of the posterior abdominal cavity's anatomical landmarks and evaluated the relationship between each anatomical landmark with respect to the renal hilum and renal artery.Results The perirenal fascia posterior layer and perinephric fat on the renal side were observed,and several anatomical landmarks gradually appeared on the posterior abdominal wall.The diaphragm extended across the upper retroperitoneal space near the superior pole of the kidney,and the psoas major and the quadratus lumborum muscles were located at the lower retroperitoneal space,near the inferior part of the kidney.The intersection of the upper diaphragm muscle with the lower psoas major and quadratus lumborum muscles were bordered by the lateral and medial arcuate ligaments.The lateral arcuate ligament arched across the upper part of quadratus lumborum,while the medial arcuate ligament arched across the upper part of psoas major.The medial arcuate ligament points extended towards the upper border of the renal hilum.These landmarks enable us to locate the position of the kidney,reach the renal hilum and identify the renal vessels in all 35 cases.Conclusions The relative position of the muscles and ligaments of the posterior abdominal wall are consistent and can be clearly seen under retroperitoneoscopy.Based on the position of the diaphragm and psoas major,the kidney can be located.In addition,based on the position of the medial arcuate ligament,the renal hilum and renal artery can be located.Assistance from these anatomical landmarks will simplify the retroperitoneal laparoscopic renal surgery.

Targeting multiple signaling pathways in LNCaP prostate cancer cell line by trichostatin A / 中国临床药理学与治疗学

AIM: To investigate the molecular mechanisms underlying the antitumor effect of trichostatin A(TSA) on LNCaP prostate cancer cells.METHODS: Colony formation analysis was performed to assay the effect of TSA on LNCaP colony forming ability.Western blotting was used to analyze protein acetylation standard as well as the expression of a panel of signaling molecules after TSA exposure.RESULTS: TSA inhibited the colony forming ability of LNCaP cells at a very low concentration.TSA exposure caused elevated acetylation of total cellular proteins as well as accumulation of acetylated-H_3.In addition,signaling molecules which play key roles in prostate cancer such as AR,ErbB2,Raf-1,CDK4,and Akt were depleted by TSA in a dose and time-dependent manner.CONCLUSION: TSA exhibits significant antitumor activity against LNCaP cells by simultaneously interfering with multiple signaling pathways such as HER2/MAPK,AR,and PI-3K-AKT pathways.