[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

[Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy].

Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (ß=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (ß=0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.

[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

[Efficacy of partial nephrectomy in patients with localized renal carcinoma: a 20-year experience of 2 046 patients in a single center].

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

[Analysis of solitary rectal ulcer syndrome in 7 children].

Objective: To analyze the clinical features, treatment and prognosis of solitary rectal ulcer syndrome (SRUS) in children. Methods: The clinical data of 7 children who were diagnosed with SRUS in Department of Gastroenterology in Guangzhou Women and Children' Medical Center from January 2019 to December 2021 were retrospectively analyzed. The clinical data including general demographics, clinical presentations, endoscopic and histologic features, treatment and outcome were extracted from hospital medical records. Results: The 7 patients were all males, and the age of onset was 6-12 years. The course before diagnosis was 2-36 months. The most common symptom was rectal bleeding (6 cases) and most common findings at initial colonoscopy were ulcer in 3 cases and protuberance in 4 cases, both located only in rectum. The intestinal histopathology of 5 cases showed characteristic fibromuscular obliteration of lamina propria. Five children were treated with mesalamine granules or suppositories, and 2 cases underwent local excision. The follow-up lasted for 5-24 months and found symptoms relieved in 5 cases, improved in 1 case, and no remission in 1 case. Colonoscopy after the treatment was performed in 5 children, among whom 2 cases achieved mucosal healing. Conclusions: SRUS in children is mainly presented with rectal bleeding, and has characteristic histological change of ulcer and protuberance in endoscopy. Pathology is crucial for diagnosis and differential diagnosis. Both the medical and surgical treatment are effective for SRUS.

[Laparoscopic pyeloplasty combined with ultrasonic lithotripsy via nephroscope for treatment of ureteropelvic junction obstruction with renal calculi].

OBJECTIVE: To investigate the efficacy and safety of laparoscopic pyeloplasty combined with ultrasonic lithotripsy via nephroscope in the treatment of ureteropelvic junction obstruction (UPJO) with renal calculi. METHODS: From June 2016 to January 2022, eight patients including five males and three females underwent laparoscopic pyeloplasty combined with ultrasonic lithotripsy via 19.5F(1F≈0.33 mm) nephroscope in Peking University People' s Hospital. The age ranged from 23-51 years (mean: 40.5 years) and the body mass index (BMI) ranged from 18.8-32.4 kg/m2 (mean 27.0 kg/m2). The lesion located on the left side in all of the eight patients. Two patients had solitary kidney and one patient had horseshoe kidney. Solitary stone was seen in one patient and the other seven patients suffered multiple stones, with two patients had staghorn stones. The largest diameter of stones ranged from 0.6-2.5 cm (mean: 1.5 cm). CT or ultrasound showed that moderate nephrosis was seen in five patients and severe nephrosis was seen in three patients. During surgery, after exposure of renal pelvis and proximal ureter, a small incision of 1.5 cm was performed in the anterior wall of the renal pelvis, and a 19.5F nephroscope was introduced into renal pelvis through laparoscopic trocar and renal pelvis incision. Stones were fragmented and sucked out by 3.3 mm ultrasonic probe placed through nephroscope. After stones were removed, modified laparoscopic pyeloplasty was performed. RESULTS: Surgery was successfully completed in all of the eight patients without conversion to open surgery. The operation time ranged from 160-254 min (mean 213 min) and the time of nephroscopic management time was 25-40 min (mean: 33 min). The hemoglobin was decreased by 3-21 g/L (mean: 10.3 g/L). The stone-free rate was 75% (6/8 cases), stones were incompletely removed in two patients due to abnormal intrarenal structure. The modified Clavien classification system (MCCS) grade ⅢA complication occurred in one patient postoperatively, which was nephrosis due to intrarenal bleeding, and nephrostomy was performed. With the mean follow-up of 30 months (ranged from 2-68 months), there was no evidence of obstruction in all the patients, and one patient underwent percutaneous nephrolithotomy to treat residual calculi. CONCLUSION: Laparoscopic pyeloplasty combined with ultrasonic lithotripsy via 19.5F nephroscope is feasible and safe, and could be a complementary method to treat UPJO and renal calculi.

A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. METHODS: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. RESULTS: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. CONCLUSIONS: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

MicroRNA-1286 inhibits osteogenic differentiation of mesenchymal stem cells to promote the progression of osteoporosis via regulating FZD4 expression.

OBJECTIVE: The aim of this study was to investigate whether microRNA-1286 could inhibit the osteogenic differentiation of human marrow mesenchymal stem cells (hMSCs) by regulating FZD4 expression and promoting the progression of osteoporosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-1286 in the serum of patients with osteoporosis. Meanwhile, microRNA-1286 expression in different stages of osteogenic differentiation of hMSCs was measured by qRT-PCR as well. After overexpression of microRNA-1286 and FZD4 in hMSCs, the mRNA expression levels of microRNA-1286, alkaline phosphatase (ALP), RUNX2 and osteocalcin (OCN) were detected by qRT-PCR. The protein expression levels of RUNX2 and OCN were detected by Western blot. Meanwhile, alkaline phosphatase (ALP) activity and expression in cells were examined using ALP assay kit and ALP staining method, respectively. Cell mineralized nodules were detected through the alizarin red staining test. Bioinformatics method was used to predict the binding site of microRNA-1286 to FZD4. Subsequent luciferase reporter gene assay was performed to verify whether microRNA-1286 could combine with FZD4. After overexpression or knockdown of microRNA-1286, the mRNA and protein expressions of FZD4 were analyzed using qRT-PCR and Western blot assay, respectively. After the simultaneous overexpression of microRNA-1286 and FZD4 in hMSCs, the mRNA expression levels of ALP, RUNX2 and OCN, ALP activity and content, and cell mineralization ability were successively examined. RESULTS: The expression of microRNA-1286 in the serum of patients with osteoporosis was significantly higher than that of the normal population. Meanwhile, microRNA-1286 expression decreased with the increase of osteogenic differentiation days of hAMSCs. After the overexpression of microRNA-1286, ALP, RUNX2, and OCN levels, ALP activity, RUNX2, and OCN protein levels, as well as mineralized nodule formation were significantly reduced. However, results were reversed when FZD4 was simultaneously up-regulated. Luciferase reporter gene assay results verified that microRNA-1286 could bind to FZD4. After the overexpression of microRNA-1286, the mRNA and protein expressions of FZD4 were found significantly down-regulated. However, results were reversed after knocking down microRNA-1286. Furthermore, the simultaneous overexpression of microRNA-1286 and FZD4 could counteract the inhibitory effect of over-expression of microRNA-1286 on osteogenic differentiation of hMSCs. CONCLUSIONS: MicroRNA-1286 can regulate FZD4 expression and inhibit osteogenic differentiation of hMSCs, thereby promoting the development of osteoporosis.

[Endoscopic treatment for ureterovesical junction stenosis in patients with kidney transplantation: 13 cases report].

OBJECTIVE: To evaluate the safety and efficacy of endoscopic treatment for ureterovesical junction (UVJ) stenosis in patients with kidney transplantation. METHODS: A retrospective study was conducted among the patients with kidney transplantation diagnosed as UVJ stenosis from 2012 March to 2018 July in Urology and Lithotripsy Center, Peking University People's Hospital. Only the patients who received endoscopic treatment were included, with staged or same-session nephrostomy followed by a retrograde ureteroscopy to evaluate the ureteral stenosis. Incisions with laser, mono- or bipolar energy, or balloon dilation were used to manage the stenosis depending on different situations. Demographic characteristics and clinical data were gathered and analyzed, including age, gender, preoperative serum creatinine, hemoglobin, operation time, success rate, postoperative serum creatinine, hemoglobin, postoperative complications rate, and long-term stenosis recurrence rate. RESULTS: In this study, 13 patients were included (9 males and 4 females). All the UVJ stenoses were diagnosed with preoperative ultrasound, CT scan, MRI, or urethrography. The mean age was 45 years (range 34-57 years). The mean preoperative serum creatinine was 243 µmol/L. Four patients developed UVJ stenosis 1 month after kidney transplantation, while the rest developed long-term stenosis. Fifteen operations were performed in all, of which 14 cases were successful while one failed. The first 8 cases received first-stage nephrostomy and second-stage endoscopic management of the stenosis, while the last 7 cases received the same session surgery. The mean operation time was 95.4 min vs. 68.9 min, and the immediate success rate was 87.5% vs. 100.0% in the first 8 cases and last 7 cases, respectively. The mean decrease of postoperative hemoglobin was 0.6 g/L and mean postoperative serum creatinine was 105 µmol/L. No postoperative fever, severe hematuria, and urine leak were observed. The mean postoperative hospital stay was 2.8 days. Three patients were able to remove ureteral stents and no recurrence was found with a follow-up time of 9, 17, and 82 months. The long-term stenosis recurrence rate was 76.9% (10/13). CONCLUSION: Endoscopic approach for the treatment of UVJ stenosis in patients with kidney transplantation was safe and efficient in our study cohort. However, long term stenosis recurrence rate was high and needed to be paid attention to.

[Treatment of crossing vessels in laparoscopic pyeloplasty].

OBJECTIVE: To investigate the management of crossing vessels compression in laparoscopic pyeloplasty. METHODS: From January 2016 to June 2018, a total of 21 patients who were admitted to Peking University People's Hospital with ureteropelvic junction obstruction (UPJO) associated with crossing vascular compression were reviewed. There were 15 males and 6 females who formed this group, with a mean age of (33.9±15.0) years. There were 4 cases of mild hydronephrosis, 12 cases of moderate hydronephrosis and 5 cases of severe hydronephrosis before operation. All the patients underwent laparoscopic pyeloplasty in our hospital, including 13 on the left and 8 on the right. Laparoscopic pyeloplasty (Anderson-Hynes) were performed in all the patients. Hem-o-lok suspension (14 cases in the suspension group) or translocation of the crossing vessels (7 cases in the translocation group) were used for the intraoperative management of the crossing vessels. Double J tubes were removed 8 weeks postoperatively. The patient demographic data were collected (including operation time, treatment time of crossing vessels, intraoperative blood loss, time of drainage tube removal after operation, and average length of hospital stay), postoperative outcomes were evaluated and the patients were followed up regularly. RESULTS: In all the patients, the crossing vessels were successfully reserved, and none of them were ligated intra-operatively. Mean operative times were (202.2±57.0) min. The duration of intraoperative treatment of crossing vessels was (10.5±3.2) min, (6.1±2.0) min in the suspension group, and (13.7±5.2) min in the translocation group, respectively. Intraoperative blood loss was (47.8±25.6) mL, postoperative drainage time was (4.8±2.6) d, and length of hospital stay was (11.5±3.3) d. Postoperative slight urinary leakage occurred in 1 case. Preoperative pyelectasis of the affected side of all the patients was (3.4±1.7) cm, compared with postoperative pyelectasis of (1.9±1.3) cm. The difference was statistically significant (P<0.05). Postoperative follow-up of all the patients was carried out until December 2018. There was no significant difference in kidney size in all the patients before or after the operations, and hydronephrosis was alleviated compared with that before surgery. CONCLUSION: For UPJO patients with crossing vascular compression, according to the location of the crossing vessels, Hem-o-lok suspension or vessel transposition can be adopted to relieve the crossing vascular compression and improve the success rate of the surgery.

Mechanisms of endogenous repair failure during intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.

Imaging Validation of Drug-Eluting Beads Transarterial Chemoembolization of Hepatocellular Carcinomas in Living Donor Liver Transplantation.

OBJECTIVE: The aim of this study is to determine whether post-transarterial chemoembolization imaging (computed tomography or magnetic resonance imaging) could accurately predict the tumors' necrosis on pathologic specimens. BACKGROUND: Transarterial chemoembolization with drug-eluting beads has been proven to be an effective way to bridge patients with hepatocellular carcinomas to liver transplantation. MATERIALS AND METHODS: From September 2012 to June 2017, 59 patients with a total of 78 hepatocellular carcinomas, who received transarterial chemoembolization with drug-eluting beads before liver transplantation in Kaohsiung Chang Gung Memorial Hospital, were included in the study. All patients and hepatocellular carcinomas have pre-transarterial chemoembolization and post-transarterial chemoembolization images (computed tomography or magnetic resonance imaging) and pathological findings for correlation. Tumor response was evaluated according to modified Response Evaluation Criteria in Solid Tumors. The ranges of necrotic percentage are 100%, 91-99%, 51-90%, and <50%. RESULTS: The accuracy rate between the imaging and pathology correlation was 40% for computed tomography and 42% for magnetic resonance imaging. The recurrent rate of the complete respond group is 11.5%, the partial respond group is 16.0%, and the stationary group is 28.6%. CONCLUSION: Computed tomography and magnetic resonance imaging sensitivity is not satisfactory for microscopic evaluation of residual tumors after transarterial chemoembolization with drug-eluting beads. However, survival is good after liver transplantation no matter what the microscopic findings were.

MiR-93 blocks STAT3 to alleviate hepatic injury after ischemia-reperfusion.

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is correlated with ischemia-reperfusion (I-R) injury. The previous studies showed a decreased miR-93 expression after I-R injury of heart or brain organs, but without knowledge in liver tissues. This study aims to investigate effects of MiR-93 on the hepatic injury after ischemia/reperfusion. MATERIALS AND METHODS: Rat liver I-R model was generated. Liver function indexes including alanine transaminase (ALT) and aspartate aminotransferase (AST) were quantified, and serum tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels were quantified. Hepatic tissue apoptosis was measured by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and expression of microRNA-93 (miR-93), STAT3, and phosphorylated STAT3 (p-STAT3) were measured. Dual luciferase reporter gene assay confirmed targeted relationship between miR-93 and STAT3. Agomir or miR-93 agomir was injected into the peritoneal cavity of I-R model, followed by ALT and AST assays. Serum levels of TNF-α, IL-1ß, and IL-6 were measured, followed by TUNEL assay for comparing STAT3 and p-STAT3 expression. RESULTS: Comparing to sham group, I-R group rat showed significantly elevated serum ALT, AST, TNF-α, IL-1ß, and IL-6 contents, along with significantly elevated hepatic cell apoptosis, plus decreased miR-93 expression, whilst STAT3 and p-STAT3 expression was enhanced. Intraperitoneal injection of miR-93 agomir significantly decreased STAT3 or p-STAT3 expression, and decreased cell apoptotic rate. Serum levels of ALT, AST, TNF-α, IL-1ß, and IL-6 were significantly decreased, accompanied by improved liver function. CONCLUSIONS: Hepatic I-R injury is accompanied by miR-93 down-regulation, plus STAT3 up-regulation. Overexpression of miR-93 significantly depressed STAT3 expression in liver I-R injury, alleviated hepatic injury or apoptosis, decreased inflammatory response, and improved liver function.

Open Right Hemicolectomy Is a Safe and Suitable Procedure for Surgical Training: A Comparative Study With 133 Patients.

BACKGROUND AND AIMS: A right hemicolectomy is a technically demanding procedure and the quality of the operation influences the short- and long-term outcomes. An increasing number of certified centers employ surgeons who are specialized in this procedure. Residency training is obligatory, but trainee surgeons often cannot perform technically demanding procedures because of economical and certification requirements imposed on the center. This study was performed to evaluate the suitability of right hemicolectomy as a training procedure. MATERIAL AND METHODS: Between 2009 and 2013, 133 patients received a right hemicolectomy during cancer treatment. Patient data were analyzed in two cohorts: cohort 1 contained 90 patients who were operated by a resident under supervision, and cohort 2 included 43 patients who were operated by a specialized senior surgeon. Outcome and safety were evaluated by mortality rate, anastomotic leakage, complication rate, and operation time. The resection status and the number of resected lymph nodes were surrogate parameters for oncological quality. Gender, age, American Society of Anesthesiologists classification, body mass index, and general risk factors were compared in both cohorts. RESULTS: There was no significant difference in the rate of anastomotic leakage between the two groups (p = 0.799). Oncological criteria were met in both cohorts and the oncological quality was similar between groups. Furthermore, there were no significant differences in risk factors, operating time, postoperative complications, and mortality between the groups. CONCLUSION: Oncological open right hemicolectomy is a safe and suitable training procedure for residency training under standardized conditions.

SALL4 promotes glycolysis and chromatin remodeling via modulating HP1α-Glut1 pathway.

SALL4 has recently been identified to promote chemo-resistance in multiple types of cancer, but the underlying mechanism remains to be fully established. Open chromatin structure is important for DNA damage response (DDR) and DNA repair. Here, we demonstrate that SALL4 promotes open chromatin by destabilizing heterochromatin protein 1α (HP1α) by recruiting ubiquitin E3 ligase CUL4B to HP1α. The silencing of SALL4 in cancer cells decreased the expression levels of Glut1 and inhibited glycolysis in cancer cells. The upregulation of HP1α in human cancer cells suppressed open chromatin, glycolysis and Glut1 expression levels. Therefore, SALL4 promotes the expression of Glut1 and open chromatin through a HP1α-dependent mechanism. Impaired DDR in SALL4-deficient human cancer cells can be rescued by the restored expression of Glut1, indicating the importance of HP1α-Glut1 axis in SALL4-mediated DDR. These findings demonstrate that SALL4 could induce drug resistance by enhancing DDR and DNA repair through promoting glycolysis and subsequent chromatin remodeling.

[Clinical application of retroperitoneal laparoscopic surgery combined with mini-flank incision "hybrid surgery" for partial nephrectomy of complex renal tumors].

OBJECTIVE: To evaluate the clinical effect and safety of retroperitoneal laparoscopic surgery combined with mini-flank incision "hybrid surgery" for partial nephrectomy of complex renal tumors. METHODS: Between April 2015 and December 2016, the clinical data from 16 patients with complex renal tumors who underwent the "hybrid surgery", including 10 males and 6 females, were retrospectively reviewed. The average age was (50.2±10.7) years, 9 cases were located in the left side and 7 cases in the right side, the mean tumor size was (6.1±1.0) cm, and the mean R.E.N.A.L. nephrometry score was 9.3±1.3. All the patients received the "hybrid surgery", the first step was to adequately mobilize the kidney and tumor, prepared the renal artery by retroperitoneal laparoscopy, and then the incision about 10-12 cm was done under the twelve rib to convert to open surgery. After the renal artery was clamped, the tumor was removed and the wound was closed under direct vision. The operative time, ischemia time, estimated blood loss, intraoperative and postoperative complications and short-term renal function were recorded. RESULTS: All the 16 patients' "hybrid surgeries" were successfully performed. The mean operative time was (164.9±23.6) min, mean ischemia time was (32.4±6.2) min, and mean estimated blood loss was (204.0±125.1) mL. The mean drainage tube removal time was (4.1±1.0) d, and the mean postoperatively hospital stay was (6.9±1.5) d. There were 2 patients with Clavien III grade complications. One patient was injured with collecting system, and 1 patient received a second emergency surgery for acute postoperative bleeding. The mean 1 day postoperative serum creatinine level was (126.3±26.4) µmol/L, which was statistically significant (P<0.05) compared with the preoperative serum creatinine level(74.3±16.9)µmol/L. There were no significant differences (P>0.05) in comparing the 1 month postoperative serum creatinine level (92.6±18.2) µmol/L, 3 months postoperative serum creatinine level (80.8±18.4) µmol/L with the preoperative serum creatinine level. During 3 to 20 months follow-up periods, no local recurrence or distant metastasis occurred. CONCLUSION: This "hybrid surgery" combined retroperitoneal laparoscopic surgery with mini-flank incision for partial nephrectomy is safe and effective. It could decrease the operative difficulty and be worthy of further application for some selected complex renal tumor patients.

[Comparison of three surgical methods of ureteropelvic junction obstruction in therapeutic effect and complication].

OBJECTIVE: To compare various data of open pyeloplasty, laparoscopic pyeloplasty and endopyelotomy as a treatment of ureteropelvic junction obstruction (UPJO), and to investigate and discuss the feasibility and effect of the three methods. METHODS: In the study, 109 cases of UPJO treated by different surgical approaches in Peking University People's Hospital from January 2004 to December 2014 were retrospectively investigated. The patients were divided into three groups according to the treatment they received: open peyloplasty group (32 cases), laparoscopic peyloplasty group (31 cases) and endopyelotomy group (46 cases).We compared the data of the operative time, intraoperative blood loss, perioperative complications and post-operative hospital stay among the three groups. The mean follow-up time was(51.9±40.1) months (6-132 months). RESULTS: None of the laparoscopic peyloplties was converted to open peyloplasty. All endpyelotomies were successfully completed. The operative time was as follows: laparoscopic peyloplasty group (195.97±55.22) min, open peyloplasty group (121.19±33.95) min and endopyelotomy group (74.04±33.95) min,and there were significant differences among the three groups respectively(P<0.001). There was no significant difference on the operative blood loss between open peyloplasty group and laparoscopic peyloplasty group (P=0.163). The operative blood loss of endopyelotomy group was 5(0,310)mL,which was lower than the other two groups, and this result had significant differences with the other two groups respectively(P<0.001). There were significant differences on the post-operative hospital stay (days) among open peyloplasty group, laparoscopic peyloplasty group and endopeylotomy group (P<0.05,respectively).The success rate was comparable between open peyloplasty group and laparoscopic peyloplasty group( 93.8% vs. 90.3%, P=0.672), while the endopeylotomy group had a lower success rate compared with both open surgery group and laparoscopic group(69.6% vs. 93.8%, P=0.01; 69.6% vs. 90.3%, P=0.048, respectively). The complication rates of open peyloplasty group, laparoscopic peyloplasty group and endopeylotomy group were comparable(15.6%, 16.1% and 13.0%, respectively, P>0.05). CONCLUSION: The laparoscopic peyloplasty group had a longer operative time than open peyloplasty group, while its post-operative stay was shorter. There was no significant difference on the operative blood loss between open peyloplasty group and laparoscopic peyloplasty group. Although the success rate of endopyelotomy was lower than those of the other two groups, it had advantages over the aspect of operative time, operative blood loss and post operative stay.