Role of ceRNA network in inflammatory cells of rheumatoid arthritis / 中南大学学报(医学版)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.

The effect of combining extracorporeal shock waves with continuous static stretching in treating triceps spasticity after a stroke / 中华物理医学与康复杂志

Objective:To observe any effect of supplementing continuous static stretching (CSS) with extracorporeal shock wave therapy (ESWT) in treating triceps surae spasm after a stroke.Methods:Sixty-four stroke survivors with triceps surae spasm were randomly divided into a conventional rehabilitation group, a shock wave group and a combined treatment group. In addition to conventional rehabilitation, the shock wave group received extracorporeal shock wave therapy twice a week and the combined treatment group received the shock waves during continuous static stretching. After 6 weeks of treatment all of the subjects were assessed using the Modified Ashworth Scale (MAS), the Fugl-Meyer Assessment (FMA) and Brunnstrom classification of their functional recovery stage.Results:Before treatment there was no significant difference among the three groups. After the 6 weeks of treatment the average triceps surae tension in all three groups had eased significantly. At that point the average MAS and FMA scores of the shock wave group and the combined treatment group were significantly better than those of the conventional group. The combined treatment group then showed significantly better therapeutic effect than the shock wave group.Conclusions:Applying extracorporeal shock waves during continuous static stretching can significantly improve the stretching′s ability to reduce spasticity and improve motor functioning, at least of the triceps surae. Combining shock waves with modern traction methods is recommended for clinical application.

Analysis of risk factors for clinical cure and biochemical recurrence in patients after radical prostatectomy / 中华泌尿外科杂志

Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.

Surgical technique and efficacy of P. R.E.S.S. bladder cuff excision / 中华泌尿外科杂志

Objective:To explore the surgical technique and efficacy of pure retroperitoneoscopic extravesical standardized seeable (P.R.E.S.S.) technique for bladder cuff excision (BCE).Methods:Ninety five patients with UTUC from five domestic centers (30 cases from Changzheng Hospital, 21 cases from Peking University First Hospital, 20 cases from Yuhuangding Hospital, 21 cases from Dalian Medical University affiliated No.2 Hospital and 3 cases from General Hospital of Eastern Theater Command)between August 2017 and December 2020 were retrospectively analyzed. There were 57 males and 38 females with a mean age of (67.7±10.0) years and median tumor size of 3.0 cm. All patients underwent pure retroperitoneoscopic radical nephroureterectomy with a single surgical position and four (36 cases) or five (59 cases) trocar layout according to the surgeon’s prefer habit and experience. The demographics of the two groups were the age of [(66.3±11.2)years vs. (68.6±9.1)years], male/female ratio of (25/11 cases vs. 32/27 cases), body mass index of [(25.0± 3.0)kg/m 2 vs. (24.8±3.4)kg/m 2], tumor maximum diameter of [2.8(1.6, 3.5)cm vs. 3.0(2.0, 4.0)cm], left/right side tumor of(19/17 cases vs. 34/25 cases), T 1-2/T 3-4/Tis stage of(25/10/4 cases vs. 49/10/0 cases), and multifocal tumors of(3 cases vs. 2 cases), and the difference was not statistically significant( P>0.05). On the other hand, the differences of hydronephrosis of the operated kidney(13 cases vs. 39 cases, P=0.004), and tumor location (in renal pelvis or calyx or upper/middle/lower ureter being 23/9/4 cases vs. 35/4/20 cases, P=0.005), were statistically significant. The umbilical artery cord was used as anatomical landmark in the process of P. R.E.S.S. bladder cuff excision. The pelvic floor and extraperitoneal space around the ureter were expanded, the bladder wall was opened to form pneumovesicum, and a sufficient bladder cuff resection and exact bladder cuff closure was performed. Perioperative outcomes and follow-up data were analyzed, and the clinical outcomes between the four and five trocars were compared to evaluate the impact of trocar layout on the surgical outcomes. Results:There were 91(95.8%) cases successfully undergoing P. R.E.S.S. BCE technique, with one case converted to open BCE due to bleeding and three cases converted to distal ureter Hem-o-lok clipping because of poor exposure. Median operative time was 180(125, 230)min, and estimated blood loss was 100(50, 100)ml. The overall complication rate was 10.5%(10/95), including 2 cases(2.1%) of intraoperative bleeding, with 1 case treated by transfusion (400 ml), the other case converted to open surgery without transfusion. There were 8 cases of postoperative complications(8.4%), including 7 cases of Clavien-Dindo grade Ⅱ(3 cases of secondary hemorrhage, one case for each of drug allergy, acute renal insufficiency, blood creatinine increased to 490 μmol/L, or lung infection with lymphatic leakage), 1 case of grade Ⅲa(intestinal obstruction treated with insertion of the intestinal obstruction catheter under local anesthesia), and all these patients were discharged smoothly. The difference between the four and five trocars was not statistically significant in the following variables, including the rate of surgical conversion(8.3% vs. 1.7%), estimated intraoperative blood loss(100 ml vs. 60 ml), ratio of intraoperative lymph node dissection (25.0% vs.20.3%), P. R.E.S.S. bladder cuff excision success rate(91.7% vs.98.3%), the incidence of intraoperative and postoperative complications (13.8% vs.8.5%), pT 1-2/pT 3-4/pTis stage(22/11/3 cases vs.37/19/3 cases) and the proportion of recurrence or metastasis(8.3% vs.3.4%)(all P>0.05). However, the differences in the operation time(190 min vs.170 min, P=0.011)and postoperative hospital stay(5 d vs.6 d, P=0.005) were statistically significant. Conclusions:P. R.E.S.S. bladder cuff resection technique is safe and feasible during the procedure of pure retroperitoneoscopic radical nephroureterectomy by a single surgical position and facilitates seeable adequate bladder cuff excision by establishing an enlarged pelvic lateral extraperitoneal space and pneumovesicum. Five-trocar technique is more suitable for patients with lower ureteral tumors but may be associated with a longer postoperative hospital stay compared with the four-trocar technique.

Ponatinib inhibits growth of patient-derived xenograft of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein in nude mice / 南方医科大学学报

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.