Tumor necrosis factor (TNF) blockers are promising therapeutic agents for patients with conventional therapy insensitive inflammatory diseases.Unfortunately,their use has been associated with an increased rate of malignancies,leukemia,psoriasis and other immune diseases. The U.S. Food and Drug Administration(FDA) is requiring stronger warnings in the prescribing information for TNF blockers. Healthcare Professionals should pay close attention to severe adverse effects of TNF blockers and drug safety.

BACKGROUND: Traditional solid bone can not receive satisfied effects in repairing irregular bone defects in oral maxillofacial surgery due to uneven distribution of cells and growth factors. Therefore, it is a research direction to prepare injectable tissue engineering bone.OBJECTIVE: To explore the effects of chitosan/β-tricalcium phosphate/recombinant human bone morphogenetic protein-2(CS/β-TCP/rhBMP-2) composite on mandibular defect repair.DESIGN, TIME AND SETTING: A randomized controlled animal experiment. The experiment was performed atthe animal laboratory, Medical College of Jinnan University from May 2008 to March 2009.MATERIALS: The injectable tissue engineering bone was prepared by using complex of liquid CS and solid β-TCP as scaffold materials, and combined with freeze-dried rhBMP-2.METHODS: Twenty-four New Zealand white rabbits were prepared for double sides mandibular defect models, and randomized into 4 groups: ①CS/p-TCP/rhBMP-2 group: 1 mL CS/β-TCP/rhBMP-2 complex was injected into the defects.②CS/β-TCP group:0.5 mL CS/β-TCP complex was injected into defects. ③Autograft bone group: repairing the defects with sclerotin of the iliac crest.④Blank control group: no implantation. MAIN OUTCOME MEASURES: At weeks 2, 4 and 8 after surgery, the material degradation and new bone formation were evaluated with, haematoxylin-eosin staining, and electron microscope; the bone mineral density was detected by dual energy X-ray absorptiometry (DXA) to determine bone formation rate and quality.RESULTS: ①Gross observation demonstrated that the size and thickness of osteotylus in CS/β-TCP/rhBMP-2 group was equivalent with the autograft group, which were greater than that of the other groups.②Histologicalobservation demonstrated that there were more bone matrixes in the CS/β-TCP/rhBMP-2 group and autograft group than that in the CS/β-TCP group and blank control group at each time points. ③Scanning electron microscope image suggested that at 8 weeks after operation, the bone bed and the materials in CS/β-TCP/rhBMP-2 group were connected with bone, and the gap was diminished. The degradation of the materials was so obvious that the complete structure of materials could not be found. ⑤DXA detection appealed that the bone density of each group was gradually increased with time prolonged. The quantities of bone density in CS/β-TCP/rhBMP-2 group in weeks 2, 4 and 8 were significantly higher than CS/β-TCP group and blankcontrol group (P < 0.05).CONCLUSION: ①CS/β-TCP/rhBMP-2 has good biocompatibility, degradability and the capacity of bone guidance and bone induction. ②CS/β-TCP can be served as a promising carrier for BMP-2, which is a potential degradable biological material for repairing bone defects.

Objective:To nvestigate the clinical curative effects and advantages on neoadjuvant chemoradiation therapy (nCRT) combined with laparoscopy in lower rectal reserving annus surgery.Methods:we make a retrospective analysis of 141 patients (nCRT group) who received nCRT combined with laparoscopic rectal cancer resection and of 141 cases simply received laparoscopic rectal cancer resection at the same period in the department of coiorectal surgery,Cancer Hospital of China Medical University、Liaoning Cancer Hospital&Institute,from December 2013 to December 2015.Results:Two groups in operation time,anus exhausting time,hospital stay time,number of harvest lymph node,incision infection rate,anastomotic leakage rate are not statistic differences;Two groups of reserving anus rate (136/141 vs 125/141,P＜0.05),intraoperating bleeding (54.8 ± 23.4ml vs 69.7 ± 29.1 mL,P＜0.05),positive rate of distance resection margin (0/141VS 2/141,P＜0.05),length of distance resection margin(2.35 ± 0.70VS2.02 ± 0.46,P＜0.05),local recurrence rate (2/141 VS 9/141,P＜0.05) are statistic differences.Conclusion:Neoadjuvant chemoradiation therapy(nCRT) combined with laparoscopic rectal resection can improve reserving anus rate and reduce local recurrence rate.

Aim To investigate the regulatory effects of Paeoniflorin on G protein-coupled signaling by synoviocytes of collagen-induced arthritis (CIA) rats. Methods CIA was induced by chicken type Ⅱcollagen. Pae (25, 50, 100 mg?kg-1) was administered to CIA rats from d 16 to d 23 after immunization. Arthritis was evaluated by hind paw swelling and arthritis index. Expression of inhibitory G protein (Gi) was detected by Western blotting technique. The level of cAMP in synoviocytes was measured by radioimmunoassay. Protein kinase A (PKA) activity was assessed by Kinase-Glo Luminescent Kinase Assay. Results There was remarkably secondary inflammation in CIA rats. The expression of Gi in synoviocytes increased. While cAMP level and PKA activity of synoviocytes decreased. The inflammatory responses of CIA rats were inhibited after administration of Pae. At the dose of 100 mg?kg-1, Pae reduced Gi expression. cAMP level and PKA activity were enhanced by Pae at the doses of 50 and 100 mg?kg-1 respectively. In ivtro, Pae (2.5, 12.5, 62.5 mg?L-1) reduced Gi expression, but enhanced the level of cAMP and PKA activity. Conclusion G protein-coupled signaling was associated with the pathogenesis of synovitis in CIA rats. Pae has anti-inflammatory effects on CIA rats by modulating G protein -coupled signaling.

Objective To compare the clinical effects of three-dimensional (3D) and two-dimensional (2D) laparoscopic surgeries for rectal cancer (RC) after neoadjuvant chemoradiation therapy (nCRT).Methods The retrospective cohort study was conducted.The clinicopathological data of 126 patients with RC who received laparoscopic surgery after nCRT in the Liaoning Cancer Hospital from January 2013 to January 2014 were collected.Of 126 patients,63 undergoing 3D laparoscopic surgery and 63 undergoing 2D laparoscopic surgery were respectively allocated into the 3D and 2D groups.Surgery was performed by the same doctors' team.Patients received surgery at 6-8 weeks after nCRT,and surgery followed the principle of total mesorectal excision.Observation indicators:(1) intra-and post-operative situations;(2) postoperative pathological examination;(3)follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect local tumor recurrence and patients' survival up to January 2017.Patients received reexaminations once every 3 months within 1 year postoperatively and once every 6 months after 2-3 years postoperatively.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Comparisons of count data were analyzed using the chi-square test.Comparison of ordinal data was done by the nonparametric test.Survival curve was drawn using the Kaplan-Meier method.Survival was analyzed using the Logrank test.Results (1) Intra-and post-operative situations:all the patients underwent successful laparoscopic surgery for RC,without conversion to open surgery and perioperative death.Operation time,volume of intraoperative blood loss,time to anal exsufflation and number of patients with postoperative urinary dysfunction were (125±10)minutes,(54±23)mL,(44±5)hours,0 in the 3D group and (137±12)minutes,(62±20)mL,(46±5) hours,5 in the 2D group,respectively,with statistically significant differences between the 2 groups (t=5.777,2.038,2.575,x2 =7.138,P＜0.05).Number of patients with preserving anus,number of lymph node dissected,number of patients with anastomotic fistula and duration of hospital stay were 60,14.9±2.1,2,(9.5±0.8)days in the 3D group and 58,14.3± 1.7,4,(9.9±2.0)days in the 2D group,respectively,with no statistically significant difference between the 2 groups (x2 =0.133,t=1.606,x2 =0.175,t =1.329,P＞0.05).Two and 4 patients with anastomotic leakage in the 3D and 2D groups received defunctioning stoma,and finally anastomotic leakage healed,without anastomotic stenosis.Of 5 patients with urinary dysfunction in the 2D group,4 received indwelling catheter for 3 weeks and then can micturate autonomously after indwelling catheter removal,1 received indwelling catheter for 3 months and then can micturate autonomously after indwelling catheter removal,without suprapubic cystostomy.(2) Postoperative pathological examination:0 and 4 patients in the 3D and 2D groups had positive circumferential margin,with a statistically significant difference (x2=5.676,P＜0.05).One and 2 patients in the 3D and 2D groups had positive distal margin,with no statistically significant difference (x2 =1.606,P＞0.05).Number of patients with stage Ⅱ and Ⅲ of postoperative pathological staging were 30,33 in the 3D group and 32,31 in the 2D group,respectively,with no statistically significant difference between the 2 groups (x2=0.127,P＞0.05).(3) Follow-up and survival situations:126 patients were followed up for 36.0-48.0months,with a median time of 39.5 months.During the follow-up,0 and 3 patients in the 3D and 2D groups were complicated with local tumor recurrence,with a statistically significant difference between the 2 groups (x2 =4.232,P＜0.05).One-and 3-year overall survival rates were 98.4％,82.5％ in the 3D group and 96.8％,79.4％ in the 2D group,respectively,with no statistically significant difference between the 2 groups (x2 =0.206,P＞0.05).One-and 3-year disease-free survival rates were 92.7％,77.8％ in the 3D group and 90.5％,73.0％in the 2D group,respectively,with no statistically significant difference between the 2 groups (x2=0.421,P＞0.05).Conclusion Compared with 2D laparoscopic surgery,3D laparoscopic surgery for RC after nCRT is safe and feasible,it can also shorten operation time,reduce intraoperative bleeding,alleviate the influence of intestinal peristalsis function,protect pelvic nerves better and improve operation quality.

Objective To investigate the clinical effects and advantages of flexible 3D laparoscopic surgery on rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods The data of 152 patients who received laparoscopic rectal cancer resection after nCRT excluding the cases of high rectal cancer, cardiac and pulmonary dysfunction were analyzed from January 2015 to January 2016 in the Department of Colorectal Surgery of Liaoning Cancer Hospital. The distances from the annal edge to the inferior tumor margin were within 8 cm in these patients. Among these patients, 76 cases received the 3D laparoscopic surgery after nCRT (3D-nCRT), and 76 cases undergone the 2D laparoscopic surgery after nCRT (2D-nCRT). Results Between two groups, the number of lymph node harvest (14.8±2.1 vs. 14.3±1.7), positive rate of the distal margin [1.3 % (1/76) vs. 2.6 % (2/76)], reserving anus rate [92.1 % (70/76) vs. 81.2 % (67/76)], local recurrence rate [1.3 % (1/76) vs. 3.9 % (3/76)] and anastomotic leakage rate [2.6 % (2/76) vs. 3.9 % (3/76)] had no statistical differences (all P>0.05), while the operative time [(125.3±10.2) min vs. (136.6±12.0) min], intraoperative bleeding [(54.1±23.2) ml vs. (61.9±19.5) ml], anus exhaust time [(43.5±5.0) h vs. (45.4±5.6) h] and positive rate of circumferential resection margin (CRM) [1.3 % (1/76) vs. 9.2 % (7/76)] had statistical differences (all P< 0.05). Conclusion Flexible 3D laparoscopic surgery on rectal cancer after nCRT can shorten operative time, reduce intraoperative bleeding, alleviate the influence of intestinal peristalsis function, and improve operative quality.

Objective To analyze the incidence and clinical features of urothelial tumors in renal allograft recipients.Methods A retrospective analysis of 1042 patients received renal allografts who had taken immunosuppression for at least six months between 2006 and 2011 in The First Centre Hospital of Tianjin was performed.Results Eleven cases of uroepithelial tumors were diagnosed in the 1042 cases of renal transplantation ( 1.06％ ),of whom 9 cases were noticed by hematuria ( 81.8 ％ ),2 cases ( 18.2％ ) by medical examination.Six patients were diagnosed with multifocal urothelial carcinomas.Surgery was performed on all the patients with renal tumors and followed by chemotherapy or radiotherapy.Conclusion Malignancies in urinary tract after renal transplantation should be bore in mind.Early diagnosis is very important.The treatment options include reducing immunosuppressive agents and removing tumor lesions completely.

Objective:To establish the methods of isolated culture and functional identification of mice bone marrow derived tolerogenic dendritic cells (CD11b+F4/80 +TDCs) in vitro.Methods: Mice bone marrow cells were isolated and cultured to obtain iDCs with the simulation of mouse rmGM-CSF and rmIL-4.CD11b+F4/80 +TDCs were purified by fluorescence-activated cell sorting on day 6.The morphological changes of TDCs were observed with the inverted microscope dynamically .The expression of CD11b+F4/80 +TDCs were analyzed by the flow cytometry .Tolerogenic function of CD11b+F4/80 +TDCs was evaluated by the expression of MHCⅡ, CD83, IDO, TLR-2, IL-10 and TGF-β1.The expression of MHCⅡ was analyzed by the flow cytometry , and the expression of CD83, IDO and TLR-2 were analyzed by immune-histochemistry.The levels of IL-10 and TGF-β1 in the supernatant of CD11b+F4/80 +TDC were analyzed by ELISA .Meanwhile mature DCs ( mDCs) induced by LPS were used as control .Results:The fresh isolated bone marrow cells look like round and small under microscope .After two days of culture , cells became big and formed into clusters . Five or six days later, cells clusters increased, and the morphology of cells became irregular .At the same time, more dendrite ap-peared on the surface of cells .The percentage of CD11b+F4/80 +TDCs induced by rmGM-CSF and rmIL-4 was about 23%, and the purity of the purified BM CD11b+F4/80 +iDC was about 99%.Compared with mDCs, CD11b+F4/80 +TDCs expressed low levels of MHCⅡand CD83 and high levels of IDO, TLR-2, IL-10 and TGF-β1.Conclusion:CD11b+F4/80 +TDCs derived from mouse bone marrow could be induced successfully by rmGM-CSF and rmIL-4 in vitro.CD11b+F4/80 +TDCs showed tolerogenic function by the expressions of IL-10, TGF-β1, IDO and TLR-2.

Objective To evaluate the efficacy and safety of solifenacin in the treatment of overactive bladder (OAB) syndrome in patients who have undergone transurethral resection of the prostate (TURP). Methods According to the Overactive Bladder Symptom Score (OABSS), 64 cases with OAB symptoms after TURP were randomly assigned into study and control groups with 32 cases in each group. Patients in the study group were treated with solifenacin (5 mg once daily) for a two week period beginning the first day after catheter removal. Patients in the control group were not treated with solifenacin. The mean urgency episodes, micturition episodes, nocturia, urge incontinence, volume voided per micturition, Qmax and OABSS scores were recorded on the 7th and the 14th day after catheter removal. Treatment-emergent adverse events with solifenacin in the study group were recorded and evaluated as well. All cases were followed-up for 8 weeks after catheter removal. Results There were statistically significant differences (P<0.01) in favor of the study group over the control group in the aspect of urgency, micturition episodes, nocturia, urge incontinence, volume voided per micturition and OABSS scores. The incidences of treatment related adverse events were 12.5% (4/32) in the study group with no serious adverse event observed. Conclusions Solifenacin is effective in the treatment of OAB syndrome after TURP and is well tolerated as well. Application of solifenacin should be recommended earlier after TURP.

Objective:To investigate the learning curve of laparoscopic transanal total mesorectal excision (taTME) for rectal cancer operated by one or two surgery teams.Methods:The retrospective cross-sectional study was conducted. Based on the concept of real-world research, the clinical data of 1 458 patients undergoing laparoscopic rectal cancer taTME from 44 medical centers who were registered in the Chinese taTME registry collaborative (CTRC) database from May 2010 to May 2020 were collected. The 1 458 patients were divided into cohorts with one surgery team or two surgery teams according to the operation method. Patients with one surgery team underwent taTME by transabdominal operation and then by transanal operation. Patients with two surgery teams underwent taTME by transabdominal and transanal operation simultaneously with duration of the simutaneous operation time ≥30 minutes. The entire surgical process of patients with two surgery teams is not required to be performed by two surgery teams simutaneously. The clinical data were collected from the medical centers with similar operation amount according to the operation time sequence to analyze the difference between different operation stages and explore the learning curve. The operation time was taken as the parameter to carry out cumulative sum analysis and draw the learning curve of laparoscopic rectal cancer taTME in each medical center. The clinicopathological characteristics of patients from two medical centers with the largest difference in learning curves were analyzed. Observation indicators: (1) screening results of clinical data; (2) clinical data collection of patients with one surgery team; (3) surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages; (4) learning curve of the one surgery team; (5) clinical data collection of patients with two surgery teams; (6) surgical situations of laparoscopic rectal cancer taTME from the two surgery teams; (7) learning curve of the two surgery teams. The cumulative sum was calculated by the CUSUM=∑i=1nXi-U, where Xi represented the operation time of each taTME, U represented the average operation time of all cases, and n represented the operation number. Fitting process was conducted on scatter plot of learning curves. Taking the apex of learning curve as the boundary, the learning curve was divided into two stages. The abscissa corresponding to the apex of learning curve was the number of operations that needed to be performed to cross the learning curve. Measurement data with normal distribution were represented as Mean±SD. Comparison between two groups was conducted using the t test and comparison between multiple groups was conducted using the ANOVA. Measurement data with skewed distribution were represented as M( P25,P75), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was analyzed using the rank sum test. Count data were analyzed using the chi-square test or Fisher exact probability. Results:(1) Screening results of clinical data:the clinical data of 661 patients from 7 medical centers with one surgery team and two surgery teams were collected. (2) Clinical data collection of patients with one surgery team: the clinical data of 312 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected including 42 cases in the number 2 medical center, 97 cases in the number 20 medical center, 82 cases in the number 33 medical center, 35 cases in the number 37 medical center and 56 cases in the number 39 medical center, respectively. (3) Surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages: three medical centers including the number 2, number 37 and number 39 medical center with close operation volume provided the clinical data of cases distributed in five operation stages. Among the five operation stages, the proportion of high-quality operation of total mesorectal excision (TME) was ≥17/18, the incidence of postoperative complications was ≤13.3%(4/30) and the incidence of anastomotic leakage was ≤10.0%(3/30). There was no significant difference in the TME quality, postoperative complications or anastomotic leakage among the five operation stages ( P>0.05). There was no significant difference in the operation time among the five operation stages ( χ2=6.950, P>0.05). (4) Learning curve of the one surgery team: the number of operations corresponding to the turning point of learning curve in number 2 and number 20 medical center was 22 and 39, respectively. The number of operations corresponding to the turning points of learning curve in number 33 and number 37 medical center was 15, 66 and 10, 28, respectively. The number of operations corresponding to the turning point of learning curve in number 39 medical center was 20. The overall curve of number 20 medical center was in line with the trend of learning curve and 39 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 20 and number 33 medical center. Cases with the gender of male or female, age, body mass index, cases classified as stage 1, stage 2, stage 3 or stage 4 of the American Society of Anesthesiologists (ASA) Classification, cases with neoadjuvant therapy, duration of postoperative hospital stay of the number 20 medical center were 77, 20, (60±10)years, 24 kg/m 2(22 kg/m 2, 26 kg/m 2), 1, 88, 8, 0, 8, 8, 11 days (9 days, 13 days), respectively, versus 51, 31, (64±11)years, 23 kg/m 2(21 kg/m 2, 26 kg/m 2), 0, 35, 43, 1, 31, 16 days (13 day, 21 day) of number 33 medical center, showing significant differences in the above indicators between the two medical centers ( χ2 =6.442, t=-2.265, Z=-2.032, -6.870, χ2 =22.120, Z=-8.408, P<0.05). (5) Clinical data collection of the two surgery teams: the clinical data of 259 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected, including 46 cases in the number 2 medical center, 47 cases in the number 8 medical center, 78 cases in the number 18 medical center, 43 cases in the number 33 medical center and 45 cases in the number 44 medical center, respectively. (6) Surgical situations of laparoscopic rectal cancer taTME from the two surgery teams: four medical centers including the number 2, number 8, number 33 and number 44 medical center with close operation volume provided the clinical data of cases distributed in four operation stages. Among the four operation stages, the proportion of high-quality operation of TME was ≥50.0%(13/26), the incidence of postoperative complications was ≤35.0%(14/40) and the incidence of anastomotic leakage was ≤22.5%(9/40). There was no significant difference in the TME quality, postoperative complications or operation time among the four operation stages ( χ2 =3.252, 4.733, 8.848, P>0.05). There was a significant difference in the incidence of anastomotic leakage among the four operation stages ( P<0.05). (7) Learning curve of the two surgery teams: the number of operations corresponding to the turning point of learning curve in number 2 and number 8 medical center was 28 and 16, respectively. The number of operations corresponding to the turning points of learning curve in number 18, number 33 and number 44 medical center was 12 and 58, 10 and 36, 14 and 36, respectively. The overall curve of number 2 medical center was in line with the trend of learning curve and 28 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 2 and number 33 medical center. The age and cases with tumor in stage T0 and (or) Tis, stage T1, stage T2, stage T3 or stage T4 of the T staging of the number 2 and number 33 medical center were (60±12)years, 3, 1, 9, 11, 20 and (65±10)years, 2, 3, 22, 15, 0, respectively, showing significant differences in the above indicators between the two medical centers ( t=-2.280, Z=-4.033, P<0.05). Conclusion:Thirty-nine cases of operations was the minimum number for the one surgery team to cross the learning curve of laparoscopic rectal cancer taTME and 28 cases of operations was the minimum number for the two surgery teams to cross the learning curve of laparoscopic rectal cancer taTME.