BACKGROUND:Autologous bone marrow mesenchymal stem cel transplantation for the treatment of cardiovascular disease has become one of the hotspots, but it is unclear whether the proliferation and directional differentiation of autologous bone marrow mesenchymal stem cels varies changes with age. OBJECTIVE: To explore the proliferation and differentiation changes of rat bone mesenchymal stem cels in different ages. METHODS:The bone marrow mesenchymal stem cels from Sprague-Dawley rats in different age groups were purified and cultured, and then examined by flow cytometry in terms of cel cycle. Meanwhile, neonatal rat cardiomyocytes were co-cultured with bone marrow mesenchymal stem cels. The morphologic changes of bone marrow mesenchymal stem cels and the protein expression of troponin T were detected with immunofluorescence technique. RESULTS AND CONCLUSION: The percentage of bone marrow mesenchymal stem cels in G0/G1 phase was increased with age; while the percentage of expression of troponin T proteins-positive bone marrow mesenchymal stem cels were decreased with age. These findings indicate that the proliferation and differentiation abilities of rat bone marrow mesenchymal stem cels descend with age.

Objective To perform a systematic review and meta-analysis of the predictive abilities of CHADS2 and CHA2DS2-VASc in stroke and thromboembolism risk stratification of atrial fibrillation (AF) patients. Methods We searched PubMed and EMBASE for Eng-lish-language literature on comparisons of the diagnostic performance between CHADS2 and CHA2DS2-VASc in predicting stroke, or sys-temic embolism, in AF. We then assessed the quality of the included studies and pooled the C-statistics and 95%confidence intervals (95%CI). Results Eight studies were included. It was unsuitable to perform a direct meta-analysis because of high heterogeneity. When analyzed as a continuous variable, the C-statistic ranged from 0.60 to 0.80 (median 0.683) for CHADS2 and 0.64-0.79 (median 0.673) for CHA2DS2-VASc. When analyzed as a continuous variable in anticoagulation patients, the subgroup analysis showed that the pooled C-statistic (95%CI) was 0.660 (0.655-0.665) for CHADS2 and 0.667 (0.651-0.683) for CHA2DS2-VASc (no significant difference). For non-anticoagulation patients, the pooled C-statistic (95%CI) was 0.685 (0.666-0.705) for CHADS2 and 0.675 (0.656-0.694) for CHA2DS2-VASc (no significant differ-ence). The average ratio of endpoint events in the low-risk group of CHA2DS2-VASc was less than CHADS2 (0.41%vs. 0.94%, P＜0.05). The average proportion of the moderate-risk group of CHA2DS2-VASc was lower than CHADS2 (11.12%vs. 30.75%, P＜0.05). Conclu-sions The C-statistic suggests a similar clinical utility of the CHADS2 and CHA2DS2-VASc scores in predicting stroke and thromboem-bolism, but CHA2DS2-VASc has the important advantage of identifying extremely low-risk patients with atrial fibrillation, as well as classi-fying a lower proportion of patients as moderate risk.

Objective To investigate the effect of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on Toll-like receptor 4 (TLR4)-mediated proinflammatory phenotype of cultured vascular smooth muscle cells (VSMCs) in mice.Methods NADPH oxidase agonist platelet-derived growth factorBB (PDGF-BB) and inhibitor apocynin were used respectively to treat cultured VSMCs from C57BL/6J and TLR4-/-mice.The fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate was used to detect the reactive oxygen species (ROS) level in VSMCs.An enzyme-linked immunosorbent assay was used to detect the expressions of interleukin (IL)-6,IL-1β,and tumor necrosis factor-α (TNF-α) in VSMCs.Tetrazolium blue staining and Boyden chamber assay were used to detect the proliferation and migration of VSMC.Results The ROS levels were increased in VSMCs both from C57BL/6J and TLR4-/-mice after PDGF-BB treatment,and this could be inhibited by apocynin.PDGF-BB pretreatment significantly upregulated the expressions of IL-6 (52.69 ±3.49 ng/ml vs.35.04 ±2.74 ng/ml; P =0.001),IL-1β (79.68 ±2.33 ng/ml vs.62.38 ±0.54 ng/ml;P=0.000),and TNF-α (218.35± 5.42 ng/mlvs.124.74± 4.59 ng/ml; P=0.000) in VSMCs from C57BL/6J mice,and the abilities of proliferation (1.69 ± 0.53 vs.1.04 ± 0.40; P =0.000) and migration (42.11 ±4.05 vs.1.69 ± 0.53; P =0.000) were increased significantly; apocynin pretreatment significantly inhibit the expressions of IL-6 (42.11 ± 4.05 ng/ml vs.52.69 ± 3.49 ng/ml; P =0.010),IL-1β (67.57 ± 1.36 ng/ml vs.79.68 ±2.33 ng/ml; P =0.000) and TNF-α (156.18 ± 6.98 ng/ml vs.218.35 ± 5.42 ng/ml;P =0.000),as well as proliferation (1.23 ±0.42 vs.1.69 ±0.53; P =0.000) and migration (42.11 ±4.05 vs.52.69 ± 3.49; P =0.000).While there were no significant changes in the expressions of IL-6,IL-1β,and TNF-α in VSMCs from TLR4-/-mice after PDGF-BB and apocynin pretreatment.Conclusions NADPH oxidase-derived ROS involved in the TLR4-mediated VSMC inflammatory phenotype as well as proliferation and migration,which may be the important mechanisms of its influencing on the occurrence and development of atherosclerosis.

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.

The aim of this study was to investigate the effect of transmembrane 9 superfamily protein member 2 (TM9SF2) in proliferation and migration of triple negative breast cancer cell line MDA-MB-231.The expression of TM9SF2 in triple negative breast cancer cell line MDA-MB-231 and nontumorigenic mammary epithelial cell line MCF-10A were measured by Western blot. MDA-MB-231 cells were treated with siRNA-TM9SF2 to knock-down the expression of TM9SF2. The effect of silencing TM9SF2 was measured with Western blot.The proliferation of cells was tested by MTS,and the migration was measured with Transwell and wound-healing assay.Proteins related to proliferation (PI3K,AKT,SRC and ERK) and migration (Snail,Slug and N-cadherin) were measured with Western blot.Protein expressions of TM9SF2 was better improved in triple negative breast cancer MDA-MB-231 cell line than MCF-10A.Compared with the control group, the siRNA-TM9SF2 infected group had lower expressions of PI3K, Snail, Slug and N-cadherin, and at the same time phosphorylation of AKT was decreased. The results suggest TM9SF2 can promote the proliferation and metastasis of triple negative breast cancer MDA-MB-231 cell line.

Objective To compare the effectiveness and safety of endoscopic submucosal dissection ( ESD) with endoscopic piecemeal mucosal resection ( EPMR) for early esophageal cancer and precancerous lesions with length more than 5 cm. Methods A retrospective analysis was performed on data of 85 patients diagnosed as early esophageal cancer and precancerous lesions with length more than 5 cm in Fujian Medical Association of Early Esophageal Carcinoma from January 2012 to July 2017. The patients were divided into ESD group (52 cases) and EPMR group (33 cases), and the effectiveness and safety between the two groups were compared. Results There was no significant difference on the complete resection rate between the two groups[86. 5％ (45/52) VS 87. 9％ (29/33), P>0. 05]. The operative time (58. 53±30. 50 min VS 32. 06±9. 12 min), postoperative fasting time (4. 18±1. 30 d VS 3. 67±0. 96 d), postoperative hospital-stay time (7. 45±2. 44 d VS 6. 54±1. 73 d), and postoperative antibiotics using time (3. 48±2. 33 d VS 1. 96±2. 20 d) in ESD group were higher than those in EPMR group (all P<0. 05). There were no significant difference in the rate of intraoperative complication and short-term postoperative complication, such as fever, chest pain, and postoperative bleeding, between the two groups ( all P>0. 05 ) . But the postoperative stricture rate of ESD group was higher than that of EPMR group[23. 1％ (12/52) VS 6. 1％(2/33), P<0. 05]. During the follow-up of 3-63 months, 5 cases recurred in ESD group and 1 case in EPMR group, with no significant difference ( P>0. 05). Conclusion ESD and EPMR have equivalent efficacy and safety on the treatment of early esophageal cancer and precancerous lesion. EPMR has a shorter operative time, lower rate of post-operative stricture, and is easier to master.

Objective:To investigate the application value of obliquus externus abdominis pedicle flap graft technique in repair of giant abdominal incisional hernia.Methods:The retrospective and descriptive study was conducted. The clinical data of 14 patients with giant abdominal incisional hernia who were admitted to Affiliated Hangzhou First People′s Hospital of Zhejiang University School of Medicine from June 2015 to June 2018 were collected. There were 5 males and 9 females, aged (67±10)years, with a range from 45 to 80 years. All the 14 patients underwent repair of abdominal wall defect and functional reconstruction with obliquus externus abdominis pedicle flap graft technique. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) hernia-related quality of life; (4) follow-up. Follow-up using outpatient examination was performed at postoperative 1 and 12 months, and once a year thereafter to detect the recurrence of incisional hernia or abdominal bulging up to June 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison within groups was analyzed using the paired sample t test. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages. Results:(1) Surgical situations: all the 14 patients underwent repair of abdominal wall defect and functional reconstruction with unilateral obliquus externus abdominis pedicle flap graft technique successfully, and reinforced repair with mesh. All the meshes were standard polypropylene meshes which were placed in the retro muscular or preperitoneal space. The operation time, volume of intraoperative bleeding, mesh size of the 14 patients were (153±34)minutes, (119±59)mL, (450±156)cm 2, respectively. (2) Postoperative situations: the duration of hospital stay of the 14 patients were (14±3)days. Of the 14 patients, 1 had type Ⅲ seroma and was cured after conservative treatment. There were no complications such as ischaemia and necrosis of external oblique muscle flap, incision dehiscence, infection of operation site, intestinal obstruction or intestinal fistula observed in the 14 patients. (3) Hernia-related quality of life: the score of hernia-related quality of life of the 14 patients before operation and at postoperative 12 months were 38±8 and 77±15 respectively, showing a significant difference ( t=12.729, P<0.05). (4) Follow-up: 14 patients were followed up for 12-48 months, with a median follow-up of 16 month. During the follow-up, none of the 14 patients had recurrence of incisional hernia or abdominal wall bulging. Conclusion:Obliquus externus abdominis pedicle flap graft technique can be used for repair of giant abdominal incisional hernia, which will lead to less surgical complications and improve hernia-related quality of life of patients.

Objective: To investigate the effects CXCL1 derived from TAMs on the progression of HCC by CXCL1 in tumor microenvironment (TME) ． Methods : PMA induced human monocyte (THP-1) to obtain undifferentiated macrophages (M0) and then co-cultured with Huh 7 HCC cells．The biomarkers of macrophage phenotype and mRNA level of HCC were analysed by qRT-PCR. Colony formation assay，cell viability assay and transwell assay were performed to evaluate the biological alteration of HCC cells in TME．Epithelial-mesenchymal transition (EMT) molecular genetics were detected using western blot．The levels of CXCL1 in TME were measured by ELISA assay. Results : High CXCL1 expression in HCC patients predicted poor prognosis．Abundant macrophages were found in CXCL1 high expression HCC tissues．In macrophages and HCC co-cultured model，significantly increasing CXCL1 expression was detected in both two cells and the biomarkers of M2 macrophages，CD163 and CD206 were elevated．The growth and migration of HCC cells were promoted． Conclusion Co-culture of macrophages with HCC cells induces macrophages pro-tumor phenotype and CXCL1 secretion which promotes the progression of HCC.

[Abstract] Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1（TGIF1）axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24, 5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_ 0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assayconfirmedthatthereisatargetingrelationshipbetweencirc_0001429andmiR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.