Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1

BACKGROUND: Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. RESULTS: In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. CONCLUSIONS: Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors / 药物分析学报

MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone de-rivatives Al-A43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phos-phatase and tensin homology deleted on chromosome ten(PTEN),at 10 uM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC50 value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G0/G1 phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.

Construction of healthy enterprises in coal industry / 中国职业医学

@#Promoting the construction of healthy enterprises in the China's coal industry will help coal enterprises to fulfill their ， ， legal and social responsibilities contribute to the construction of healthy cities and protect the health of occupational ， ， individuals from various aspects. In recent years the patriotic health campaign the health promotion project of industrial and ， ， ， mining enterprises the construction of standardized management system of coal mine safety the construction of green mines and the construction project of staff quality have laid the foundation for the construction of healthy enterprises in China's coal ， industry. However the development of coal industry in China is unbalanced and insufficient. There are many problems such as a ， general lack of professional talents the exist of a large number of small coal mines and the underprivileged technology of coal ， ， ， mining poor working environment in underground coal mines many occupational hazards in workplace and relatively few special incentive measures for the construction of healthy enterprises in the coal industry. It is recommended that coal ， enterprises with advanced productivity take the lead to demonstrate coal mine industry construction actively promote advanced ， ， and applicable technology and equipment steadily improve the professional level of coal industry workers comprehensively ， ， improve the environment of mining areas strengthen the monitoring and treatment of occupational hazards improve and ， - implement special incentive measures for healthy enterprises and comprehensively promote the high quality development of coal industry and the construction of healthy enterprises. So as to effectively protect the health occupational rights and interests of workers and provide assistance for occupational health work in the new era.

Comparison of efficacy and safety between two different methods of nephroureterectomy in two centers / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC).@*METHODS@#We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries.@*RESULTS@#Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups.@*CONCLUSION@#CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.

prognostic value of heart-type fatty acid binding protein in patients with acute coronary syndrome

The effect of heart-type fatty acid binding protein [H-FABP] remains unclear on the quality of the prognoses of patients with acute coronary syndrome [ACS]. The authors searched the EMBASE, PubMed, Cochrane Library, and Medline electronic databases from their respective inceptions throughout June 2017. Odds ratios were pooled from individual studies, and conducted heterogeneity analysis, quality assessment, and publication bias analysis. A total of four studies with 1,994 patients were included [554 positive patients; 1,440 negative patients]. Pooled analysis of these studies showed that patients positive for H-FABP had higher incidence for mortality [OR, 6.39; p <0.01] and cardiac events [OR, 3.94; P<0.01] than negative patients, but myocardial infarction [MI] [OR, 1.43; P=0.32] showed no significant differences. ACS patients positive for H-FABP had higher rates in cardiac events and mortality. The incidence of MI showed no significant difference, possibly because this study was based on limited data from randomized studies. Additional substantial randomized controlled trials certainly needed to verify these discovery

Effect of oral polyethylene glycol at different time for painless colonoscopy preparation / 中国内镜杂志

Objective To compare the efficacy and comfort of oral polyethylene glycol at different time for painless colonoscopy preparation. Methods According to time of oral compound polyethylene glycol electrolyte powder, 173 painless colonoscopy patients were divided into group A, group B and group C. Patients in group A took 4 boxes of compound polyethylene glycol electrolyte powder for colonic preparation at 22:00 on day 1 before the check, the time of painless colonoscopy is 8:30 ~ 10:30. Group B patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 5:00 am on check day, the time of painless colonoscopy is 10:30 ~ 12:30. Group C patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 7:00 am on check day, the time of painless colonoscopy is 13:30 ~ 15:30. At last, we compare the colon cleanliness and comfort of patients among the three groups. Results There was no significant difference in instetinal cleanliness among the 3 groups (P > 0.05), but there was greatly significant difference in subjective tolerance among 3 groups (P < 0.05). Conclusion The 3 methods of having boxes of compound polyethylene glycol electrolyte power all have the satisfying effect for colonic preparation, but fractionated dose polyethylene glycol electrolyte power provides a better tolerance for bowel preparation of painless colonscopy.

Effect of oral polyethylene glycol at different time for painless colonoscopy preparation / 中国内镜杂志

Objective To compare the efficacy and comfort of oral polyethylene glycol at different time for painless colonoscopy preparation. Methods According to time of oral compound polyethylene glycol electrolyte powder, 173 painless colonoscopy patients were divided into group A, group B and group C. Patients in group A took 4 boxes of compound polyethylene glycol electrolyte powder for colonic preparation at 22:00 on day 1 before the check, the time of painless colonoscopy is 8:30 ~ 10:30. Group B patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 5:00 am on check day, the time of painless colonoscopy is 10:30 ~ 12:30. Group C patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 7:00 am on check day, the time of painless colonoscopy is 13:30 ~ 15:30. At last, we compare the colon cleanliness and comfort of patients among the three groups. Results There was no significant difference in instetinal cleanliness among the 3 groups (P > 0.05), but there was greatly significant difference in subjective tolerance among 3 groups (P < 0.05). Conclusion The 3 methods of having boxes of compound polyethylene glycol electrolyte power all have the satisfying effect for colonic preparation, but fractionated dose polyethylene glycol electrolyte power provides a better tolerance for bowel preparation of painless colonscopy.

Change of memory function and decrease of nitric oxide level of whole brain in the transgenic mice expressing human tau 40 with P301L mutation / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).</p><p><b>METHODS</b>The human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.</p><p><b>RESULTS</b>Exogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.</p><p><b>CONCLUSION</b>Tau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.</p>

Mid-term Follow-up of Neonatal Pleural Effusion.

Objectives: To investigate the clinical course and mid-term prognosis of neonates admitted with pleural effusion. Methods: Case records of 38 neonates admitted with pleural effusion were retrieved and analyzed. Results: 16 (42%) patients had congenital and 22 (58%) patients had acquired causes of pleural effusion. The most common causes of congenital pleural effusion and acquired pleural effusion were chylothorax (18%) and congestive heart failure (13%), respectively. Poorer outcome was observed with fetal hydrops, preterm birth (<34 weeks) and associated defects. Conclusions: Most of the neonates with pleural effusion have good outcome in the mid-term follow-up.

Expression of MicroRNA-146a in peripheral blood mononuclear cells in patients with systemic lupus erythematosus / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the expression pattern of microRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), with an attempt to identify the role of microRNA in the pathogenesis of SLE.</p><p><b>METHODS</b>SLE-related genes were searched from the published literatures. Using the microRNA target gene prediction databases, we predicted the putative microRNA targets in these SLE-related genes. For some of the corresponding microRNAs (hsa-miR-146a), quantitative real-time polymerase chain reaction was performed to determine the expression levels of these microRNAs in PBMCs of SLE patients (SLE group) and healthy controls (control group).</p><p><b>RESULT</b>The discrepancy of cycle threshold of hsa-miR-146a in PBMCs was significantly higher in SLE group (4.52±1.18) than in control group (2.76±1.38) (P=0.02), and the expression level of hsa-miR-146a was significantly lower in SLE group.</p><p><b>CONCLUSION</b>The expression of hsa-miR-146a decreases in SLE patients, indicating that hsa-miR-146a may play a role in the pathogenesis of SLE.</p>