BackgroundSeveral immune‐mediated diseases have been shown to be associated with an increased risk of cardiovascular disease. However, studies evaluating the association between inflammatory bowel disease and risk of cardiovascular disease reported inconsistent results. We assessed the association between inflammatory bowel disease and risk of ischemic heart disease in a meta‐analysis of cohort studies.Methods and ResultsWe conducted a literature search of PubMed and Embase up to October 2016 to identify relevant studies. The summary relative risks were calculated using the random‐effects models. To explore the source of heterogeneity, we performed subgroup and sensitivity analysis. We included 10 cohort studies that satisfied our inclusion criteria. Patients with inflammatory bowel disease were associated with an increased risk of ischemic heart disease (relative risk: 1.244; 95% CI, 1.142–1.355). Considerable heterogeneity was observed. Crohn's disease showed a significantly increased risk of ischemic heart disease (relative risk=1.243; 95% CI, 1.042–1.482) and a positive association was also observed in ulcerative colitis (relative risk=1.206; 95% CI, 1.170–1.242).ConclusionsBased on meta‐analysis of cohort studies, we found an increased risk of ischemic heart disease in patients with inflammatory bowel disease. Large long‐term prospective studies are warranted to confirm our results.

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Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time-and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Key words: selective COX-2 inhibitor; cell growth; cell cycle; hepatocellular carcinoma cellsCyclooxygenases (COX) are key rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H2, the precursor of various compounds including prostaglandins (PGs), prostacyclin and thromboxanes. There are at least 2 isoforms of COX: COX-1 and COX-2. COX-1 is expressed constitutively in a wide variety of tissues whereas COX-2 is highly inducible and is expressed in response to a variety of proinflammatory agents and cytokines. 1,2 Overexpression of COX-2 has been demonstrated in various tumor tissues such as colon cancer, pancreatic cancer and hepatocellular carcinoma. [3][4][5][6][7] Although several studies have shown the upregulation of COX-2 in cirrhotic tissues adjacent to hepatocellular carcinoma (HCC) and welldifferentiated HCC, the precise role of COX-2 in carcinogenesis remains unclear. 7,8 A few reports have shown that NSAIDs inhibited the growth of various cancer cell lines including those derived from hepatocellular carcinoma. 9 -11 The question arises whether COX-2 also is a target for the prevention or treatment of hepatocellular carcinoma, as it is for colon cancer. 12 There is little evidence, however, of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in hepatocellular carcinoma cell lines. MATERIAL AND METHODS Cell lines and cell cultureFour human hepatocellular carcinoma cell lines, PLC/PRF5, HepG2, Mahlavu and HuH-7, were obtained from the American Type Culture Collection. Cells (2 ϫ 10 5 cells) were grown for 24 hr in DMEM (PLC/PRF5 and HepG2) (ICN; Biomedicals Inc., Aurora, MI), minimum essential Eagle's medium (Mahlavu) (ICN) and RPMI 1640 (HuH-7) (ICN) supplemented with 10% FBS at 37°C under 5% CO 2 /95% air in 100 mm 2 cell culture dishes. Then, NS-398 (Cayman Chemical, Ann Ar...

Metformin is used as a first-line therapy for type 2 diabetes, with reports of its usefulness for the prevention and control of several types of cancers. This study investigated the effects of metformin on hepatocellular carcinoma (HCC). The human HCC cell lines HepG2 and PLC/PRF/5 were cultured and treated with metformin or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of adenosine monophosphate (AMP)-activated protein kinase. Changes in cell viability and cell cycle distribution were evaluated by MTT and flow cytometry, respectively. Apoptosis was assessed by fluorescent-dye staining. An HCC model was established in 6- to 8-week-old BALB/c-nu mice by subcutaneous injection of PLC/PRF/5 cells. After 1 week, mice were treated intragastrically with metformin or vehicle. Tumor xenograft tissues were examined using immunohistochemistry for evaluation of the the expression of cyclin D1, p21CIP and p27KIP. HCC cells and tissues from the in vitro and in vivo experiments, respectively, were subjected to protein extraction and western blotting. We found that metformin treatment reduced HCC cell viability in a dose-dependent manner similar to AICAR treatment. In addition, metformin treatment induced HCC cell cycle arrest at G1/G0 phase and apoptosis. Intragastric treatment of the mouse PLC/PRF/5 cell xenograft model with metformin showed that metformin not only blocked tumor progression, but also reduced tumor morbidity. Treatment with metformin upregulated the expression of p21CIP and p27KIP, but downregulated cyclin D1 levels, both in vitro and in vivo. Metformin treatment also upregulated the expression of phosphorylated AMPK protein in xenograft tissues. These findings indicate that metformin warrants further evaluation as a novel therapeutic and preventive strategy against HCC.

Objective: To systematically review the effects of Tai Chi exercise as a nonpharmacological therapeutic strategy on the physical and mental health in individuals with knee osteoarthritis. Data sources: A systematic literature retrieval has been conducted in PubMed, Web of Science, EMbase, CENTRAL, OVID, CINAHL, Physiotherapy Evidence Database, Chinese Biomedical Database and China National Knowledge Infrastructure up to June 2020 to identify the relevant randomised controlled trials (RCTs). Methods: Two authors assessed independently the risk of bias using the Cochrane Collaboration’s tool. Standardised mean difference (SMD) and 95% CI were calculated and data were combined using the fixed or random-effect model. The strength of evidence was rated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A total of 16 RCTs involving 986 patients with knee osteoarthritis met the established inclusion criteria. The strength of evidence for the main outcomes was low or moderate. The systematic review illustrated the efficacy of Tai Chi exercise in treating and managing knee osteoarthritis. Patients’ outcomes practising Tai Chi exercise were improved significantly, including pain (SMD = ‒0.69, 95%CI: ‒0.95 to ‒0.44, P < 0.001), stiffness (SMD = ‒0.59, 95%CI: ‒0.91 to ‒0.27, P < 0.001), physical function (SMD = ‒0.92, 95%CI: –1.16 to ‒0.69, P < 0.001), dynamic balance (SMD = 0.69, 95%CI: 0.38 to 0.99, P < 0.001), physiological and psychological health (SF-36 PCS: SMD = 0.48, 95%CI: 0.28 to 0.68, P < 0.001; SF-36 MCS: SMD = 0.26, 95%CI: 0.06 to 0.45, P = 0.01). No adverse events associated with Tai Chi exercise were reported. Conclusion: Tai Chi exercise was beneficial for ameliorating physical and mental health of patients with knee osteoarthritis and should be available as an alternative non-pharmacological therapy in rehabilitation programmes.

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yclooxygenase 2 (COX-2) is a highly inducible, rate-limiting enzyme involved in the production of prostaglandins (PGs), prostacyclins and thromboxanes. COX-2 is expressed in response to a variety of proinflammatory agents and cytokines.1, 2) Overexpression of COX-2 has been demonstrated in various tumors such as colon cancer, pancreatic cancer and hepatocellular carcinoma (HCC).3-5) Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently being assessed for use in the prevention and treatment of colorectal cancer, based on epidemiologic, preclinical and experimental evidence. 6, 7) Although several studies have shown the up-regulation of COX-2 in cirrhotic tissues adjacent to HCC and well-differentiated HCC, the precise role of COX-2 in hepato-carcinogenesis remains unclear. 5,8) A recent report of ours has also shown that NS-398, a selective COX-2 inhibitor, inhibited growth and induced cell cycle arrest in HCC cell lines. 9) However, the mechanism by which COX-2 inhibitors cause growth inhibition and cell cycle arrest in HCC cells is not known.There is increasing evidence that perturbation of cell cycle regulation is an important contributing factor to cancer, including HCC. 10,11) There are two key checkpoints in the cell cycle, the G1-S and G2-M checkpoints. Cyclins, cyclin-dependent kinases (CDKs) and cyclin/CDK complexes have been found to control the progression of cells through the G0-G1, S and G2-