C-C chemokine receptor type 7 (CCR7) is involved in the development and progressions of chronic inflammatory diseases and cancer; therefore, signaling pathways that regulate CCR7 expression may represent novel molecular therapeutic targets. Previous studies by our group revealed that CCR7 is important in colon cancer progression and a is linked with cyclooxygenase (COX)‑2‑derived prostaglandin (PG)E2. Induction of COX‑2 and membrane‑associated PGE synthase 1 (mPGES‑1), which are overexpressed in numerous cancer types, cooperatively enhance PGE2 expression, which contributes to carcinogenesis and cancer progression. The present study investigated whether CCR7 expression is associated with the levels of mPGES‑1-derived PGE2. The results showed that mPGES‑1‑dependent release of PGE2 was markedly induced in colon cancer cells after transient transfection with mPGES‑1 overexpression vector, accompanied by elevated CCR7 expression. PGE2 levels and CCR7 expression were markedly attenuated in colon cancer cells in which mPGES‑1 was blocked, which identified mPGES‑1 as a potential therapeutic target for the regulation of CCR7 expression. Finally, overexpression of CCR7 was partly mediated through the AKT/glycogen synthase kinase 3β signaling pathway dependent on the binding of mPGES‑1-derived PGE2 to the prostaglandin EP4 receptor. Thus, in addition to inhibitors of mPGES‑1 expression, EP4 antagonists and AKT/GSK-3β inhibitors may emerge as potential therapeutics to reduce CCR7 expression in colon cancer.
The alpha-glucosidase inhibitor acarbose has been used for more than 20 years in the management of hyperglycemia.Owing to its unique mode of action in the gastrointestinal tract,its properties are very different from other antidiabetic medications.Patients on long-term treatment to control a chronic disease are not only interested in good treatment efficacy,but are also even more interested in the safety and side effects of their medications.Significant aspects of acarbose predominantly regarding safety and tolerability in the management of type 2 diabetes and prediabetes are reviewed.It is concluded that acarbose is a convenient long-term treatment option,with benefits for both type 2 diabetics and patients in a prediabetic state.
Cyclo-oxgenase 2 (COX-2) is involved in prostaglandin synthesis in central nervous system, and it also plays a role in human carcinogenesis. Our purpose of this study is to investigate the COX-2 expression in different development stages of colorectal cancer, and to discuss the relationship between the gene expression and clinicopathological features of the cancer.COX-2 expression was examined by immunohistochemical staining in 76 surgical specimens of colorectal cancer (44 of advanced stage and 32 of early stage), thirty-three adenomas and 18 normal colonic mucosal tissues taken by endoscopic biopsy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to evaluate the relation of COX-2 to prognosis.COX-2 expression, divided into 4 grades from "-" to "+++", is respectively 83.3%, 16.7%, 0% and 0% in normal colonic mucosal tissues; 12.1%, 42.4%, 36.4% and 9.1% in adenomas; 6.3%, 28.1%, 46.9% and 18.7% in early colorectal cancers (ECCs), and 6.8%, 20.5%, 18.2% and 54.5% in advanced colorectal cancers (CRCs). The differences in COX-2 expression between advanced CRCs and early colorectal cancers (ECCs) as well as between the advanced CRCs and adenomas were statistically significant (P < 0.01); but there was no significant difference between ECCs and adenomas. Kaplan-Meier survival analysis showed a significant difference in the survival curves between low high COX-2 groups (P < 0.05). Cox proportional hazards regression showed that COX-2 expression was related to poorer long-term outcome with a hazard ratio of 2.665 unadjusted for other variables (P < 0.05), and COX-2 expression was an independent risk factor of poor prognosis.COX-2 expression is gradually up-regulated in the development from normal epithelium to adenomas and from ECCs to advanced CRCs. Alhough the COX-2 protein can not be regarded as a tumor marker to diagnose CRCs early, COX-2 expression can be regarded as an independent risk factor of poor prognosis for postoperative patients with advanced CRCs.
Qualitative research methods,originated from social science,have been used in research on adverse drug reaction(ADR).Different from quantitative research methodology,qualitative research is mainly used to investigate the attitude,recognition,experience and perspectives from health care workers or patients so to have a better understanding of humanity and opinions.This will be significant for understanding of the knowledge and concerns from patients about ADR.The results from qualitative research can complement the shortage of quantitative research and reflect the ADR in a more comprehensive way so to provide basis for better safe and rationale use of drugs.
To compare clinical practice guideline recommendations on the use of oral patent Traditional Chinese Medicines (PTCMs) for uncomplicated acute lower respiratory tract infections (ALRTIs) in adults with the existing evidence using results of a systematic review of randomized controlled trials (RCTs). A systematic review on RCTs and a systematic review of current guidelines on orally taken PTCMs for uncomplicated ALRTIs were performed. PubMed, Cochrane Library, EMBASE and four Chinese databases were searched from inception to September 2016 for RCTs testing orally taken PTCMs for uncomplicated ALRTIs (excluding pneumonia). Two reviewers independently screened each study, extracted study data, and assessed risk of bias. Disagreements were resolved through discussion or by consultation with a third reviewer. Clinical practice guidelines for uncomplicated ALRTIs containing PTCM recommendations were identified and quality appraised. The quality of pooled evidence of the RCTs and the guidelines was assessed with GRADE and AGREE II respectively. The consistency of the evidence base in RCTs and the guideline recommendations were then compared. For the systematic review of RCTs, 4810 papers were identified, among which 29 RCTs (5093 patients) were included in the review. PTCMs compared to placebo increased the effective treatment rate of cough (3 trials, 949 patients, risk ratio (RR) 2.50, 1.16 to 5.43; low certainty); improved assessment of global health (3 trials, 948 patients, RR 1.70, 1.44 to 2.01; low certainty); and increased the effective rate of specific symptom relief (1 trial, 478 patients, RR 4.01, 2.76 to 5.81; moderate certainty). 21 trials (3432 patients) compared effects of different PTCMs. For the guideline evaluation, 29 PTCMs were recommended for the use of uncomplicated ALRTIs, of which27 had no supportive evidence from RCTs. The evidence base of PTCMs for uncomplicated ALRTIs is weak and the guideline recommendations were based on almost no clinical trial evidence. Rigorous clinical research is urgently needed to inform the clinical use of these herbal medicines. Further training in evidence-based medicine methods for Traditional Chinese Medicine guideline developers is essential.
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