Modified rubber band ligation for treatment of grade II/III hemorrhoids: clinical efficacy and safety evaluation-a retrospective study.

BACKGROUND: Massive, delayed bleeding (DB) is the most common major complication of Rubber Band Ligation (RBL) for internal hemorrhoids caused by premature band slippage. In this study we modified conventional RBL to prevent early rubber band slippage and evaluated its clinical efficacy and safety. METHODS: Study participants were consecutive patients with grade II or III internal hemorrhoids treated with RBL at Ningbo Medical Center of Lihuili Hospital from January 2019 to December 2020. Postoperative minor complications such as pain, swelling, anal edema, prolapse recurrence and major complications like DB were retrospectively reviewed. RESULTS: A total of 274 patients were enrolled, including 149 patients treated with modified RBL and 125 treated with conventional RBL. There was no statistically significant difference between the two groups at baseline. Five cases of postoperative DB have been observed in the conventional RBL group, compared to none in the modified ones, with a significant difference (P < 0.05). Within three months after surgery, 8 cases in the modified RBL group experienced a recurrence rate of 5.4%, whereas 17 patients in the conventional RBL group experienced a recurrence rate of 13.6%. The difference was statistically significant (P < 0.05). The VAS score, edema, and incidence of sensation of prolapse between the two groups were not significantly different at 3 and 7 days after surgery (P < 0.05). There were also no significant differences in HDSS and SHS scores between the two groups after surgery (P > 0.05). CONCLUSION: Modified RBL may be associated with a lower rate of complications, especially with lower DB rate in comparison with standard RBL. Further studies in larger samples and different design are necessary to confirm these results.

For colorectal cancer patients with type II diabetes, could metformin improve the survival rate? A meta-analysis.

OBJECTIVE: Current research is controversial about whether metformin can improve the survival rate of patients with colon cancer. Therefore, we conducted a meta-analysis to identify the association between metformin and the survival rate of colorectal cancer (CRC) patients with type II diabetes. METHODS: We conducted a search in databases including Pubmed, EMBASE and Cochrane Library. All articles were published in the last decade, and the quality of each study was evaluated by the Newcastle-Ottawa Scale. Odds ratios (ORs) and its corresponding 95% confidence intervals (CIs) for each study were calculated and summary relative risk estimates with corresponding 95% CIs were generated using the random-effects model. Heterogeneity and publication bias were assessed. RESULTS: Ten articles were included in this meta-analysis. The included articles were all cohort studies. In a pooled analysis of all studies, metformin using was associated with increased overall survival (OS) rate (OR, 0.54; 95% CI, 0.47 to 0.63) and cancer-specific survival (CS) rate (OR 0.59; 95% CI 0.43 to 0.82) of CRC patients with diabetes. We found that the effect of metformin is associated with geographical region through subgroup meta-analysis. CONCLUSIONS: Metformin using was associated with an increased OS rate and CS rate of colorectal cancer.

A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway.

PURPOSE: Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 shows similar activities in GC has not been examined. MATERIALS AND METHODS: Cell proliferation assay, colony-forming assay, flow cytometric analysis, wound healing assay, and Transwell invasion assay were performed to examine the effects of CL-6 on proliferation, apoptosis, migration, and invasion on human AGS and MGC-803 cell lines. Western blot was used to evaluate protein levels of Bax, Bcl-2, YAP, p-YAP, and Lats, and gene expression was measured by real-time quantitative PCR (RT-qPCR). RESULTS: CL-6 dose dependently reduced proliferation, increased apoptosis, and inhibited the migration and invasion abilities of AGS and MGC-803 cells. CL-6 also increased levels of pro-apoptotic protein Bax, decreased levels of antiapoptotic protein Bcl-2, and increased the Bax/Bcl-2 ratio. CL-6 treatment also inhibited YAP and YAP protein and mRNA expression, while it induced the expression of Lats and p-YAP (Ser127). CONCLUSION: CL-6 induces apoptosis of GC cells by activating the Hippo-YAP signaling pathway. These results indicate the therapeutic potential of the novel curcumin derivative CL-6 in GC.

Inhibitory effect of isavuconazole, ketoconazole, and voriconazole on the pharmacokinetics of methadone in vivo and in vitro.

The aim of this study was to investigate the possible effect of orally administered isavuconazole, ketoconazole, or voriconazole on the pharmacokinetics of methadone in rats. Twenty Sprague-Dawley (SD) rats were divided randomly into four groups: Group A (control), group B (5 mg/kg isavuconazole), group C (5 mg/kg ketoconazole), and group D (5 mg/kg voriconazole). A single dose of methadone was administrated half an hour later. Methadone in plasma concentrations and its metabolite EDDP in microsomes were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS), and pharmacokinetic parameters were calculated by DAS version 3.0. The Cmax of methadone in groups C and D increased to 2.7-fold and 5-fold, respectively. While AUC increased in three groups and group D increased the most. Also, isavuconazole, ketoconazole, and voriconazole showed inhibitory effect on human and rat microsomes. The inhibition ratios of isavuconazole, ketoconazole, and voriconazole in rat liver microsome were 97.87%, 96.74% and 78.9%, respectively (p < 0.01), while in human liver microsome, inhibition ratios were 86.97%, 96.46%, and 53.11%, respectively. And the IC50 for inhibition activity of isavuconazole, ketoconazole, and voriconazole in rat microsomes were 7.76 µM, 8.33 µM, and 4.45 µM, respectively. Our study indicated that taking methadone combine with ketoconazole, isavuconazole, or voriconazole could reduce the metabolism rate of methadone and prolong the pharmacological effects in vivo and in vitro.

The characteristics and pivotal roles of triggering receptor expressed on myeloid cells-1 in autoimmune diseases.

Triggering receptor expressed on myeloid cells-1 (TREM-1) engagement can directly trigger inflammation or amplify an inflammatory response by synergizing with TLRs or NLRs. Autoimmune diseases are a family of chronic systemic inflammatory disorders. The pivotal role of TREM-1 in inflammation makes it important to explore its immunological effects in autoimmune diseases. In this review, we summarize the structural and functional characteristics of TREM-1. Particularly, we discuss recent findings on TREM-1 pathway regulation in various autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), type 1 diabetes (T1D), and psoriasis. This receptor may potentially be manipulated to alter the inflammatory response to chronic inflammation and possible therapies are explored in this review.

Drug-drug interaction of losartan and glimepiride metabolism by recombinant microsome CYP2C9*1, 2C9*3, 2C9*13, and 2C9*16 in vitro.

OBJECTIVE: Co-administration of anti-hypertension and anti-diabetic drugs is common in clinical settings. METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). RESULTS: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 ± 0.055 µM, 0.424 ± 0.032 µM, 2.557 ± 0.058 µM, and 0.667 ± 0.039 µM, respectively. The inhibitory effect of glimepiride on losartan metabolism by CYP2C9*13 was marginal. The apparent Ki value of glimepiride with CYP2C9*3 (0.0416 ± 0.0059 µM) was significantly lower than with CYP2C9*1 (0.1476 ± 0.0219 µM) and CYP2C9*16 (0.2671 ± 0.0456 µM). On the other hand, losartan weakly inhibited the hydroxylation of glimepiride by P450 2C9 enzymes competitively. The potencies for inhibition of glimepiride hydroxylation were determined to be CYP2C9*1~CYP2C9*3~CYP2C9*16 > CYP2C9*13 by 4 µM losartan. No significant inhibition was observed when 0.5 µM losartan was used. CONCLUSIONS: Given these results, the potential inhibition of losartan metabolism by CYP2C9*3, CYP2C9*13, and CYP2C9*16 in vivo by glimepiride deserves further investigation. These results may provide valuable information for optimizing the anti-hypertension efficacy of losartan when glimepiride is co-administered to patients.