Magnesium demethylcantharidate inhibits hepatocellular carcinoma cell invasion and metastasis via activation transcription factor FOXO1.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, develops rapidly and has a high mortality rate. Relapsed metastasis is the most important factor affecting prognosis and is also the main cause of death for patients with HCC. Cantharidin is a kind of folk medicine for malignant tumors in China. Because of its cytotoxicity, the application of cantharidin is very limited. Magnesium demethylcantharidate (MDC) is a derivative of cantharidin independently developed by our laboratory. Our results show that MDC has anticancer activity and exhibited lower toxicity than cantharidin. However, whether MDC affects the invasion and metastasis of HCC cells and the underlying molecular mechanisms remain obscure. Transwell and Matrigel assays showed that MDC could effectively inhibit the invasion and metastasis of the HCC cell lines SMMC-7721 and SK-Hep1 in a dose-dependent manner. Moreover, MDC significantly inhibited the expression of invasion and metastasis related proteins MMP-2 and MMP-9. In addition, our study found that MDC inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 by activating transcription factor FOXO1. Interestingly, the combination of MDC and sorafenib significantly inhibited the invasion and metastasis of HCC cell lines SMMC-7721 and SK-Hep1 compared with the single drug treatment via the activated transcription factor FOXO1. Our work revealed that MDC obviously inhibited the invasion and metastasis of HCC cells, and suggested that MDC could be a potential candidate molecule against the invasion and metastasis of HCC.

A Modified Pressure Dressing to Avoid Severe Bleeding After Circumcision With a Disposable Circumcision Suture Device and a Discussion on the Mechanism of Bleeding With the Disposable Circumcision Suture Device.

INTRODUCTION: A novel type of a disposable circumcision suture device (DCSD) has been proved to be effective and safe; however, a few cases of severe bleeding took place after circumcisions. AIM: To evaluate the effectiveness of a modified double-layer pressure dressing to avoid severe bleeding after circumcision with the DCSD, in our department in a prospective randomized controlled study, and discuss the mechanism of bleeding with DCSD. METHODS: Patients with redundant foreskin or phimosis were included between September 2018 and November 2019 and divided into 2 groups: In group A, the conventional pressure dressing was performed; in group B, an modified double-layer pressure dressing was performed. MAIN OUTCOME MEASURE: The main outcomes and complications (surgical time, incidence of glans ischemia, severe bleeding rate, infection rate, pain level, total cost, and overall satisfaction) were collected and analyzed. RESULTS: A total of 624 patients were recruited for this study. There was no difference in the average age and body mass index between 2 groups. No patient suffered obvious glans ischemia. In group B, lower pain level, lower incidences of severe bleeding, and better satisfaction were recorded. CONCLUSION: The mechanism of bleeding with the DCSD was discussed in this study, and the modified pressure dressing was proved effective, safe, and easy to perform. W Jiang, J-li Fu, W-l Guo, et al. A Modified Pressure Dressing to Avoid Severe Bleeding After Circumcision With a Disposable Circumcision Suture Device and a Discussion on the Mechanism of Bleeding With the Disposable Circumcision Suture Device. Sex Med 2021;9:100288.

Research Note: Epidemiological cutoff values and acquired resistance mechanisms of three veterinary antibiotics against Escherichia coli from chicken respiratory tract infections.

Florfenicol, apramycin, and danofloxacin are antibiotics approved only for veterinary use and that have good therapeutic effects on chicken respiratory infections caused by Escherichia coli. We established epidemiological cutoff values (ECV) for these antibiotics using 363 E. coli isolates from tracheal samples of chickens in 5 veterinary clinics in Guangdong Province, China. The minimum inhibitory concentrations (MIC) were determined using the agar dilution method as per Clinical and Laboratory Standards Institution guidelines. The ECV were then calculated using the statistical method and verified by normalized resistance interpretation and ECOFFinder software programs. The ECV of florfenicol, apramycin, and danofloxacin against E. coli were 16, 16, and 0.125 µg/mL, respectively. Susceptibility tests indicated that these isolates were resistant to florfenicol (66.7%), apramycin (22.3%), and danofloxacin (92.3%). Strains carrying floR were distributed in the range of MIC ≥32 µg/mL for florfenicol. Apramycin resistance was found in 77 strains (77/363, 21.1%), and isolates that carried aac(3)-IV were all in the range of MIC ≥512 µg/mL. Danofloxacin resistance was found in the range of MIC ≤0.125 µg/mL, but there were no mutations in the quinolone resistance-determining regions and plasmid-mediated quinolone resistance genes qnrA, qnrB, qnrC, qnrD, aac-(6')-Ib-cr, qep, and oqxB. The presence of the qnrS gene was verified in a few of the strains with an MIC of 0.06 µg/mL. The establishment of ECV was significant for monitoring of resistance development and therapy guidance.

The first isolation of Clostridium difficile RT078/ST11 from pigs in China.

We investigated the molecular characteristics and antimicrobial susceptibility of Clostridium difficile isolated from animals in China. We obtained 538 rectal swabs from pigs, chickens and ducks in 5 provinces during 2015 and 2016. C. difficile isolates were characterized by detection of toxin genes, multilocus sequence typing and ribotyping. And antimicrobial susceptibility testing was performed using the agar dilution method. Out of 538 samples, 44 (8.2%) were C. difficile positive with high prevalence in pigs (n = 31). Among these, 39 (88.6%) were toxigenic including 14 (31.8%) that were A+B+CDT+ and 13 (29.5%) A+B+. The remaining 12 (27.3%) were A-B+. We identified 7 ST types and 6 PCR ribotypes. The most predominant type was ST11/RT078 with toxin profile A+B+CDT+ and all were isolated from piglets with diarrhea. ST109 isolates possessed two different toxigenic profiles (A-B-CDT- and A-B+CDT-) and although it was not the most prevalent sequence type, but it was widely distributed between chickens, ducks and pigs in the 5 provinces. All C. difficile isolates were fully susceptible to vancomycin, metronidazole, fidaxomicin, amoxicillin/clavulanate and meropenem but retained resistance to 4 or 5 of the remaining antibiotics, especially cefotaxime, tetracycline, ciprofloxacin, cefoxitin. The RT078/ST11 isolates were simultaneously resistant to cefotaxime, tetracycline, cefoxitin, ciprofloxacin and imipenem. This is the first report of the molecular epidemiology of C. difficile isolated from food animals in China. We identified the epidemic strain RT078/ST11 as the predominate isolate among the animals we screened in our study.

Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

BACKGROUND AND AIM: Stroke-associated pneumonia (SAP) is a common complication in patients with acute ischemic stroke (AIS). This study explored the potential relationship between serum vitamin D levels and SAP. METHODS: This study recruited 863 consecutive AIS patients. In-hospital SAP was defined as a complication that occurred after stroke, during hospitalization, that was confirmed radiographically. Serum vitamin D levels were measured within 24 hrs of admission and the patients were divided into vitamin D sufficient (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L) groups. RESULTS: In this study, 102 (11.8%) patients were diagnosed with SAP. Compared to the patients without SAP, patients with SAP had significantly lower vitamin D levels (P = 0.023). The incidence of SAP was significantly higher in patients with vitamin D deficiency than in those with vitamin D insufficiency or sufficiency (21.2% vs 16.2% & 9.5%, P = 0.006). After adjusting for confounders, vitamin D deficiency and insufficiency were independently associated with SAP (OR = 3.034, 95% CI = 1.207-7.625, P = 0.018; OR = 1.921, 95% CI = 1.204-3.066, P = 0.006, respectively). In multiple-adjusted spline regression, vitamin D levels showed a linear association with the risk of SAP (P < 0.001 for linearity). CONCLUSION: Reduced vitamin D is a potential risk factor of in-hospital SAP, which can help clinicians identify high-risk SAP patients.

Epidemiology and clinical characteristics of patients with glaucoma: An analysis of hospital data between 2003 and 2012.

PURPOSE: To assess demographic and clinical characteristics of glaucoma patients in an Ophthalmologic Hospital of Jinan, China from 2003 to 2012. MATERIALS AND METHODS: Medical charts of patients with primary open-angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were reviewed. The main outcome measures of patients with glaucoma included basic demographic data (age at presentation, gender, and residence), clinical characteristics (admission date, intraocular pressure, and naked vision), and previous history (injury, cardiovascular disease, diabetes mellitus, hypertension, smoking, and alcohol consumption). RESULTS: Data from 1458 glaucoma patients were reviewed, of which PACG and SG patients accounted for 45.40% and 47.19%, respectively. The average age of all patients with glaucoma increased from 56.05 years in 2003 to 57.83 years in 2012, and the proportion of patients from rural areas rose from 46.43% to 59.13% during 10-year period. Female gender, cardiovascular disease, and hypertension were associated with PACG. POAG was related to smoking and alcohol consumption. There was positive correlation between SG and history of injury and diabetes mellitus. CONCLUSION: PACG and SG are the major types of glaucoma. Gender, injury, diabetes mellitus, cardiovascular disease, hypertension, smoking, and alcohol consumption were associated with different types of glaucoma.