Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients.

Tigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is unclear. In this study, we found that tigecycline cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT), and D-dimer. In addition, through functional studies, we found that tigecycline inhibit platelet adhesion and aggregation, and the coagulation function of patients gradually recover after discontinuation. Gene sequencing results suggested that tigecycline significantly regulate the expression of genes related to platelet function pathways and increase the incidence of single nucleotide polymorphisms and the number of alternative splices in the Chinese hamster ovary (CHO) cells treated with tigecycline. An abnormal function and low numbers of platelets are common in patients with hematological malignancies. Our study can explain the mechanism of abnormal coagulation caused by tigecycline. Additionally, doctors who apply tigecycline to cure infections in tumor patients should be warned.

Hemolymphangioma with multiple hemangiomas in liver of elderly woman with history of gynecological malignancy: A case report.

BACKGROUND: Hepatic hemolymphangioma is an extremely rare benign congenital malformation composed of cystically dilated lymphatic and blood vessels, and they have nonspecific clinical symptoms and laboratory results. In this study, hepatic hemolymphangioma with multiple hemangiomas in an elderly woman was initially reported and analyzed. CASE SUMMARY: A 61-year-old female patient, with a history of hysterectomy and bilateral adnexectomy, was referred to the hepatobiliary surgery department with the complaint of multiple hepatic hemangiomas that had been diagnosed 2 years prior in a preoperative contrast-enhanced computed tomography (CECT) examination. Upon entering our hospital, no abnormal physical examination and laboratory data were found. The latest CECT revealed a new 7.0 cm × 6.2 cm cystic-solid lesion with multiple internal divisions in segment II of the liver, with delayed CECT enhancement characteristics that presented as solid parts with internal division. On the positron emission tomography (PET)/CT, no significant uptake of 18F-fluorodeoxyglucse was observed. Finally, hepatic hemolymphangioma was confirmed based on the pathological and immunohistochemical results after surgery. At 1-year follow-up, her posthepatectomy evaluation was uneventful, and she had recovered full activity. In addition, no postoperative recurrent or residual lesion was found on CECT imaging. CONCLUSION: Hepatic hemolymphangioma with multiple hemangiomas was reported and observed by CECT and PET/CT imaging.

Evaluation of microRNAs as potential biomarkers in circulating HPV-DNA-positive non-small cell lung cancer patients.

The aim of the present study was to identify the potential risk of circulating-HPV-DNA in non-small cell lung cancer (NSCLC) and to analyze abnormally expressed miRNAs in circulating HPV-DNA-positive NSCLC. HPV universal primers were used to detect the presence of HPV-DNA in the peripheral blood of 100 patients with NSCLC. The relationship between circulating-HPV-DNA and NSCLC patients characteristics was analyzed. Then, eight differentially expressed miRNAs in NSCLC were screened based on the TCGA database. The levels of miRNAs in circulating HPV-DNA-positive NSCLC patients were detected by real-time quantitative PCR. ROC curves were generated to evaluate the diagnostic performance. Circulating-HPV-DNA was found in 16 patients. The proportion of HPV-DNA-positive patients with poorly differentiated NSCLC, advanced lung cancer and lymph node metastasis was higher than that of HPV-DNA-negative patients. The levels of miR-183, miR-210 and miR-182 were significantly higher and miR-144 was significantly lower in HPV-DNA-positive NSCLC than those in HPV-DNA-negative NSCLC patients. When using a single miRNA to identify circulating HPV-DNA-positive NSCLC patients, miR-210 had a higher area under the ROC curve (AUC) than other miRNAs, and its sensitivity and specificity were also higher. In addition, the combination of two miRNAs was more effective than a single miRNA. Among them, miR-210+ miR-144 had the highest AUC value and showed the best prediction performance. Circulating-HPV-DNA may serve as a risk factor in NSCLC. Plasma miR-183, miR-210, miR-182 and miR-144 can be used as reliable biomarkers to identify circulating HPV-DNA-positive NSCLC.

Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury.

This study is aimed at investigating the association between the electroacupuncture (EA) pretreatment-induced protective effect against early cerebral ischemic injury and autophagy. EA pretreatment can protect cerebral ischemic and reperfusion injuries, but whether the attenuation of early cerebral ischemic injury by EA pretreatment was associated with autophagy is not yet clear. This study used the middle cerebral artery occlusion model to monitor the process of ischemic injury. For rats in the EA pretreatment group, EA pretreatment was conducted at Baihui acupoint before ischemia for 30 min for 5 consecutive days. The results suggested that EA pretreatment significantly increased the expression of autophagy in the cerebral cortical area on the ischemic side of rats. But the EA pretreatment-induced protective effects on the brain could be reversed by the specific inhibitor 3-methyladenine of autophagy. Additionally, the Pearson correlation analysis indicated that the impact of EA pretreatment on p-mTOR (2481) was negatively correlated with its impact on autophagy. In conclusion, the mechanism of EA pretreatment at Baihui acupoint against cerebral ischemic injury is mainly associated with the upregulation of autophagy expression, and its regulation of autophagy may depend on mTOR-mediated signaling pathways.

Down-regulation of SENCR promotes smooth muscle cells proliferation and migration in db/db mice through up-regulation of FoxO1 and TRPC6.

BACKGROUND: The inappropriate proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in the atherosclerotic process. SENCR was reported to be associated with cell migration in human smooth muscle cells. However, the regulation role of SENCR in SMCs is still not fully understood. METHODS: qRT-PCR and Western blotting were performed to detect the mRNA and protein levels of SENCR, FOXO1 and TRPC6 in SMCs of db/db mice and SMCs exposed to high glucose. The regulation of SENCR on the expression of FoxO1 and TRPC6 were examined with luciferase report assays. Furthermore, we investigated the effect of SENCR on VSMCs proliferation and migration using MTT assay and cell migration assay, respectively. RESULTS: Here, we found that SENCR was down-regulated in db/db mice and in SMCs exposed to high glucose. According to the result of luciferase assays, it was shown that SMCs knockdown enhanced the expression of FoxO1 and FoxO1 overexpression increased the expression of TRPC6. In addition, qRT-PCR revealed that SENCR overexpression reversed the effect of high glucose on mouse VSMCs proliferation and migration. CONCLUSION: In this study, our data indicated that down-regulation of SENCR promoted smooth muscle cells proliferation and migration in db/db mice through up-regulation of FoxO1 and TRPC6.