[Clinical analysis of 2 820 cases of drug-induced liver injury].

Objective: To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment. Methods: A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed. Results: Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ(2) = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ(2) = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant (H = 61.300, P < 0.001). Conclusion: In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

Low expression of lncRNA MGC27345 is associated with poor prognosis in gastric cancer patients.

OBJECTIVE: A series of evidence showed that long non-coding RNAs (lncRNAs) play an essential regulatory role in the occurrence and development of human cancer, and is a potential biological target in the fight against cancer. PATIENTS AND METHODS: In this research, we investigated the role of lncRNA MGC27345 in gastric cancer (GC), the expression of MGC27345 in GC was detected by quantitative Real-Time PCR in GC tissue from 235 patients. The correlations between MGC27345 expression and clinicopathological variables and survival were evaluated by the Chi-square test. Kaplan-Meier method (log-rank test), univariate and multivariate Cox regression assays were carried out for the identification of the survival and independent risk factors for GC. RESULTS: MGC27345 expression levels were significantly decreased in GC tissues than in adjacent normal specimens. Lower expression of MGC27345 was found in advanced tumor stages. GC patients with low-expression of MGC27345 had a poorer overall survival compare to those with high-expression of MGC27345. Furthermore, MGC27345 was an independent protective prognosis factor in GC development. CONCLUSIONS: Our data indicated that MGC27345 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

MiR-141 promotes cell proliferation and invasion in non-small cell lung cancer by targeting KLF9.

OBJECTIVE: Non-small cell lung cancer is the cancer with the highest mortality rate in the whole world. MicroRNA-141 (miR-141) has been reported to be an abnormal expression in multiple tumors including in non-small cell lung cancer. The aim of this study was to verify the potential roles of miR-141 in non-small cell lung cancer and evaluate the effects on cell proliferative and invasive abilities. PATIENTS AND METHODS: MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were conducted to calculate the tissues and cell lines' proliferative and invasive abilities. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blotting were utilized to evaluate the mRNA and protein levels of specific genes. RESULTS: MiR-141 was significantly upregulated, while krüppel-like factor 9 (KLF9) downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. MiR-141 and KLF9 mRNA levels had a negative correlation in NSCLC tissues. The overexpression of miR-141 promoted the proliferation and invasion of A549 cells, while caused contrast results when knockdown miR-141. In addition, KLF9 was a direct target gene of miR-141 and KLF9 partially reversed the roles of miR-141 in A549 cells. MiR-141 promoted the proliferation and invasion by binding to KLF9 in NSCLC. CONCLUSIONS: MiR-141 promoted the proliferation and invasion by targeting the KLF9 in non-small cell lung cancer, and the newly identified miR-141/KLF9 axis provides novel insight into the pathogenesis of non-small cell lung cancer.

Synthesis and cytotoxic activity of 3-phenyl-2-thio-quinoxaline 1,4-dioxide derivatives in hypoxia and in normoxia.

A series of novel 3-phenyl-2-ethylthio/ethylsulfinyl/ethylsulfonyl/phenylthio/ phenylsulfonyl-quinoxaline 1,4-dioxide derivatives were synthesized and screened for their cytotoxicity in vitro on human leukaemia cell line HL-60, human esophagus cancer cell line ECA-109, human prostate cancer cell line PC-3, human gastric carcinoma cell line SGC-7901, and human breast cancer cell line MCF-7 in hypoxia and in normoxia. Half of tested compounds showed higher cytotoxic activity both in hypoxia and in normoxia. The mechanism of one potent compound, 67, in hypoxia showed that the mitochondria pathway is involved in the antitumor activity of this class of compounds.

Synergistic effects of DL111-IT combined with mifepristone on termination of early pregnancy in rhesus monkeys.

The objectives of this study were to determine the synergistic effects of DL111-IT in combination with mifepristone (RU486) on termination of early pregnancy in rhesus monkeys. Pregnancy was confirmed by tactile sensation of pregnant uterus via anus with finger and ultrasound examination. Pregnancy termination was obtained with vaginal bleeding and abortion materials including fetuses and placentae after treatment. With multiple doses of DL111-IT or RU486 given alone between d24 and d50 of gestation, pregnancy arrests were obtained in 40% (2/5) of monkeys treated with DL111-IT intramuscularly (im) (25 mg x kg(-1) x d(-1) x 3 days), in 20% (1/5) of monkeys treated with 9 mg x kg(-1) x d(-1) x 2 days, and 4.5 mg x kg(-1) on day 3 with RU486 intragastrically (ig). DL111-IT (25 mg x kg(-1) on day 1, im) in combination with RU486 (the same treatment as above) resulted in 100% (10/10) termination of pregnancy and uterine bleeding lasted 6.6 +/- 1.3 days. RU486 (as above treatment) in combination with misoprostal (Miso, 109 microg x kg(-1) on day 3, ig) showed 71.4% (5/7) termination of pregnancy, and uterine bleeding lasted 12.9 +/- 9.6 days. The synergistic effect of DL111-IT plus RU486 enhances termination of early pregnancy and significantly shortens the bleeding time than RU486 plus Miso does in rhesus monkeys.

Termination of early pregnancy in the mouse, rat and hamster with DL111-IT and RU486.

The effectiveness of DL111-IT and RU486 given alone and in combination for terminating early pregnancy was tested in the rat, mouse, and hamster. In the mouse and rat, the combination of RU486 and DL111-IT is much more effective in terminating pregnancy than either of the two compounds used alone (single or multiple treatment). A low-effective dose of DL111-IT in combination with a non-effective or a sub-effective dose of RU486, exerted additive or synergistic effects resulting in resorption of embryos and termination of pregnancy. The serum progesterone concentrations were significantly suppressed by these combinations when pregnancy was terminated. In the hamster, single treatment with DL111-IT plus RU486 exhibited a strong effect on interrupting early pregnancy. The ED50 of RU486 in combination of a non-effective dose of DL111-IT was decreased to 163-fold lower dose than RU486 given alone. It is concluded that in mouse, rat, and hamster, the synergistic action between DL111-IT and RU486 not only greatly enhances efficacy in terminating pregnancy but also reduces substantially the dose required to produce this effect.