To investigate the molecular mechanism of hydroxycamptothecin (HCPT)-mediated anti-hepatic fibrosis by evaluting its effects on expression of tumor growth factor-beta 1 (TGFb1), alpha-smooth muscle actin (a-SMA) and collagen I (Col I) in hepatic satellite cells (HSCs). Cultured HSCs were treated with different concentrations of HCPT: low-dose group, 0.25 mg/L; middle-dose group, 0.5 mg/L; high-dose group, 0.75 mg/L; and control group, 0 mg/L. Cell proliferation was assessed by the MTT assay. The mRNA expressions of TGFb1, a-SMA and Col I were determined by reverse transcription-polymerase chain reaction. The protein expressions of TGFb1 and a-SMA were detected by Western blot. The content of Col I in the cultured HSCs' supernatant was measured by enzyme-linked immunosorbent assay. The MTT absorbance values of the low-dose group (0.631+/-0.074), middle-dose group (0.469+/- 0.012) and high-dose group (0.204+/- 0.001) were significantly lower than that of the control group (0.793+/-0.098; F = 82.86, P less than 0.01). Compared with the control group, the HCPT-treated groups showed significantly down-regulated gene expressions of TGFb1 (control: 0.716+/-0.064 vs. low: 0.611+/-0.040, middle: 0.510+/-0.014, high: 0.403+/-0.026), a-SMA (control: 0.696+/-0.075 vs. low: 0.579+/-0.037, middle: 0.470+/-0.024, high: 0.299+/-0.017), and Col I (control: 1.019+/-0.056 vs. low: 0.835+/-0.022, middle: 0.696+/-0.055, high: 0.322+/-0.104) (all, P less than 0.01). Meanwhile, HCPT-treated HSCs showed significantly reduced protein expressions of TGFb1 (control: 0.872+/-0.053 vs. low: 0.654+/-0.047, middle: 0.545+/-0.042, high: 0.436+/-0.039) and a-SMA (control: 0.858+/-0.050 vs. low: 0.620+/-0.045, middle: 0.525+/-0.042, high: 0.434+/-0.052) (all, P less than 0.01). The Col I levels secreted by HSCs were significantly lower in the HCPT-treated groups (low: 168.367+/-16.453 ng/ml; middle: 141.284+/-11.731 ng/ml; high: 132.910+/-10.048 ng/ml) than in the control group (188.733 +/-18.299 ng/ml) (all, P less than 0.01). The mechanism of HCPT-mediated anti-hepatic fibrosis may involve down-regulation of TGFb1 expression to inhibit HSC proliferation and activation, as well as reduction of Col I synthesis and secretion.
Actins ; metabolism ; Animals ; Camptothecin ; analogs & derivatives ; pharmacology ; Cell Proliferation ; Cells, Cultured ; Collagen Type I ; metabolism ; Hepatic Stellate Cells ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

Objective To determine if preventive antibiotics is effective in stroke associated pneumonia in patients with acute stroke.Methods Medline (January 1950 to January 2017),EMBASE (January 1974 to January 2017),Cochrane Library (January 2009 to January 2017),CNKI (January 1979 to January 2017)and Wanfang data (January 1998 to January 2017) were searched for randomized controlled trial comparing preventive antibiotics with placebo/blank controls for stroke associated pneumonia in patients with acute stroke.The included studies were screened out strictly based on the criterion of inclusion and exclusion.The quality of included studies was evaluated and the data were extracted by two researchers independently.RevMan 5.1 was used for Meta analysis.Results A total of 4 studies involving 3894 patients were included.The results of Meta-analysis indicated that there was no significant difference in the incidence of stroke associated pneumonia between preventive antibiotics and control groups (OR=0.96,95％CI:0.72-1.29,P=0.810);and there were no statistically significant differences in mortality (OR=1.05,95％CI:0.88-1.25,P=0.570) and good outcome (modified Rankin scale ≤ 2,OR=1.02,95％CI:0.89-1.17,P=0.780).There were no serious adverse reactions related to the studied drugs in 4 studies.Conclusion Preventive antibiotics could neither reduce the incidence of stroke associated pneumonia nor decrease the mortality or improve the proportion of good outcome.

OBJECTIVETo assess the feasibility, safety and effectiveness of video-assisted thoracoscopic sympathectomy (VATS) for the treatment of congenital long QT syndrome.

METHODSUnder general anaesthesia, pleural cavity was entered via two or three small incisions in the left intercostal space. The left thoracic sympathetic chain was identified and resected from T2 approximately T5. The lower one at the third of the left stellate ganglion was also resected.

RESULTSVATS resulted in a significant shortening in corrected QT intervals in three patients. The average QT interval of the four patients was 537.5 ms before VATS and 512.5 ms after VATS. The heart rate of the patients remained unchanged. There were no major peri-operative complications apart from mild ptosis of the left upper eyelid in one patient who recovered in the following days. The syndrome recurred in one patient in syncopal events in four months after VATS.

CONCLUSIONVATS is a safe as well as an effective technique for the treatment of congenital long QT syndromes.

Adult ; Child ; Female ; Humans ; Long QT Syndrome ; congenital ; surgery ; Male ; Sympathectomy ; methods ; Thoracic Surgery, Video-Assisted ; methods

Aim To investigate the effect of lactate dehydrogenase inhibitor on LPS/D-Gal-induced acute liver injury in mice. Methods BALB/ C mice were divided into four groups:solvent control group, lactate dehydrogenase inhibitor NHI-2 group, lipopolysaccharide(LPS)/ D-galactosamine(D-Gal)group and LPS/D-Gal+NHI-2 group. To induce acute liver injury, mice were injected intraperitoneally with LPS(10 μg·kg-1)and D-Gal(700 mg·kg-1), NHI-2 was intraperitoneally injected 30 min before LPS/D-Gal exposure. Liver tissue and serum were harvested 1.5 or 6 h after LPS/D-Gal exposure, serum lactate, serum aspartate aminotransferase(ALT), serum alanine aminotransferase(AST), serum tumor necrosis factor alpha(TNF-α)liver malondialdehyde(MDA)and liver caspase-3/8/9 levels were determined. HE staining was used to evaluate the degree of liver injury. TUNEL staining was used to evaluate hepatocyte apoptosis. Survival curve was used to record survival situation of tested mice. Results Serum lactate level of model mice was significantly reduced after treatment with NHI-2. Compared with LPS/D-Gal group, level of serum TNF-α showed no significant difference, but serum ALT and AST level of LPS/D-Gal+NHI-2 group significantly decreased, injury of liver structure was remarkably attenuated, level of MDA and activity of caspase-3/8/9 in liver were significantly down-regulated, and the number of TUNEL-positive cells was significantly reduced. Treatment with NHI-2 also significantly improved the survival rate of LPS/D-Gal-insulted mice. Conclusion Lactate dehydrogenase inhibitor alleviates LPS/D-Gal-induced acute liver injury in mice.

BACKGROUNDSARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper.

METHODSFull or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods.

RESULTSThere were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals.

CONCLUSIONThe results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.

Evolution, Molecular ; Genome, Viral ; Genotype ; Phylogeny ; Point Mutation ; SARS Virus ; genetics

Objective: To examine the impact of metabolic syndrome (MS) on the clinicopathological characteristics and prognosis of patients with colorectal cancer (CRC). Methods: The clinical data of 650 patients with CRC admitted in Shanxi Provincial Cancer Hospital between January 2010 and December 2011 were retrospectively analyzed. Among 650 patients there were 190 cases complicated with MS (MS group) and 460 cases without MS (non-MS group), the clinicopathological features and prognosis were compared between two groups. Results: The serum insulin and insulin-like growth factor-1 (IGF-1) levels in MS group were significantly higher than those in non-MS group [(9.2±4.7) vs.(6.8±4.7)μIU/L, t=8.88, P<0.01 and (200.2±44.1) vs.(136.7±63.2)mg/L,t=12.63, P<0.01]. The proportions of stage T₃ and T₄ cancer, extra-regional lymph node metastasis (ELN), and TNM stage Ⅲ and Ⅳ patients in MS group were significantly higher than those in non-MS group [(83.2% (158/190) vs. 72.6% (334/460), χ²=8.19, P=0.04; 9.5% (18/190) vs. 4.8%(22/460),χ²=8.61, P=0.04; 56.3% (107/190) vs. 45.2%(208/460), χ²=8.22, P=0.04, respectively]. The 5-year disease-free survival (DFS) in MS group was significantly lower than that in non-MS group [57.9%(99/171)vs. 66.1%(279/422), P<0.01]. Multivariate analysis indicated that MS(HR=1.623, 95%CI:1.511-1.963, P=0.03), IGF(HR=1.382, 95%CI:1.031-1.765, P=0.02) and, ELN(HR=4.270, 95%CI:2.177-7.463, P<0.01)were independent factors affecting the prognosis of CRC patients. Conclusion Metabolic syndrome is one of the risk factors affecting the prognosis of CRC patients.