Objective To analyze the effects of acute depletion of liver-specific insulin signaling on secretion of apolipoprotein B (apoB) and triglyceride (TG).Methods Based on Cre-LoxP principle,a promoter of hepatic tissue specific albumin gene was inserted into upstream of the cre recombinase gene.Albumin-Cre adenovirus (Ad-CRE) and GFP adenovirus (Ad-GFP) were amplified in 293A cells and purified before intravenous administration to mice.After adenovirus infection for 2 days,4 days and 6 days,blood samples from mice were collected and hepatic tissues were frozen.The secretion rates of hepatic newly synthesized apoB and very low density lipoprotein (VLDL)-TG were determined by injection of Triton WR-1339.The levels of plasma cholesterol (TC) and TG were measured.The expressions of insulin receptor and other lipoprotein metabolism related proteins in hepatic tissues were analyzed by Western blot.Results After 2 d,4 d and 6 d of the Ad-CRE injection into mice,insulin receptor expression was reduced by 30.50％ (P＜0.05),60.12％ (P＜ 0.01) and 99.54％ (P＜0.001),and VLDL-TG secretion rate was decreased by 20.43％ (P＜0.05),33.63％ (P＜0.05) and 44.21％ (P＜0.01),respectively.Expressions of sterol regulatory binding proteins 1,fatty acid synthase,and the related proteins of VLDL-formation were decreased,but there were no changes in hepatic secretion of apoB100 and hepatic lipids.The hepatic secretion of apoB48 was increased by 35.07％ (P＜0.05) 6 d after Ad-CRE injection.Conclusions Acute depletion of hepatic insulin receptor might reduce VLDL-TG secretion in manner of time-dependent,and increase the assembly and secretion of smaller apoB-containing lipoproteins in mice liver,which is probably associated with decreased lipogenesis.

Objective To investigate the influence of selective HGF/cMet inhibitor-NK-4 against colon(cancer) and reveal the potential signaling pathway mechanism of NK-4 effect on colon cancer cell.Methods LoVo colon cancer cells were treated with NK-4(a selective inhibitor of c-Met phosphorylation)at different times.MTT assay and flow cytometry were used to measure cell proliferation and apoptosis.The expression of c-Met,p-c-Met,MEK2,p-ERK and C-myc were measured by Western blot.Results In NK-4-treated group, cells proliferation were inhibited and apoptosis induced in a dose-dependent manner,and resulted in(significant) downregulation of p-c-Met and MEK2/ERK pathway-related protein.The effect of HGF/on LoVo was the opposite.The ratios of p-c-Met,MEK2,p-ERK and C-myc expression between blank group and the NK-4(1?g/mL)-treated for 24h group were 2.58,1.89,1.67 and 2.21(P

OBJECTIVE: To study the role of estrogen receptor (ER) and progesterone receptor (PR) in the formation of cholesterol calculus and investigate the effects of Shengqing Capsule (SQC), a Chinese patent herbal medicine with the function of soothing liver and draining gallbladder, on ER and PR expressions. METHODS: A total of 80 female guinea pigs were divided into normal control group, untreated group, ursodeoxycholic acid group (UDCA group) and SQC group. The cholesterol gallstone was induced by feeding the guinea pigs with high-fat lithogenic diet. SQC and UDCA were separately administered to the guinea pigs in the SQC group and UDCA group. After 7-week administration, all the animals were sacrificed to calculate the incidence of calculus formation and detect the expressions the ER and PR in the epithelial tissue of gallbladder by immunohistochemical method. RESULTS: Gallstone was cholesterol calculus detected by infrared spectrum. The incidence of calculus formation in the SQC group (27.78%) was significantly lower than that in the untreated group (81.25%) (X(2)=9.721 5, P=0.001 8). On the basis of Reiner standard, the expression distribution of ER and PR increased gradually from the normal control group through the SQC group and UDCA group to the untreated group. Except for the former two groups and the latter two groups, the differences between the other groups and UDCA group were statistically significant (P<0.05). Besides, the differences of positive expression rates between groups were statistically significant (P<0.05). CONCLUSION: Increased expressions of ER and PR are closely related to the formation of cholesterol stone. And Shengqing Capsule can down-regulate the expressions of ER and PR.

Objective To assess the value of magnetic resonance (MR) imaging (MRI) in depicting the depth of myometrial infiltration, cervical invasion and lymph nodes metastasis in patients with endometrial carcinoma compared with surgicopathologic findings. Methods Thirty-eight patients with endometrial carcinoma diagnosed by pathology were inspected by MRI in this prospective study. MR images were analyzed by two radiologists to report the depth of myometrial infiltration, infiltration of the uterine cervix and lymph nodes metastasis. MRI and surgicopathologic staging of endometrial carcinoma were based on FICO classification. MRI findings were compared with surgicopathologic findings. Results The overall accuracy rate of MRI in staging endometrial carcinoma was 77.1 %. The results of Kappa statistics showed that there was strong consistency between MRI and surgicopathology for staging of endometrial carcinoma (k= 0.677). Respective diagnostic accuracy, sensitivity, specificity, negative and positive predictive values in assessing myometrial infiltration(>l/2 depth) were 91.4 %, 83.3 %, 95.6 %, 91.7 % and 90.9 %; those in cervical infiltration were 94.2 %, 80.0 %, 96.7 %, 96.7 %, and 80.0 %; and those in lymph node assessment were 96.2 %, 66.7 %, 100 %, 95.8 % and 100 %. Conclusion MRI is highly accurate in depicting the depth of myometrial infiltration, cervical invasion, lymph nodes metastasis and local-regional staging of endometrial carcinoma.

Objective:To evaluate the clinical outcomes of patients after intensity modulated radiation therapy (IMRT) for hepatocellu-lar carcinoma (HCC) with portal vein tumor thrombosis (PVTT) or inferior vena cava tumor thrombosis (IVTT). Methods:A registry data-base of 41 patients treated with IMRT for HCC with PVTT or IVTT in Radiotherapy Center of No.3 Hospital of Beijing Chinese People Armed Police Forces between January 2013 and May 2015 were analyzed retrospectively. The biological effective dose of radiation was ranged 48-94Gy. Short-term effects and prospective efficacy were observed. Log-rank test, Cox regression were used for survival analysis and prognostic factor identification. Results: Grade 2 or higher level gastrointestinal reaction was observed in 12 patients (29.3%). Hematological toxicity was observed in 11 patients (26.8%), and radiation-induced liver disease was observed in 6 patients (14.6%). We found that 29.3%of patients achieved a complete response and 31.7%of patients achieved a partial response. The stable and progressive disease rates were 39.0%and 0.0%, respectively. Median patient survival was 11 months, and the 1-year survival rate was 34.1%. The significant independent variables associated with the overall survival included Child-Pugh grade, AFP test, and CHE lev-el. Conclusion:IMRT is a safe and effective treatment for PVTT or IVTT in patients with HCC.

BACKGROUND:The currently published literatures about Tuina manipulation for lumbar disc herniation include clinical observations, retrospective study and summary of clinical experience, which have shortcomings in the study design, choice of cases and outcome measures. Reviews may enrol randomized and intended references, and has no analysis or evaluation on the quality of involved literatures, leading to the bias and subjective views.
OBJECTIVE:To research the application laws of Tuina manipulation for treating lumbar disc herniation through literature analysis within 10 years.
METHODS:The key words of“lumbar disc herniation, traditional Chinese medicine, Tuina, manipulation, massage, rehabilitation, poking channels, point pressing, palpating pressing, and finger pressing”in Chinese were used to search the literature about Tuina manipulation in treatment of lumbar disc herniation within recent 10 years published in the Wanfang database, Vip database and CNKI database. The top 20 manipulations of Tuina for lumbar disc herniation were and statistical analyzed with hierarchical clustering statistical method.
RESULTS AND CONCLUSION:The hierarchical clustering analysis results showed that, Tuina manipulations for lumbar disc herniation are as fol ows:(1) manipulations acted on soft tissue, including rol ing, holding, pushing and pressing;(2) manipulations acted on acupuncture point, including Urinary Bladder Meridian of Foot-Taiyang acupuncture points (Shengshu, Dachangshu, Guanyuanshu, Zhibian, Chengfu, Weizhong, Chengshan and Kunlun), Gal Bladder Meridian of Foot-Shaoyang acupuncture points (Huantiao and Yanglingquan), Yaoyangguan point in Du Meridian, Zusanli point in Stomach Meridian of Foot-Yangming, and tender points;(3) manipulations acted on human bones and joints, including waist inclined pul method, waist back-stretching method, pelvic traction method and straight-leg raising method. The findings indicate that the potential application laws of Tuina manipulation for treating lumbar disc herniation are given priority to pressing acupuncture points (Urinary Bladder Meridian of Foot-Taiyang acupuncture point, Gal Bladder Meridian of Foot-Shaoyang acupuncture point, Du Meridian, Stomach Meridian of Foot-Yangming acupuncture point and tender points), at the same time companied with manipulations acted on soft tissue (rol ing, holding, pushing spinal method), and bones and joints (waist inclined pul method, waist back-stretching method, pelvic traction method and straight-leg raising method).

OBJECTIVE: To study the mechanisms of Shengqing Capsules, a compound Chinese herbal medicine for dispersing stagnated liver qi and promoting bile flow, in prevention and treatment of pigment gallstone. METHODS: Liver cells from guinea pigs with pigment gallstone were primarily cultured in vitro. The serums containing different concentrations of Shengqing Capsules were prepared by serum pharmacological method. The primary cultured hepatocytes with excessive expression of nuclear factor-kappaB (NF-kappaB) were stimulated with lipopolysaccharides (LPS) and the effects of the drug-containing serums on the NF-kappaB expression were detected by Western-blotting. RESULTS: Shengqing Capsules down-regulated the NF-kappaB expression increased by LPS stimulation. The effect is dose-dependent. CONCLUSION: Shengqing Capsules can down-regulate the NF-kappaB expression increased by LPS stimulation. It may be one of the important mechanisms of this Chinese herbal medicine in prevention and treatment for pigment gallstone formation and the inflammatory reaction in biliary tract.

Objective To explore the clinical application value of left atrial function with feature tracking cardiac magnetic resonance imaging (FT-CMR) by evaluating preliminarily left atrial strain and strain rate in patients with atrial fibrillation. Methods Thirty patients with paroxysmal atrial fibrillation, thirty patients with persistent atrial fibrillation and twenty-two healthy subjects were enrolled. All the subjects underwent cardiac magnetic resonance imaging with the real steady-state free precession(SSFP) sequence. FT-CMR parameters included left atrial strain and strain rate parameters, left atrial volume and function parameters were detected by using offline cardiovascular analysis software, respectively. Left atrial strain and strain rate parameters included left atrial total strain(Εs), passive strain(Εe), active strain(Εa), peak positive strain rate(SRs), peak early negative strain rate(SRe)and peak late negative strain rate(SRa). Volume and function parameters included maximum of left atrial volume(LAVmax), minimum of left atrial volume(LAVmin), total left atrial emptying fraction(LATEF), passive left atrial emptying fraction(LAPEF)and active left atrial emptying fraction(LAAEF). The differences in the general data among the paroxysmal atrial fibrillation group, the persistent atrial fibrillation group and the control group were compared by usingχ2 test or ANOVA analysis. The differences in all parameters between the atrial fibrillation group and the control group, the paroxysmal atrial fibrillation group and the persistent atrial fibrillation group were compared by using independent t test. Left atrial strain and strain rate parameters on an intra-observer and inter-observer were determined by intraclass correlation coefficient(ICC)analyses. Results Compared to control group, LAVmax and LAVmin in atrial fibrillation group were significantly increased(t=9.737,7.889,P<0.001);The LATEF and LAPEF had no significant difference, the LAAEF in two groups had statistically significant difference(t=-4.762,P<0.001).The absolute value of Es, Ee, Ea, SRs, SRe, SRa in atrial fibrillation group were significantly reduced than in control group(t=-7.732,-6.610,-6.493,-7.546, 6.864, 5.917,P<0.001). Compared with paroxysmal atrial fibrillation group, LAVmax and LAVmin in persistent atrial fibrillation group were increased obviously, LATEF and LAPEF were significantly decreased, and the differences were statistically significant(t=-4.575,-5.524, 4.002, 4.028,P<0.001).The LAAEF in two groups had no statistically significant difference. Compared with strain and strain rate in two groups, absolute value of Es, Ee, Ea, SRs, SRe, SRa in persistent atrial fibrillation group significantly decreased than in paroxysmal atrial fibrillation(t=4.310, 3.128, 4.465, 5.496,-3.290,-3.863,P<0.001). The intra-group and inter-group had well correlation coefficients between the observers in the left atrial strain and strain rate parameters of the subjects(ICC=0.85—0.94,0.81—0.90). Conclusions FT-CMR technique can be used to assess the left atrial strain and strain rate in patients with atrial fibrillation;Left atrial reservoir, conduit and booster-pump functions in patients with atrial fibrillation were impaired. Patients with persistent atrial fibrillation had worse left atrial function throughout the entire cardiac cycle compared with those with paroxysmal atrial fibrillation.

OBJECTIVETo explore the protective mechanisms of sevoflurane against acute lung injury (ALI) induced by one-lung ventilation (OLV) in view of cyclooxygenase-2 (COX2) and 5-lipoxygenase (5-LOX) pathways.

METHODEighteen healthy Japanese white rabbits were randomized into sham-operated group (S group), OLV group (O group) and OLV + sevoflurane group (OS group). COX2 and 5-LOX protein and mRNA expressions in the lungs were detected by Western blotting and real-time PCR, respectively. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotrienes B2 (LTB2) in the lung tissues were quantified with ELISA. Histological scores and lung wet/dry weight (W/D) ratios were determined for lung injury assessment.

RESULTSCOX2 and 5-LOX protein and mRNA expressions and the contents of LTB2, TXA2 and PGI2 in the lungs, lung W/D ratio and histological scores were significantly higher while PGI2/TXA2 ratio was significantly lower in O group and OS group than in S group (P<0.05). Compared with those in O group, COX2 and 5-LOX expressions, pulmonary contents of LTB2, TXA2 and PGI2, and lung W/D ratio all decreased significantly but PGI2/TXA2 ratio was significantly elevated in OS group (P<0.05).

CONCLUSIONOLV may activate COX2 and 5-LOX pathways to result in increased production of arachidonic acid metabolites. Sevoflurane protects against OLV-induced ALI probably by reducing AA metabolites and regulating PGI2/TXA2 ratio through inhibitions of COX2 and 5-LOX pathways.

Acute Lung Injury ; etiology ; metabolism ; Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; Cyclooxygenase 2 ; metabolism ; Lung ; drug effects ; metabolism ; Methyl Ethers ; adverse effects ; One-Lung Ventilation ; adverse effects ; RNA, Messenger ; genetics ; Rabbits

Objective To design and synthesize novel triazole antifungal derivatives with 1 ,3 ,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation ,aminolysis reaction ,cy-clization ,nucleophilic substitution ,etc. All the compounds were characterized by 1 H NMR ,MS spectra. The in vitro antifun-gal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi ,especially against Candida albicans. Compounds 10d ,10i , 10l , and 10n were found to be the most effective , with a minimum inhibitory concentration (MIC80 ) of 0.003 9 μg/ml .They are 16-fold more potent than ICZ ( MIC80 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC80 0.25 μg/ml) .Conclusion The 1 ,3 ,4-oxadiazole side chain could affect the antifungal activities. That could be due to the prop-er incorporation between the 1 ,3 ,4-oxadiazole substituted phenyl ring with the target enzyme.