The clinical examination results of 310 patients with advanced schistosomiasis were analyzed,the results showed that the conditions of most of the cases were severe.which should be paid aRenfion to.

Objective: To prepare a drug delivery system based on L-carnitine modified and quercetin (QUE)-coloading chitosan-stearic acid (LC-SA/CS-SA) nanomicelles, investigate the properties of micelles, and evaluate the enhanced absorption effect of the micelles by in vivo intestinal absorption in rats. Methods: The CS-SA copolymer was synthesized by the amidation of free amino groups on CS. The chemical structure of CS-SA was characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Taking PTX was the main drug and quercetin as the auxiliary drug, the particle size distribution, Zeta potential, drug loading and entrapment efficiency of the micelles were investigated. The micromorphology of the micelles was observed by transmission electron microscope (TEM). The critical micelle concentration (CMC) of LC-SA/CS-SA micelles was measured by fluorescent probe method. The in vitro release of paclitaxel from polymeric micelles was evaluated by dialysis method. The absorption rate coefficient (Ka) of paclitaxel (PTX)-loaded micelles was assessed by in vivo intestine absorption in rats. Results: The results of FT-IR and 1HNMR indicated that the copolymer (CS-SA) was synthesized. The LC-SA/CS-SA@ QUE+PTX micelles showed regular spherical shapes with particle size of (148.3 ± 1.7) nm, PDI of 0.16 ± 0.07, Zeta potential of (24.600 ± 0.167) mV and CMC of 14.31 µg/mL. Compared to the commercial formulation of PTX, LC-SA/CS-SA@QUE+PTX micelles and LC-SA/CS-SA@PTX micelles showed significantly sustained release behaviors. The enhanced absorption effect of PTX in the micelle system was confirmed by intestine absorption test in rats. Conclusion: The LC-SA/CS-SA@QUE+PTX micelles, as a potential oral absorption promoter, enhanced the intestinal absorption of PTX in rats.

OBJECTIVE: To observe the effect and mechanism of Bauhinia championii flavones (BCF) on anti-hypoxia/reoxygenation injury in cardiomyocytes via inhibiting necroptosis. METHODS: The cardiomyocytes hypoxia/reoxygenation injury model was developed and pretreated with Bauhinia championii flavones. ELISA was used to evaluate the contents of TNF-α, and the activities of T-AOC were determined by ultraviolet spectrophotometric method. The protein expression of RIPK3 was observed by Western-blotting, and the necroptosis rate was determined by using Annex v-FITC/PI double staining. RESULTS: Compared with model group, Bauhinia championii flavones pretreatment alleviated cardiomyocytes injury, increased T-AOC level, decreased the activity of TNF-α, down-regulated the expression of RIPK3, and inhibited cardiomyocytes necroptosis (P<0.05). It had synergistic effect when combined BCF with necrostatin-1 (P<0.05). CONCLUSION: BCF can inhibit necroptosis and has protective effects on hypoxia/reoxygenation injury, which are associated with increasing the level of T-AOC, down-regulating TNF-α and RIPK3, and decreasing the cardiomyocytes necroptosis rate.

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg^-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg^-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg^-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg^-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, geraniin can reduce activities or contents of ALT, AST, ALP, TBIL in serum and MDA in liver of mice (P<0.05, P<0.01), but increase activities of T-SOD and GSH-Px in liver (P<0.05,P<0.01), while inhibiting the contents of TNF-α, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (P<0.05,P<0.01). HE staining showed that acute liver injury of mice was alleviated obviously by geraniin. Conclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

Objective:To explore the mechanism of gentiopicroside （GPS） in preventing acute liver injury induced by carbon tetrachloride （CCl₄） in mice and its effect on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. Method:Sixty mice were randomly divided into a normal control group， a model group， a silymarin group （150 mg·kg^-1）， and high- （200 mg·kg^-1）， medium- （100 mg·kg^-1）， and low-dose （50 mg·kg^-1） GPS groups， with 10 in each group. The mice in the groups with drug intervention were administered correspondingly by gavage at 10 mL·kg^-1， and those in the normal control group and the model group receive an equal volume of distilled water， once per day. Ten days after administration， mice in the normal control group were subjected to the intraperitoneal injection of peanut oil （10 mL·kg^-1） and those in other groups were injected with peanut oil （10 mL·kg^-1） containing 0.12% CCl₄ for the induction of acute liver injury model. After fasting for 16 hours， blood was collected from eyeballs and liver tissues were collected. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver tissues. The content or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）， total superoxide dismutase （T-SOD）， and γ-glutamyl transpeptidase （γ-GT） in the serum， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in liver tissues were determined by biochemistry techniques. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in liver tissues were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of TLR4， MyD88， and NF-κB in liver tissues. The expression of phosphorylated NF-κB （p-NF-κB） was detected by immunohistochemistry. Result:Compared with the normal control group， the model group showed increased levels of ALT， AST， ALP， TBIL， γ-GT， and MDA （P<0.01）， and blunted activities of T-SOD and GSH-Px （P<0.01）. Compared with the model group， the high- and medium-dose GPS groups exhibited declining levels of ALT， AST， ALP， TBIL， γ-GT， and MDA （P<0.05， P<0.01） and potentiated T-SOD and GSH-Px activities （P<0.05， P<0.01）. Compared with the normal control group， the model group displayed elevated levels of TNF-α， IL-1β， and IL-6 in liver tissues （P<0.01） and increased protein expression of TLR4， MyD88， and p-NF-κB （P<0.01）. Compared with the model group， the high- and medium-dose GPS groups showed decreased TNF-α， IL-1β， and IL-6 content in liver tissues （P<0.05， P<0.01） and dwindled TLR4， MyD88， and p-NF-κB protein expression （P<0.05， P<0.01）. Conclusion:GPS possesses a protective effect on mice with acute liver injury induced by CCl₄， and its mechanism of action may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway and inhibition of oxidative stress.

Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl₄) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg^-1) and FGD groups (475, 950, 1 900 mg·kg^-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg^-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (P<0.01), the levels of TNF-α, IL-1β, IL-6 in liver tissue were remarkably increased (P<0.01), but the serum activities of SOD, GSH-Px were significantly decreased (P<0.01), the expression of NF-κB was enhanced in liver tissue (P<0.01), and PPAR-γ was down-regulated (P<0.01), indicating the successful modeling of acute liver injury. Compared with the model group, FGD could reduce the activities of AST, ALT, ALP and the contents of TBIL, MDA (P<0.05, P<0.01), decease the level of TNF-α, IL-1β, IL-6 (P<0.05, P<0.01), and down-regulate the expression of NF-κB (P<0.05, P<0.01), but up-regulate the activities of SOD, GSH-Px and the expression of PPAR-γ (P<0.05, P<0.01). The liver tissue lesions were alleviated to varying degrees. Conclusion: FGD has a protective effect on CCl₄-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.
Humans ; Ethanol/toxicity* ; AMP-Activated Protein Kinases/metabolism* ; Fatty Liver ; Triglycerides ; MicroRNAs/genetics* ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics*

Aim To investigate whether DCP has pro- teetive effeet on 2 ,4-dimethylnitrosamine ( DMN) -induced liver fibrosis rat model and its effect on MAPK signaling pathway.Methods Hats were intraperitoneal ly injected with DMN to establish HF model,and then were randomly divided into five groups, namely model group, colchicine group, DCP low-dose, medium-dose and high-dose groups,and control group.The rats were given DMN continuously for six weeks.Serum was col-lected afterwards to detect biochemical indexes of liver function.HE and Masson staining and immunohisto- chemical experiments were performed on liver tissues.RT-PCR was applied to detect the expression of inflammatory factors.Western blot was used to detect the ex pression of proteins related to MAPK pathway,the preventive effect of DCP on HF was observed, and its in-tervention effect on MAPK pathway was explored.Results The liver function of rats in model group was severely impaired, with obvious hepatocyte damage, inflammatory cell infiltration and increased interstitial fibrosis , suggesting that the preparation of HF model was successful.Conclusions DCP can interfere with MAPK signaling pathway to inhibit the inflammatory response and alleviate the progression of HF in rats.

Objective To explore the technique outcome of fixing the ventral stress pedicle screws into the injured vertebrae, as a method to enhance the posterior internal fixation. Methods From March 2002 to March 2005, 33 single thoracolumbar fractures were studied retrospectively. Among which, 16 cases were treated with the above method(group A), and the other 17 were treated with traditional two-level fixation(group B). Group A involved 11 males and 5 females, aged 48 years averagely(range, 32-74 years); and group B included 12 males and 5 females, aged from 21 to 61 years(mean, 40 years). All the patients underwent the operation within up to 3 weeks after fracture. For the injured vertebral bodies, their pedicles were intact on either unilateral or bilateral side, and their lower half and endplate were free from split. In group A, the pedicle screws in the injured vertebrae were used to achieve the ventral press vertical to the distraction for the stress neutralization, and also with the routine distraction and lordosis restoration, simultaneously. The mean follow-up period was 11 months with a range from 6 to 24 months. Results After operation, the optimal Cobb angle and anterior column restoration were achieved through the ventral reduction from the injured vertebral body, which was the contribution from the vertical stress pedicle screw. The degree in anterior movement of injured vertebrae pre- and postoperatively was much more in group A than group B, and the difference was of statistical significance(P