Objective To investigate the molecular mechanism of Loureirin A mediated anti-hepatic fibrosis by evaluting its effects on proliferation , secretion ofα-smooth muscle actin (α-SMA) and transforming growth factor-beta1 (TGF-β1), and expression of rat hepatic stellate cells in vitro . Methods Primary hepatic stellate cells were isolated and cultured from Sprague-Dawley rats. After activating and inducing primary hepatic stellate cells from qHSC to aHSC, the activated hepatic stellate cells model in vitro was established. Then we observed the morphological changes of static hepatic stellate cells and activated hepatic stellate cells with inverted phase contrast microscope. Cultured hepatic stellate cells were treated with different concentrations of loureirin A and the inhibitory rate of HSCs proliferation was measured by MTT assay. The expression of Frizzled-4 was measured by western blot analysis. The content ofα-SMA and TGF-β1 in the cultured HSCs'supernatant were measured by enzyme-linked immunosorbent assay (ELISA) . Results Loureirin A the proliferation of inhibited activated hepatic stellate cells in a time-dose-dependent manner compared with the control group,IC50=0.30 μg/μL. After loureirinA treatment of the HSCs, western blot analysis showed that Frizzled-4 expression level was obviously lower than control group. Loureirin A also inhibitedα-SMA and TGFβ1 (P<0.05) secretion in the cultured HSCs'supernatant in different degree by the assay of ELISA. Conclusions The molecular mechanism of Loureirin A and Wnt signaling pathway mediated anti-hepatic fibrosis and anti-angiogenesis may involve down-regulation the expression of Frizzled-4, inhibiting the synthesis and secretion ofα-SMA,TGF-β1and the proliferation of HSCs.

Objective: To examine the correlation between paliperidone plasma concentration and clinical efficacy in the patients with schizophrenia. Methods:Totally 50 schizophrenia patients were treated by paliperidone. The plasma concentration of paliperidone was monitored by RP-HPLC at the weekend of the 2 nd, 4 th and 6 th week, the clinical efficacy was evaluated using the positive and negative syndrome scale ( PANSS) , and the correlation between paliperidone plasma concentration and clinical efficacy was analyzed. Results:The mean plasma concentration of paliperidone was (31. 89 ± 17. 36) ng·ml-1 at the weekend of the 6th week, and no cor-relation was found between paliperidone plasma concentration and the clinical efficacy (r=0. 146,P=0. 074). Paliperidone plasma concentration in 12 patients with adverse drug reactions (ADR) was higher than that in the patients without ADR [(45. 87 ± 19. 21)ng ·ml-1 vs (27. 06 ± 11. 13) ng·ml-1, P <0. 01]. Conclusion: Paliperidone plasma concentration shows significant individual differences. With the increase of paliperidone plasma concentration, clinical efficacy isn't necessarily improved, while the incidence of ADR may be increased. Therefore, the monitoring of paliperidone plasma concentration is recommended to optimize the therapeutic reg-imen.

Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica(CMM)through the different effects of Mahuang decoction(MHD)and Maxing Shigan decoction(MSD)on animal temperature tropism.Methods The equipment with cold/hot pads was used to investigate the variety ofthe temperature tropism between two groups of mice treated by MHD and MSD,respectively.Meanwhile,the activities ofadenosine triphosphatase(ATPase),superoxide dismutase,succinate dehydrogenase,and malondialdehyde were measured.Results After treated by MHD,the macroscopic behavioral index of remaining rate on warm pad(40 ℃)of mice decreasedsignificantly(P < 0.05),suggesting the enhancement of cold tropism,meanwhile,the internal indices of ATPase activity and oxygen consuming volume increased significantly(P < 0.05),suggesting the enhancement of energy metabolism.On theother hand,the above-mentioned indices in MSD group changed on the inverse way.Conclusion The relative drug natureof MHD and MSD revealed in this study is consistent with the theoretical prognostication or definition.It indicates that theinternal cold and hot nature of CMM could be reflected in ethological way on the changes of animal temperature tropismwhich might be internally regulated by body energy metabolism.

Objective To study the effects of oxytocin antagonists-atosiban on pregnancy outcome after thaw embryo transfer (TET).Methods Between Jul.and Dec.2012,a total of 120 women undergoing TET in Reproductive Medical Center,General Hospital of Tianjin Medical University were randomly allocated into atosiban and control group.They were all transferred 2 or 3 top quality embryos at phase of 7-8 cells.Patients in atosiban group were administered by intravenous administration of atosiban before 30 minutes of embryo transfer with a total administered dose of 37.5 mg.In the control group,no special treatment was given before embryo transfer.All patients in 2 groups underwent progesterone luteal support regularly after embryo transfer,then the clinical rate of pregnancy,implantation and early abortion was compared.Results The clinical pregnancy rate per cycle and implantation rate per transfer were 60％(36/60) and 30.0％ (48/160) in the atosiban group,which were higher than 42％ (25/60) and 20.3％ (31/153) in the control group (all P ＜ 0.05).Early abortion rate was 6％ (2/36)in the atosiban group,which was no statistical difference comapring with control group [16％ (4/25),P ＞ 0.05].Conclusion It was suggested that atosiban treatment before embryo transfer can improve the outcome of pregnancy,and increase clinical pregnancy rate and implantation rate after TET.

AIM:To detect the endogenous expression of B-cell leukemia/lymphoma 6 member B (BCL6B) in FHC and LoVo cells, and to investigate the effects of BCL6B on proliferation and migration of LoVo cells for further explo-ring the underlying mechanism .METHODS:The endogenous expression of BCL 6B in the FHC and LoVo cells was detec-ted by RT-PCR and Western blot .The methods of MTT assay , colony formation assay , wound healing assay and Transwell chamber experiment were employed to examine the biological functions of BCL 6B in the LoVo cells.The mRNA and protein levels of BCL6B, cyclin D1 and matrix metalloproteinase-9 ( MMP-9) were determined by RT-PCR and Western blot , re-spectively.The level of phosphorylated protein kinase B (p-AKT) was detected by Western blot.RESULTS:BCL6B ex-pression was notably repressed in the LoVo cells as compared with the FHC cells , which were significantly increased by transfection with pcDNA3.1-BCL6B.The abilities of proliferation and migration of the LoVo cells at 72 h were inhibited by 28.33%(P<0.01) and 36.11%(P<0.05) in BCL6B group.The mRNA levels of cyclin D1 and MMP-9 in the cells of BCL6B group were decreased by 39.90%(P<0.01) and 77.36% (P <0.05), and the protein levels of cyclin D1, MMP-9 and p-AKT were reduced by 44.00%(P<0.05), 47.06%(P<0.01) and 32.88% (P<0.05), respectively. CONCLUSION:BCL6B inhibits proliferation and migration of the LoVo cells , and the PI3K/AKT signaling pathway is in-volved in this process .

Objective:To study the content determination method for the effective components in WudangⅡFlos lonicerae Caulis to lay foundation for the quality evaluation. Methods: An ultrasonic method was used. The effects of extraction solvent, ultrasonic time, ultrasonic power and ratio of solid to liquid on the contents of rutin and mignonette nucleoside were studied, and the extraction conditions were optimized by a 4-factor and 3-level orthogonal experiment. The chromatographic conditions were as follows:a Phenome-nex Luna-C18(250 mm ×4.60 mm, 5 μm) column was adopted for chlorogenic acid, and a Fortis Xi Phenyl column (250 mm × 4. 6 mm, 5 μm) was used for rutin, loganin and luteoloside;the mobile phase was acetonitrile (B)-0. 4% phosphoric acid (C) solu-tion (15 ∶85) for chlorogenic acid and loganin, and acetonitrile (B) -0. 5% glacial acetic acid aqueous solutjion (D) with gradient e-lution for rutin and luteoloside;the column temperature was 30℃, and the detection wavelength was 327,237,354 and 348 nm, re-spectively. Results:The optimum extraction conditions for rutin and luteoloside from WudangⅡFlos lonicerae Caulis were as follows:the extraction solvent was 60% ethanol, the solid-liquid ratio was 1 ∶30, the ultrasonic power and the ultrasonic time were 350 W and 50 min for rutin, and 250W and 60min for luteoloside. The content of chlorogenic acid, loganin, rutin and luteoloside was 10. 27, 6. 33, 0. 401 and 0. 450 mg·g-1 in the samples, respectively. Conclusion:The method is simple and convenient, accurate and re-producible, which can be used to control the quality of WudangⅡFlos lonicerae Caulis and provide reference for the further develop-ment.

This paper was to explore the effect of blood oxygen saturation (SO2) on oxidative damages of erythrocytes under the condition of oxidative stress. Keeping SO2 of cultured erythrocytes in vitro at the states of 0.3, 0.5, 0.7, 0.9 and 0.98, respectively, we induced oxidative stress by tert-buthylhydroperoxide (BHP, 0.15 mmol/L of final concentration). After incubation, antioxidant capacity was assessed by measuring content of reduced glutathin hormone (GSH) in erythrocytes. Methemoglobin (MetHb) content, lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and denatured globin-chains on the plasma membrane were measured to assess the extent of oxidative damages. The results showed that in the presence of BHP, GSH contents increased from 0.3 to 0.98 groups; MetHb, TBARS and globin-chains levels all dropped with the rise of SO2. In conclusion, antioxidant capacity and oxidative damages of erythrocytes are closely related to SO2, declined SO2 could promote oxidative damages of erythrocytes.
Cells, Cultured ; Erythrocytes ; cytology ; metabolism ; physiology ; Glutathione ; blood ; Humans ; Methemoglobin ; metabolism ; Oxidative Stress ; drug effects ; Oximetry ; methods ; Oxygen ; blood ; Thiobarbituric Acid Reactive Substances ; metabolism ; tert-Butylhydroperoxide ; toxicity

OBJECTIVETo probe into the new idea along with establishment of a novel method for dynamic monitoring and early-warning on the wild resources of traditional Chinese medicines (TCMs).

METHODThe alterations of wild traditional Chinese medicinal resources were assessed through the price ratio between drug and foodstuff (PRDF) indicating the balance between supply and demand of the specific TCMs, referred to the price ration between pork to foodstuff which is used in national monitoring to the balance between pork supply and demand.

RESULTSince the price of rice was tightly controlled by government, it was selected as a relatively stable reference to build the PRDF in order to take away the non-marketing influence to TCMs price such as CPI and inflation rate. The modified relative alteration trend of TCMs price had been researched through comparing different formulae to build PRDF, including absolute average month price of TCMs, month average price ratio of TCMs to foodstuff (rice) , month-on-month change of TCMs to rice, year-on-year change of TCMs to rice, and difference in value of period-on-period change (DVPPC). In the research, Cordyceps, Glycyrrhiza and totally five herbs were selected as model drugs and the price data were collected from 2002 to 2008. The results showed that DVPPC calculated of relative long time window was more sensitive and stable to reflect the relative alteration trend of TCMs price. For instance, the DVPPC of Ligustici showed continuously increase trend in recent years. This suggested appearance of unbalance between supply and demand of Ligustici, and forced policy intervention to maintain reasonable and continuable utilization of Ligustici resource.

CONCLUSIONThe proposed method and the formula of DVPPC revealed some useful guidance for dynamic monitoring the wild resources of TCMs.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.