抑郁症是一种基因与环境交互影响的重大精神疾病,以显著而持久心境障碍为主要临床特征,主要累及青壮年人群(20～45岁).随着现代社会生活节奏的加快和竞争压力的增加,其发病率越来越高.2018年世界卫生组织资料显示,抑郁症是世界范围内最常见的致残原因,目前有超过3亿人患有抑郁症[1];2019年,Huang等[2]的研究显示,我国抑郁症的终生患病率为6. 8％.抑郁症是一种多病因、异质性的复杂精神疾病,与其他许多慢性躯体疾病相比,其病因和病理生理机制的研究仍处于初级阶段.

目的:观察慢性温和应激(CMS)抑郁模型大鼠前额叶哺乳动物雷帕霉素靶蛋白(mTOR)、S6K和脑衰反应蛋白2(CRMP2)的表达变化,并探讨栀子苷抗抑郁作用的机制.方法:40只雄性Wistar大鼠随机平均分为4组:正常对照组、模型组、氟西汀组(阳性对照,5 mg·kg-1·d-1)和栀子苷组(50 mg·kg-1·d-1).正常对照组予以常规饲养,其余各组建立大鼠CMS抑郁症模型.造模28 d后,氟西汀组和栀子苷组灌胃给与相应药物,正常对照组和模型组给与等量生理盐水,1次/d,持续14 d,给药期间各组大鼠均继续给予CMS.给药结束后进行糖水偏好实验、旷场实验和强迫游泳实验行为学检测;分别采用RT-qPCR和Western blot检测前额叶m-TOR、S6K、CRMP2 mRNA和蛋白表达.结果:模型组大鼠表现出明显的抑郁样行为,前额叶m-TOR、S6K和CRMP2表达显著降低,与正常对照组比较,差异有统计学意义(P<0.01);经药物治疗后,CMS大鼠的抑郁样行为明显减少,前额叶m-TOR、S6K和CRMP2表达抑制被显著逆转(P<0.05或P<0.01).结论:前额叶m-TOR/S6K/CRMP2信号抑制介导CMS大鼠抑郁样行为的发生,栀子苷可以缓解CMS大鼠抑郁样行为,同时逆转CMS所致的前额叶m-TOR、S6K和CRMP2的低表达.

目的:探讨槲皮黄酮对脂多糖(lipopolysaccharide,LPS)诱导人肝细胞L02炎性损伤的改善作用及其对NLRP3炎症小体表达的影响.方法:采用体外LPS诱导L02细胞炎性损伤模型,将细胞分为正常对照组、LPS(100 μg/L)诱导组、LPS+低剂量(20 μg/mL)槲皮黄酮组、LPS+中剂量(50 μg/mL)槲皮黄酮组、LPS+高剂量(100μg/mL)槲皮黄酮组,采用CCK8法检测细胞相对存活率,采用ELISA法检测炎性因子白细胞介素1β(interleukin-1β,IL-1β)及肿瘤坏死因子α(tumor necrosis factor α,TNF-α)水平,采用Western Blot法检测NLRP3炎症小体及Caspase-1表达水平.结果:与LPS诱导组相比,不同浓度槲皮黄酮组中L02细胞相对存活率升高(P＜0.05),细胞上清炎性因子IL-1β及TNF-α水平降低(P＜0.05),L02细胞中NLRP3炎症小体及Caspase-1表达降低(P＜0.05),均表现出浓度依赖性.结论:槲皮黄酮可抑制人肝细胞L02炎症反应,进而改善炎症对L02细胞的增殖抑制作用,其作用机制可能与抑制NLRP3炎症小体表达有关.

Objective To express the new Delhi metallo-beta-lactamase-4 (NDM-4) by using bioengineering techniques,determine the kinetic parameters of enzyme reaction with its hydrolyzed substrate,and to study the effects of pH and temperature on NDM-4 activity.Methods Clinically separated blaNDM-4 gene was amplified by polymerase chain reaction (PCR) and cloned into pET30a vector to construct a recombinant prokaryotic expression plasmid.The latter was transformed into E.coli BL21 (DE3).The engineered bacteria strain [E.coli BL21 (DE3)-pET30a-NDM-4] was measured for resistance to various β-lactam antibiotics,and then used to induce NDM-4 expression.The overexpressed recombinant enzyme was purified by Ni2+-NTA column,identified by SDS-PAGE and mass spectrometry,and determined for the kinetic parameters,optimum pH and temperature of enzyme reaction with its hydrolyzed substrates.Results The recombinant plasmid pET30a-NDM-4 was verified by sequencing.The engineered bacteria strains harboring blaNDM-4 gene were resistant to β-lactam antibiotics.The relative molecular mass of the over-expressed recombinant enzyme was about 28 400.After purification,the NDM-4 protein was at a concentration of 0.4 g/L,presenting high hydrolysis activity against almost all β-lactam antibiotics including Carbapenems,particularly at the optimum pH of 7.5,and the optimum temperature of 35 ℃.Conclusion NMD-4 with high hydrolysis activity against β-lactam ring was successfully overexpressed and obtained by using a prokaryotic expression system.This provides a material basis for further study of the action mechanisms and enzymatic properties of NMD-4.

Microglia-mediated neuroinflammation plays an important role in Alzheimer's disease development. Resveratrol, a natural polyphenol from the Japanese knotweed (Polygonum cuspidatumand), is known to protect against neuroinflammation, but the mechanism remains unclear. To begin to explore potential mechanisms, we created a model of inflammatory injury in BV-2 murine microglial cells based on the induction of amyloid-β. We found that resveratrol (10 and 50 nM) significantly inhibited Aβ-induced proliferation and activation of BV-2 cells, as well as their release of the proinflammatory cytokines, IL-6 and TNF-α. Resveratrol also suppressed the overexpression of cleaved caspase-1 and IL-1β, and decreased Aβ-stimulated degradation of IkBα and phosphorylation of NF-κB phosphorylation. Western blot analysis showed that Aβ upregulated the TXNIP/TRX/NLRP3 pathway, while resveratrol treatment inhibited it. We conclude that resveratrol protects microglia from Aβ-stimulated inflammation by suppressing the inflammatory response, at least in part by inhibiting the TXNIP/TRX/NLRP3 signaling pathway.

Objective To investigate the inhibitory effects of sulforaphane on human gastric cancer cells (HGC27) and its possible mechanism. Methods HGC27 cells were divided into four groups:sulforaphane low dose, middle dose and high dose groups (20, 40 and 80 μg/mL) and the control group. CCK8 assay was used to detect the survival rate of HGC27 cells. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were measured using DCFH-DA and HPLC, respectively. Western blot was performed to analyze the expression of Bax, Bcl-2 and p53. Results With different concentrations of sulforaphane treatment, the relative survival rates of HGC27 cells decreased in a dose-and time-dependent manner (P<0.05). ROS and ATP content decreased significantly (P<0.05). The expression levels of Bax and p53 were increased, but the expression of Bcl-2 was decreased significantly (P<0.05). Conclusion Sulforaphane can inhibit the growth of HGC27 cells, and the possible mechanism may be related with inhibition of ROS and ATP generation, upregulation of Bax and p53 expression and downregulation of Bcl-2 expression.

目的 探讨槲皮素对脂多糖诱导人肝细胞炎性损伤的改善作用及其机制.方法 采用不同浓度的槲皮素(0、50、100、200、400、800、1600μmol/L)干预人肝细胞(L02细胞),比较细胞相对存活率.将细胞分为正常对照组、脂多糖诱导组、脂多糖+低剂量(50μmol/L)槲皮素组、脂多糖+中剂量(100μmol/L)槲皮素组、脂多糖+高剂量(200μmol/L)槲皮素组,各个浓度槲皮素组中加入相应浓度槲皮素溶液,2 h后除正常对照组外均加入0.1μg/ml脂多糖.计算各组L02细胞的相对存活率,检测各组上清液白细胞介素(IL)-6、IL-1β、肿瘤坏死因子α(TNF-α)水平,以及L02细胞的诱生型一氧化氮合酶(iNOS)、环氧化酶(COX-2)、硫氧还蛋白相互作用蛋白(TXNIP)、NACHT-LRR-PYD结构域蛋白3(NLRP3)蛋白相对表达水平.结果 不同浓度槲皮素干预组间L02细胞的相对存活率差异无统计学意义(P>0.05).脂多糖诱导组L02细胞相对存活率低于正常对照组(P<0.05),且上清液IL-6、IL-1β、TNF-α以及iNOS、COX-2、TXNIP、NLRP3蛋白水平均高于正常对照组(均P<0.05).脂多糖诱导组、脂多糖+低剂量槲皮素组、脂多糖+中剂量槲皮素组、脂多糖+高剂量槲皮素组的细胞相对存活率依次升高(均P<0.05).不同浓度槲皮素干预组上清液IL-6、IL-1β、TNF-α以及iNOS、COX-2、TXNIP、NLRP3蛋白水平均低于脂多糖诱导组(均P<0.05).结论 槲皮素可改善脂多糖所致L02细胞的炎性损伤,其可能通过降低TXNIP/NLRP3通路活性发挥作用.

Epilepsy is a chronic and recurrent disease of the central nervous system, with a complex pathology. Recent studies have demonstrated that the activation of glial cells serve an important role in the development of epilepsy. The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1) in mediating the activation of glial cells through the toll-like receptor 4 (TLR4)/nuclear factor (NF)-B signaling pathway in seizure, and the underlying mechanism. The brain tissue of post-surgery patients with intractable epilepsy after resection and the normal control brain tissue of patients with craniocerebral trauma induced intracranial hypertension were collected. The expression level and distribution pattern of HMGB1, OX42 and NF-B p65 were detected by immunohistochemistry. HMGB1, TLR4, receptor for advanced glycation end products (RAGE), NF-B p65 and inducible nitric oxide synthase (iNOS) expression levels were detected by western blotting, and serum cytokine levels of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-, transforming growth factor (TGF)- and IL-10 in patients with epilepsy and craniocerebral trauma were detected by ELISA. And cell model of epilepsy was established by coriaria lactone (CL)-stimulated HM cell, and the same factors were measured. The potential toxic effect of HMGB1 on HM cells was evaluated by MTT and 5-ethynyl-2-deoxyuridine assays. The results demonstrated that compared with the control group, levels of HMGB1, TLR4, RAGE, NF-B p65 and iNOS in the brain of the epilepsy group were significantly increased, and increased cytokine levels of IL-1, IL-6, TNF-, TGF- and IL-10 in patients with epilepsy were also observed. At the same time, the above results were also observed in HM cells stimulated with CL. Overexpression of HMGB1 enhanced the results, while HMGB1 small interfering RNA blocked the function of CL. There was no significant toxic effect of HMGB1 on HM cells. In conclusion, overexpression of HMGB1 potentially promoted epileptogenesis. CL-induced activation of glial cells may act via up-regulation of HMGB1 and TLR4/RAGE receptors, and the downstream transcription factor NF-B.

The paxillin and M2 macrophage are all involved in cell proliferation and tumor progression, and this study aims to explore the interaction between them in colon cancer and the role of paxillin in cancer progression. Expression of mRNAs and proteins was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, separately. Endogenous expression of genes was modulated by recombinant plasmids and cell transfection. The levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA). The cell viability, invasion and migration were detected using the MTT assay, the transwell assay and the wound-healing cell migration assay, respectively. A nude mouse model for human colon cancer was constructed for tumor orthotopic expression. Paxillin was up-regulated in tumor-associated macrophages (TAMs). Paxillin was up-regulated in process of M2 macrophage polarization. M2 macrophage polarization was inhibited with paxillin suppressed. Down-regulated paxillin inhibited cell proliferation and invasion in colon cancer through suppressing M2 macrophage polarization. PI3k/Akt inhibitor repressed M2 macrophage polarization through down-regulating paxillin. PI3k/Akt inhibitor inhibited the function of the macrophage in promoting cell proliferation and invasion of colon cancer through down-regulating paxillin. Down-regulated paxillin in macrophages inhibited tumor growth of colon cancer. With the PI3K/AKT pathway inhibited, down-regulated paxillin suppressed colon cancer cell proliferation and invasion by inhibiting the M2 macrophage polarization, thereby restraining the tumor progression.

Background/Aims: Ginsenoside Rb1 (Rb1) has been reported to have varieties of neuroprotective effects. This study aimed to evaluate the effects of Rb1 on pentylenetetrazol (PTZ)-induced rat brain injury and Mg2+ free-induced neuron injury and analyzed the detailed molecular mechanisms in vivo and in vitro. Methods: Seizure duration and latency were measured in epilepsy kindled rat. The cognitive impairment was assessed by Morris water maze (MWM) test. Oxidative stress parameters, malondialdehyde (MDA) and glutathione (GSH) were measured by the 2-thiobarbituric acid methods and the DTNB-GSSG reductase recycling methods. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Neuronal apoptosis was measured by Annexin V-FITC and propidium iodide (PI) staining. Immunohistochemistry and immunofluorescence staining were performed to evaluate Nrf2 and HO-1 expressions. Expression of Nrf2, HO-1, Bcl-2, iNOS and LC3 were evaluated by western blot. Results: The PTZ-injured rats presented longer seizure duration and shorter seizure latency. Rb1 ameliorated these effects, as well as the cognitive deficits caused by PTZ exposure. Besides, Rb1 dose-dependently increased GSH levels, decreased MDA levels and alleviated neuronal damage in PTZ-treated rats. In vitro, Rb1 increased cell viability and decreased neuronal apoptosis in a dose-dependent manner under Mg2+ free condition. Moreover, in vivo and in vitro, Rb1 enhanced both the Nrf2 and HO-1 expressions. Furthermore, upregulation of the expression of Bcl-2 and downregulation of the expression of iNOS and LC3 were observed. However, knockdown of Nrf2 adversely affected the protective effects of Rb1 in epileptic hippocampal neurons. Conclusion: Rb1 conferred neuroprotective effects against PTZ-induced brain damage and Mg2+ free-induced neuron injury by activating Nrf2/ARE signaling.

OBJECTIVE:To identify the molecular mechanism that modulates the killing effect of natural killer (NK) cells to colorectal cancer cells. MATERIALS AND METHODS:Expressions of miR-24 and Paxillin were detected by qRT-PCR and Western blot. Secretions of IFN-γ and TNF-α were measured by ELISA. The killing effect of NK cells was detected by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter assay was conducted to confirm the regulation of miR-24 on Paxillin. RESULTS:miR-24 was overexpressed in NK cells from patients with colorectal cancer than healthy volunteers. Secretions of IFN-γ and TNF-α in activated NK cells were significantly increased, indicating the enhancement of the killing effect of NK cells. Paxillin expression was overexpressed in activated NK cells. Interference of Paxillin significantly decreased Paxillin expression, secretions of IFN-γ and TNF-α, and the killing effect of NK cells to colorectal cancer cells. In addition, we confirmed that Paxillin was a direct target of miR-24, and miR-24 was negatively correlated with Paxillin. Moreover, overexpression of miR-24 inhibited secretions of IFN-γ and TNF-α, and decreased cytotoxicity by downregulating Paxillin expression. Finally, we observed that overexpression of Paxillin significantly decreased tumor volume of colorectal cancer. CONCLUSION:Overexpression of miR-24 supressed the killing effect of NK cells to colorectal cancer cells by downregulating Paxillin expression.

Objective To observe the effects of sulforaphane on the apoptosis in human gastric cancer HGC27 cells, and to study the possible mechanism of it. Methods The proliferation activity of HGC27 cells treated with sulforaphane was analyzed by CCK8 kit. Apoptosis rates were assessed by flow cytometry. After HGC27 cells were treated with sulforaphane, and the expression levels of Bcl-2, Bax, caspase-3, PI3K, Akt and p-Akt were measured by Western Blot. After HGC27 cells were treated with LY294002, sulforaphane and LY294002+sulforaphane, the expression levels of PI3K, Akt and p-Akt were also investigated by Western Blot. Results The proliferation of HGC27 cells was significantly suppressed by sulforaphane in dose-dependent and time-dependent manners. The apoptotic rates of HGC27 cells in 10, 20, 40 μg/ml of sulforaphane groups (10.29% ± 1.57%, 23.68% ± 1.69%, 35.29% ± 2.38% vs. 2.52% ± 0.74%) were greatly increased compared with the control group. The expression levels of Bax (18.92 ± 2.18, 34.06 ± 5.06, 44.08 ± 5.69 vs. 12.51 ± 2.15) in 10, 20, 40 μg/ml of sulforaphane groups were greatly increased compared with control group(P＜0.05). The expression levels of Bcl-2 (56.39 ± 5.27, 33.06 ± 4.26, 25.61 ± 4.01 vs. 78.25 ± 7.26), PI3K (51.06 ± 5.27, 42.06 ± 5.21, 23.08 ± 4.51 vs. 79.07 ± 8.12), p-Akt/Akt (58.62 ± 5.34, 35.24 ± 4.06, 14.52 ± 2.56 vs. 82.64 ± 8.25) in 10, 20, 40 μg/ml of sulforaphane groups were greatly decreased compared with control group (P＜0.05). The expression levels of PI3K (56.41 ± 5.36, 34.37 ± 4.52, 23.11 ± 3.05 vs. 81.24 ± 7.16), p-Akt/Akt (49.52 ± 5.84, 31.06 ± 4.09, 21.05 ± 2.28 vs. 77.52 ± 7.06) in the LY294002, sulforaphane and the LY294002+sulforaphane groups were greatly decreased compared with the control group (P＜0.05). Conclusions Sulforaphane may inhibit proliferation and promote apoptosis of HGC27 cells probably by inactivating PI3K/Akt signaling pathway.

The mechanism by which gastrin promotes pancreatic cancer cell metastasis is unclear. The process of directing polarized cancer cells toward the extracellular matrix is principally required for invasion and distant metastasis; however, whether gastrin can induce this process and its underlying mechanism remain to be elucidated. In this study, we found that gastrin-induced phosphorylation of paxillin at tyrosine 31/118 and RhoA activation as well as promoted the metastasis of PANC-1 cancer cells. Depletion of Gα12 and Gα13 inhibited the phosphorylation of paxillin and downstream activation of GTP-RhoA, blocked the formation and aggregation of focal adhesions and facilitated polarization of actin filaments induced by gastrin. Suppression of RhoA and ROCK also exhibited identical results. Selective inhibition of the CCKBR–Gα12/13–RhoA–ROCK signaling pathway blocked the reoriented localization of the Golgi apparatus at the leading edge of migrated cancer cells. YM022 and Y-27632 significantly suppressed hepatic metastasis of orthotic pancreatic tumors induced by gastrin in vivo. Collectively, we demonstrate that gastrin promotes Golgi reorientation and directional polarization of pancreatic cancer cells by activation of paxillin via the CCKBR–Gα12/13–RhoA–ROCK signal pathway. A hormone found in high levels in pancreatic cancer sufferers helps the disease spread by co-ordinating cellular migration. Pancreatic cancer is one of the most deadly forms of cancer, being highly aggressive and likely to metastasize. Honggang Yu at Renmin Hospital of Wuhan University and scientists across China have demonstrated that gastrin, a hormone expressed at higher levels in patients with pancreatic cancer, helps to co-ordinate directional cell migration and ensure the disease spreads effectively. By activating two key molecules via a specific signalling pathway, gastrin ensures the correct orientation of the Golgi apparatus, a cellular organelle tasked with packaging proteins for transportation. This in turn activates directional migration of the cancer cells. The results explain why gastrin is over-expressed in both tumors and blood in cancer patients, and may inform future therapies.

Background : An increasing number of miRNAs were confirmed to be involved in the initiation and progression of colorectal cancer (CRC) by acting as cancer suppressor genes and oncogenes. The purpose of this study was to uncover the role of miR-449b in CRC and its underlying mechanisms. Methods : The expression profile of miR-449b in human CRC tissues and cell lines was determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The effect of miR-449b on CRC was assessed by CRC cell migration and invasion as determined using a transwell assay. A luciferase reporter assay was also carried out to explore the interaction between MMP2 3′UTR and miR-449b. Results : The current study revealed that the relative expression of miR-449b was decreased significantly in human CRC tissues and cell lines; meanwhile, miR-449b in metastatic CRC tissues was significantly lower than that in non-metastatic CRC tissues. We also observed that the forced miR-449b in CRC cells significantly restrained cell migration and invasion in vitro . In contrast to miR-449b, our study found that both the MMP-2 mRNA and protein levels were increased in CRC cells. MiR-449b negatively regulated MMP2 in CRC cells, and the result was corroborated by luciferase reporter assay. Most importantly, overexpression of MMP2 significantly reversed the miR-449b-mediated inhibition on the invasion and migration of CRC cells. Conclusion : Our data provided encouraging evidence that miR-449b possessed a strong inhibitory effect on CRC cell migration and invasion by negative regulation of MMP2. Keywords : Colorectal cancer; MiR-449b; MMP2; Migration; Invasion

OBJECTIVE To explore the effects of schizandrae polysaccharide(SP) on inflammatory reaction of lipopolysaccharide(LPS)-induced rat hepatocytes,and study the potential mechanism.METHODS Primary rat hepatocytes were cultured in vitro,and hepatocytes were divided into five groups,including control group,LPS-induced group,low dose-,medium dose-,and high dose SP groups.The effect of SP on the proliferation of hepatocytes were investigated using CCK-8 assay.ELISA was used to investigate the influence of SP on the secretory levels of inflammatory cytokine (IL-6 and TNF-α).Western blot was used to assess the impacts of SP on the Traf3/NF-κB signaling pathway.RESULTS SP significantly improved the inhibitory effect of LPS-induced hepatocytes proliferation (P＜0.05).Varying concentrations of SP could significantly inhibit the secretion of IL-6 and TNF-α in hepatocytes compared with LPS-induced group (P＜0.05).Western blot results showed that the expression levels of Traf3 and NF-κ B in all SP groups significantly decreased compared with LPS-induced group(P＜0.05).CONCLUSION SP can significantly inhibit the inflammatory reaction of rat hepatocytes and its molecular mechanism may involve in down-regulating the activation of Traf3/NF-κB signaling pathway.

Objective:To investigate the in vitro release behavior and stability of diphenyl diester suspension. Methods:The dis-solution of biphenyl diester dry suspension was detected by HPLC, and the effects of different stirring speed (50, 75, 100 r·min-1 ) and different dissolution media (pH 6. 8 phosphate buffer, 0. 05 mol·L-1 hydrochloric acid solution,water,pH 4. 5 acetate buffer) on dissolution were investigated. The influencing factors testing ( high temperature, high humidity and strong light exposure) , accelerated stability testing[the temperature of (37 ± 5) ℃ and the relative humidity of 76％ ± 5％] and long-term stability testing[(25 ± 3) ℃and the relative humidity of 60％ ± 5 ％] of biphenyl diester dry suspension were carried out. Results:The dissolution behavior of bi-phenyl diester suspension in pH 6. 8 phosphate buffer (50 r·min-1 ) was faster and smoother. The results of influencing factors testing showed that biphenyl diester dry suspension should not be stored under the conditions of high temperature and high humidity. After the samples were stored under the conditions of accelerated testing and long-term stability testing for 6 months, the indicators did not change significantly. Conclusion:The in vitro release of prepared biphenyl diester dry suspension meets the requirements with promis-ing stability.

Objective To investigate the protective effect of schizandrae polysaccharide for oxidative stress in rat hepatocytes,and study the molecular mechanism of schizandrae polysaccharide in inhibiting oxidative stress.Methods Primary rat hepatocytes were cultured in vitro,and the rat hepatocytes were divided into five groups:control group,H2O2-induced group,and low,medium and high-dose schizandrae polysaccharide groups.The effect of schizandrae polysaccharide on the relative survival rate of hepatocytes was observed using CCK-8 assay.The levels NO and MDA were measured by related kits.The expression levels of P67-phox,P47-phox,SOD1,HO-1,Rac1 and p-Rac1 in cells were determined by Western blot.Results Compared with H2 O2-induced group,schizandrae polysaccharide could significantly improve the survival rate of hepatocytes (P ＜ 0.05) and inhibit the levels of NO and MDA in hepatocytes (P ＜ 0.05);the expression levels of HO-1 and SOD-1 in all schizandrae polysaccharide groups were significantly increased (P ＜ 0.05),while the levels of P67-phox and P47-phox were significantly decreased (P ＜ 0.05).Moreover,the phosphorylation levels of Rac1 were significantly decreased in all schizandrae polysaccharide groups (P ＜0.05).Conclusion Schizandrae polysaccharide can significantly inhibit the oxidative stress injury of hepatocytes and its underlying mechanism may involve suppressing the phosphorylation of Rac1.

Objective To study the impacts of quercetin on alcohol-stimulated liver injury in rats.Methods Thirty Sprague-Dawley rats were randomly divided into control,model,quercetin treatment (40mg/kg,80mg/kg,160mg/kg) groups.Ethanol plus 0.5ml fish oil were used to induce alcoholic liver injury for 6 weeks.Liver injury was evaluated using pathological examination and serum ALT levels.The plasma endotoxin and serum TNF-α,IL-1 and IL-18 levels were analyzed by ELISA method.The expression of CD14,LBP,TNF-α,IL-1 and IL-18 proteins in the liver were measured by Western blot.Results The increased serum ALT,fatty degeneration,focal necrosis and inflammatory cell infiltration in the liver were investigated in model group.In addition,plasma endotoxin,serum TNF-α,IL-1,IL-18 levels,and the expression levels of CD14,LBP,TNF-α,IL-1,and IL-18 proteins significantly elevated in model group compared with control group (P ＜ 0.05).However,quercetin treatment improved histological changes,and significantly reduced the levels of plasma endotoxin and serum TNF-α,IL-1,IL-18,as well as the expression of CD14,LBP,TNF-α,IL-1 and IL-18 proteins (P all ＜ 0.05).Fatty degeneration was still investigated in quercetin treatment group,but focal necrosis and inflammatory cell infiltration disappeared.Conclusion Quercetin can protect liver against necrosis and inflammation induced by alcohol,and the mechanism may involve its effect on the reduction of plasma endotoxia,and inhibition of Kupffer cell activity and proinflammatory cytokine expression.

Objective To understand the cardiovascular adverse reactions of domperidone.Methods The literatures about cardiovascular adverse reactions of domperidone were collected by searching CNKI,Wanfang database,VIP database and Canadian and British adverse reactions,etc.The collected data was analyzed to learn about the mechanism of adverse reactions and its influence on the patients.Results Domperidone could induce the adverse reactions,such as sudden cardiac arrest,premature ventricular contraction,ventricular fibrillation,atrial fibrillation,cutting-edge reverse,arrhythmia,myocardial infarction,and tachycardia,etc.The related factors that caused the adverse reactions included the objects,such as,the incidence rate of adverse reaction induced by domperidone was higher in female patients or youth and middle-aged patients.In addition,irrational dosage,status of basic disease and combination use of drugs could cause adverse reactions.Conclusion Domperidone should be used strictly according to the prescription or instruction,and the drug has to be stopped and the symptoms should be treated immediately if the adverse reactions occurr.

Objective: To study the inhibitory effect of total alkaloids from lotus seed on human hepatoma HepG2 cells.Methods: The effect of total alkaloids from lotus seed on the growth of HepG2 cells was studied by CCK-8 kit.The apoptosis rate of HepG2 cells was detected by flow cytometry.Results: When the action time was the same, with the increase of drug concentration, the inhibitory rate of total alkaloids from lotus seed on HepG2 cells increased, in a dose-dependent manner.At 72 h, the half inhibitory concentration (IC50) of total alkaloids from lotus seed on HepG2 cells was 1.501 μg·ml-1.At the same concentration, the inhibitory rate of the total alkaloids from lotus seed on HepG2 cells increased with the extension of the action time.At 72 h, the inhibition rate of 10 μg·ml-1 total alkaloids from lotus seed reached 72%.After treated with the total alkaloids from lotus seed at different concentrations, the apoptosis rate of HepG2 cells significantly increased in a dose-dependent manner.Compared with the blank control group, the difference was statistically significant (P <0.05), and the apoptosis rate of HepG2 cells was 85.6% treated with 20 μg·ml-1 total alkaloids from lotus seed.Conclusion: The total alkaloids from lotus seed can induce cell apoptosis and inhibit the proliferation of human hepatoma HepG2 cells.