Method for active ingredients' in vivo target identification of traditional Chinese medicine using magnetic nanoparticles / 中国中药杂志

Target identification is an important prerequisite for the study of medicine action mechanism. Currently,drug target identification is mostly based on various cell models in vitro. However,the growth microenvironment,nutrition metabolism,biological properties as well as functions are quite different between in vitro cell culture and physiological environment in vivo; wherefore,it is a challenging scientific issue to establish an effective method for identifying drug targets in vivo condition. In this study,we successfully prepared a kind of magnetic nanoparticles( MNPs) which can be chemically modified by the hydroxyl structure of natural bioactive compound echinacoside( ECH) via the epoxy group label on the surface of MNPs. Therefore,organ-selective and recoverable nanoscale target-recognizing particles were prepared. We then intravenously injected the ECH-binding MNPs into rats and distributed them to specific organs in vivo. After cell endocytosis,ECH-binding MNPs captured target proteins in situ for further analysis. Based on this method,we discovered several potential target proteins in the spleen lysates for ECH,and preliminarily clarified the immuno-regulation mechanism of ECH. Collectively,our strategy developed a proof-of-concept technology using nanoparticles for in vivo target identification,and also provided a feasible approach for drug target prediction and pharmacological mechanism exploration.

Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-κ B and MAPK Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-neuroinflammation effect of extract of Fructus Schisandrae chinensis (EFSC) on lipopolysaccharide (LPS)-induced BV-2 cells and the possible involved mechanisms.@*METHODS@#Primary cortical neurons were isolated from embryonic (E17-18) cortices of Institute of Cancer Research (ICR) mouse fetuses. Primary microglia and astroglia were isolated from the frontal cortices of newborn ICR mouse. Different cells were cultured in specific culture medium. Cells were divided into 5 groups: control group, LPS group (treated with 1 μg/mL LPS only) and EFSC groups (treated with 1 μg/mL LPS and 100, 200 or 400 mg/mL EFSC, respectively). The effect of EFSC on cells viability was tested by methylthiazolyldiphenyltetrazolium bromide (MTT) colorimetric assay. EFSC-mediated inhibition of LPS-induced production of pro-inflammatory mediators, such as nitrite oxide (NO) and interleukin-6 (IL-6) were quantified and neuron-protection effect against microglia-mediated inflammation injury was tested by hoechst 33258 apoptosis assay and crystal violet staining assay. The expression of pro-inflammatory marker proteins was evaluated by Western blot analysis or immunofluorescence.@*RESULTS@#EFSC (200 and 400 mg/mL) reduced NO, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in LPS-induced BV-2 cells (P<0.01 or P<0.05). EFSC (200 and 400 mg/mL) reduced the expression of NO in LPS-induced primary microglia and astroglia (P<0.01). In addition, EFSC alleviated cell apoptosis and inflammation injury in neurons exposed to microglia-conditioned medium (P<0.01). The mechanistic studies indicated EFSC could suppress nuclear factor (NF)-?B phosphorylation and its nuclear translocation (P<0.01). The anti-inflammatory effect of EFSC occurred through suppressed activation of mitogen-activated protein kinase (MAPK) pathway (P<0.01 or P<0.05).@*CONCLUSION@#EFSC acted as an anti-inflammatory agent in LPS-induced glia cells. These effects might be realized through blocking of NF-κB activity and inhibition of MAPK signaling pathways.

Coagulation dysfunction in different phases of bloodstream infection-induced sepsis: A clinical study / 医学研究生学报

Objective Bloodstream infection (BSI)-induced sepsis may cause severe coagulation dysfunction. In this study, we analyzed the characteristics of coagulation dysfunction in different phases of BSI-induced sepsis.Methods We retrospectively analyzed the clinical data on 43 cases of BSI treated in our Department of Critical Care Medicine from January 2016 to September 2018. According to the Diagnostic Criteria for Sepsis 3.0, we divided the patients into a sepsis group and a septic shock group, compared the traditional indexes of coagulation function and parameters of thromboelastography (TEG) between the two groups, and analyzed the obtained data with the ROC curves.Results Compared with the sepsis group, the septic shock group showed significantly prolonged prothrombin time (PT) (13.7 \[12.5-17.4] vs 16.7 \[15.0-20.9\] s, P0.05).Conclusion Coagulation dysfunction in BSI-induced sepsis is characterized by elevated values of DD and FDP, and in case of septic shock, it features low coagulation of clotting factors (R≥8.5 min) and fibrin function (K≥2.65 min). The patient with septic shock may experience significantly reduced PLT with basically normal platelet function.

Prognostic value of thromboelastography for trauma-induced coagulopathy / 医学研究生学报

Objective Coagulation disorder is an independent risk factor of death in trauma patients. This study aimed to investigate the prognostic value of thromboelastography (TEG) for patients with trauma-induced coagulopathy.Methods This retrospective study included 124 cases of trauma-induced coagulopathy treated in our Department of Critical Care Medicine from September 2015 to July 2018. We collected the clinical data and laboratory Results of the patients within 2 hours after admission, divided the patients into a survival group (n=108) and death group (n=16) according to their 90-day prognosis after trauma, and compared the TEG parameters between the two groups. Using logistic regression analysis and ROC curves, we identified the optimal prognostic factors and compared the platelet (PLT) count and mortality rate among those with different cut-off values.Results In comparison with the survival group, the death group showed a significant increase in the clot formation time (CFT) (3.2 \[2.2-4.8\] vs 5.2 \[5.0-9.8\] min, P45.65 mm (86 \[46-114\] vs 116 \[84-171\]×109/L, P<0.05), and mortality was remarkably higher in the former than in the latter group (31.8% vs 1.2%, P<0.05).Conclusion Among the TEG parameters, MA / maximal clot strength is a valuable indicator for the prognosis of trauma-induced coagulopathy, and MA<45.65 mm indicates early PLT dysfunction and poor prognosis.

Knockout of IgG receptor FcγRⅡB aggravates systemic and adipose tissue inflammatory responses in mice / 基础医学与临床

Objective To investigate the effect of knockout of IgG receptor( FcγRIIB) on systemic and adipose tis-sue inflammation and fat tissue lipid metabolism treated with high-fat diet ( HFD) . Methods We used 10 male mice with IgG receptor FcγRIIB knockout ( FcγRIIB-/-) and another 10 male FcγRIIB+/+mice as control, and trea-ted them with HFD. At the end of the 17th week, mice were weighed, the blood was taken by cardiac puncture af-ter sacrifice. Adipose tissue was collected to measure inflammation and lipid metabolism. Results Compared with FcγRIIB+/+mice, FcγRIIB-/-mice had significantly increased levels of inflammatory cytokines, IL-6, TNF-α, and IFN-γ in the serum, and increased macrophage infiltration in adipose tissue. M1 polarization gene MCP-1 and TNF-α increased ( P＜0.05) and M2 polarization gene ARG and IL-10 did not differ significantly. However, there was no significant difference in body mass, adipocyte size and expression of lipid metabolism related genes PPARG, CEBPα, FASn, HSL, ATGL, UCP-1 and GLUT4. Conclusions Under HFD treatment, knocking out the IgG re-ceptor FcγRIIB aggravates the inflammatory response of the whole body and adipose tissue, but cannot influence lipid metabolism of adipose tissue and body weight.

Inhibitory effects of acteoside on LPS-induced inflammatory response on BV-2 microglial cells / 中国中药杂志

To investigate the inhibitory effects of acteoside (ACT) on BV-2 microglial cells and the potential mechanism,LPS was used to treat BV-2 cells with or without ACT (12.5,25,50 μmol•L ⁻¹). Then, the expressions of inflammatory factors (NO,TNF-α,IL-6) and inflammation related proteins (iNOS,COX-2,p-IKKβ,IKKβ,p-ⅠκB,ⅠκB) were detected. In addition,the nuclear translocation of NF-κB was explored. The results showed that ACT could significantly suppress the inflammatory response against LPS stimulation by decreasing the expressions of NO,IL-6,TNF-α,iNOS,COX-2 and the phosphorylations of IKKβ and IκB. Moreover,the nuclear translocation of NF-κB p65 was inhibited by ACT. Taken together, ACT could significantly inhibit the inflammatory response of BV-2 microglial cells which were induced by LPS via inhibition of NF-κB signaling pathway.

Progress of methodology for identifying target protein of natural active small molecules / 中国中药杂志

Drug targets are special molecules that can interact with drugs and exert pharmacological functions in human body. The natural active small molecules are the bioactive basis of traditional Chinese medicine, and the mechanism study is a hot topic now, especially for the identification of their target proteins. However, little progress has been made in this field until now. Here, we summarized the recent technologies and methods for the identification of target proteins of natural bioactive small molecules, and introduced the main research methods, principles and successful cases in this field. We also explored the applicability and discussed the advantages and disadvantages among different methods. We hope this review can be used as a reference for the researchers who engaged in natural pharmaceutical chemistry, pharmacology and chemical biology.

Application of chemical activation to in vitro fertilization by round spermatid injection in mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To search for an optimal activation protocol by comparing the chemical activation effects of single-activator and combined activation protocols on mouse oocytes following injection of round spermatids (ROSI) from spermatogenic cells cultured in vitro.</p><p><b>METHODS</b>Using different concentrations of ethanol, ionomycin (Ion), calcium ionophore A23187 (CIA), strontium chloride (SrCl2), cycloheximide (CHX), and 6-dimethylaminopurine (6-DMAP) , we activated post-ROSI oocytes for different times, and activated them by combined protocols at optimal concentrations and action times according to different activation channels. We compared the activation effects of single-activator and combined activation protocols by comparing the rates of fertilization, cleavages, and morulas and blastocysts.</p><p><b>RESULTS</b>With a single activator, the optimal protocols of different activators were as follows: 7% ethanol for 6 min, 5 micromol/L CIA for 5 min, 5 micromol/L Ion for 5 min, 2 mmol/L 6-DMAP for 2 h, 10 mmol/L SrCl2 for 1.5 h, and 10 microg/ml CHX for 1.5 h, among which 10 mmol/L SrCl2 for 1.5 h achieved the highest rate of morulas and blastocysts, significantly better than CHX (P < 0.05) but with no remarkable difference from other activators. The ethanol + 6-DMAP group showed a significantly higher rate of morulas and blastocysts (29.63%) than all other combined activation groups and single-activator groups except SrCl2 (P < 0.05), and it also exhibited higher rates of normal fertilization, cleavages and morula than the SrCl2 group, but with no significant difference.</p><p><b>CONCLUSION</b>The single-activator 10 mmol/L SrCl2 for 1.5 h and the combined activation of 7% ethanol for 6 min + 2 mmol/L 6-DMAP for 2 h are the optimal protocols for chemical activation of mouse oocytes following ROSI, and the combined activation of ethanol + 6-DMAP is even superior to the single-activator protocol.</p>

Epidemiological survey of prevalence of fatty liver and its risk factors in a general adult population of Shanghai / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the prevalence and major risk factors of fatty liver among adult residents in Shanghai.</p><p><b>METHODS</b>A cross-sectional survey with multiple-stage stratified cluster and random sampling was performed. All residents aged 16 and above were invited to participate in the survey; they came from four communities of Yangpu District and Pudong New District. Questionnaire, physical examination, serum lipid-profile, and 75 gram oral glucose tolerance test and ultrasonographic examination of liver were undertaken. Analysis of data was performed through SPSS 11.0 for Windows statistical package.</p><p><b>RESULTS</b>A total of 3175 residents took part in the survey, which was 75% of adult residents of the investigated communities and 2.26/10 000 of Shanghai municipal residents. Of the 3175, 1218 were males and 1957 were females. The mean age of the participants was 52.4+/-15.1 years and ranged from 16 to 88 years. Fatty liver was detected with ultrasound examination in 661 participants (20.82%), among which 3.48% had alcoholic fatty liver, 4.08% had suspected alcoholic fatty liver, and 92.43% had nonalcoholic fatty liver. The age-adjusted, sex-adjusted prevalence of fatty liver in Shanghai adult residents was 17.29%, the prevalence of alcoholic fatty liver, suspicious alcoholic fatty liver, and nonalcoholic fatty liver in Shanghai adult residents were 0.79%, 1.15%, and 15.35%, respectively. The prevalence of fatty liver was increased with aging in males and in females. Among participants younger than 50 years old, the prevalence of fatty liver in males was significantly higher than that in females, but in participants older than 50 years the case was just the opposite, higher in females. The mean age (years), body mass index (BMI), waist circumference, blood pressure, fasting and two hour serum glucose level, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and the presence of obesity, diabetes mellitus, hypertension, dyslipidemia, and gallstones in the fatty liver group was significantly higher than those in the group without fatty liver, but the high-density lipoprotein cholesterol (HDL-C) level and the educational level were both lower in the fatty liver group. Logistic regression analysis demonstrated that the prevalence of fatty liver was only positively correlated to nine risk factors, including male sex, educational level, waist circumference, BMI, fasting glucose level, HDL-C, TG, hypertension and diabetes mellitus. In heavy drinkers, obesity increased the risk for fatty liver by 4.8-fold, but heavy drinking only increased the risk for fatty liver 1.5-fold (95% CI 0.9-2.6, P=0.1685).</p><p><b>CONCLUSION</b>There is a high prevalence of fatty liver among adult residents in Shanghai, and nonalcoholic fatty liver is the major type. Metabolic disorders such as obesity and diabetes mellitus, hypertension and hyperlipidemia are more closely associated with fatty liver than heavy drinking in Shanghai.</p>

Influential factors related to metabolic syndrome on the outcome of non-diabetic subjects in a community of Shanghai by two-year follow-up / 中华内分泌代谢杂志

Objective To investigate the influence of factors related to metabolic syndrome(MS)on the outcome in subjects without diabetes mellitus in a community.Methods A two-year follow-up study was conducted in 885 subjects who were enrolled in the epidemiologic survey carried out in Pingliang Community, Shanghai in 2002.Oral glucose tolerance test,lipid prefde,blood pressure(BP),body mass index(BMI),waist and hip circumferences were measured.Results (1)The baseline of BMI,fasting plasma glucose(FPG),2h plasma glucose after glucose loading(2hPG),BP,triglyceride(TG)in the subjects with impaired glucose regulation(IGR)increased significantly as compared to those with normal glucose regulation(NGR)(all P