Objective To investigate the effect of mTOR signaling pathway on bleomycin-induced pulmonary fibrosis.Methods 30 healthy male C57BL/6 mice aged 6～8 weeks were fed for 1 week and divided into control group(NC group,n=5),bleomycin group(BLM group,n=5),and rapamycin+bleomycin group(Rapa+BLM group,n=5).Mice were euthanized by cervical dislocation at 7 and 28 days,and lung tissues were collected.HE staining was used to observe inflammatory infiltration in lung tissue,and Masson's staining was used to assess the severity of lung fibrosis.Western blot and qPCR were used to detect the expression levels of collagen Ⅰ,collagen Ⅲ and α-SMA to evaluate the degree of lung fibrosis.Western blot was used to detect the expression of mTOR,P70S6K and their phosphorylation levels in each group.Results Compared with the NC group,the BLM group showed thickened alveolar septa,obvious inflammatory changes,and collagen deposition.The protein expression of Collagen Ⅰ,Collagen Ⅲ,and α-SMA were significantly increased(P<0.01),with increased mRNA expression of Collagen Ⅰ,Collagen Ⅲ,and α-SMA(P<0.05),and elevated p-mTOR and p-p70S6K expression(P<0.05).Compared with the BLM group,the Rapa+BLM group showed improved lung tissue structure,reduced inflammation and collagen deposition,a downward trend in Collagen Ⅰ,Collagen Ⅲ,and α-SMA protein expression(P>0.05),a downward trend in Collagen Ⅰ mRNA(P>0.05),and decreased Collagen Ⅲ and α-SMA mRNA expression(P<0.05).Conclusion Abnormal mTOR activation was observed in bleomycin-induced pulmonary fibrosis;inhibiting mTOR signaling pathway activation can effectively alleviate the formation of pulmonary fibrosis.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

OBJECTIVE： To investigate absorption kinetic characteristics of main active components as 4-（glucoseoxy）- glucoseoxybenzyl cinnamate （A1）， 2-isobutyl malic acid （A2）， 1，4-bis [4-（glucoxy） benzyl]-2-isobutyl malic acid ester （A3）， dihydrophenanthrenes 1 （A4） and 1，4-bis [4-（glucosoxy） benzyl]-2-isobutyl malic acid ester-2-（4-O-cinnamoyl-6-O-acetyl） glucoside （A5） from ethanol extract of Bletilla striata in the intestines of rats. METHODS： Using puerarin as internal standard， UPLC-MS/MS was used to determined the concentration of A1-A5 in intestinal circulation fluid. The determination was performed on Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile （containing 0.1％ formic acid）-water （containing 0.1％ formic acid） （gradient elution） at the flow rate of 0.35 mL/min. The column temperature was 45 ℃， and sample size was 3 μL. The positive ion and negative ion scanning were carried out in the multiple reaction monitoring mode by electrospray ion source. The ion pairs for quantitative analysis were m/z 593.2→431.1 （A1）， m/z 189.0→129.0 （A2）， m/z 725.3→457.2 （A3）， m/z 347.1→332.1 （A4）， m/z 1 059.3→793.1 （A5）， m/z 417.0→267.0 （internal standard）. In the in vivo intestinal circulation perfusion model， using accumulative absorption transfer rate （A） and absorption and transformation rate constant （Ka） as indexes， the effects of different doses of ethanol extract from B. striata （low-， medium-， high-dose were 166， 333，667 μg/mL，respectively）， bile， P-glycoprotein （P-gp） inhibitors （verapamil） and different intestinal segments on the absorption of above 5 components were investigated. RESULTS： The linear range of A1， A2， A3， A4 and A5 were 0.22-14.00， 0.34-21.75， 1.99-127.16， 0.15-9.75， 0.16-10.00 μg/mL（r＞0.99）. The limits of quantitation were 0.22， 0.34， 1.99， 0.15， 0.16 μg/mL， respectively. The lowest detection limits were 0.028， 0.085， 0.251， 0.035 and 0.010 μg/mL. RSDs of inter-day and intra-day were all lower than 10％. The recoveries ranged 83.60％-106.91％. Matrix effect did not affect the determination of the substance to be measured. A and Ka values of A1 in B. striata ethanol extract low-dose and medium-dose groups were significantly higher than high-dose group； A value of A3 in low-dose group was significantly higher than medium-dose and high-dose groups （P＜0.05 or P＜0.01）. A and Ka values of A1 and A3 in non-ligation group were significantly lower than control group， while A and Ka values of A4 were significantly higher than control group （P＜0.05 or P＜0.01）. A and Ka values of A1 and A3 in P-gp inhibitor group were significantly lower than control group （P＜0.05 or P＜0.01）. A values of A1 in jejunum group， ileum group and colon group， Ka value of A1 in colon group， A and Ka values of A2 in colon group， A value of A3 in ileum group， A and Ka values of A4 in ileum group and colon group， A values of A5 in jejunum group and ileum group as well as Ka value of A5 in jejunum group were all significantly lower than duodenum group. Ka values of A3 in jejunum group， ileum group and colon group were significantly higher than duodenum group （P＜0.05 or P＜0.01）. CONCLUSIONS： Established UPLC-MS/MS method is specific， sensitive and simple， and it can be used for quantitative analysis and pharmacokinetic study of A1-A5. The 5 active components in B. striata ethanol extract are absorbed by the whole intestine， and the intestinal segments are different. A1 and A3 are absorbed more in intestinal tract and may be saturated. Bile can inhibit intestinal absorption of A1 and A2， but promoted intestinal absorption of A4. A1-A5 may not be the substrate of P-gp.

Objective: To assess the relationship between body mass index (BMI) and mortality in adults of Shanxi, China. Methods: Baseline data were from the '2002 China Nutrition and Health Survey’ in Shanxi province. All the death-related investigation and follow-up visits were carried out from December 2015 to March 2016. The follow-up program covered 5 360 people from all the 7 007 participants aged 18 years and over that having complete core information, with a rate as 76.5%. Participants of this study were divided into eight groups, according to the appearance of BMI. Taking the group with the lowest mortality density as the reference group, Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of deaths by the whole population, gender and age groups (≥60 years, <60 years). Results were then adjusted by age, gender, smoking, alcohol use and education level from the baseline survey. Sensitivity analysis was also conducted. Results: Results from the study showed that among the total number of 67 129 person- years from the average period of 12.5 years, there were 615 deaths occurred, with the mortality density as 916 per 100 000 person-years. Taking the BMI range of 26.0-27.9 kg/m² as the reference, the aHRs of death increased to 1.90 (95%CI: 1.26-2.86), 1.68 (95%CI: 1.15-2.45), 1.49 (95%CI: 1.08-2.06) and 1.72 (95%CI: 1.07-2.76) after the multivariate adjustment, in these four groups (BMI<18.5, 18.5-19.9, 22.0-23.9 and ≥30.0 kg/m²), respectively. Low body weight (BMI<18.5 kg/m²) was associated with higher risks of death in the elderly of ≥60 years, with the aHR of death as 1.94 (95%CI: 1.20-3.15). Conclusions When BMI appeared as ≤19.9 kg/m², 22.0-23.9 kg/m² and ≥30.0 kg/m², the risks of death would increase. In addition to programs that focusing on obesity, special attention should be paid to the high risk of mortality which was caused by low-weight and malnutrition in the elderly.

Objective To evaluate the dynamic changes of left ventricular mechanical synchrony in the early period after acute myocardial infarction (AMI) by two-dimensional speckle tracking imaging (2D-STI) and real time three-dimensional echocardiography (RT-3DE),and analyze the correlation with phase analysis of single photo emission computed tomography gated myocardial perfusion imaging (SPECT GMPI) in porcine models,and further to investigate the clinical significance of left ventricular mechanical dyssynchrony in patients with AMI.Methods Bama minipigs(n =11) were subjected to left anterior descending (LAD) occlusion by balloon to introduce AMI porcine models.All animals underwent 2D-STI and RT-3DE at the baseline (before AMI),1 day,1 week and 4 weeks after LAD occlusion,respectively.In addition,SPECT GMPI was measured at baseline and 1 day after AMI.Data was analyzed and compared the dynamic changes of left ventricular mechanical synchrony before and after AMI.Then the correlation between echocardiography and SPECT GMPI in evaluating left ventricular mechanical synchrony before and after AMI were calculated.Results Eight pigs were successfully established as AMI models and complete the study.SPECT GMPI,2D-STI and RT-3DE showed that the left ventricular mechanical synchrony indexes were significantly higher at 1 day after AMI than those before AMI,which means the appearance of left ventricular mechanical dyssynchrony.Compared with those 1 day after AMI,GLS,Time SD,Tmsv16-SD％ and Tmsv16-Dif％ did not change significantly at 1 week after AMI,but they significantly increased at4 weeks after AMI (all P ＜0.05).At baseline and 1 day after AMI,the GLS measured by 2D-STI and the SPECT GMPI parameter phase bandwidth (BW) showed good correlation(r =0.708-0.719,P ＜0.05),Time SD was significantly correlated with the SPECT GMPI parameter phase standard deviation (SD)(r =0.717-0.830,P ＜0.05),while Tmsv16-Dif％ derived from RT-3DE had a better positive correlation with BW (r =0.713-0.857,P ＜0.05),as similar as Tmsv16-SD％ with SD(r =0.803-0.957,P ＜0.05).Conclusions Left ventricular mechanical dyssynchrony is present 1 day after AMI.Compared with that 1 day after AMI,left ventricular mechanical dyssynchrony doesn't change significantly at 1week after AMI,but further aggravates at 4 weeks after AMI.The parameters of 2D-STI and RT-3DE have good correlation with the mechanical synchrony parameters measured by SPECT GMPI.2D-STI and RT-3DE can be used as reliable methods to evaluate left ventricle mechanical dyssynchrony early after AMI.

Objective To assess left ventricular remodeling (LVRM) after acute myocardial in-farction (AMI) quantitatively by SPECT gated myocardial perfusion imaging (GMPI), and further explore its influencing factors. Methods Twelve Ba-Ma miniature swine were used to establish AMI model. GMPI was performed at the baseline (before AMI), 24 h, 1 and 4 weeks after AMI. Infarct expansion index, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction ( LVEF) and myocardial perfusion defect were measured. Meanwhile, creatine kinase isozyme MB (CK-MB) and hypersensitive cardiac troponin I (hs-cTn I) were detected. The changes of LVEDV and LVESV before and after AMI (ΔLVEDV and ΔLVESV) were calculated. Repeated measurement analy-sis of variance, the least significant difference t test and Pearson correlation analysis were performed. Re?sults Nine AMI swine were successfully created. LVRM was present 24 h after AMI. LVEDV and LVESV were significantly greater than those before AMI and aggravated within 1 week after AMI, then were down-wards at 4 weeks after AMI. Before AMI, 24 h, 1 and 4 weeks after AMI, the LVEDV was (34.44±7. 90), (47.56±22.66), (71.89±14.90) and (70.33±19.47) ml (F = 28.836, P<0.001), and the LVESV was (10.11±5.49), (25.33±11.62), (40.89±15.88) and (35.44±17.11) ml (F = 22.450, P<0. 001). In-farct expansion index increased progressively within 4 weeks after AMI (F= 16.054, P<0.001). LVEF was significantly lower after AMI than that before AMI (F = 18.267, P<0.001) and improved at 4 weeks after AMI compared to that at 1 week ((52.56±14.96)％ vs (45.11±15.80)％; t= 2.440, P<0. 05). There was a significant correlation between the change in perfusion defect and the ΔLVEDV or ΔLVESV (r values:0. 731 and 0.700, both P<0.05) at 1 week after AMI. In addition, hs-cTn I at 24 h was correlated withΔLVEDV at 24 h and 4 weeks after AMI, respectively (r values: 0.669 and 0.693, both P<0.05). Conclu?sions LVRM and cardiac dysfunction occur in the early period after AMI. LVRM and cardiac dysfunction are most severe at 1 week after AMI, and recover at 4 weeks after AMI, whereas infarct expansion is aggra-vated within 4 weeks. Infarct size and hs-cTn I are closely related to the degree of LVRM.

Aim Modelorganismzebrafishwasusedto study metabolites and metabolite profile of the gallic acid and protocatechuic acid of effective fractions of Polygonum capitatum,and discuss the feasibility and rationality of the model organism zebrafish in the study ofdrugmetabolism.Methods Thetwocomponents were exposed to model organism zebrafish after 24 h of solution treatment by using ultra-high performance liq-uid chromatography-quadrupole-time-of-flight tandem mass spectrometry technology (UHPLC-Q-TOF MS ) method with mass defect filter (MDF ),and the data was treated with data mining software(Metabolite Tool-sTM).Results Afterzebrafishmetabolism,themain reactions of gallic acid and protocatechuic were methyl-ation sulfated. In addition to the two parent com-pounds,six phase II metabolites were identified,in-cluding four methyl sulfate products and two sulfation products.Conclusions Themetabolismofthegallic acid and protocatechuic acid of effective fractions of Polygonum capitatum by zebrafish presents phase Ⅱmetabolites,which is highly consistent with the meta-bolic mechanism of rats.Thus it indicates the rationali-ty of the methods.At the same time,it also provides the experimental basis for clarifying the substance basis of the drug.

This study aimed at exploring the application of microtox technology to the evaluation of comprehensive toxicity of Sheng Mai injections.Characteristic parameters of vibrio fischeri (CS234) were measured by methodology inspection under different conditions to optimize the reaction condition with reliable technology.It was the first experiment to accomplish the comprehensive toxicity of Sheng Mai injections from various manufacturers using vibrio fischeri under the target condition.It was found that parameters of the optimum condition contained 0.9 mL recovery liquid volume in each freeze-dried vial and 50 μ L bacteria suspension of each sample,being included in 2 mL solution in aggregate under 10 mins' detection time after adding bacteria suspension with the favorable pH value ranging from 5 to 10 and luminous intensity from 0.8 to 1.2 million within 10 mins.The relative standard deviation values of replication experiment and precision test were all below 15％.Under this optimum detection condition,it was found that the EC50 values were 22.10％,34.10％ and 46.04％,respectively,presenting significant statistical differences (P＜0.05).These results demonstrated that the growth of biological detection standards of Sheng Mai injection was highlighted a long way to go.Besides,the microtox-based fast test for the evaluation of the comprehensive toxicity of Sheng Mai injection showed a prospective application to controlling the quality of different products from manufacturers.