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1.
China Pharmacy ; (12): 91-97, 2021.
Article in Chinese | WPRIM | ID: wpr-862272

ABSTRACT

OBJECTIVE:To systematically evaluate the efficacy and safety of sodium-glucose co-transporter 2 (SGLT-2)inhibitors combined with insulin in the treatment of type 1 diabetes mellitus(T1DM),and to provide evidence-based reference for clinical treatment of T1DM. METHODS:Retrieved from PubMed,Cochrane library,Embase,Clinical Trials,CNKI,CBM and Wanfang database,randomized controlled trials(RCT)about SGLT-2 inhibitor(trial group)versus placebo(control group)in the treatment of T1DM based on insulin treatment were collected during the inception to Feb. 2020. After data extraction of literatures met inclusion criteria,Cochrane risk bias evaluation tool 5.1.0 was used to evaluate its quality,and Meta-analysis was perfomed by using Stata 12.0 software. RESULTS:A total of 11 RCTs were included,involving 7 003 patients. The results of Meta-analysis showed that the decrease of HbA1c [SMD=-0.49,95%CI(-0.53,-0.44),P<0.001],the proportion of patients with HbA1c≥ 0.5% and without severe hypoglycemia [OR=3.93,95% CI(3.49,6.21),P<0.001],the proportion of patients with HbA1c≥ 0.5% [OR=2.65,95%CI(2.25,3.12),P<0.001],the target rate of HbA1c level<7.0% [OR=2.85,95%CI(2.44,3.33),P<0.001] and the decrease of body weight [SMD=-0.83,95%CI(-0.96,-0.70),P<0.001] in trial group were significantly larger or higher than control group;the decrease values of daily insulin dosage,fasting blood glucose,postprandial blood glucose,systolic blood pressure and diastolic blood pressure in trial group were significantly higher than those in the control group,with statistical significance(P≤0.011). The total incidence of ADR [OR=1.14,95%CI(1.04,1.26),P=0.007],the incidence of SGLT-2 inhibitor related ADR [OR=2.17,95%CI(1.75,2.99),P<0.001],the incidence of severe ADR [OR=1.48,95%CI(1.24,1.77),P<0.001], the incidence of genital infection [OR=3.84,95%CI(3.14,4.69),P<0.001],the incidence of diarrhea [OR=1.47,95%CI(1.09,1.97),P=0.011],the incidence of fluid reduction related ADR [OR=2.05,95%CI(1.37,3.08),P=0.001],the incidence of ketosis related ADR [OR=4.18,95%CI(3.15,5.55),P<0.001],the incidence of ketoacidosis [OR=4.33,95%CI(3.01,6.23),P<0.001] and the incidence of severe ketoacidosis [OR=5.06,95%CI(2.61,9.81),P<0.001] were significantly higher than control group, with statistical significance. There was no statistical significance in the incidence of hypoglycemia,severe hypoglycemia,urinary tract infection or kidney injury between 2 groups. CONCLUSIONS:SGLT-2 inhibitors for the treatment of T1DM can significantly improve the blood glucose,reduce body weight and daily insulin dose,lower systolic blood pressure and diastolic blood pressure,while dose not increase the risk of hypoglycemia,urinary tract infections and renal impairment but increase the risk of total ADR as well as the risk of ADR such as genital infection,diarrhea,ketoacidosis,to which should be paid attention.

2.
Chinese Critical Care Medicine ; (12): 464-467, 2019.
Article in Chinese | WPRIM | ID: wpr-753993

ABSTRACT

Objective To explore the effects of lipopolysaccharide (LPS) on the expression of inflammatory genes in A549 cells line under different concentrations and different action time, this study laid the foundation for further establishment of acute respiratory distress syndrome (ARDS) cell model in the optimal concentration-time way. Methods A549 cells line was incubated routinely in 5%CO2 incubator at 37 ℃ with high glucose DMEM medium which included 10% fetal calf serum. Cells in logarithmic phase was cultured for passage, the cells was count to adjust cell density to (5-7)×105 and tile evenly in six-hole plate. Cells were cultivated for 2 days and once the cells confluence to 50%-60%, serum-free medium DMEM was changed for 12 hours cultivation. 10 mg LPS was added to 10 mL DMEM for oscillated blending to prepare 1 g/L stock solution. 0.5, 1.0 and 2.5 mL LPS stock solution was taken respectively and diluted LPS stock solution for 50 mL constant volume to prepare 0, 10, 20 and 50 mg/L LPS working solution. Then 0, 10, 20 and 50 mg/L LPS solution was added to react for 0, 1, 3 and 5 hours respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine mRNA expression of A549 cells line interleukins (IL-6, IL-1β) and tumor necrosis factor-α(TNF-α). LPS action of 10 mg/L for 0 hour was used as the time control group, LPS action of 0 mg/L for 1 hour was used as the concentration control group, and the gene expression was calculated with 2-ΔΔCt method. Results ① As to the time factor, with the same action of LPS concentration, the relative expression levels of inflammatory genes (IL-6, IL-1β and TNF-α) in A549 cells line after being treated with 10 mg/L LPS for 1 hour were significantly higher than those for 0 hour respectively [IL-6 mRNA (2-ΔΔCt): 5.71±0.42 vs. 1.00±0.00, IL-1β mRNA (2-ΔΔCt): 5.63±0.30 vs. 1.00±0.00, TNF-α mRNA (2-ΔΔCt): 5.38±0.61 vs. 1.00±0.00, all P < 0.01], and there were no significant changes in the expression levels of inflammatory genes in A549 cells line of other time groups. ② As to the concentration factor, with the same action time, the relative expression levels of inflammatory genes (IL-6, IL-1βand TNF-α) in A549 cells line after being treated with 10 mg/L LPS for 1 hour were significantly higher than with 0 mg/L for 1 hour respectively [IL-6 mRNA (2-ΔΔCt): 5.70±0.64 vs. 1.00±0.00, IL-1β mRNA (2-ΔΔCt): 6.25±0.25 vs. 1.00±0.00, TNF-α mRNA (2-ΔΔCt): 5.57±0.25 vs. 1.00±0.00, all P < 0.01], there were no significant changes in the expression levels of inflammatory genes in A549 cells line of other concentration groups. Conclusion The LPS concentration of 10 mg/L and the action time of 1 hour are the most suitable concentration-time conditions for establishing ARDS cell models of A549 cells line.

3.
Chinese Journal of Epidemiology ; (12): 697-701, 2019.
Article in Chinese | WPRIM | ID: wpr-805456

ABSTRACT

Objective@#To investigate the relations between dietary intake during pregnancy and the incidence of their babies with small for gestational age (SGA).@*Methods@#Data on demographics, dietary intake of protein, fat, and carbohydrates of the pregnant mothers during the first, second and third trimester, were collected. Information related to birth weight and gestational age of the infants were also gathered. A total of 8 102 women, who delivered their babies at the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016, were enrolled in this project. Among them, 961 mothers had infants with SGA but the other 7 141 of them having normal infants. Unconditional logistic regression model was used to analyze the effect of dietary nutrient intake on SGA the first, second and third trimester.@*Results@#We found that low dietary intake of protein during the first trimester and following trimesters during pregnancy were positively associated with higher risk of SGA (OR=1.534, 95%CI: 1.217-1.934; OR=1.268, 95%CI: 1.005-1.599; OR=1.310, 95%CI: 1.036-1.655). When adjusting for maternal pre-pregnancy BMI, we found that when mothers were with a pre-pregnancy BMI less than 18.5 or with low maternal intake of protein during the first trimester, positive association with higher risk of SGA (OR=1.872, 95%CI: 1.033-3.395; OR=1.754, 95%CI: 1.125-2.734), was noticed. However, for mothers with a pre-pregnancy BMI between 18.5 and 24.0 or with low protein intake during the first trimester, significant association with higher risk of SGA (OR=1.465, 95%CI: 1.089-1.972) was found.@*Conclusions@#Through our observation, maternal dietary intake during pregnancy seemed to be associated with the risk of SGA but the effects of dietary intake were different, according to the BMI of pre-pregnancy population. Early pregnancy appeares as the key period for dietary intake which may influence the SGA.

4.
Chinese Journal of Epidemiology ; (12): 682-685, 2019.
Article in Chinese | WPRIM | ID: wpr-805453

ABSTRACT

Objective@#To explore the effect of lipopolysaccharide intervention program on Legionella pneumonia.@*Methods@#C3H/HeN mice (6-8 weeks old) were used as experimental animals. The mice were randomly divided into lipopolysaccharide intervention, non-lipopolysaccharide intervention and control groups. Each group was again divided into three time points: 12 h, 24 h and 48 h. Mice in the lipopolysaccharide intervention group were intraperitoneally injected with E. coli lipopolysaccharide (100 ng per mice), and the rest groups were intraperitoneally injected with normal saline. After 24 hours, mice in the lipopolysaccharide intervention and the non-intervention groups mice were infected with Legionella by tracheal injection and the control group was given the same amount of saline. All the mice were killed at 12, 24 and 48 hours respectively. The mice were anatomized, lungs of the mice were separated and weighed. Organ coefficients (lung weight/body weight of mice) were calculated. 1 ml Orbital blood was collected. Toll-like receptor 4 (TLR4) levels of peripheral blood mononuclear cells were measured by flow cytometry. The contents of TNF-α and IL-1β in the upper left lung lobe were measured by ELISA.@*Results@#In the lung organs, the coefficients of lipopolysaccharide non-intervention group were higher than the other groups and there was no significant difference seen between the lipopolysaccharide intervention group and the controls. TLR4 peaked at 12 hours in both the lipopolysaccharide intervention and the non-intervention groups while the TLR4 level in the intervention group was higher than that in the non-intervention group. There were no significant differences appeared on the TLR4 expression levels between the two Legionella pneumonia modelled groups at 24 or 48 hours. There was no significant difference seen regarding the concentration of TNF-α and IL-1β between the intervention and the control groups. The secretion levels of TNF-α and IL-1β in the non-intervention group were higher than those in the intervention group at each time point.@*Conclusion@#The lipopolysaccharide intervention program may alleviate the inflammatory symptoms of Legionella infection.

5.
Acta Pharmaceutica Sinica B ; (6): 795-804, 2018.
Article in English | WPRIM | ID: wpr-690863

ABSTRACT

Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury, but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes (CMs) for driving the differentiation of cardiac stem cells (CSCs). Forced hypoxia-inducible factor 1 (HIF-1) expression and physical hypoxia (5% O) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1 by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor (PD98059), but not inhibitors of JNK (SP600125), Notch (DAPT), NF-B (PTDC), JAK (AG490), or STAT3 (Stattic) suppressed hypoxia-induced Jagged1 protein expression in CMs. c-Kit CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed GATA4, SM22 or vWF, but not Nkx2.5 and cTnI. Moreover, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU/Nkx2.5 cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced differentiation. Our results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling, and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures HIF-1/Jagged1/Notch signaling.

6.
Chinese Pharmacological Bulletin ; (12): 1131-1135, 2017.
Article in Chinese | WPRIM | ID: wpr-613660

ABSTRACT

Aim To investigate the effects of midazolam on porcine isolated coronary artery rings pre-contracted by potassium chloride(KCl)and the possible mechanism.Methods The vessel tension recorder system was used.Isotonic tension of porcine isolated coronary artery rings precontracted by KCl(30 mmol·L-1)was recorded.The vasorelaxing action of midazolam and effects of various drugs were observed in the rings.Results Midazolam(3×10-6~1×10-4 mol·L-1)respectively concentration-dependently reduced the contraction induced by KCl,and there was significant difference between the rings with intact and denude endothelium(P<0.05).On KCl-induced precontraction,midazolam′s relaxation was depressed by L-NAME and the blend of L-NAME and L-Arg(P<0.05),but was not affected by Indo,L-Arg and 1400W.The contraction was not prevented by pretreatment with the inhibitor of Na+/Ca2+ exchanger(KB-R7943).The inhibitor of KATP(Gli)restrained the diastolic function of midazolam(P<0.05),while the inhibitor of BKCa(TEA),Kir(BaCl2),KV(4-AP)had no obvious effect.Conclusions Midazolam produces remarkable vasodilatation on KCl pre-contracted porcine isolated coronary artery rings.Its relaxtion effect is via concentration-dependent and endothelium-dependent mechanisms and relevant to the production of NO.Na+/Ca2+ exchanger is not involved midazolam′s vasodilatation on KCl pre-contracted porcine coronary artery rings.The relaxant mechanism of midazolam may be concerned with KATP.The Kir,BKCa and KV may be not involved.

7.
Chinese Journal of Pathophysiology ; (12): 1386-1392, 2017.
Article in Chinese | WPRIM | ID: wpr-608985

ABSTRACT

AIM: To explore the expression and significance of receptor tyrosine kinase anexelekto (Axl) in nasopharyngeal carcinoma (NPC).METHODS: Immunohistochemistry was used to detect the Axl protein expression of 78 patients with NPC and 32 patients with nasopharyngeal chronic inflammation (NPI).The correlations between the Axl protein levels and the clinical parameters of NPC patients were analyzed.NPC cells were cultured in vitro, and the expression of Axl in well differentiated CNE1 cells, poorly-differentiated CNE2Z cells and undifferentiated C666-1 cells was detected by immunofluorescence staining.After treatment of the CNE1and C666-1 cells with Axl specific inhibitor TP-0903, CCK-8 assay was used to detect cell viability, flow cytometry was adopted to analyze the cell cycle distribution, qPCR was used to examine the mRNA levels of Axl and proliferating cell nuclear antigen (PCNA), and Western blot was used to examine the protein expression of Axl and p-Axl.RESULTS: Axl protein was localized in the cell membrane and cytoplasm.The rate of high expression of Axl in NPC was significantly higher than that in NPI (P<0.01).High Axl expression showed no correlations with NPC patients'' age, gender and M stage, while positively correlated with the clinical stage, T stage and N stage (P<0.05).Axl protein showed a low level in the CNE1 cells, but showed a high level in CNE2Z and C666-1 cells.TP-0903 inhibited cell viability in concentration and time dependent manners.TP-0903 at 2 nmol/L showed significant inhibitory effects, as evidenced by arresting the cell cycle at G0 phase and reducing Axl activity and PCNA expression.CONCLUSION: High expression of Axl promotes the clinical progress of NPC.TP-0903 significantly inhibits the viability of NPC cells, suggesting that Axl may be a valuable target in the NPC treatment.

8.
Article in Chinese | WPRIM | ID: wpr-491000

ABSTRACT

BACKGROUND:Activation of Notch signaling plays a critical role in stem cel differentiation, and this effect seems to be cel-type dependent. Little is reported on the role of activation of Notch1 signaling in the differentiation of c-Kit+ bone marrow mesenchymal stem cels. OBJECTIVE:To analyze the influence of activation of Notch1 signaling on the differentiation of c-Kit+ bone marrow mesenchymal stem cels. METHODS:The Notch1 intracelular domain (N1-ICD) was obtained from the cDNA library by PCR and cloned intoBamHI/AgeI digested adenoviral GV314 plasmid to construct N1-ICD overexpressing shuttle plasmid, and the positive clones were verified by sequencing. N1-ICD shuttle plasmid and helper plasmids pBHGloxΔE1,3 Cre were used to co-transfect HEK293T cels to obtain N1-ICD overexpressing adenoviral particles (N1-ICD-Ad). The c-Kit+ subpopulation were isolated from bone marrow mesenchymal stem cels of the Sprague-Dawley rat femurviamagnetic activated cel sorting. After transfection of the c-Kit+ BMSCs with N1-ICD-Ad adenovirus, we assessed the activation of Notch1 signaling and differentiation in c-Kit+ bone marrow mesenchymal stem cels by quantitative RT-PCR and immunofluorescent staining. RESULTS AND CONCLUSION:N1-ICD coding sequence was successfuly generated from the cDNA library, and then was cloned into the linearized adenoviral vectors GV314. The resistant clones were verified by sequencing. With the assistance of packaging plasmids, recombinant N1-ICD-Ad adenovirus plasmids were successful packaged in HEK293T cels, and its title was 2×1012 PFU/L. c-Kit+ bone marrow mesenchymal stem cels with the purity of 91.6% were successfuly isolated from the bone marrow mesenchymal stem cels of the Sprague-Dawley rat femur. Compared with the blank and negative controls, N1-ICD-Ad infection in the c-Kit+ bone marrow mesenchymal stem cels led to substantial accumulation of N1-ICD in the cytoplasm and nuclei, significantly unregulated expressions of Hes1 (a downstream gene of Notch) and cardiomyocyte differentiation genes Nkx2.5 and cTnT, significantly increased the expression of von Wilebrand factor, an endothelial cel differentiation gene, and mildly increased the expression of smooth muscle22α, a smooth muscle cel differentiation gene. These experimental results indicate that the activation of Notch1 signaling contributes to multi-lineages differentiation of c-Kit+ bone marrow mesenchymal stem cels, and the construction of N1-ICD overexpressing adenoviral vector makes the foundation for further research on the role of Notch1 signaling in stem cel biology.

9.
Herald of Medicine ; (12): 644-648, 2015.
Article in Chinese | WPRIM | ID: wpr-464297

ABSTRACT

Objective To optimize the formulations of venlafaxine hydrochloride ( VH ) emulsions by using central composite design-response surface methodology. Methods The effect of amounts of Arlacel P135, VH, PEG-400, and NaCl on the emulsion viscosity, centrifugation breakage, and mean diameter was systemically investigated, respectively. The desirable formulation that combining these three response variables was constructed. Linear equations and a second-order polynomial equation were fitted to the data, and the outcome equation was used to predict the responses in the optimal region. Results There was a quantitative relationship between 4 factors and 3 evaluation indexes and evaluation the “desirability” . The optimal formulation of the VH emulsion were as follows:taking 0. 48 g of Arlacel P135, 0. 40 g of VH, 0. 26 g of PEG-400, and 0. 025 g of NaCl. The experimental values of the response variables were highly closed to the predict values. Conclusion The model presents good prediction and can be used to optimize the preparation of VH emulsion, which obtaining stable W/O emulsion.

10.
Article in Chinese | WPRIM | ID: wpr-419803

ABSTRACT

Objective To observe the effects of drainage with vacuum and closure (VAC) on acute wounds, and explore the mechanism of drainage with VAC in promoting wound healing.Methods Twenty-four acute wounds were inflicted on the backs of 12 New Zealand white rabbits (each rabbit two wounds), and the rabbits were divided into a drainage with VAC group and a control group randomly. The drainage with VAC group was treated with drainage with VAC. The control group was treated with wet saline gauze. The wounds were observed 3 and 7 days after treatment. Patho-morphological changes in tissues from the compressed area were observed by HE staining. The expression level of Cx 43 mRNA was detected using a RT-PCR.Results At the 3rd and 7th day after treatment, the wounds of the drainage with VAC group were clean, fresh and had less edema compared with those of the control group. Pathomorphological tissue changes were more obvious in the drainage with VAC group. The expression of Cx 43 mRNA in the drainage with VAC group had declined significantly compared with the control group.Conclusion Drainage with VAC can promote inflammatory cell infiltration, down-regulate the expression of Cx 43 mRNA, and promote wound healing.

11.
Article in Chinese | WPRIM | ID: wpr-389829

ABSTRACT

Objective To investigate the effect of the ubiquitin-proteasome pathway inhibitor MG132 on the natural resistance to cisplatin in the human cervical cancer line (HCE1) muhicellular spheroid (HCE1/MCS) model and to probe it if MG132 could reverse the HCE1/MCS resistance to cisplatin, as well as the possible mechanism of drug resistance.Methods (1) HCE1/MCS was obtained using liquid overlay and rotating technique.(2)Four groups were established (MG132 group, cisplatin group, MG132 + cisplatin group, the control group).Cell viability were measured by trypan blue exclusion assay.Cell cycle and apoptosis were detected by flow cytometry.(3) The expression of nuclear factor (NF) kB of both HCE1 monolayer cells (HCEI/MC) and HCE1/MCS was detected by western blot, and the expression of B cell lymphoma/leukemia-2 (bcl-2) was detected by immunohistochemistry.Results (1) HCE1/MCS was established successfully.(2) Cell inhibited rate of HCE1/MC and HCE1/MCS was: in MG132 group, (11.67 ± 2.34) % vs (10.78 ± 1.17) % (P > 0.05) ; in MG132 + cisplatin group, (92.67 ± 2.52)% vs (91.33 ±2.18)% (P>0.05); in cisplatin group, (45.01±7.44)% vs (9.45±5.98)% (P<0.05).(3)The rate of apoptosis of HCE1/MC and HCE1/MCS were: in MG132 group, 8.14% and 5.97% ; in MG132 + cisplatin group, 99.01% and 95.22% ; in cisplatin group, 33.61% and 0.88%.(4)The expression level of NF-kB and the high expression rate of bcl-2 were: in HCE1/MCS of control group, 0.67 and 60% ; in HCE1/MCS of cisplatin group, 0.85 and 83% ; in HCE1/MCS of MG132 group, 0.39 and 20% ; in HCE1/MCS of MG132 + cisplatin group, 0.47 and 33%.Conclusions (1) HCE1/ MCS present natural resistance to cisplatin and may become a good model for the study of cervical cancer drug resistance in vitro.(2) MG132 could induce the inhibition and apoptosis of HCE1/MCS cells and partially reverse the natural resistance of HCE1/MCS to cisplatin, of which partially reverse the natural resistance may be in relation to the down-regulation of NF-kB and bcl-2 expression.

12.
Article in Chinese | WPRIM | ID: wpr-386755

ABSTRACT

Objective To investigate the roles of cystatin C (CysC) and serum creatinine (Scr) in acute renal injury of patients with shock. Method A total of 71 patients with shock, 42 male and 29 female, were enrolled from February 2006 to June 2007. Patients with kidney disease or renal insufficiency were excluded. All of patients were assigned to 4 groups as per the duration of shock. The blood samples were taken from patients for measurements of CysC and Scr during the periods of 1 hr,2 hr,and 4 hr of shock and 72 hr and 7 days after correction of shock. The corrected GFR (cGFR) and decreased GFR (dGFR) were calculated. The levels of Scr and dGFR could be used to classify the acute renal injury into stages according to the Acute Kidney Injury Diagnosis Criteria. The positive detection rates of different methods were compared. The levels of CysC, Scr and cGFR were statistically analyzed. Data were studied by using Pearson's correlation analysis, Results The elevation of CysC appeared sooner than that of Scr in all shock patients. Contrarily, the high level of CysC lowered to normal level much slower than that of SCR after correction of shock. The CysC increased 1 hour after shock. The GFR was negatively correlated with CysC and Scr, especially in the early stage of shock. Conclusions The renal dysfunction appears in the early stage of shock. The CysC assayed is more sensitive in the stage 1 of renal injury than Scr.

13.
China Pharmacy ; (12)1991.
Article in Chinese | WPRIM | ID: wpr-531645

ABSTRACT

OBJECTIVE: To investigate the uptake of self-assembled sodium alginate(SA) nanoparticles labeled by FITC(sSAN-FITC) in Caco-2 cells and the influencing factors.METHODS: Fluorescence microscope was utilized to exam the uptake of sSAN-FITC in Caco-2 cells.Multifunction continuous spectrum enzyme-linked immunosorbent assay system was used for the detection of the fluorescence intensity of FITC in the cells and quantitative assay of the effect of sSAN concentration,its action time and pH on the uptake of sSAN-FITC in Caco-2 cells,with blank group as control.RESULTS: Pictures of Caco-2 cells taken by fluorescence microscope showed uptake of sSAN-FITC by Caco-2 cells.As compared with blank control group,among the 3 factors,the fluorescence intensity increased with the increase of the sSAN concentration and the prolonging of the action time(P

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