Objective To evaluate the regulatory role of mTOR signaling in activation of renal interstitial fibroblasts and the potential effect on interstitial fibrosis. Methods 8-week old female C57BL/6 mice (n=30) underwent unilateral ureteral obstruction (UUO) to induce renal interstitial fibrosis. Animals were randomly divided into rapamycin (2 mg·kg-1· d-1) group and UUO group (vehicle-treated) (n=15 each group). Daily intraperitoneal injection of rapamycin or saline was applied to animals from day 1 before operation to the end of experiment.Three mice were sacrificed at day 1,3,7,14 respectively and kidneys were harvested for further analysis.NIH3T3 cells were stimulated by TGF-β for 12 hours with the presence or bsence of rapamycin (100 nmol/L). Results Immunofluorescent co-staining revealed that active fibroblasts highly expressed pS6K and α-SMA in kidney interstitium.Administation of rapamycin significantly inhibited activation of mTOR signaling in fibroblasts and ameliorated interstitial fibrosis of obstructed kidneys.Real-time PCR confirmed that rapamycin decreased the mRNA expression of FSP1,TGF-β,CTGF and Col4A1 in fibrotic kidneys. In vitro experiment revealed that TGF-β induced highly expression of pS6K and αSMA in cultured NIH3T3 cells,which could be markedly inhibited by rapamycin. Conclusions mTOR signaling highly activates in interstitial fibroblasts during kidney fibrosis.Inhibition of mTOR signaling by rapamycin decreases the activation of fibroblasts and ameliorates interstitial fibrosis.

Pharmacokinetic analysis has attracted more and more attentions in the research field of bioactive natural product. However, there is limited study on the pharmacokinetics of polysaccharides. This paper focused on the research progresses of pharmacokinetics of polysaccharide, summarized the applications of chromatography, isotope labeling method, spectrophotometry, fluorospectrophotometry and biological assay in the analysis of polysaccharide pharmacokinetics, elucidated the behaviors of absorption, distribution, degradation and excretion of polysaccharide in experimental animals, and revealed the effects of physicochemical characteristic, administration dose and route on the pharmacokinetic properties of polysaccharide, which could be served as a reference for the related works.
Administration, Oral ; Animals ; Injections ; Intestinal Absorption ; Metabolic Clearance Rate ; Molecular Weight ; Polysaccharides ; administration & dosage ; analysis ; pharmacokinetics ; urine ; Tissue Distribution

0.05).Amplitudes of OPs and b wave were significantly decreased after experiment in STZinduced diabetic group(P

Objective To evaluate the effect of prefilling blood reservoir with mannitol-adeninephosphate MAP) solution on the damage to erythrocytes in intraoperative salvaged blood in patients.Methods One hundred and fifty blood samples were collected from 150 patients who were scheduled for elective spinal surgery requiring blood salvage,and were equally and randomly divided into 5 groups (n =30 each) using a random number table:group N,group N1,group N2,group M1 and group M2.The blood reservoir was not prefilled before surgery in group N,while the blood reservoirs in N1,N2,M1 and M2 groups were prefilled with normal saline (NS) 100 ml,NS 200 ml,MAP solution 100 ml and MAP solution 200 ml,respectively.Blood sauples were obtained for erythrocyte osmotic fragility test after the salvaged blood was washed,and hemolysis rates in different concentrations of hypotonic NaCl solution were calculated.The concentration of free hemoglobin in the clear supernatant liquid (FHb) of washed blood placed for 0 h (T0),1 h (T1) and 2 h (T2) were detected.Results Compared with N and N1 groups,the hemolysis rate of washed erythrocytes under 0.48％ 0.68％ NaCl solutions was significantly decreased,the concentration of FHb at T1 was decreased,and no significant change was found in FHb at T2 in group M1.Compared with N and N2 groups,the haemolysis rates of washed erythrocytes under 0.48％-0.68％ NaCl solutions were significantly decreased,and the concentrations of FHb at T1,2 were decreased in group M2.The concentration of FHb was significantly lower at T2 in group M2 than in group M1.Conclusion Prefilling blood reservoir with MAP solution can mitigate the damage to erythrocytes in the intraoperative salvaged blood in patients,and the efficacy of prefilling of 200 ml is superior to that of prefilling of 100 ml.

ObjectiveTo compare the effects of normal saline (NS), 10% hydroxyethyl starch (HES) and hypertonic-hyperoncotic solution (HHS,7.5% NaCl/10% HES) on regional cerebral blood flow (rCBF), brain edema and blood-brain barrier (BBB) in a rat model of traumatic head injury (THI) complicate with hemorrhagic shock. Methods60 SD rats were randomized into 5 groups: sham group (n=12), model group (n=12), NS group (n=12), HES group (n=12) and HHS group (n=12). rCBF and mean arterial pressure (MAP) were determined before and after THI, hemorrhagic shock and resuscitation. Cerebral water content and Evans Blue (EB) content were assessed 3 h after resuscitation.ResultsMAP and rCBF were restored to baseline values immediately after resuscitation in all resuscitated group and began to decrease 15 min, 30 min or 45 min later, respectively(P<0.05). 3 h after resuscitation, the brain water content was higher in NS group than those in sham or HHS group(P<0.05). EB contents of injured hemispheres were higher in model and NS group than those in HES or HHS group(P<0.05). ConclusionSmall-volume resuscitation with HHS can restore MAP and rCBF, decrease brain edema and improve BBB in a rat model of THI complicate with hemorrhagic shock.

Objective To evaluate the safety and efficacy of Zonisamide(ZNS) as adjunctive therapy in patients with refractory partial seizures receiving other antiepileptic drags (AEDs).Methods This was a randomized,double-blind,placebo-controlled study conducted at multi-centers.All 240 subjects were randomized to either the ZNS group or the placebo group in a 1:1 ratio.The double-blind treatment phase included a titration phase during which zonisamide dose inereased from 100 mg/day to 300 mg/day over 4 weeks and then a 12-week fixed-dose phase.The primary efficacy endpoint was,the median % reduction from baseline in all pattial seizure frequency(CPS+SPS+SGS)during the fixed-dose phase.The important secondaw endpoint wag the responder rate.Safety profiles and tolerance were also evaluated.Results The FAS analysis showed the median reduction from baseline in the ZNS group was greater than in the placebo group(48.4%vs 26.6%),the difference was significant for ZNS compared with placebo(F=4.904,P=0.028);The responder rates for all partial seizures(48.6%vs34.9%,X2=4.046,P=0.044)and for complex seizures(52.2% vs 33.3%,X2=5.607,P=0.018)were significantly higber in the ZNS group than in the placebo group in the FAS population.The overall adverse events(AEs)profile was comparable between the two groups.The most frequent AEs considered to be related to zonisamide by the investigator were headache,dizziness,somnolence,anorexia,nausea,etc.Conclusions ZNS is superior to placebo in reducing the frequency of partial seizures and well-tolerated.ZNS could be a choice of adjunctive therapy in patients with refractory partial seizures.

This paper analyzed the characteristics of post-disaster medical assistance systems in Anglo-American countries and Japan. In consideration of China's national conditions at present, it come up with recommendations that the government should formulate and perfect the legal system of postdisaster medical assistance, improve the related systems of medical care, establish post-disaster medical assistance responding as a long-term management mechanism, establish and improve emergency preparedness, and post-disaster psychological intervention in mechanisms.

Objective To study the changes and management of systemic and pulmonary hemodynamics during anhepatic period in patients undergoing orthotopic liver transplantation without veno-venous bypass.Methods Sixty-eight patients with end-stage liver disease undergoing orthotopic liver transplantation were enrolled in this research. Monitoring and recoding CVP, MAP, CI, HR, MPAP, PAWP PVR, SVR at different time points: preincision, before anhepatic, 5, 30 min of anhepatic, 5, 30, 60 min of neohepatic,ending of operation, 12 h and 24 h after operation. All the patients were divided into three groups according CVP during anhepatic period: group A(CVP <4 mmHg) ,group B(4 mm Hg≤CVP≤6 mmHg) ,group C (CVP>6 mmHg). Besides, calculating the concentration of dopamine, norepinephrine ,epinephrine and the volume of urine during of operation. Results There were different changes during different operation periods. During anhepatic period, HR, PVR and SVR increased, while CVP, CI, MAP, PAP, PAWP decreased(P<0.05). At early neohepatic period, HR decreased and CVP,PAWP, MPAP,CI,PVR SVR increased ,At the beginning of neohepatic period, MAP dacreased or increased quickly, and became steadily after 5 min. Among the three groups, the changes of hemodynamics in group B was slightest,and the concentration of dopamine, norepinephrine and epinephrine was smallest (P< 0.05 ). Conclusions The systemic and pulmonary emodynamics fluctuated sharply during anhepatic and early neohepatic period. It is important and useful to manage CVP 4 -6 mmHg, MABP ≥ 60 mmHg by infusing liquid and vasoconstrictors,such as dopamine, norepinephrine or epinephrine during anhepatic period.

Based on the character of the molecular structure, the prodrugs of phosphates and phosphonates were divided into two categories. The first is the drug which contained the phosphate group, introducing protected groups to increase lipophilicity and improve bioavailability. The other one is the drug which had no phosphate group, introducing the phosphate group into molecules to enhance the solubility, regulate the distribution coefficient and enhance the drug-like property. This review focuses on the application of phosphates and phosphonates in drug research and development based on improvement of physico-chemical property, drug safety and the pharmacokinetics.

Objective To study related factors of the duration of untreated psychosis (DUP) in Tibetan patients with schizophrenia in Qinghai Province. Methods The related factors on DUP were investigated in totally 188 Tibetan pa?tients with schizophrenia using questionnaires of mental health services and symptom onset for schizophrenia. All the Ti?betan patients were provided with the National Continuing Management and Intervention Program for Psychoses (686 Pro?gram). Results The median (low quartile, upper quartile) of DUP in Tibetan patients with schizophrenia was 375 days (4 days, 1661 days). The patients were divided into short DUP group (DUP≤375days, 90 patients) and long DUP group (DUP>375 days, 98 patients). There were significant differences in mode of onset,marital status, educational level, family type, place of residence between short DUP group and long DUP group (P<0.05). Logistic regression analysis found that lack of family structure (OR=2.340, 95%CI:1.130~4.847, P=0.022), chronic onset (OR=2.136, 95%CI:1.172~3.891, P=0.013) and living in pastoral areas (OR=2.239, 95%CI:1.097~4.571, P=0.027) were risk factors of DUP. Conclusion Ti?betan patients with schizophrenia have a longer DUP and related risk factories of DUP are lack of family structure, chron?ic onset and living in pastoral areas.