Objective To study the expression and significance of the p38 mitogen-activated protein kinase (MAPK) and cAMP-responsive element binding protein (CREB 1) in experimental diabetic mellitus rats, and their relationship with extracllular matrix (ECM) restructuration. Methods Sixty male Wistar rats, with their kidneys removed surgically, were divided in two groups: control group (n=30) and diabetic group (n=30). Diabetic model was reproduced by intraperitoneal injection of Streptozocin (STZ, 65mg/kg). Six rats of each group were sacrificed at 1, 2, 4, 8 and 12weeks after STZ injection. Immunohistochemistry was used to assess the expression of p-p38 MAPK and p-CREB 1 in both control and diabetic groups. Western blot was performed to determine the activity of p-p38 MAPK and p-CREB 1 in both groups. Semiquantitative competitive reverse transcription polymerase chain reaction (PCR) was performed to detect the expression of mRNA of p38 MAPK, CREB 1 and fibronectin (FN). Results Compared with the control group, expression of p-p38 MAPK in diabetic glomeruli was significantly enhanced at 1, 2, 4, and 8 weeks, then it lowered at 12 weeks. P-CREB 1 was increased at 2, 4, 8 weeks, also decreased at 12 weeks. Elevation of FN mRNA began after 4 weeks in diabetic rats. Conclusions Glomerular p38 MAPK activity was increased in early stage of diabetes. This activated p38 MAPK pathway in diabetic glomeruli may in part play a role in the pathogenesis of extracellular matrix restructuring.

Aim To observe the effect of valsartan on expression of Smads of HKCs stimulated by TGF-?1.Methods HKCs were divided into three groups:control group,TGF-?1 group and valsartan group.Total protein was firstly abstracted at 30 min after stimulation to detect p-Smad2/3 protein by Western blot.Total RNA and protein were abstracted at 48 hours after stimulation.The expressions of Smad2/3,Smad7 were measured by Western blot.Smad2mRNA and Smad7mRNA were measured by RT-PCR.Meanwhile, The protein synthesis of Col Ⅰ in the supernatants of the HKCs was detected by Western blot.MTT assay was used to investigate the effect of valsartan on proliferation of HKCs stimulated by 5 ?g?L-1 TGF-?1 at different time and different drug concentration.Results Western blot analysis indicated that TGF-?1 stimulation could increase the expression of Smad2/3 and activate phosphorylation of Smad2/3 at 48 hour.At the same time,Smad7 decreased.Valsartan could reduce the level of Smad2/3 and p-Smad2/3 but it did not have any effect on the expression of Smad7 protein.RT-PCR analysis also showed that the expression of Smad2mRNA or Smad7mRNA was higher after TGF-?1 stimulation than control group,while valsartan could down-regulate the expression of Smad2mRNA.There was no difference of the expression of Smad7mRNA between the TGF-?1 stimulation group and valsartan treatment group.Valsartan could also greatly ameliorate the secretion of Col Ⅰ in the supernatants of the HKCs stimulated by TGF-?1 detected by Western blot.Compared with control group,TGF-?1 supressed the proliferation of HKCs,While 1,10 and 100 ?mol?L-1 valsartan ameliorated it and the effect was dependent of dose.Conclusion Valsartan has some renal protective effects on renal interstitial fibrosis,partly through inhibiting TGF-?/Smads signaling pathway.

Aim To investigate the effects of valsartan on activation of signal transducers and activators of transcription 1,3 in glomerular mesangial cells(GMCs) under high concentration of glucose.Methods we used high concentration glucose and valsartan to stimulate the cultured rat GMCs in vitro.The protein expressions of signal transducer and activatior of transcription 1,3(STAT1,STAT3),p-STAT1 and p-STAT3 were observed by Western blot.The protein synthesis of TGF-?_1,fibronectin and type IV collagen in the supernatants of the GMCs were detected by enzyme-linked immunoadsorbent assay(ELISA) and radioimmunoassay.TGF-?_1 mRNA was measured by reverse transcription and polymerase chain reaction(RT-PCR).Results Compared with low glucose control group,the expressions of p-STAT1,p-STAT3 and TGF?_1 mRNA were significantly increased in GMCs under high concentration glucose medium and there observed the high concentration of TGF-?_1,fibronectin and type IV collagen in the supernatants.The expression levels of p-STAT1,p-STAT3 and TGF-?_1 mRNA were significantly lower in the valsartan group than in those the high concentration glucose group.The concentration of TGF-?_1,fibronectin and type IV collagen in the supernatants in the valsartan group were lower than that in the high concentration glucose control group.Conclusion Valsartan can inhibit overproduction of TGF-?_1 and ECM proteins in GMCs under high concentration of glucose,partly by regulating the phosphorylation of STAT1 and STAT3.

Objective To investigate pulmonary function in terms of tidal respiration and the influencing factors on it in ＜ 34 weeks premature infants with RDS at corrected gestational age of 40 weeks.Methods A total of 49 of ＜ 34 weeks premature infants with RDS (RDS group) and 36 of ＜ 34 weeks premature infants without RDS (non-RDS group) followed throughout entire twelve months were collected fromn December 2013 to October 2015.Of them,35 RDS patients and 20 non-RDS patients had the pulmonary function examination.A total of 26 full term infants with hyperbilirubinemia (full term group) were recruited for comparison study.The differences in parameters of tidal respiration were compared among the three groups.The RDS patients were further divided into the mild RDS subgroup and severe RDS subgroup according to the severity of illness.Result ①The TPEF [(0.17 ± 0.04) s vs.(0.23 ± O.09) s],VPEF [(6.74±2.70) mLvs.(9.33±2.92) mL],TPEF/TE [(29.06±4.21)％ vs.(38.27± 7.16) ％],VPEF/VE [(32.54 ± 4.43) ％ vs.(39.64 ± 5.88) ％] in RDS group were significantly lower than those in full term group (P ＜0.05).The TPEF [(0.19 ±0.06) s vs.(0.23 ±0.09) s],TPEF/TE [(30.31 ±11.53)％ vs.(38.27±7.16)％],VPEF/VE [(34.39±8.44)％ vs.(39.64±5.88)％] in non-RDS group were significantly lower than those in full termn group (P ＜ 0.05).The TPEF,TPEF/TE,VPEF/VE in RDS group were lower than those in non-RDS group,but the differences were not significant (P ＞ 0.05).②The TPEF,VPEF,TPEF/TE,VPEF/VE in mild RDS group were higher than those in severe RDS group,but the differences were.not significant (P ＞ 0.05).③ Logistic regression analysis indicated that the gestational age was the protective factor of pulmonary function in premature infants with RDS.Conclusions Small airway resistance in ＜ 34 weeks premature infants with RDS is higher than that in full term infants.There was no significant difference in pulmonary function between RDS premature infants and non-RDS premature infants.The gestational age was the influencing factor of pulmonary function in premature infants with RDS.

Objective To explore how the severity of periventricular-intraventricular hemorrhage (PIVH)impact on physique and neurodevelopment in premature infants.Methods A total of 80 preterm infants with PIVH admitted to NICU of Qingdao Women and Children's Hospital from December 2013 to June 2015 were eligible.According to the Papile classification,the premature infants were divided into 4 groups.They were grade Ⅰ PIVH group,grade Ⅱ PIVH group,grade Ⅲ PIVH group and grade Ⅳ PIVH group.The infants with grade Ⅰ PIVH and grade Ⅱ PIVH belong to the low-grade PIVH group.The infants with grade Ⅲ PIVH and grade Ⅳ belong to the severe-grade PIVH group.All of them were regularly followed up for 12 months.Neurodevelopmental outcomes of infants at 6 and 12-month correction age were assessed by using the 20 items neuromotor assessment applying for 0-1 year old and the Bayley scales of infant development-Ⅱ.The differences in physical and neurophysical development of premature infants among 4 groups were compared.Results There were no significant differences in physical growth indicators such as body weight,body length and the incidence of weight growth retardation among 4 groups (all P＞0.05).The incidence of neurobehavioral abnormalities in infants with grade Ⅲ-Ⅳ PIVH was significantly higher than that of infants with grade Ⅰ-Ⅱ PIVH at 12-month correction age (21.05％ vs 3.28％,x2 =4.284,P=0.038).Physical development index(PDI) of grade Ⅰ-Ⅱ PIVH infants was significantly higher than that of grade Ⅲ-Ⅳ PIVH infants at 6-month correction age(F=11.500,P＜0.05).At 12-month correction age,grade Ⅰ-Ⅱ PIVH infants showed a significant higher mental development index(MDI) scores and PDI scores than those of grade Ⅲ-Ⅳ PIVH infants(F=14.227,16.515,all P＜0.05).Of the 80 cases assessed,infants with grade Ⅲ-Ⅳ PIVH had significantly higher rates of cerebral palsy(21.05％ vs 1.64％,x2 =6.300,P=0.012) and developmental delay (26.32％ vs 4.92％,x2=5.185,P=0.023) compared with grade Ⅰ-Ⅱ PIVH infants.Conclusions The severe PIVH can have negative effect on the neurodevelopmental outcomes of preterm infants and might induce mental retardation,cerebral palsy and other neurodevelopmental disabilities.Therefore,the regular follow-up and early intervention in preterm infants with PIVH should be implemented to improve the quality of their lives.

Objective To develop a scientific system of core information of health and evaluation index for the elderly Chinese people,which is suitable for the situation of our country.Methods The framework was established by extensive literature review and topic discussions.The index system was constructed with the Delphi method.Results 58 experts in different fields of health were selected in the two rounds of Delphi consultation research.The effective response rates in the two rounds were 96.88％ and 100％ respectively.The average value of the authoritative coefficient was between 0.80 and 0.96.And coefficients of variation were between 6.20 and 12.13.Based on the Delphi consultation research,the core information of health and evaluation index system for the elderly Chinese people were composed of 8 primary indicators closely associated with the positive awareness of aging and senescence and 31 other indicators.Conclusions The architecture of the core information of health and evaluation index system for the elderly Chinese people is stable,and the consultant experts tend to reach a consensus.The evaluation index system contains the most influential factors for the elderly Chinese people,and has the affirmative scientificity,applicability and feasibility.

Aim To investigate the effects of valsartan on the expression of TGF-?1 mRNA and the activation of p38 mitogen-activated protein kinase(p38MAPK),mitogen activated protein kinase kinasse3/6(MKK3/6)and cAMP response element-binding protein1(CREB1) in glomerular mesangial cells under high concentration of glucose.Methods High concentration glucose and valsartan were used to stimulate the cultured rat GMCs in vitro.The protein expressions of p38 MAPK,CREB1,p-p38 MAPK,p-MKK3/6 and p-CREB1 were observed by Western blot analysis.TGF-?1 and fibronectin(FN) mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).The protein synthesis of FN and type Ⅳ collagen in the supernatants of the GMCs was detected by radioimmunoassay.Results Compared with low glucose control group,the expressions of p-p38 MAPK,p-MKK3/6,p-CREB1 protein,TGF-?1 and FN mRNA,FN and type Ⅳ collagen in the supernatants were significantly increased in GMCs under high concentration glucose medium.The expression levels of p-p38 MAPK,p-MKK3/6 and p-CREB1 were significantly lower in the valsartan group than those in the high concentration glucose group.So did the mRNA of TGF-?1 and FN.The concentration of FN and type Ⅳ collagen in the supernatants in the valsartan group was lower than that in the high concentration glucose control group.Conclusion Valsartan can inhibit over production of TGF-?1 and ECM proteins in GMCs under high concentration of glucose,partly by regulating the phosphorylation of p38 MAPK,MKK3/6 and CREB1.

Objective To investigate the effects of rapamycin on p-JAK2,STAT3,p-STAT3 and PCNA in ranal tissue of IgAN rats.Methods The animal models of IgA nephropathy were devided into control group,IgAN model group,losartan group and rapamycin group.The clinical efficacy of rapamycin,and its influences on the protein and mRNA expressions of STAT3,p-STAT3,p-JAK2 and PCNA were determined by western blot,RT-PCR and immunohistochemical techniques respectively.Results The protein and mRNA expressions of p-STAT3,STAT3,p-JAK2 and PCNA were significantly increased in kidney of IgAN rats(P

Objective To further understand the cellular events of myocarditis,we have examined the myocardial mitochondria structure and activity of ATPase in mice with myocarditis,and observe the interventional effect of different doses of carptopril.Methods Sixty male Balb/c mice were randomly divided into 5 groups:infected coxsackie B3 virus(CVB3)group,infected CVB3 and treated with carptopril(in a dose of 10,30,or 100 mg/kg,twice a day)groups and control group.Captopril was administered after infection.The activity of Na+-K+-adenosine triphosphatase(Na+-K+-ATPase)and Ca2+-adenosine triphosphatase(Ca2+-ATPase)of myocardial mitochondrial as well as the morphological of myocardial mitochondrial were investigated on day 14.Results The activity of mitochondrial Na+-K+-ATPase and Ca2+-ATPase were significantly higher(Pa0.05).Conclusions The favorable effects of captopril exerts on myocyte mitochondria were shown in a dose-dependent manner.Thirty and 100 mg/kg,twice a day captopril protecs the membrane integrity and thus plays a role at the recovery of depressed mitochondrial Na+-K+-ATPase and Ca2+-ATPase activity and also in myocytes injury.

Objective To study the effect of Shenqi Fuzheng injection (SQFZI,参芪扶正注射液) on renal function in patients after cardiac surgery and cardiopulmonary bypass (CPB).Methods Forty patients ready for receiving CPB and cardiac surgery were randomly assigned to two groups,20 being in each group. Patients in the SQFZI group were administered of 250 ml SQFZI intravenously before anesthesia,125 ml SQFZI before CPB in CPB mechanical equipment,and 250 ml SQFZI once a day after operation for 3 days. Equal volume balanced solution was received in control group.Creatinine (Cr) in blood and Cr,microalbumin (m-Alb),?_2-microglobulin (?_2-MG) and N-acetylglucosaminidase (NAG) in urine were measured and endogeneous creatinine clearance (CCr) was calculated in 40 patients at the time points of before anesthesia, at the end of operation,and 1,3 and 5 days after operation.Results Urinary levels of m-Alb,?_2-MG and NAG were increased significantly after CPB in both groups at different time points at the end of and after the operation (all P0.05).Conclusion CPB has a deteriorating effect on renal function,and the application of SQFZI in peri-operational period has a protective effect on renal function in patients who undergo CPB.