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.

Purpose To investigate the role of S3I-201 on tubular interstitial lesion in lupus nephritis.Methods MRt/MpJ mice were designated as the control group.MRL/lpr nice were randomly divided into LN group,S3I-201 group and DMSO group.The serum and 24 h-urine were collected to detect the serum creatinine,blood urea nitrogen and urine protein.Immunohistochemistry was used to detect the expression of FN.Western blotting analysis was used to determine the expression of E-cadherin,α-SMA,MCP-1,ICAM1,STAT3 and p-STAT3.Results Compared with the expression level in control group,the protein level of α-SMA,MCP-1,ICAM1 and FN were increased in renal tissue of MRL/lpr mice,while the expression of E-cadherin was markedly decreased.And the STAT3 was activated in renal tissue of MRL/lpr mice.The administration of S3I-201 could inhibite the activation of STAT3 and ameliorate the expression of E-cadherin,α-SMA,MCP-1,ICAM-1 and FN.Conclusion S3I-201 can relieve the tubular interstitial leison,which maybe concerned with the phosphorylation of STAT3.

Objective To evaluate the applied value of multislice CT (MSCT) in the selection of living donor kidneys and excision methods.Methods Ninety living renal donors underwent MSCT assessment.The nonenhanced,arterial,venous and excretory phase examinations were performed.Using maximum intensity projection and volume rendering techniques for vascular imaging,two blinded radiologists independently analyzed and evaluated all MSCT images.According to the CT reconstructive images,radiologists and physicians selected the left renal or the right renal donors,and chose laparoscopic or open live donor nephrectomy.Results On the 90 cases of donors,78 donors underwent nephrectomy in the left kidney.Seventy-one left kidney donors having no significant variation received the routine laparoscopic live donor nephrectomy.Seven left kidney donors on both sides had relatively obvious anatomical variations such as accessory renal artery,multi-branch renal vein and renal vein in the back of the abdominal aorta,and they were subjected to the left kidney open donor nephre.ctomy.Other 12 donors having significant variation in the left kidney were given nephrectomy in the right kidney,and all of them received hand-assisted laparoscopic live donor nephrectomy.All intraoperative records of urine collection system and renal vascular anatomy were consistent with the preoperative evaluation of MSCT,and the accuracy was 100 ％.Two imaging experts in the evaluation of renal artery,renal vein and urine collection system showed good consistency.Nephrectomy was successfully performed on 90 cases of donors,and.postoperative recipients had no renal vein thrombosis and other vascular complications.Conclusion MSCT can provide accurate and valuable information for the selection of living donor kidneys and excision methods as a “one-stop” technique for the preoperative evaluation of living renal donors.

Objective:To determine the content of self-manufactured and imported lurasidone hydrochloride tablets in order to e-valuate their internal qualities. Methods:The determination of lurasidone hydrochloride tablets was performed by HPLC. The HPLC system consisted of a Waters C8 column (250 mm × 4. 6 mm, 3. 5 μm) and the mobile phase of 0. 05 mol·L-1 phosphate buffer solu-tion (pH 3. 0)-acetonitrile(60∶40), the detection wavelength was 230 nm, the flow rate was 1. 2 ml·min-1 and the column tempera-ture was 40℃, and the injection volume was 20μl. Results:The linear range of lurasidone hydrochloride was 0. 100 8-0. 806 4 mg· ml-1(r=0. 999 5). The average recovery was 99. 95% with RSD of 0. 31%(n=9). Conclusion:The method is simple, rapid, ac-curate, and reliable. The method can determine lurasidone hydrochloride tablets satisfactorily. According to the results, there are few differences among the self-manufactured and imported lurasidone hydrochloride tablets.

Objective To observe the clinical efficacy of butylphthalide soft capsules for treatment of acute cerebral infarction and its effect on the neurological function and inflammatory reaction of patients.Methods A total of 100 patients with acute cerebral infarction in the First Hospital of Zhangjiakou City and the Third Hospital Affiliated to Hebei North University from January 2016 to October 2016 were selected and divided into control group (n =50) and treatment group (n =50) according to the treatment protocols.The patients in the control group were given anti-platelet aggregation,statins,and other routine treatment;based on this,the patients in treatment group were orally administrated with butylphthalide soft capsules.The elbow venous blood of patients in the two groups was collected and the C reactive protein(CRP),interleukin-6 (IL-6) levels,the platelet aggregation rate were detected.The change of National Institute of Health stroke scale(NIHSS) score of patients after four weeks treatment was compared between the two groups.The recovery of neurological function of patients in the two groups was evaluated by modified Rankin grading after three months treatment.Results There was no statistic difference in the CRP,IL-6 levels and platelet aggregation rate before treatment between the two groups (P ＞ 0.05).The CRP,IL-6 levels and platelet aggregation rate of patients in the two groups after one week treatment were significantly lower than those before treatment (P ＜ 0.05);and the CRP,IL-6 levels and platelet aggregation rate of patients in the treatment group were significantly lower than those in the control group after one week treatment (P ＜ 0.05).The NIHSS score of patients in the treatment group was significantly lower than that in the control group after four weeks treatment (P ＜ 0.05);the Rankin score of patients in the treatment group was significantly lower than that in the control group after three months treatment (P ＜ 0.05).The total effective rate of patients in the treatment group was significantly higher than that in the control group (x2 =13.22,P ＜ 0.05).Conclusion Butylphthalide soft capsules can significantly reduce the inflammatory reaction in patients with acute cerebral infarction,improve and recover the neurologic impairment;and its curative effect is remarkable.

Objective To investigate the therapeutic effect of Losartan on ADM,ET-1 and their receptors in the kidney of diabetic rats.Methods Experimental diabetes was induced in uninephrectomized rats by STZ.The animals were divided into three groups: group A(control group),group B(diabetic group) and group C(Losartan-treated group).Immunohistochemistry,Western bloting,in situ hybridyzation and RT-PCR were used to detect the protein and mRNA expressions of ADM,ADMR,ET-1 and EDNR-A.Results Compared with group A,the expressions of ADM,ADMR,ET-1 and EDNR-A in group B significantly increased.After Losartan treatment,those indicators decreased.Conclusion The expressions of ADM,ET-1 and their receptors may be responsible for the renal protective effect of Losartan in diabetic rats.

Aim To investigate the immunomodulatory effects of sea cucumber fucoidan ( SC-FUC) on macro-phage and the signaling pathways. Methods Cell via-bilities in response to different concentrations of SC-FUC were analyzed by MTT, phagocytosis ability was detected by neutral red,and nitric oxide ( NO) produc-tion was examined by Griess reaction kit. The mRNA expression levels of IL-6 , IL-10 , Toll-like receptors (TLRs) and related signal molecules MyD88, TRIF, NF-κB were assayed by real-time PCR. All the experi-ments were based on murine RAW264. 7 cell line. Re-sults SC-FUC could promote RAW264 . 7 cell prolif-eration, phagocytosis as evidenced by uptake of neutral red and release of NO. The effects were significant at the early stage (6 h and 12 h) . SC-FUC could up-reg-ulate the expression of IL-6 , IL-10 , TLR4 , TLR5 , TLR9. Moreover, mRNA expressions of TLRs signaling molecules were increased, as well as MyD88, TRIF, NF-κB. Conclusions SC-FUC could activate macro-phage, and then promote the immune function by pro-moting production or expression of NO, IL-6, IL-10. It is speculated to be relevant to activated cell surface re-ceptors in macrophage, including TLR4, TLR5, TLR9, and NF-κB signaling pathways.

Purpose To investigate the role of PTEN in podocyte injury in patients with diabetic nephropathy ( DN) . Methods Uri-nary samples from 30 patients with DN and 10 healthy volunteers were collected to detect the level of PCX by ELISA. Renal biopsies were reviewed to observe the morphological changes. All patients with DN were divided into three groups by glomerular lesion. The ex-pression of p-Akt and PTEN in glomeruli was detected by immunohistochemistry. Results The levels of PCX in the urine were signifi-cantly higher in patients with DN compared with those in healthy volunteers, and gradually increased along with glomerular lesion aggra-vating. The expression of p-Akt and PTEN increased in patients with DN compared with healthy volunteers. Although the expression of p-Akt and PTEN decreased with the aggravation of glomerular lesion, they were still higher than that in volunteers. There were obvious-ly positive correlation between the level of PCX and 24-h urinary protein and negative correlation between the level of PCX and the ex-pression level of p-Akt and PTEN. Conclusion PTEN down-regulation may be associated with podocyte injury in DN, which may be associated with the phosphorylation of Akt.

AIM:To investigate the effects of P2X4 receptor on peri-sciatic administration of recombinant rat TNF-α(rrTNF)-induced mechanical allodynia.METHODS:Male Sprague-Dawley rats (180~200 g) were used in the experiments.The levels of P2X4 receptor on day 3, day 7 and day 14 after peri-sciatic administration of rrTNF were exam-ined by Western blot, and the location of P2X4 receptor in the spinal dorsal horn was observed by double immunofluores-cence staining.The changes of 50%paw-withdrawal thresholds of the rat were detected by behavioral test, and the level of TNF-αin the spinal dorsal horn was also examined by Western blot when TNP-ATP was intrathecally injected before the ad-ministration of rrTNF.RESULTS:Compared with control group, the expression of P2X4 receptor in the spinal dorsal horn on the ipsilateral side significantly increased on day 3, day 7 and day 14 (P<0.01) after rrTNF (100 ng/L) administra-tion.P2X4 receptor was co-localized only with microglia, but not with neurons or astrocytes.Intrathecal injection of TNP-ATP before rrTNF administration prevented mechanical allodynia induced by rrTNF and inhibited the upregulation of TNF-αin the spinal dorsal horn.CONCLUSION:P2X4 receptors in microglia may be involved in rrTNF-induced mechanical allodynia by the upregulation of TNF-αin the spinal dorsal horn.

Objective To explore the roles of spinal microglial Src-family kinases (SFKs) in diabetic neuropathic pain. Methods Male Sprague-Dawley rats, weighing 200 ~ 220 g, were used in the experiments. The level of p-SFKs in spinal dorsal horn was detected by single immunofluorescence staining on day 7th , 14th and 28th after intraperitoneally injection of Streptozotocin (STZ) and its location was detected by double immunofluorescence staining. The changes of 50% paw-withdrawal thresholds of rat were detected by behavioral tests when PP2 , a specific inhibitor of SFKs , was intrathecally administered before intraperitoneally injection of STZ. Results Compared with vehicle group, the blood glucose level increased on day 1 (P < 0.001) and the hyperglycemia persisted at least for 28 days (P < 0.001) after intraperitoneally administered of STZ (50 mg/kg). Paw-withdrawal threshold (PWT) decreased gradually from day 1 (P < 0.05) and reached the minimum on day 28 (P < 0.001) after STZ administration. Meanwhile, the expression of p-SFKs in spinal dorsal horn markedly increased on day 7 (P < 0.01), day 14 (P < 0.01) and day 28 (P < 0.01). The p-SFKs was mainly co-localized only with microglia , but not with neurons or with astrocytes. Intrathecally administered of PP2 before STZ reversed STZ-induced mechanical hyperalgesia. Conclusion Microglial SFKs in spinal dorsal horn maybe play a pivotal role in diabetic neuropathic pain.