The renin-angiotensin system plays an important role in the pathogenesis and chronic progress of renal diseases. The increased plasma level of angiotensin can induce the changes of haemodynamics and diverse cytokines secreted by the kidney, and the change promotes the renal injury. How to block renin-angiotensin system has been a focus of nephrology. Recently, with the emerging of angiotensin receptor antagonist, the relationship between the angiotensin receptor antagonist and renal diseases has being realized.

TRP(transient receptor potential) ion channel is a kind of membrane proteins which are widespreadly present in various cells,which is used to identify various mixed flavor and warm,heat,cold,and other temperature.Originally cloned as a proatate-specific protein.TRPM8 is now best known as a cold-and menthol-activated channel implicated in thermosensation.We provide a brief review of current knowledge concerning the biophysical properties,gating mechanisms,pharmacology and(patho)physiology of this TRP channel.

Objective To investigate the effects of a highly selective protein kinase A (PKA) inhibitor, H89, injected intrathecally (IT) on hyperalgesia and phosphorylation of cAMP element binding protein(pCREB) in the dorsal horn neurons of the spinal cord induced by chronic constriction injury (CCI) to the sciatic nerve.Methods Fifty-eight adult female SD rats weighing 230-270 g were used in this study. CCI was produced by 4 loose ligatures place on the sciatic nerve of right hind leg at 1 mm interspace with 3-0 silk suture. The experiment was carried out in two parts. In part Ⅰ 28 animals were randomized to receive H89 1 (group H1), 2 (group H2 ) or 4 nmol (group H4) or 10 ?l of DMSO (the solvent) 10mmol?L-1 (control group) intrathecally (IT) (n = 7 each) 7 days after surgery. The paw-withdrawal latency following mechanical (MWL) and thermal stimulation (TWL) were recorded before (baseline) and 15, 30 and 60 min after drug administration. In part Ⅱ 24 rats were randomized to receive H89 1, 2 or 4 nmol or 10 ?l of DMSO 10 mmol?L-1 IT as in part Ⅰ (group H1, H2, H4 and control group, n = 6 each) . Another 6 animals received 10 ?l of DMSO 10 mmol?L IT 7 days after sham operation. The animals were killed 30 min after drug administration and lumbar (L4.5) segment of spinal cord was removed for determination of pCREB expression in the dorsal horn neurons of spinal cord using immuno-histochemical technique. Results MWL and TWL were significantly increased after drug administration in group H2(at 15min) and group H4(at 15 and 30 min) as compared to the baseline values(P

Objective: To investigate the influence of transfection of TCRVJ37.1 gene in cytotoxicity of PBMC of healthy donor to breast cancer cell line MCF-7/S. Methods :pcDN*31vp'1 packaged by lipofectamine were transfected to healthy donor's PBMC,Flow Cytometer Analysis and MTT Colorimetric Assay were used respectively to test the expression of pcDNA3.1VB7.1 gene and the cytotoxicity of PBMC before and after gene transfection of healthy donor to breast cancer cell line MCF-7/S. Results: The expression of TCRVJ37.1 gene after transfection was obviously higher.There was distinguish differences of cytotoxicity before and after gene transfection. Conclusion:The modified healthy donor's PBMC by TCR gene could have stronger cytotoxicity to breast cancer cell line.

Objective To investigate the effect of propofol on the response of spinal cord to pain stimulation induced by intraplantar injection of formalin Methods Thirty SD rats of both sexes weighing 200 250g were randomly divided into six groups Pain stimulation was produced by subcutaneous injection of formalin (2 5%100?l) into the plantar region of unilateral front paw Group F received intraplantar injection of formalin only (n=6);group FP received intraperitoneal propofol 100?g?kg -1 10min after formalin injection (n=6); group PF received formalin injection 10min after intraperitoneal propofol 100?g?kg -1 (n=6); group P received intraperitoneal propofol 100?g?kg -1 only; group FS received intraperitoneal normal saline 10ml?kg -1 10min after formalin injection; and group S received intraperitoneal normal saline 10ml?kg -1 only 1 h after last injection (intraperitoneal or intraplantar) the animals were anesthetized and cervical spinal cord (where sensory nerves from front paw enter) was removed and sliced and examined for fos expression in the spinal cord using fos immunohistochemistry technique Results After formalin injection large numbers of fos like immunoreactive neurons (FLINs) were found in the ipsilateral dorsal horn Most of FLINs were confined to the medial part of outer area of laminal I and II Intraperitoneal propofol injected either before or after formalin stimulation significantly suppressed fos expression in all laminal (P

Objective To investigate the analgesic effect of a specific p38MAPK inhibitor SB203580 in a rat model of chronic constriction injury (CCI) to sciatic nerve. Methods Male SD rats weighing 220-250 g were used in this study. The neuropathic pain model was established by CCI to sciatic nerve. The rats were anesthetized with intraperitoneal (i.p.) pentobarbital 40 mg?kg-1. Left sciatic nerve was exposed and 4 loose ligatures were placed on left sciatic nerve at 1 mm intervals with 4-0 silk suture. The animals were allowed 7 days to recover from surgery. Intrathecal (IT) SB203S80 was given through a needle inserted at L5,6 interspace. In experiment A, 40 rats wee randomly divided into 5 groups (n = 8 each): control group and 4 SBgroups (SB203580 0.1, 0.5, 2.5 and 5.0 ?g were given respectively) . Response of the hindpaw to mechanical stimulation with von Frey filament (MWT) was measured before (T0,baseline) and at 0.5, 3, 6, 12 and 24 h (T1-5) after IT SB203580 injection. In experiment B, 36 animals were randomly divided into 6 groups (n = 6 each): (1) sham operation group; (2) CCI group; (3) DMSO group; (4) SB 0.1 ?g group; (5) SB 0.5 ?g group and (6) SB 5.0 ?g group. The animals were lulled at 6h after IT SB203580 administration and L5,6 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immuno-cytochemistry. Results The rats developed hyperalgesia after CCI and IT SB203580 administration significantly increased MWT in a dose dependent manner. The number of pCREB positive neurons in the L4,5 spinal dorsal horn was significantly increased after CCI. Interthecal administration of SB203580 0.5 or 5.0 ?g significantly inhibited the CCI-induced increase in pCREB expression. Conclusion Intrathecal administration of SB203580 can attenuate the hyperalgesia induced by CCI and inhibition of CREB phosphorylation in the spinal dorsal horn is involved in the mechanism.

Objective To investigate the clinical value of radiotherapy combing with super selective esophageal intra-arterial infusion chemotherapy in advanced esophageal carcinoma. Methods 38 cases with medial or late stage of esophageal carcinoma wererandomly divided into two groups,the one group was treated with radiotherapy as the sole measure of treatment,while the other group was treated with radiotherapy combing with super selective esophageal intra-arterial infusion chemotherapy. All the patients were followed up within 3 to 24 months. Results In the most cases,the clinical symptoms and X-ray findings were improved obviously after treatment. But the rate of grade Ⅰof radiography was different obviously between two groups after different treatments.Conclusion Radiotherapy combing with interventional chemotherapy can increase drug concentration locally and therefore, has a better drug effect. On the other hand, it candecrease toxic reaction and can also decrease tumor volume effectively. So it can be a effective stratagem to those cases of locally advancedesophageal carcinoma which have poor reaction or severe radiotherapy reaction to merely radiotherapy.

Objective To investigate the changes in acetylation of histone in the spinal dorsal horn in a rat model of persistent postoperative pain.Methods Ninety-six malc Sprague-Dawley rats,weighing 200-250 g,aged 6-8 weeks,were randomly divided into 2 groups (n=48 each) using a random number table:sham operation group (group S) and persistent postoperative pain group (group PPP).The rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established according to the method described by Flatters.After the rats were anesthetized with intraperitoneal chloral hydrate,the skin and superficial muscle of the medial thigh were incised and retractors inserted.This tissue was retracted for 1 h.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 1,3,7,14,and 21 days after operation.Four animals were sacrificed in each group after measurement of MWT at each time point for detection of acetylated histone H3 (Ac-H3) and acetylated histone H4 (Ac-H4) expression (by Western blot analysis) and the number of Ac-H3 and Ac-H4 positive cells in the spinal cord horn (by immunofluorescence histochemistry).Results Compared with group S,the MWT was significantly decreased at 3,7,14 and 21 days after operation,the expression of Ac-H3 and Ac-H4b was significantly down-regulated at 3,7 and 14 days after operation,and the number of Ac-H3 and Ac-H4 positive cells was significantly decreased at 7,14 and 21 days after operation in group PPP (P＜0.05 or 0.01).The MWT,expression of Ac-H3 and Ac-H4b,and the number of Ac-H3 and Ac-H4 positive cells were significantly higher at 21 days after operation than at 14 days after operation in group PPP (P＜0.05).Conclusion Acetylation of histone in the spinal dorsal horn is decreased after operation,which may be involved in the development and maintenance of persistent postoperative pain in rats.

Objective:To detect differentiallyexpressed microRNAs (miRNAs)in plasma of schizophrenia and explore biomarker for diagnosis of schizophrenia.Methods:The discovery cohort tincluded 6 patients with schizophrenia meeting diagnostic criteria of schizophrenia of the Diagnostic and Statistical Manual of Mental Disor-der,Fourth Edition (DSM-IV),as well as 6 healthy control subjects,whose age and gender were matched to pa-tients.The expression of 754 miRNAs (Sanger human miRBase v14)in the discovery cohort was investigated by Taqman Array (Human MicroRNA A +B Cards Set v3.0).Then the quantitative reverse-transcription polymor-phism chain reaction (qRT-PCR)assay was conducted to validate differentially expressed miRNAs in an independ-ent replication cohort,which included 25 schizophrenia patients and 18 healthy control subjects.The student's t-tests were used to analyze the differential expression of miRNA between schizophrenia patients and controls.All analyses were performed in Significance Analysis of Microarrays (SAM)software.Results:Twenty down-regulated miRNAs were observed in discovery cohort.Four miRNAs,hsa-miR-15b-5p were down-regulated in both discovery and rep-licated cohorts.Conclusion:The present study suggests that aberrant expression of miRNA might be of potential im-portance as biomarkers in the diagnosis of schizophrenia.

BACKGROUND: It is indistinct that whether ketamine can exert antinociceptive effect througb influencing the transmission of nocuous information in spinal cord; Nitric oxide (NO) in spinal cord participates mainly in the formation and development of hyperalgesia, and it can also induce Fos protein expression. It is still controversal whether it contributes to the transmission and mediation of ketamine to pain signal.OBJECTIVE: To observe the response to formalin stimulation in spinal cord of the rats and the effect of ketamine.DESIGN: Balanced randomized animal trial.SETTING: Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College; Jiangsu Provincial Key Laboratory of Anesthesiology.MATERIALS: This trial was carried out in the Jiangsu Provincial Key Laboratory of Anesthesiology, Xuzhou Medical College from January to March 2000. Totally 30 Sprague-Dawley rats were chosen and balanced randomized into 6 groups: formalin group (n=6), formalin + ketamine group (n=6), ketamine +formalin group (n=6), ketamine group (n=6), formalin+normal saline group (n=3) and normal saline group (n=3). The gender ratio was the same in each group.METHODS: Formalin group:The rats were stimulated for one hour by subcutaneous injection of 0.05 volume fraction of 200 μL in the center of palm of unilateral fore-claw. Formalin +ketamine group: The rats were stimulated for 10 minutes by formalin, then for one hour by intraperitoneal injection of 100 rg/kg ketamine. Ketamine + formalin group: The rats were injected with ketamine for 10 minutes, then with formalin for one hour. Ketamine group: the same dosage of ketamine was intraperitoneally injected into the rats for one hour. Formalin + normal saline group: The rats were stimulated for 10 minutes by formalin, then intraperitoneally given 10 mL/kg normal saline for one hour. Normal saline group: the same volume of normal saline was intraperitoneally injected into the rats for one hour.MAIN OUTCOME MEASURES: ① Behavioral performance of the rats in each group. ② Spinal sections were chosen, and stained with c-fos genetic immunohistochemical and NADPH-d histochemical methods. The changes of the number of Fos-like immuno-positive neurons (FLI) and FLI/nitric oxide synthase (NOS) double-labeled neurons in the 4-layer sections (layer Ⅰ -Ⅱ ,layer Ⅲ-Ⅳ ,layerⅤ-Ⅵ ,layer Ⅶ-X )of spinal dorsal horn of the rats were observed.RESULTS: All the thirty rats entered the stage of result analysis. ① Behavioral changes: The rats of formalin group and formalin+ normal salinegroup had apparent pain response; Several minutes after injection with ketamine, righting reflex disappeared and did not recover at perfusion period.Prolonged sleep was found without obvious pain response performance. ② FLI neuron expression: A lot of FLI positive neurons were found in the spinal dorsal horn of injec tion side of the rats in the formalin group and formalin+ normal saline group, and they distributed principally in the layer Ⅰ - Ⅱ of spinal dorsal horn.The distribution in the ketamine + formalin group and formalin + ketamine group was basically similar to that in the formalin group and formalin + normal saline group, but positive neuron counts were significantly reduced (P ＜ 0.01). ③ The expression of FLI/NOS double-labeled neurons: The number of double-labeled neurons in the spinal dorsal horn layer Ⅰ - Ⅱ of the rats in the ketamine+ formalin group and formalin+ ketamine group were significantly less than that in the formalin group and formalin+normal saline group [(1±1), (1±1), (7±3), (8±3),P ＜ 0.01].CONCLUSION: Some neurons of ipsilateral corresponding spinal segments participate in the transmission and mediation of pain signal. Ketamine can suppress the activities of these neurons and exert antinociceptive effect. The antinococeptive function of ketamine may be caused by the activity depression of the NOS-positive neurons in spinal cord.