Sphingosine-1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions in both intracellular and extracellular compartments. It interacts with five G protein-coupled receptors subtypes (S1PR(1-5)) to generate multiple downstream signaling. Activation of S1PR1 has been validated to be involved in the process of immune modulation. Fingolimod (FTY720), the novel S1PR1 agonist, has been approved for the treatment of multiple sclerosis in clinical trials. The study towards discovery of selective S1PR1 agonists has become hot spot for immunological diseases. This article summarized the research progress of S1PR1 agonists, emphasizing their structure types, structure-activity relationship and direction of development.

OBJECTIVE:To survey and objectively evaluate the present situation and trend of the antihistamine agents used in 18 hospitals of Hangzhou.METHODS:To make a survey of the use of above mentioned drugs in 18 hospitals of Hangzhou during the period 2000～2002 in respect to the sum of money for drugs and manufacturing factories.RESULTS:In comparison with 2001,the sum of money for consumption of antihistamine agents increased 17.89%in 2000,and decreased 4.58%in 2002.Joint venture and imported products accounted for 70%of share of market.Lortadine and Cetirizine were still the first choice in therapy of allergic reactions.CONCLUSION:Consumption of antihistamine agents decreased,but kinds of drugs had no obvious change.

Objective:To investigate the clinical efficacy of intramedullary nailing combined with bone cement in repair of segmental bone defects after tumor resection.Methods:A retrospective analysis was conducted of the 5 patients with malignant bone tumor who had been treated at Department of Orthopaedics, Qiannan People's Hospital from April 2018 to September 2019 for remaining segmental bone defects following limb salvage surgery. They were 4 males and one female, aged from 11 to 55 years (average, 35.4 years). Their defects ranged from 6 to 21 cm (average, 12.3 cm) after tumor resection. By the Karnofsky performance score (KPS) for long-term quality of life, all of them scored less than 50 points. Of them, 3 were treated by interlocking intramedullary nails and bone cement filling, and 2 by elastic intramedullary nails and bone cement filling. In the 2 cases with defects of 21 cm and 13 cm, the fixation was assisted by a plate and an external fixator. Defect length after resection, operation time and intraoperative bleeding were recorded; the efficacy was evaluated by the Enneking functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system, visual analogue scale (VAS), and KPS.Results:All the 5 patients had uneventful surgery, with operation time ranging from 112 to 225 min (average, 154.2 min), intraoperative bleeding from 300 to 500 mL (average, 382 mL), and defect length after resection from 6 to 21 cm. The 5 patients were followed up for 6 to 28 months. Of them, 2 died of disease progression 6 and 7 months after surgery, respectively. According to the Enneking's evaluation, one patient scored 28 points, 2 patients 23 points and 2 patients 21 points, giving a high degree of satisfaction. Their VAS scores 6 months after surgery ranged from 1 to 6, averaging 3.6; their postoperative KPS scores ranged from 60 to 80, averaging 72.Conclusion:In repair of segmental bone defects after tumor resection, intramedullary nailing combined with bone cement filling can relieve pain of patients and lead to satisfactory short-term curative efficacy.

This study run through the process of developing behavioral medicine discipline in a general hospital with action research method,based on the balanced scorecard (BSC) framework.The four perspectives of the behavioral medicine BSC covered the main areas in hospital discipline development,including patients and community,healthy financial disciplines,clinical service process and efficiency,and research,innovation and growth.By the implementation of the discipline BSC,this hospital clarified its discipline development strategy,provided a communication platform,determined the objective and monitored the discipline effectively,and provided a mode which can integrate the discipline development and providing clinical services.The hospital set up the first neurology behavioral medicine clinic in Jinan Region though the exploration of the path and methods for developing behavioral medicine discipline,which had practical guiding significance for behavioral medicine development and services.

Objective To investigate the expression and significance of Periostin,VEGF and MMP-9 in breast invasive ductal carcinoma.Methods Immunohistochemistry was employed to detect the expression of Periostin,VEGF and MMP-9 in breast invasive ductal carcinoma and normal breast tissue.Results In breast invasive ductal carcinoma and normal breast tissue,the positive rates of Periostin were 63.8 ％ (37/58) and 0 (x2 =24.272,P =0.000).The figures were 69 ％ (40/58) and 8 ％ (2/25) for the positive rates of VEGF (x2 =25.977,P =0.000),respectively,as well as 70.69 ％ (41/58) and 16.0 ％ (4/25) for the positive rates of MMP-9 (x2 =21.050,P =0.000),respectively.There were significant differences among the groups (P ＜ 0.05).In breast invasive ductal carcinoma,the expression of Periostin was correlated with clinical stage (x2 =4.835,P =0.028),whereas not correlated with age (x2 =1.155,P=0.282),histological grade (x2 =0.05,P =0.972),lymphatic metastasis (x2 =1.660,P =0.198).The expression of VEGF was correlated with clinical stage (x2 =4.230,P =0.040),lymphatic metastasis (x2 =9.667,P =0.002),whereas not correlated with age (x2 =0.506,P =0.477),histological grade (x2 =0.532,P =0.767).The expression of MMP-9 was correlated with clinical stage (x2 =8.456,P =0.004),lymphatic metastasis (x2 =5.494,P =0.019),whereas not correlated with age (x2 =0.153,P =0.695),histological grade (x2 =0.224,P =0.894).The expression of Periostin,VEGF and MMP-9 were positively correlated with each other in breast invasive ductal carcinoma (r =0.348,P =0.001; r =0.303,P =0.021; r =0.469,P =0.000).Conclusion Periostin,VEGF and MMP-9 are correlated closely with the occurrence and development of breast invasive ductal carcinoma,which might be valuable in evaluating the invasiveness,metastasis and prognosis.

AIM:To study the correlation of serum uric acid ( UA) level with carotid plaques and arterial stiff-ness in the patients with essential hypertension ( EH) , and to explore the predictive value of serum UA for evaluating EH preclinically .METHODS:A total of 92 patients with EH and 30 healthy individuals were enrolled .The value of UA and other indicators were detected .B-mode ultrasound examination was performed to measure the common carotid artery intima -media thickness ( IMT) and the sites of plaque in the internal carotid-artery, external carotid artery and carotid bifurca-tions.Carotid-femoral arterial pulse wave velocity ( CFPWV) was assessed by Complior?atherosclerosis measurement in-strument.RESULTS:The serum level of UA in the patients with EH was higher than that in control group [(361.51 ± 83.81) μmol/L vs (317.03 ±62.22) μmol/L, P<0.05].The mean value and abnormal rate of IMT between hyperten-sion group and control group were significant difference [(0.69 ±0.14) mm vs (0.60 ±0.12) mm, 42.39%vs 10.00%, P<0.05].In 92 EH patients, 45 cases had carotid plaques .These 45 cases were divided into 3 groups according to the plaque severity, among which the serum UA level had statistically significant differences [(285.25 ±78.41) μmol/L, (341.19 ±63.99) μmol/L and (401.33 ±88.49) μmol/L, P<0.05].Compared with rigid plaque group ( n=34), the serum UA level in soft plaque group (n=11) was significantly higher [(389.00 ±69.45) μmol/L vs (323.03 ± 72.71) μmol/L, P<0.05].A stepwise multiple linear regression analysis demonstrated that age ( r=0.414), systolic blood pressure (r=0.224), pulse pressure (r=0.270) and uric acid (r=0.219) were predisposed factors for higher CFP-WV (P<0.05).CONCLUSION:UA is one of the risk factors causing hypertension .Serum UA level may reflect the sever-ity and stability of carotid plaques .The increased arterial stiffness is closely related to the increased serum UA level in EH .

Objective To investigate the diagnostic value of acridine orange fluorescene(AO-F) in bladder cancers. Methods One thousand and sixteen bladder cancer patients were reviewed retro-spectively. The positive-rates of AO-F in different stages, grades, size, quantity, position of tumors, hematuria and treatment ways were evaluated. Results The total positive rate of AO-F was 78.05 % (793/1016). The positive-rate was 74.69% (611/818) in superficial stage and 91.92% (182/198) in invasive bladder cancer, 67.24% (351/522) in grade Ⅰ and Ⅱ , 90. 37% (413/457) in grade Ⅲ. The percentage of positive AO-F was 80.30% (750/934) in patients with hematuria, 52.44% (43/82) in patients without hematuria. The percentage was 79.87% (710/889) when the tumor size was more than 2 cm, 65.35% (83/127) when size less than 2 cm. 83.07% (363/437) sample was positive in multiple tumors, 74.27% (430/579) in single tumor. The percentage was 77.21% (105/136) in tumors involving trigone or neck of bladder, 78.07% (687/880) in tumors without involving these re-gions. There was 69.68% (393/564) in treatment with TURBt, 87.87% (268/305) in partial resec-tion, 91.74% (100/109) in total resection. A good association was observed between stage, grade, hematuria appearance, tumor size, quantity of carcinoma, treatment way and AO-F positive-rate, and a linear correlation was present between grade, stage and positive cytology. There was no significant association between position of the tumor and AO-F positive-rate. Conclusions The function of AO-F is significant in diagnosis of bladder cancer.

Objective To investigate the correlation between immune cell function and the infection after renal transplantation through monitoring of immune function intracellular ATP by Cylex ImmuKnow assay,and explore its significance in individual immunosuppressive therapy of renal transplantion recipients.Method We collected 44 renal transplant patients suffered from pulmonary infection from January 2014 to March 2015.The patients were divided into two groups according to the clinical status,namely,ImmuKnow monitoring group (n =22) and empirical treatment group (n =22).Thirty-two non-infection recipients were collected as controls.All the kidney transplantation recipients received immunosuppressive therapy based on calcineurin inhibitors,mycophenolate mofetil and prednisone,and ATG for induction therapy after transplantatior.The immune cell function levels were measured by Cylex ImmuKnow assay.The whole blood samples were collected before infection onset,at the time of infection,and 1 week after infection resolution.Result When infection occurred,ATP concentrations in CD4+ T cells of the kidney transplant recipients were significantly lower than those in non-infection group [(151.30--71.35 ng/mL vs.(308.34 ± 141.29 ng/mL,P＜0.05).When the infection got controlled,the ATP concentrations in CD4+ T cells increased to those before infection occurred.The average hospitalization time in ImmuKnow monitoring group was 12.27 ± 0.74 days,which was significantly shorter than in empirical treatment group (16.64 ± 1.98 days,P＜ 0.05).The incidence of acute rejection was 4.5％ in ImmuKnow monitoring group,and 13.6％ in empirical treatment group (P＞0.05).Conclusion The examination of ATP in CD4+ T cells by Cylex Immuknow assay could reflect the status of cellular immunity,provide reliable and objective basis for the diagnosis and treatment of infection after renal transplantation,and guide the clinical individualized immunosuppressive therapy.

Objective investigate the correlation between plasma soluble receptor for advanced glycation endproducts (sRAGE) and arterial stiffness in patients with different types of metabolic syndrome (MS).Methods A total of 180 subjects were drawn from a epidemiologic follow-up study,including 60 cases non-metabolic syndrome (NMS),60 cases metabolic syndrome without diabetes mellitus (NDMMS),60 cases metabolic syndrome with diabetes mellitus (DMMS).Carotid femoral arterial pulse wave velocity (CFPWV) was assessed by the French KangPuLe atherosclerosis measurement instrument,and plasma sRAGE levels were measured by ELISA.Comparison of mean in multiple groups was conducted by analysis of variance.Multivariate analysis was done with multiple linear stepwise regression analysis.P ＜ 0.05 was considered as statistically significant difference.Results Compared with NMS group,plasma sRAGE levels were significantly lower in DMMS and NDMMS groups [(635.07 ± 229.20) pg/mL vs.(671.17 ± 358.16) pg/mL vs.(992.99 ± 427.83) pg/mL,P =0.001].CFPWV of DMMS group was significantly higher than that of NMDMS and NMS groups (14.22 ±3.14) m/s vs.(12.15 ±2.79) m/s vs.(11.66 ± 2.52) m/s,P =0.002).Plasma sRAGE level was negatively correlated with CFPWV (r =-0.278,P =0.005).(3) Multiple linear regression analysis demonstrated that age (β =-0.091,95％ CI-0.096 ～-0.095,P =0.031),HDL-C (β =1.295,95％ CI 1.231 ～ 1.360,P =0.022) and sRAGE (β =0.119,95％ CI 0.118 ～ 0.130,P =0.032) had a significant effect on CFPWV.Conclusions The increased arterial stiffness is closely related to the discreased plasma sRAGE levels in MS.Plasma sRAGE maybe a novel target for vascular disease prevention and treatment in patients with metabolic syndrome.

Objective:The purpose of this study is to determine levels of Ghrelin,TNF-α,IL-1 and IL-6 in peripheral blood of patients with chronic hepatitis B,liver cirrhosis,and non-alcoholic fatty liver disease which diagnosed at different extent of damage,and based on it to have a further study on the relevance between Ghrelin and inflammatory cytokines in peripheral blood in above diseases.Methods:Ghrelin,TNF-α,IL-1 and IL-6 in peripheral blood were determined by ELISA method.Results:In patients with chronic hepatitis B andhepatic cirrhosis,Ghrelin level increased significantly as compared with that in normal control group (P＜0.05,P＜0.01).Ghrelin levels in decompensated liver cirrhosis (degree B and C)groups were much higher than in chronic hepatitis B group (P＜0.05). Ghrelin level in group of non-alcoholic fatty liver disease decreased significantly as compared with that in normal control group (P<0.01). Ghrelin and inflammatory cytokines,including TNF-α,IL-1 and IL-6 showed a positive relevances in groups of chronic hepatitis B and liver cirrhosis,but not in NAFLD group which showed a negative correlations.Conclusion:Ghrelin has a higher level in peripheral blood of patients with chronic hepatitis B and liver cirrhosis,but it has a lower level in patients with non-alcoholic fatty liver disease,suggesting correlation of Ghrelin level with the occurrence and the procession of chronic liver diseass.