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 explore the feasibility and advantages of endoscopic thyroidectomy via breast areola approach.Methods Endoscopic thyroidectomy via breast areola approach was performed in 113 cases between August 2002 and May 2005.Preoperative diagnosis included 46 cases of adenoma,62 cases of nodular goiter,and 5 cases of Graves' disease.Results The operation was successfully completed endoscopically in 112 cases,and was converted to conventional thyroidectomy in 1 case because of bleeding.The tumor was 2.3?1.6 cm in diameter(range,0.8~7.0 cm).The operating time was 136.7?58.0 min(range,50~310 min),the intraoperative blood loss was 42.5?62.7 ml(range,10~200 ml),the postoperative drainage volume was 87.1?78.1 ml(range,15~310 ml),the time to resume normal activities was 2.2?0.9 d(range,1~4 d),and the length of postoperative hospital stay was 5.5?1.9 d(range,2~9 d).Out of the 113 cases,analgesic requirement was necessary in 18 cases (15.9%).Postoperative complications occurred in 6 cases,including 2 cases of recurrent laryngeal nerve injuries,1 case of superior laryngeal nerve injuries,1 case of hemorrhage,1 case of hypocalcemia,and 1 case of recurrence of Graves' disease.Pathological results showed 43 cases of thyroid adenoma,58 cases of nodular goiter,5 cases of Graves' disease,3 cases of thyroid cancer,and 4 cases of Hashimoto's thyroiditis.Conclusions Endoscopic thyroidectomy via breast areola approach is a technically feasible and safe procedure.It can be employed as the first choice for indicated patients.

Objective To investigate the effects of ketamine in relieving postoperative pain after laparoscopic cholecystectomy(LC).Methods Forty patients undergoing selective LC from July to August 2006 were randomly divided into ketamine group and control group,with 20 patients in each group.Incision pain and non-incision pain was assessed at 1,2,4,6,12,24 h and once each day for the first 3 days postoperatively with visual analogue pain scale(VAS)and sedation scale.Adverse effects and analgesic requirements were recorded.Results Patients in ketamine group had significantly lower scores in incision pain and non-incision pain compared with those of control group(F=22.805,P =0.000;F=18.109,P=0.000).Incidence of postoperative nausea and vomiting was not significantly different(P=1.000)between ketamine(55%)and control group(60%).No significant difference was noticed in analgesic requirements between ketamine group(3 cases)and control group(9 cases)(P=0.082).Conclusions Preoperative administration of ketamine significantly improves postoperative analgesia after laparoscopic cholecystectomy,but does not reduce the incidence of postoperative nausea and vomiting.

Objective To establish the training objective systems for undergraduates in mili-tary clinical medicine in order to promote the educational reform of military medicine, and to improve the quality of talents training in military medical universities. Methods Literature analysis was made to determine the initial military clinical medical undergraduate training objectives, and a questionnaire was given to experts, on-the-job military doctors, medical graduates to know the real requirements of military doctors' position. A total of 455 valid questionnaires were collected. Then the questionnaire results were discussed and summarized by the method of expert discussion. Finally,. Delphi method was used to determine the ultimate training objective system. Results The ultimate training objective system of military undergraduate clinical medicine contains two aspects, eight fields and sixty-one standards objective systems. Conclusion Organically fusing military medical knowledge, ability and professional quality requirement into two levels and eight modules and clearly understanding the standards and requirements of each module are significantly systematic, advanced and operable, which has important reference value and guiding significance to both the military medical colleges and uni-versities and the local universities.

BACKGROUND: It has been demonstrated that pedicle screw internal fixation influencing factors involve screw structural morphology, thread parameter, bone density, moment size for tightening screw during operation, and depth of screw placement. There is little known about the correlation of pullout strength of spinal pedicle screw with device for transverse traction to extraversion angle. OBJECTIVE: To assess effect of the spinal pedicle screw with device for transverse traction on pullout strength at different extraversion angles. DESIGN: Repeated measurement. SETTING: Center for Bone Joint, the First Affiliated Hospital of Nanjing Medical University. PARTICIPANTS: This study was performed at Laboratory for Material Mechanics, Hehai University between June and November 2003. A total of 18 adult dried lumbar vertebrae (L1-5) were provided by Department of Anatomy, Nanjing Medical University, and recruited for this study. The protocol was approved by the hospital's Ethics Committee. The pedicle screw was made of stainless steel. Each pedicle screw had a diameter of 5.5 nun, total length of 150 nun (thread part 50 into included), and the same thread parameter. Electrical universal material machine (EW type) was provided by Laboratory for Material Mechanics of Hehai University. METHODS: Bone density was measured with a single photon bone density determinator. According to the bone density, the lumbar vertebrae were numbered and randomly divided into 3 groups with 6 lumbar vertebrae in each: extraversion angle 5 ° group, extraversion angle 15° group, and extraversion angle 30° group. ① Installation of pedicle screw and clamping apparatus: According to Wein-Stein method, one entry-point was selected at each side of lumbar vertebra, and at the sametime, extraversion angle 5°, 15° ,and 30° were respectively defined for extraversion angle 5° , 15° ,and 30° groups. A 50 mm-depth pinhole was drilled with a drill bit with a diameter of 3.0 nun. Pedicle screw was screwed into 50 nun, and its end part was connected to the device for transverse traction. Spinal vertebrae and the device for transverse traction were fixed with a specially made clamping apparatus. ② Determination of pullout strength and observation of pedicle and vertebral injury: Spinal vertebrae, on which pedicle screw and device for transverse traction were installed, was placed on a EW electrical universal material machine together with clamping apparatus for determining the pullout strength of pedicle screw. Sensor was connected to a computer to draw strength-displacement curve. The wave crest of the curve was considered the maximum pullout strength. At the same time, injuries to pedicle and vertebra caused by pullout of pedicle screw were observed. MAIN OUTCOME MEASURES: Pullout strength and injuries to pedicle and vertebra. RESULTS:①The mean maximum pullout strength of pedicle screw was respectively 0.878 167, 1.420 333, and 2.154 167 KN for extraversion angle 5° , 15 ° , and 30° groups. There was significant difference among the 3 groups (F = 12.554 22, P < 0.01). ② In the extraversion angle 5° group, 4 patients presented with cortical bone fracture which occurred at the entrance for pedicle screw, and 2 patients presented with fragmentation of junctional zone between pedicle and vertebral posterior edge; In the extraversion angle 15° group, 1 patient presented with cortical bone fracture which occurred at the entrance for pedicle screw, 4 patients presented with fragmentation of junctional zone between pedicle and vertebral posterior edge, and 1 patient presented with vertebral posterior coronal fragmentation; In the extraversion angle 30° group, 1 patient presented with cortical bone fracture which occurred at the entrance for pedicle screw, 2 patients presented with fragmentation of junctional zone between pedicle and vertebral posterior edge, and 3 patients presented with vertebral posterior coronal fragmentation. There was statistical significance in the intergroup rank-sum test (P < 0.01).CONCLUSION: During application of pedicle screw with device for transverse traction, proper accrescence of extraversion angle can increase pullout strength of the screw and enhance fixative strength, and excessive extraversion angle easily injures vertebra.

In recent years, the research hot in the field of solid tumor and blood tumor focuses on the myeloid-derived suppressor cells (MDSCs).In tumors, MDSCs not only exert immunosuppression by inhibiting T cell proliferation, destroying the functions of natural killer cells and recruiting regulatory T cells, but also play non-immunosuppression roles in the promotion of angiogenesis and tumor metastasis.All of these hinder the anti-tumor therapy, and particularly affect the curative effect, which are related with a poor clinical prognosis.MDSCs can be used as prognostic markers, which provide new targets for immunotherapy.

Objective To explore the feasibility and therapeutic effect of total laparoscopic hepatectomy(LH) for treating hepa‐tolithiasis .Methods 75 consecutive patients with hepatolithiasis operatively treated in our hospital from November 2003 to Novem‐ber 2012 were retrospectively analyzed .Among them ,35 cases underwent laparoscopic hepatectomy(LH group) and 40 cases under‐went open hepatectomies(OH group) .The operative modes in the two groups included the left liver lateral lobe resection ,left hemi‐hepatecomy ,common bile duct incision exploration ,choledochoscopy exploration for calculi extraction ,T tube drainage and cholecys‐tectomy .The clinical indicators including the operation time ,intraoperative blood loss ,analgesic drug use situation ,ambulation time , diet recovery time ,postoperative complication rate ,postoperative hospital stay time ,stone clearance rate and recurrence rate were analyzed and compared between the two groups .Results The operation time of the LH group was longer than that of the OH group[(205 .0 ± 40 .9) min vs .(155 .0 ± 26 .6) min ,P< 0 .01] and the postoperative hospital stay time of the LH group was shorter than that of the OH group[(12 .3 ± 2 .6) d vs .(15 .6 ± 4 .3)d ,P< 0 .01] .The intraoperative blood loss of the LH group was slightly more than that of the OH group[(330 .0 ± 259 .7) mL vs .(151 .5 ± 137 .0) mL ,P< 0 .01] .However ,the blood loss of last 10 cases in the LH group was similar to that of the OH group[(81 .0 ± 19 .70)mL vs .(78 .0 ± 22 .0)mL ,P> 0 .05) .The use rate of analge‐sic drugs in the LH group was lower than that of the OH group (0 vs .62 .5% ) .The ambulation time and the diet recovery time in the LH group were shorter than those in the OH group[(1 .5 ± 0 .5)d vs .(3 .6 ± 0 .7)d ,P< 0 .01 ;(2 .4 ± 0 .5)d vs .(4 .0 ± 0 .7) d , P< 0 .01] .No differences between the two groups were found in the occurrence rate of postoperative complications (2 .9% vs . 16 .0% ) ,stone clearance rate(instant clearance rate 91 .4% vs .90% ;final clearance rate 97 .1% vs .100% ) and the opeartion ex‐cellent rate(97 .1% vs .100% ) .No case of perioperative death occurred in the two groups(P > 0 .05) .Conclusion LH combined with choledochoscopy for treating hepatolithiasis is feasible and safe in the patients conforming to the selected standard with an e‐qual therapeutic effect to that of open hepatectomy .LH has the advanteages of minimally invasive surgery such as small incision , less pain ,fast recovery ,less complications ,etc .

BACKGROUND:Understanding the difference of miRNA-34s expression in normal tissue and tumor tissue wil contribute to screen out a miRNA with high sensitivity as the specific tumor molecular marker.
OBJECTIVE:To investigate the differential expression of miRNA-34s (miR-34a/b/c) between normal skin and keloid tissue using real-time fluorescent quantitative PCR, and to evaluate the role and mechanisms of miRNA-34s in keloid formation and development.
METHODS:Ten cases of keloid tissue and two cases of normal skin tissue were col ected as specimens. Total RNAs were extracted from keloid and nomal skin tissue by Trizol method, and miRNA-34s were further isolated by Ambion’s miRNA Isolation Kit. Real-time fluorescent quantitative PCR was applied to verify expression levels of microRNA-34s (miR-34a/b/c) in keloid tissue and normal skin tissue.
RESULTS AND CONCLUSION:miRNA-34s (miRNA-34a/b/c) expression was down-regulated in keloid tissue compared with normal skin tissue (P<0.01). The findings showed that miRNA-34s (miRNA-34a/b/c) are involved in keloid formation and development, and down-regulation of the family member may result in neoplastic growth of keloid.

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.