Objective To investigate the expressions of indoleamine 2,3-dioxygenase (IDO) and transcription factor forkhead box P3(FOXP3)in gallbladder adenocarcinoma; and to evaluate the relationship between the expressions of IDO and FOXP3 protein,and clinicopathology and lymph node metastasis of gallbladder carcinoma.Methods The expressions of IDO and FOXP3 in 51 cases of primary gallbladder cancer,90 cases of chronic cholecystitis,and 20 cases of normal gallbladder tissues were studied by immunohistochemical staining. Results The positive expression rates of IDO and FOXP3 in gallbladder carcinoma were 72.5％ (37/51) and 60.8％ (31/51),in normal gallbladder mucosa were 5％ (1/20) and 20.0％ (4/20),in cholecystitis and gallstone were 11.1％ (10/90) and 32.2％ (29/90),respectively.There were significant differences among the three groups in IDO and FOXP3 expressions (P＜0.01).The positive expression rates of IDO and FOXP3 were 7.1％ and 14.3％ for simple hyperplasia,17.7％ and 35.3％ for atypical hyperplasia,40％ and 35％ for gallbladder carcinoma (stages Ⅰ-Ⅲ),and 77.4％ and 64.5％ for gallbladder carcinoma (stages Ⅳ-Ⅴ ).There were significant differences among the four groups in IDO and FOXP3 expressions (P＜0.01).There were significant differences among the Nevin stage groups,lymph node metastasis group and gallbladder stone in IDO and FOXP3 expressions.However,there were no significant differences among the sex groups and the age groups in IDO and FOXP3 expressions (P＞0.05).In gallbladder carcinoma,the expression of IDO had a positive correlation with FOXP3 expression in lymphocyte (γ=0.406,P=0.003).Conclusion In gallbladder cancer,a high-expression of IDO and an expression of FOXP3 in lymphocyte are closely related with immune tolerance of gallbladder carcinoma.The results provide a reference for clinical use of immunotherapy in gallbladder cancer.

Objective To investigate the mechanism on JAK/STAT1 signal pathway in SAHA down-regulation of indoleamine 2,3-dioxygenase (IDO) in gallbladder carcinoma cells.MethodsWe treated gallbladder carcinoma SGC-996 cells with IFN-γ and SAHA.Western blotting was used to detect the expression of IDO,signal transducer and activator of transcription 1 (STAT1) phosphorylation and interferon regulatory factor genes-1 (IRF-1).Confocal microscopy analysis was used to detect STAT1 translocation.Transient transfections and reporter genes assay was used in detecting the activation of γ-activated sites (GAS) and interferon stimulated response elements (ISRE).ResultsIDO expressed in SGC-996 cells in dose- and time-dependent manners when stimulated with IFN-γ.SAHA down-regulated the expression of IDO induced by IFN-γ in a dose-dependent manner.SAHA blocked the expression of IRF-1 induced by IFN-γ.SAHA inhibited the IFN-γ-induced STAT1 phosphorylation and nuclear translocation.SAHA down-regulated IFN-γ-induced activation of GAS and ISRE.ConclusionsSAHA may down-regulate IDO expression through inhibiting the activation of members in JAK/STAT1 signal pathway.This may provide a new immunotherapeutic strategy to break tumor immune tolerance in gallbladder carcinoma.

Objective To compare the safety , surgery effects , pain scores of the close-distance-two-port video-assisted lobectomy and systematic dissection of the mediastinal nodes , and single-port video-assisted thora-coscopic surgery (VATS). Methods Between October 2012 and January 2015 in Peking University First Hospi-tal and Beijing Hospital , 269 patients who were going to be performed lobectomy and systematic lymph node dissection, were gathered and 205 patients were included in this study finally. Of the total, 122 patients were performed close-distance-two-port VATS , and 83 patients underwent single-port VATS. The clinical data were gathered, and statistically analyzed. Result In both groups, no severe postoperative complications or death oc-curred. No significant differences existed between the two groups in terms of intraoperative blood loss , duration and volume of chest tube drainage , postoperative pain score , hospital stay after surgery and hospitalization ex-penses (P > 0.05) but the data about operating time, number of dissected lymph nodes, complications(subcuta-neous emphysema , air-leak from the port of drainage tube and poor wound healing ) were significantly different (P < 0.05). Conclusions Compared with the single-port VATS, the method of close-distance-two-port video-as-sistant lobectomy and systematic dissection of the mediastinal nodes is safe and practicable with definite thera-peutic effect, less operation difficulty and complications.

The urate transporter 1 (URAT1) which controls urate reabsorption is a membrane transporter in the apical membrane of human renal proximal tubule epithelial cells. It was found that about 90% of patients suffer from hyperuricemia due to insufficient uric acid excretion. Therefore, the development of URAT1 inhibitors that can reduce the level of serum uric acid in vivo by enhancing renal urate excretion has been a hot spot in seeking anti-gout drugs in recent years. In this article, the representative URAT1 inhibitors with uric acid-lowering or anti-gout effects are reviewed, and related medicinal chemical strategies are analyzed, hoping to provide valuable insights into the discovery of new URAT1 inhibitors.

Objective: To investigate the mechanisms of electroacupuncture (EA) at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) in intervening diabetic gastroparesis (DGP) based on calcium-activated chloride channel. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including a normal control group (group A), a model group (group B), an EA group (group C) and a metoclopramide group (group D), with 10 rats in each group. A single intraperitoneal injection of 2％ streptozotocin (STZ) combined with 8-week high-glucose high-fat diet was used to establish a DGP rat model. After intervention, gastrointestinal propulsive rate was observed; the expression level of transmembrane protein 16A (TMEM16A) was examined by immunohistochemistry; the Ca2+ concentration in interstitial cells of Cajal (ICCs) was detected by immunofluorescence; and whole-cell patch-clamp technique was applied to detect the current intensity of calcium-activated chloride channel (ICaCC) in ICCs in gastric antrum. Results: After modeling, the blood glucose levels in group B, group C and group D were significantly increased compared with group A (all P<0.01); after intervention, compared with group B, the blood glucose levels in group C and group D were significantly decreased (P<0.05, P<0.01); the intra-group comparison of blood glucose level between after modeling and after intervention found significant difference only in group C (P<0.01). The gastrointestinal propulsive rates in group B, group C and group D were significantly different from that in group A (P<0.01 or P<0.05); the gastrointestinal propulsive rates were markedly higher in group C and group D than in group B (P<0.01, P<0.01). The expressions of TMEM16A in group B and group C were decreased compared with group A (P<0.01, P<0.05); the expressions of TMEM16A in group C and group D were increased compared with group B (P<0.01, P<0.05). The fluorescence intensity of Ca2+ was significantly lower in group B than in group A (P<0.01); the fluorescence intensity of Ca2+ was significantly higher in group C and group D than in group B (P<0.01, P<0.05). ICaCC in ICCs in group B was significantly decreased compared with group A; ICaCC in group C and group D were increased compared with group B. Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) can significantly improve gastrointestinal motility in DGP rats by up-regulating the ICaCC in ICCs.

AIM:To observe the effects of nobiletin on palmic acid (PA)-induced lipidosis in hepatocytes and to discuss the regulatory mechanism of lncLSTR. METHODS:AML12 cells were cultured in vitro. The control group, PA group (0.2 mmol/L) and protection group (exposure to nobiletin at 1 mg/L, 5 mg/L, 15 mg/L or 50 mg/L for 2 h, fol-lowed by treatment with 0.2 mmol/L PA) were established according to the experimental requirements. The lipid accumula-tion was morphologically observed by Oil red O staining in the cells. The qPCR was applied to detect mRNA expression, and the protein expression was determined by and Western blot. RESULTS:PA treatment (0.2 mmol/L) induced lipidosis, while 50 mg/L nobiletin pretreatment suppressed the lipidosis. Compared with control group, the mRNA expression of Apoc2 in PA group was significantly down-regulated (P<0.05), but increased by nobiletin pretreatment compared with PA group (P<0.05). The protein expression of Apoc2 in PA group was significantly down-regulated (P<0.05), but increased by nobiletin pretreatment (P<0.05). The expression of lncLSTR in PA group was significantly increased (P<0.05) and that was inhibited by nobiletin pretreatment (P<0.05). A negative correlation between Apoc2 protein and lncLSTR expression in PA group (R2=0.717 9, P<0.01) was observed. A negative correlation between Apoc2 protein and lncLSTR expression in protection group (R2=0.525 3, P<0.05) was also found. CONCLUSION:Nobiletin has anti-lipidosis effect on hepa-tocytes. The mechanism is partially related to the inhibition of up-regulation of lncLSTR, thus down-regulating Apoc2 expres-sion.

AIMTo explore the effects of noninvasive limb ischemic preconditioning on the anti-stress ability in mice.

METHODSMice were divided into: normal group, control group, preconditioning group and drug group. Hypoxia tolerance test, swimming with weight loading, cold tolerance test and thermostable test were performed, and tolerance time in all the stringent state were observed. SOD activity of serum in hypoxia tolerance test and lactic acid of serum in swimming with weight loading test were determined.

RESULTSThe time of hypoxia tolerance in preconditioning group was markedly increased, and SOD activity of preconditioning group mice was significantly higher than those of control group, while they were both shorter than drug group. The average time of swimming in preconditioning group was markedly increased and the level of increasing the swimming time of preconditioning was the same as caffeine. Preconditioning could increase the survival time on high temperature markedly, and there was no significantly difference in the level of increasing the survival time between preconditioning group and chlorpromazine group. Preconditioning could increase the time of cold tolerance markedly compared with normal group.

CONCLUSIONNoninvasive limb ischemic preconditioning can improve the ability of anti-hypoxia, anti-fatigue, thermoresistance and cold-resistance in mice.

Adaptation, Physiological ; physiology ; Animals ; Extremities ; blood supply ; Fatigue ; prevention & control ; Female ; Hypoxia ; prevention & control ; Ischemic Preconditioning ; methods ; Male ; Mice ; Stress, Physiological ; physiology

OBJECTIVETo observe clinical therapeutic effect of catgut implantation at Shu- and Mu-acupoints of liver, spleen and kidney on premature ovarian failure.

METHODSOne hundred and thirty-two cases of premature ovarian failure were randomly divided into a catgut implantation group and a medication group, 66 cases in each group. The catgut implantation group were treated by catgut implantation at She- and Mu-acupoints of liver, spleen and kidney, and the medication group were treated with oral administration of Estradiol Valerate 2 mg, qd, for 20 days, and 10 days later, Medroxyprogesterone Acetate 4 mg was added, b. i. d, for 10 days, averaging 6 months of medication. The therapeutic effects and changes of serum follicle-stimulating hormone (FSH) and estradiol (E2) were observed in the two groups.

RESULTSAfter treatment, serum FSH and E2 significantly improved in the two groups (P<0.01), with the serum E2 in the catgut implantation group increased more significantly than that in the medication group (P<0.01). The cured rate and the total effective rate were 84.9% and 97.0% in the catgut implantation group and 31.8% and 84.8% in the medication group, the cured rate in the catgut implantation group being better than that in the medication group (P<0.05). Ten month later, the therapeutic effect in the catgut implantation group was kept.

CONCLUSIONCatgut implantation at Shu- and Me-acupoints of liver, spleen and kidney has a good therapeutic effect on premature ovarian failure with no side effect.

Acupuncture Points ; Adult ; Catgut ; Estradiol ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Primary Ovarian Insufficiency ; therapy

OBJECTIVETo compare the therapeutic effects of acupuncture and western medicine on minimal brain dysfunction (MBD) and to search for a clinically effective therapy for MBD.

METHODSSixty-eight cases were randomly divided into an acupuncture group and a western medicine group, 34 cases in each group. The acupuncture group were treated by acupuncture at Dazhui (GV 14) and Shenque (CV 8), and the western medicine group by taking Haloperidol orally. One month constituted one course. After treatment, the total effective rate and scores of Connell's scale for diagnosis and behavior of MBD were compared between the two groups.

RESULTSThe total effective rate and the score after treatment were 97.1% and 10 +/- 0.37 in the acupuncture group and 82.4% and 15 +/- 0.93 in the western medicine group, with a very significant difference between the two groups (P < 0.01, P < 0.000 5), the acupuncture group being better than the western medicine group. Follow-up survey for 2-10 months showed the effects of the acupuncture group still were kept.

CONCLUSIONAcupuncture at Dazhui (GV 14) and Shenque (CV 8) can effectively cure MBD.

Acupuncture Therapy ; methods ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; therapy ; Child ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional

This study was aimed to investigate the effects of the introplasmic interferon-γ level in circulating T cell of patients with aplastic anemia (AA) and its clinical significance. The interferon-γ level before and after immuno-suppressive therapy was monitored by flow cytometry. The results indicated that the higher interferon-γ level was detected in 28 out of 50 AA patients, detected rate was 56%. The effective rate of immunosuppressive therapy for AA patients with higher interferon-γ level was up to 85.7% (24/28). The decrease of interferon-γ level in these patients positively correlated with hemogram recovery to normal level and obviously earlier than hematologic remission. It is concluded that the immunosuppressive therapy shows better efficacy for AA patients with high interferon-γ level, moreover the change of interferon-γ level is earlier than hematologic change, that is important for predicting the therapeutic efficacy and relapse of disease.
Adolescent ; Adult ; Aged ; Anemia, Aplastic ; drug therapy ; metabolism ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Immunosuppressive Agents ; therapeutic use ; Interferon-gamma ; metabolism ; Male ; Middle Aged ; T-Lymphocytes ; metabolism ; Young Adult