OBJECTIVE:To study the pharmacodynamic effects of volatile oil from Homalomena occulta on adjuvant-induced arthritis(AA)model rats and its mechanism. METHODS:60 rats were randomly divided into normal control group(0.5%polysor-bate 80),model control group (0.5% polysorbate 80),positive control group (Tripterygium glycosides tablets,10 mg/kg), high-dose,middle-dose and low-dose(0.08,0.04 and 0.02 ml/kg)groups of volatile oil from H. occulta. Except for normal control group,other groups were given complete Freund's adjuvant subcutaneously via right rear foot plantar to induce AA model,and giv-en relevant medicine intragastrically for 25 days,once a day,since modeling. The articular swelling degree,immune organ (thy-mus gland and spleen) index,pathological change,the contents of IL-1β and TNF-α in serum were detected. RESULTS:Com-pared with normal control group,the primary and secondary articular swelling degree and thymus gland index of rats and the serum contents of IL-1β and TNF-α increased in model control group,while spleen index decreased(P<0.05 or P<0.01);obvious tissue swelling,large amount of neutrophile granulocyte,leukomonocyte and macrophage infiltrating joint surrounding tissue,the prolifer-ation of synovial cells and obvious osteoarthritic lesion were observed in podarthrum. Compared with model control group,the pri-mary and secondary articular swelling degree and the serum content of IL-1β decreased in the volatile oil from H. occulta groups;thymus gland index increased in middle-dose and low-dose groups of the volatile oil from H. occulta;the content of TNF-α de-creased in high-dose group of the volatile oil from H. occulta(P<0.05 or P<0.01). The inflammatory cell infiltration of joint sur-rounding tissue relieved in treatment groups,synovial cells proliferation was not obvious and synovial cells morphology was im-proved. CONCLUSIONS:The volatile oil from H. occulta has the pharmacodynamic effects on AA in rat,and its mechanism might be related to the serum content reduction of IL-1β and TNF-α.

ObjectiveTo evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP)chemotherapy combined with intensity-modulated radiation therapy (IMRT)in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods71 patients (Stage Ⅲ:41,Stage ⅣA:30) with locoregionally advanced NPC were entered this study.Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m2 intravenously on d1-3 and gemcitabine 1000 mg/m2 in 30 minutes intravenous infusion on days 1 and 8,every 3 weeks for 2 cycles.Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy.The prescription doses was 66.0-70.4 Gy to the gross tumor volume,66 Gy to positive neck nodes,60 Gy to the high-risk clinical target volume,54 Gy to the low-risk clinical target volume.ResultsThe overall response rate to neoadjuvant chemotherapy was 91.2％,acute toxicity was mainly grade 1-2 myleosuppression.All patients completed IMRT.The median follow-up duration was 38 months.The 3-year nasopharyngeal local control,regional control,distant metastasis-free survival rate and overall survival rate were 93％,99％,91％,90％,respectively.Severe late toxicities included grade 3 trismus in 1 patient,grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients,respectively.No grade 4 late toxicities were observed.Conclusions The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated,convenient,effective,and warrants further studies of more proper cycles of GP regimen.

Objective To study the effect of interleukin 2(IL-2)of clinical dose range,on the proliferation of human peripheral blood T cells,with special emphasis on the number and functional phenotype of γδT cells.Methods Human peripheral blood mononuelear cells(PBMCs)were isolated by density gradient centrifugation and cultured for 2 weeks at different IL-2 concentrations.Ratio and phenotype of different T cell subpopulations before and after in vitro expansion were explored by immunofluorescence staining.Cell number was estimated by trypan blue staining and cell counting.Results Within the four functional phenotypes of Vδ1 as well as Vδ2 γδT cells,CD27~+cells(including CD27~+CD45RA~+and CD27~+CD45RA~-subsets)expressed lymphoid tissue homing receptor CCR7,whereas CD27~-cells(including CD27~-CD45RA~+and CD27~-CD45RA~-subsets)had the peripheral tissue homing potential.All the studied γδT functional subsets showed the expression of activity related receptors,and the ability of a rapid production of various amount of cytotoxicity related effectors following mitogen stimulation.Although IL-2 at high concentration suppressed the proliferation of CD4 T cells,it may promote the proliferation of γδT cells.The proliferated γδT cells were mainly CD27~-CD45RA~-effector cells.Conclusion IL-2 of the clinical dose range may promote proliferation of human peripheral blood γδT cells,which might have important biological significance in IL-2 based anti-tumor therapy.

Objective To observe the therapeutic effectiveness of valsartan in combination with amlodipine in therapy of essential hypertension and the consequent changes in red cell distribution width (RDW).Methods One hundred and ten patients of hypertension were selected,then randomly divided into treatment group (56 cases) and control group (54 cases).Valsartan and amlodipine were given to the treatment group,while the control group taking amlodipine only.Bp and RBC were carried out before and after treatment.Results Antihypertensive effect of the treatment group were statistically significant compared with the control group (P ＜ 0.05).The consequent RBC,Hct and Hb,RDW level of treatment group decreased dramatically compared with the control group (P ＜ 0.01 or ＜ 0.05).Conclusions Valsartan in combination with amlodipine in ther apy of hypertension is a prospective combination which achieves superior blood pressure control,low level of RDW and blood viscosity,as a result reducing the incidence of cardiovascular events.

Objective:To explore the mechanisms of the inhalation of atomized 1.0% anti-IL-1βand TNF-αimmunoglobulin yolk ( IgY) on treating guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin ( OVA).Methods:Healthy guinea pigs were randomly divided into the normal controls ( group C ) , the allergic asthma model group ( group M )-treated by the inhalation of atomized ovalbumin ( OVA ) , the inhalation of atomized 1.0% anti-IL-1βand TNF-αimmunoglobulin yolk ( IgY ) treatment group (group Z1)-treated asthma model guinea pigs by the inhalation of atomized 1.0% anti-IL-1βand TNF-αIgY,and positive control the inhalation of atomized budesonide treatment group (group Z2)-treated asthma model guinea pigs by the inhalation of atomized budesonide.The blood was gotten by cardiac puncture and the bronchoalveolar lavage fluid ( BALF ) was collected by bron-choalveolar lavage at 2 h,4 h,8 h and 24 h after the last time atomization.The inflammatory cells in the peripheral blood ( PB) were counted by methylene blue and eosin staining.Cytokine concentrations of IL-1β,IL-4,IL-6,IL-8,IL-13,IL-16,TNF-α,TGF-β1 and IgE in the plasma and bronchoalveolar lavage fluid (BALF) were measured using an enzyme-linked immunosorbent assay (ELISA).Results:In PB,eosinophils was decreased from 2 h to 8 h in group Z1 compared to group M.In plasma,the levels of IL-1βat 4 h and 24 h,IL-16 at 2 h,4 h and 24 h,TGF-β1 from 4 h to 24 h and IgE at 24 h,as well as the levels of IL-1βand TNF-αfrom 2 h to 8 h,IL-4,IL-6,IL-8 and IL-13 from 4 h to 24 h,IL-16 at 8 h,and TGF-β1 and IgE from 4 h to 8 h,especially the level of IL-1βand TNF-αstarting at 2 h,in BALF were significantly reduced in group Z 1 compared to group M ( P<0.05 ).The levels of IL-1βand TNF-αwere positively cor-related with that of IL-4,IL-6,IL-8,IL-13,IL-16,TGF-β1 and IgE (P<0.05).Conclusion: The inhalation of aerosolized anti-IL-1βand TNF-αIgY effectively alleviates inflammatory responses in guinea pigs with allergic asthma induced by aerosolized OVA inhalation may be due to the significant decrease in the levels of various allergic inflammatory cytokines .

Objective:To investigate therapeutic mechanism of immunoglobulin Yolk (IgY) against tumour necrosis factor alpha ( TNF-α) and interleukin-1 beta ( IL-1β) in guinea pigs with allergic rhinitis.Methods: Hartley guinea pigs were randomly divided into the control group (group C,n=17),the allergic rhinitis model group (group M,n=27),the 0.1%anti-TNF-αand IL-1βIgY treating group (group Z1,n=21) and the fluticasone propionate treating group (group Z2,n=21).The allergic rhinitis model in guinea pigs was established using ovalbumin.After treatment for 2 h,4 h,8 h,nose and bronchial lung were lavaged using 0.9%saline, the nasal lavage fluid (NLF) and bronchoalveolar lavage fluid (BALF) were collected,the precipitated cells were stained using Wright′s,the nasal mucosa and lung tissues were stained using methylene blue and eosin (HE),and TNF-α,IL-1β,IL-5 and IL-33 in nasal mucosa and lung tissues were stained using immunohistochemistry.Results:There were a large amount of eosinophils and more serious inflammation responses in nasal mucosa in the M group compared with the Z 1 and Z2 groups.In the lung tissues,there were more alveolar tube damage ,pulmonary interstitial edema ,interval thickening ,thickening of bronchial smooth muscle and inflammation cell in-filtration in the M group compared with the Z 1 and Z2 groups.The eosinophils ,lymphocytes and neutrophils were significantly decreased in NLF and BALF in the Z1 and Z2 groups compared with the M group (P<0.05).The expressions of IL-1βand TNF-αfrom 2 h to 8 h and IL-5 and IL-33 from 4 h to 8 h significantly decreased in the nasal mucosa and lung tissues in the Z 1 group compared with the M group ( P<0.05 ).Conclusion:The allergic rhinitis in guinea pigs accompany with the allergic asthma.The inhibitory capacity of anti-TNF-αand IL-1βIgY on pathological responses in guinea pigs with allergic rhinitis may be due to the significant decrease in the infiltration of eosinophils and the expressions of inflammatory cytokines in the nasal mucosas and lung tissues .

OBJECTIVETo evaluate the applicability of immune-related response criteria (irRC) in treating non-small cell lung cancer (NSCLC) by Chinese medicine (CM).

METHODSTotally 97 stage III a-IV NSCLC patients were predominantly treated with comprehensive CM. Curative effects were evaluated by three methods such as Response Evaluation Criteria in Solid Tumors (RECIST), Oncologic Curative Effect Evaluation Criteria of Chinese Medicine in Solid Tumor (draft, abbreviated as CM criteria), and irRC. The correspondency and consistency between irRC, RECIST and CM criteria were analyzed and compared. The objectivity of irRC in evaluating curative effect of Chinese medical treatment for NSCLC was assessed.

RESULTSThe correspondency rate of irRC to RECIST was 59. 79% with Kappa value of 0. 379 (U test, P <0. 01). The two criteria had certain correspondence, but with an unsatisfactory consistency. The correspondency rate of irRC to CM criteria rate was 83. 51% with Kappa value of 0.751 (U test, P <0. 01). The two criteria had good correspondence and consistency.

CONCLUSIONSCM criteria had good consistency with CM criteria in evaluating curative effect for Chinese medical treatment of advanced NSCLC. Its results could objectively reflect features and advantages of CM for treating advanced NSCLC.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; immunology ; Medicine, Chinese Traditional ; standards ; Treatment Outcome

OBJECTIVE To observe prenatal nicotine exposure (PNE) induced high sensitivity of hypo?thalamic-pituitary-adrenal (HPA) axis in offspring rats which were fed with a high-fat diet, and to explore the mechanism. METHODS Nicotine (2 mg·kg-1 per day) was injected subcutaneously to preg?nant Wistar rats from gestational day (GD) 9 to GD20,and then the young rats were naturally delivered. After weaning, half of the offspring was fed with a high-fat diet until postnatal weeks (PW) 20. The others were exposed to unpredictable chronic stress (UCS) from PW17 to PW20. The pathological changes in the hippocampus were analyzed by HE staining. The blood concentration of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) was detected by RIA kits and ELISA kits, respectively. Meanwhile, real-time PCR was used to detect the mRNA expression of ACTH releasing hormone (CRH), arginine vasopressin (AVP), vesicular glutamate transporter 2 (VGluT2), glutamic acid decarboxylase 65 (GAD65), mineralocorticoid receptor (MR),glucocorticoid receptor (GR) and glutamic acid decarboxylase 67 (GAD67). RESULTS In the normal control group,UCS treatment increased the level of serum ACTH and CORT 1.96 and 3.24 times in female rats,but 1.63 and 3.54 times in male rats. In the PNE group, UCS treatment increased the level of serum ACTH and CORT 3.96 and 5.98 times in female rats, but 3.04 and 5.22 times male rats. PNE increased the mRNA expression of AVP in the female and male rats 2.04 and 1.13 times in UCS treatment control group, and the mRNA expression of hypothalamus CRH and the ratio of VGLuT2/ GAD65 were increased 2.49 and 1.14 times in female rats, respectively. Furthermore, the nicotine group exhibited histological changes to different degrees in the hippocampus and dentate gyrus area of the hippocampus. In the female and male nicotine groups, the mRNA ratio of hippocampal MR/GR decreased by 88.0% and 86.0% in comparison with the normal control group without UCS, and the mRNA expression of GAD67 was enhanced 1.38 and 1.97 times in female and male rats without UCS. In the female UCS treatment nicotine groups, the mRNA expression of GAD67 was increased 2.17 times compared with the UCS treatment control group. CONCLUSION PNE can induce a high sensibility of HPA axis in offspring rats fed with a high-fat diet. The imbalance of hippo?campus MR/GR and the enhanced expression of GAD67 mRNA may be involved.

Objective To compare the efficiency and safety between Aripiprazole and other traditional drugs for Tourette's syndrome treatment.Methods Databases such as China National Knowledge Infrastructure,Wanfang,VIP,China Biology Medicine Disc,PubMed and Web of Science were electronically searched for studies on Aripiprazole for Tourette's syndrome treatment.According to the inclusion and exclusion criteria,studies,extracted data,and assessed quality were screened.Meta-analysis was performed by using Stata 11.0 software.Results Four studies about Aripiprazole for Tourette's syndrome treatment with 396 patients (Aripiprazole group:201 cases;control group:195 cases) were synthetically and quantitatively analyzed.Meta-analysis results showed that Aripiprazole was better than other traditional agents (placebo,Tiapride,Haloperidol) [standardized mean difference (SMD) =0.21,95％ CI:0.10-0.32].The subgroup by time of treatment analysis results indicated that Aripiprazole was superior to other drugs in 2 weeks (SMD =0.28,95％ CI:0.06-0.50).There was no significant difference in the efficacy between Aripiprazole and other drugs for treatment of Tourette's syndrome in 4 weeks and 8 weeks after treatment (SMD =0.16,0.28;95％ CI:-0.05-0.38、-0.20-0.76).The subgroup by matched drugs results suggested that Aripiprazole was better than Tiapride (SMD =0.29,95 ％ CI:0.15-0.43),but was not significantly different from Haloperidol (SMD =-0.03,95％ CI:-0.28-0.22).There was no significant difference in side effects incidence between Aripiprazole and traditional drugs for treatment of Tourette's syndrome (RR =0.83,95 ％ CI:0.36-1.89).Conclusions Compared with the conventional drugs,Aripiprazole has better therapeutic efficacy in the treatment of Tourette's syndrome in children in 2 weeks.Aripiprazole is better than Tiapride,but equal to Haloperidol in the treatment of Tourette's syndrome.The safety of Aripiprazole needs to be further verified.

OBJECTIVE:To study the time-effect and dose-effect of paeonol on the apoptosis of knee osteoarthritis(OA)artic-ular chondrocyte in rabbits and the mRNA expression of its related protein Bcl-2 and Bax. METHODS:60 big-ear rabbits were ran-domly divided into normal (normal saline) group,model (normal saline) group,paeonol high-dose,medium-dose and low-dose groups and triamcinolone acetonide(positive drug)group,with 10 rabbits in each group. Except for normal group,OA model was induced by right knee anterior cruciate ligament (ACLT) and the medial meniscus 1/3 resection in those groups. After modeling, different doses of paeonol(0.8,0.4,0.2 mg/kg),triamcinolone acetonide 0.2 mg/kg were injected into right articular cavity twice a week. 4 weeks and 8 weeks after administration,articular cartilage specimens were collected. Ultrapathological structure changes of articular chondrocytes were observed by electron microscope. Apoptosis of cartilage cell was observed by TUNEL and apoptotic index was calculated. mRNA expression of apoptosis related genes of Bcl-2 and Bax in articular cartilage tissue of rabbits were de-tected by in situ hybridization technique. RESULTS:Compared with normal group,articular chondrocyte of model group showed early and middle stage apoptosis morphology change after 4 and 8 weeks,and apoptosis index increased significantly and the mRNA expression of Bcl-2 and Bax was up-regulated (P<0.01);4 and 8 weeks later after administration,compared with model group,apoptosis index decreased and mRNA expression of Bax was down-regulated in paeonol groups,while mRNA expression of Bcl-2 was up-regulated(P<0.05 or P<0.01). Electron microscopy ultrastructural observation showed articular chondrocyte of pae-onol high-dose and middle-dose groups were in early stage of apoptosis.CONCLUSIONS:Paeonol can slow down articular chondro-cyte degeneration and destroy in OA model rabbits in time and dose dependently. Its mechanism may be associated with expression up-regulation of Bcl-2 and expression down-regulation of Bax.