BACKGROUND:More and more evidence have shown that autoimmune-induced inflammatory demyelinating mostly leads to optic neuritis that is quite an early manifestation of multiple sclerosis, but whether the pathogenesis of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice is correlated with helper T cellsubsets has rarely been reported.
OBJECTIVE:To analyze the correlation between pathogenesis of optic neuritis of mouse EAE model with helper T cellsubsets.
METHODS:The mice were injected intraperitoneal y Bordetel a pertussis to establish EAE models. Then, the animal models were subjected to immunization for 11, 15, 19 days, respectively. Mice undergoing intraperitoneal injection of normal saline served as controls (adjuvant group).
RESULTS AND CONCLUSION:Compared with the adjuvant group, the protein expression of interleukin 4 in the optic nerve decreased in the 19-day immunization group (P<0.05);the protein expression of interleukin 17 in the optic nerve increased in the 11-and 15-day immunization groups (P<0.05);the protein expression of interferonγin the optic nerve increased in the 15-and 19-day immunization groups (P<0.05);the protein expression of Foxp3 in the optic nerve decreased in the 11-, 15-and 19-day immunization groups (P<0.05). Real-time PCR results showed that compared with the adjuvant group, the mRNA expression of interferonγand Foxp3 in the optic nerve decreased (P<0.05), while mRNA expression of RORt increased in the 11-, 15-and 19-day immunization groups;the mRNA expression of interleukin 4, interleukin 17, T-beat increased in the 15-and 19-day immunization groups (P<0.05);the mRNA expression of GATA3 reduced in the 19-day immunization group (P<0.05). These results reveal that Foxp3 expression and helper T cellreduction have important influences on the development of optic neuritis in EAE mouse models, interleukin 17 may mediates inflammatory injury in the early stage, while interferon-γmakes inflammatory injury worse in the peak incidence of the disease.

Objective To investigate the effects of acupuncture at acupoints at different time points on the occurrence of postoperative nausea and vomiting ( PONV ) in patients undergoing radical rectal cancer operation.Methods One hundred and thirty ASA Ⅰ - Ⅲ patients,aged 40-59 yr,with body mass index of 20-25 kg/m2,scheduled for elective radical rectal cancer operation,were randomly divided into 5 groups ( n =25 each):control group ( group Ⅰ ),treatment with the conventional drug group (group Ⅱ ),preoperative acupuncture group ( group Ⅲ ),acupuncture during operation group (group Ⅳ ),and postoperative acupuncture group (group Ⅴ ).Granisetron 3 mg was injected intravenously before the end of the operation in group Ⅱ.Acupuncture was performed at 30 min before induction of anesthesia,at skin incision and at the end of operation in groups Ⅲ,Ⅳ and Ⅴ respectively.Bilateral Neiguan ( PC6 ),Hegu ( LI4 ),Zhigou ( SJ6 ),and Quchi ( LI11 ) acupoints were selected in groups Ⅲ,Ⅳ and Ⅴ.Acupuncture stimulation lasted for 30 min.Blood samples were collected from the peripheral vein after admission to the operating room (T0),at 1 h after skin incision (T1),at the end of operation (T2 ),and at 24 h after operation (T3) to determine the plasma gastrin concentration.The occurrence of PONV was recorded within 2 h after operation,during 2-6 h,6-12 h and 12-24 h after operation,and within 24 h after operation.Results Compared with group Ⅰ,the incidence of PONV within 2 and 24 h after operation,and the plasma gastrin concentration at T3 were significantly decreased in groups Ⅱ and Ⅲ ( P ＜ 0.05),and no significant change was found in the indexes mentioned above in groups Ⅳ and Ⅴ (P ＞ 0.05).Compared with group Ⅱ,the plasma gastrin concentration at T3 was significantly decreased in group Ⅲ,the incidence of PONV within 2 and 24 h after operation was significantly increased in groups Ⅳ and Ⅴ ( P ＜ 0.05).Compared with group Ⅲ,the incidence of PONV within 2 and 24 h after operation,and the plasma gastrin concentration at T3 were significantly increased in groups Ⅳ and Ⅴ ( P ＜ 0.05 ).Conclusion Preoperatvie acupuncture at acupoints can decrease the occurrence of PONV in patients undergoing radical rectal cancer operation,the efficacy is similar to that of the conventional drugs,and the decreased concentration of the plasma gastrin after operation is involved in the mechanism.

Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; pathology ; Drug Delivery Systems ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Lipids ; chemistry ; MCF-7 Cells ; drug effects ; Nanoparticles ; chemistry ; Paclitaxel ; pharmacology ; RNA, Small Interfering ; pharmacology ; Real-Time Polymerase Chain Reaction

Objective:To compare the concordance between subjective experience and clinician-rated in different treatment phrase of elderly patients with depressive disorder,and to explore the relevant factors.Methods:Sixty-nine consecutive elderly patiems with depressive disorder diagnosed with International Classification of Diseases-10 criteria were included.The Visual Scale for Depression(VSD) were used to evaluate subjective experience of depression,while the Hamilton Depression Scale (HAMD),Hamilton Anxiety Scale (HAMA),Minimum Mental State Examination (MMSE) were used by clinician to evaluate depression symptom,anxiety symptom and cognition at baseline,2-,4-and 52-week of the treatment respectively.Results:Compared with baseline,VSD scores were increased at 2 weeks and 4 weeks [(2.7 ± 1.6),(5.3 ± 2.0) vs.(7.0 ± 1.8),P ＜ 0.001],HAMD scores were decreased at 2 weeks and 4 weeks [(36 ± 11),(17 ±9) vs.(9 ±8),P ＜0.001],HAMA scores were decreased at 2 weeks and 4 weeks [(27 ± 10),(14 ±8) vs.(7 ±6),P ＜0.001].No significant differences were found between 4 weeks and 52 weeks.There was no correlation between VSD and HAMD scores at baseline and 2 weeks.There were significant correlations among scores of VSD and HAMD(r =-0.31,-0.74,Ps ＜ 0.05),HAMA (r =-0.36,-0.76,Ps ＜ 0.05) at 4 weeks and 52 weeks.Using logistic regression analysis,the concordance between VSD and HAMD related with the factors of HAMD,higher scores of anxiety/somatization factor were associated with lower concordance (OR =0.87),and higher scores of weight factor (OR =1.86),diurnal variation factor (OR =2.00),hopelessness factor (OR =1.13) were associated with higher concordance.Conclusion:Compared with acute depression phase,concordance between subjective experience and clinician-rated for depression may be higher at depression remission phase in elderly patients with depression,which suggests that characteristics of depression symptom may have a certain impact on the self-awareness for depression experience.

Aim To investigate the inhibitory effects of urocortin2 (UCN2) on ventral tegmental area (VTA) nervous activity of morphine addiction rats and the mechanism. Methods Morphine addiction rats and the microiontophoresis method were used to observe the effects of UCN2 on VTA neuron′s spontaneous dis-charge changing rule, as well as the inhibitory effects of UCN2 on DA neuron′s cluster spontaneous dis-charge, to identify UCN2 and DA on the same VTA neuron. Morever, the inhibitor of corticotropin-regula-ting factor′s receptor ( CRF-2 R ) and the blocker of protein kinase A ( PKA ) , AST-2 B and H89 , were used to investigate the effects of UCN2 on VTA neuron′s of morphine addiction rats. Results UCN2 could inhibit the firing rate 82% (31/38) of the tested VTA neuron ( P<0. 01 ) , the discharge frequency changed from (20. 89 ± 2. 86) Hz to (13. 66 ± 3. 93) Hz (P<0. 01). Further, the inhibitor of PKA, AST-2B and H89 could ablolish the inhibitory effects of UCN2 . Morever, the excitatory firing of VTA neurons was at-tenuated by addition of UCN2 , while AST application could inhibit the UCN2′s inhibitory effects. Conclu-sion UCN2 could regulate the effects of VTA via PKA pathway and may thereby contribute to the improvement of drug addiction.

Objective To explore the expression of human epidermal growth factor receptor -3( HER3) in human epidermal growth factor receptor-2(HER2)-positive breast cancer and its relationship with the therapeutic effect of trastuzumab and clinical prognosis .Methods Clinicopathological characteristics of 235 HER2-positive breast cancer patients undergoing surgery in Jiangsu Cancer Hospital from Jan .2007 to Jun.2012 were analyzed retrospectively.The expression of HER3 was detected using immunohistochemisty staining .The expression of HER3 and its correlation with the clinicopathological characteristics were analyzed .All patients were followed-up to find out the impact of HER3 on the disease free survival and the therapeutic effect of trastuzumab .Results The positive rate of HER3 in Luminal B ( HER2 +) and HER2-overexpressing breast cancer was 100/135 (74.1%), and 85/100(85%)respectively.The difference had statistical significance (P<0.05).The histolog-ical grading and the lymph node metastasis were significantly different in Luminal B ( HER2+) breast cancer .The tumor volume , histological grading and lymph node metastasis were significantly different in HER 2-overexpressing breast cancer .The 5-year disease free survival of HER 2-positive breast cancer patients with negative HER 3 was higher than that with positive HER3.The non-relapse survival time was not significantly different between the pos-itive and negative HER 3 expression in Luminal B ( HER2+) breast cancer patients receiving trastuzumab treat-ment , but was significantly different in HER 2-overexpressing breast cancer patients .Conclusions HER3 is cor-related with unfavourable prognosis in HER 2-positive breast cancer .The treatment targeting HER3 may improve the clinical prognosis of both HER 2-positive and HER3-positive breast cancer patients .The HER2-overexpressing breast cancer patients with negative HER 3 may benefit more from trastuzumab treatment .

Objective To assess the technical efficiency and subsystem technical efficiency of the healthcare institutions in China,including that of management system and medical system.Methods Panel data of 31 provinces' healthcare institutions were selected,and Network DEA was adopted to assess such input indicators as managerial staff and health technical personnel,and such output indicators as medical revenue and number of medical visits.Results The technical efficiency of healthcare institutions is as lower as an efficiency mean of 0.853 in five year.Provinces of Zhejiang,Shandong,Henan,Guangdong and Tibet have maintained a higher level.The healthcare system breaks down into two independent subsystems of the management subsystem and medical subsystem.The mean of the former one is 0.937,higher than 0.783 of the latter.The number of medical revenue and that of patients in the non-effective provinces were relatively inadequate.Conclusions Healthcare resources allocation in China needs to be optimized.It is imperative to adjust the input-output ratio,improve medical service quality via scientific management.

Breast Neoplasms ; metabolism ; Female ; Humans ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Progesterone ; metabolism

ObjectiveTo assess the clinical application of endoscopic submucosal dissection(ESD) for early esophageal carcinomas and pre-malignant lesions. MethodsESD was performed for early esophageal carcinomas and intraepithelial neoplasms without submucosal infiltration. First, normal saline was injected into the submucosa to elevate the lesion from the muscle layer. Then, the surrounding mucosa of the lesion were cut, and the lesion was dissected along the connective tissue of the submucosa. ResultsOf 15 early esophageal carcinomas and intraepithelial neoplasms, ranging from 2.5 to 4.5 cm (mean size 3.2 cm) , 14 (93.3%) underwent ESD successfully . All 14 lesions were confirmed pathologically, and no basal or dissected margin was involved. The mean ESD procedure time (from fluid injection to complete dissection) was 75 min ( ranging from 45 to 150 min). Minor bleeding (mean volume 30 ml) occurred in all lesions, which was stopped by electric coagulation, argon plasma coagulation and clamps. No delayed bleeding occurred. The perforation rate of ESD was 0(0/15). Fourteen patients were followed up after ESD for 6 to 18 months (mean=11.5), and healed with no residue or recurrence. ConclusionESD is a novel endoscopic procedure to reseet early esophageal carcinomas and pre-malignant lesions, with which large lesions can be resected and pathological information can be provided.

Objective To investigate and compare the effects of etomidate or propofol on spatial cognitive,exploring,learning and memory abilities and hippocampus tissue in rapid development period of rats.Methods Thirty-nine SD rats with anage from 17 to 18 days were randomly divided into group C(10 ml/kg of normal saline),group E(5 mg/kg of etomidate),group P(50 mg/kg of propofol)(n=13).They were all single injected intraperitoneally.The tests of cognitive function were performed in Open Field Test(OFT),Hole Board Test and Ymaze Test at 3 hours postanesthesia awake.HE staining method was uesed to observe the morphology of hippocampus neuron tissue and immunohistochemistry(IHC) method was uesed to detect the expression of aspartic acid specificity cysteine protease (caspase-3) in hippocampal neurons.Results In the OFT,there was no significant difference between group C((3.70 ± 1.06)s,(39.10 ± 11.89)s)and group E,P((4.40 ±2.01)s and (4.60 ± 1.96) s,(37.90 ± 11.88) s and (36.30 ± 15.68) s) about the retention time in central check and the locomotion (P ＞ 0.05).In the Hole Board Test,the rats of groups E and P(12.00 ± 3.13,10.00 ± 2.79) about the times of rats stretch into the hole were significant different comparing with group C(16.30 ±4.62) (P＜0.05).In the Ymaze Test,compared with group C,the group E in the right number and total reaction time were no significant differences (P ＞ 0.05).The right number of group P (9.80 ± 2.39) were obviously decreased as compared with group C(13.30 ±2.00)(P ＜ 0.01),and there also had significant difference between group E and group C (P ＜0.05).In addition,the total reation time between group P ((82.30 ± 10.20) s) and group C ((67.70 ± 12.18) s) was significant difference(P ＜ 0.05).In HE staining,there were obvious changes in group E and P.In IHC,the expression of caspase-3 between groups C,E and P,there were no significant differences (P ＞ 0.05).Conclusion Single intraperitoneal injection of etomidate can make a transient effects for the rapid development period of rats ' ability of exploration,but have no obvious influence of the spatial cognition and learning and memory abilities.And etomidate lead less influence on newborn rat behavior and hippocampal tissue than propofol.