Objectiye To study the mechanism by which transcranial magnetic stimulation (rTMS) affects cognitive dysfunction in vascular dementia (VD). Methods Thirty-six male Wistar rats were randomly divided into a control group, a VD group, a low frequency rTMS group and a high frequency rTMS group. Two-vessel occlusion was employed to induce VD models. Low frequency rTMS group rats were given 0.5 Hz rTMS for six weeks. High frequency rTMS group rats were given 5 Hz rTMS for six weeks. Morris' water maze test was used to measure their spatial learning ability and memory. The ultrastructures of the synapses in the four groups were detected with transmission electron microscopy. The expression of synaptophysin (SYN), brain derived neurotrophic factor (BDNF) and Nmethyl-D-aspartate receptor 1 ( NMDAR1 ) mRNA and protein in the hippocampus were determined by real-time PCR and Western blotting. Results The behavior and morphology of the rats treated with rTMS improved. The average expression of SYN, BDNF and NMDAR1 mRNA and protein in the low frequency rTMS group and the high frequency rTMS group were significantly higher than in the VD group. Conclusion rTMS can provide a rehabilitative effect for VD. The mechanism might be associated with enhancing the expression of SYN, BDNF and NMDAR1 in the hippocampus.

Objective To study the effects of repetitive transcranial magnetic stimulation(rTMS) of the supplementary motor area(SMA)on the cortical excitability in patients with Parkinson's disease(PD).Methods Sixteen patients with PD were included in this study.The motor evoked potentials(MEP)and the N30 component of somatosensory evoked potentials(SEP) were assessed for each patient before and after 1200 pulses of rTMS of the SMA at 5 Hz and an intensity of 100% of relaxed motor threshold (RMT) for the abductor pollicis brevis.Results Ten minutes after the rTMS intervention,the peak-to-peak amplitude of the SEP component P20-N30 increased significantly(P<0.05),with the P/F index decreased simultaneously(P<0.05).The MEP amplitude increased significantly,and reached the highest value at 10min after the rTMS intervention. Conclusion 5 Hz rTMS of the SMA can improve the excitability of the SMA itself temporarily.Meanwhile,it can induce a short-lasting facilitation of the excitability of M1 connected with SMA.

Objective:To investigate the relationship between VitD 3 concentration and glucose and insulin levels of OGTT in patients with CKD 3-5 stages.Methods: We included the patients with CKD 3 and 4 and 5 stages who fulfill the including standard.All patients were recorded the concentrations of [1,25 (OH):D3]concentration of glucose and insulin at fasting ,postprandial 1 h,2 h during OGTT and concentration of glycosylated hemoglobin level ,C peptide concentration.We performed the correlation analysis about [1,25 (OH):D3],glucose and insulin.Results: We totally included 91 patients with 3-5 stages CKD into our study.The D3 concentration of stage 3 were 160.9-261.3 mmol/L[(218.38±8.67)mmol/L] of stage 3,75.2-166.3 mmol/L[(117.01±4.72) mmol/L] of stage 4 and 11.8-96.5 mmol/L[(41.91±12.83)mmol/L] of stage 5 (P<0.05).The average concentrations of serum glucose at fasting,1 h after the meal and 2 h after the meal was(4.74±0.21)mmol/L,(8.31±0.43)mmol/L and(7.36±0.32)mmol/L in 3 stage and (4.92±0.25) mmol/L,(9.14±0.15) mmol/L and (9.14±0.39)mmol/L at 4 stage and (4.81±0.13)mmol/L, (10.72±0.41)mmol/L and (10.72±0.49)mmol/L at 5 stage (P<0.05).The average concentrations of insulin during OGTT at fasting,1 h after the meal and 2 h after the meal was (6.58±0.32) μU/L,(57.78±5.63)U/L and (42.77±8.45)U/L in 3 stage (6.03±0.53)U/L,(55.69±7.35)U/L and (62.52±5.39)U/L in 4 stage and (6.12±0.65)U/L,(62.82±9.73)U/L and (77.34± 8.62)U/L in 5 stage (P<0.05).Correlation analysis shows that the concentration of 1,25 (OH):D3 of different stages of patients with CKD and vitamin D 3 concentration and glucose tolerance test was found to be inversely associated with the insulin levels ( P<0.05 ) . Conclusion:There are obvious differences of concentration of vitamin D 3 between patients with 3-5 stages of chronic kidney disease (CKD).There also showed a negative correlation relationships between glucose and insulin levels ,and vitamin D3 concentration and glucose and insulin levels at OGTT of patients with 3-5 stages CKD.

To investigate the dynamics of interleukin-21 (IL-21) cytokine in the Chinese HIV patients undergoing highly active antiretroviral therapy (HAAPT).Methods A total of 25 adults with chronic HIV infections,responding to combined highly active antiretroviral therapy (HAART) guideline criteria were enrolled for a 1-year follow-up.After signing an informed consent,20 mL blood was collected from each patient at the base line,6 month and 12 month,respectively.CD4 and CD8 cell count was quantified by flux cytometry,serum HIV RNA quantified by real time PCR and IL-21 concentrations by ELISA.Results IL-21 levels increased gradually during the follow-up but did not reach the healthy levels.IL-21 correlated positively with the CD4 cells but not with CD8 T cells.HIV RNA correlated negatively with CD4 cell count but did not show any relationship with the CD8 cells.Conclusion IL-21 has potential role in the immunopathogenesis of HIV,and might be an important factor in immune construction during HAART.

Objective To define the mechanical features of mitral annulus at various sites,and to investigate the specific mechanics characterization at different mitral annulus sites in evaluation consequences of left ventricular function by dual pulse-wave Doppler (DPW) technology.Methods The DPW spectrums were obtained at lateral and aboral interval,anterior and inferior and posterior mitral annular from 112 normal adults.The peak systolic velocity (Sm),peak early diastolic velocity (Em),peak late diastolic velocity (Am),the beginning time of the peak and the time to peak were measured,and E/A,Em/Am,E/Em,left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were computed.Results 1)Sm,Em,Am and Em/Am measured in the free wall annulus were significantly greater than measured in the interval annulus of mitral annular sites.However,E/Em was opposited (P ＜ 0.05).Sm of the posterior wall mitral annulus accelerated frist and experienced shortest duration in all the mitral annular sites (P ＜ 0.01).There were no significant differences of Em time parameters among different mitral annulus sites.Am of the beginning time and peak time in the free wall annulus were significantly longer than that in the interval annulus of anterior mitral annular sites.However,the acceleration time was opposited(P ＜0.05).2) Sm was correlated with LVEF and LVFS (r =0.243 and r =0.227,P ＜0.01) only at the posterior mitral annular site,Em/Am of anterior and posterior wall mitral annulus had the highest correlations with mitral orifice flow E/A(r =0.545 and 0.545 respectively,P ＜ 0.01).Conclusions There are significant differences among the mechanics patterns at different mitral annulus sites in normal adults.The mechanics characterization at different mitral annulus sites have different conclusions of left ventricular function.

Although highly active antiretroviral therapy (HAART) can effectively reduce the HIV replication,complete recovery of CD4+ T cells does not always occur,even among patients with high virological control.Current researches on γ-chain cytokines have understood the biology and their crucial roles in initiating,maintaining,and regulating the immunologic homeostasis and the inflammatory processes.Due to the multiple functions such as the regulatory and effector cellular function in healthy and disease state,these molecules,their receptors,and their signal transduction pathways are promising candidates for therapeutic interference.The common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 are primary regulators of T cell homeostasis and thus have been considered prime immunotherapeutic candidates,both for increasing T cell levels/function and augmenting vaccine-elicited viral-specific T cell responses in immunocompromised AIDS patients.The objective of this review is to update the role of the common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 in HIV AIDS pathogenesis.

Objective To determine the incidence, clinical manifestation and part of lymphokines which represent the balance of Th1 and Th2 in the role of the immunologic mechanisms for IRIS(immune restoration inflammatory syndromes)in patients initiating HAART(Highly Active Antiretroviral Therapy).Methods A prospective study of all patients initiating HAART was performed. A period of six months tracking initiating HAART was performed. The incidence of IRIS, time of occurrence and clinical disease spectrum were recorded. The main T lymphokines including IL-2, INF-γ, IL-4, IL-10 which on behalf of the balance of Th1 and Th2 were detected. To explore the immunopathologic mechanisms for IRIS, the levels of T lymphokines at pre-HAART, initiating HAART for 1 month, 3months and 6 months were compared in IRIS group and non-IRIS group, healthy group. Results A total of 212 patients were enrolled in this study. 59 patients were diagnosed as IRIS at a median of 21 days after HAART initiation (QR 19 days).The main disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia. No matter in the IRIS group or non-IRIS group, the main lymphokines baseline of IL-2, INF-γ reduced and IL-4, IL-10 increased before HAART compared to healthy group (P ＜ 0. 05), which had the tendency to restore balance relations initiating HAART. The lymphokines levels had significant difference between baseline and 6 months initiating HAART (P ＜ 0. 05). The changed levels of lymphokines between IRIS group and non-IRIS group before HAART had significant difference compared to healthy group. IL-2, INF-γ increased level[(11.68 ± 2. 89) pg/ml vs (8.52 ±2.26) pg/ml; (22. 19 ± 6. 22) pg/ml vs (18.34 ±5. 35) pg/ml] and IL-10 decreased level [(19. 21 ± 4. 03) pg/ml vs (23. 19 ± 5.92) pg/ml] had significant difference between IRIS group and non-IRIS group initiating HAART I month(P ＜0. 05). Conclusions The incidence of IRIS during 6 months initiating HAART in HIV/AIDS was 27. 8%, IRIS usually occurred in 1 month initiating HAART. The most common disease spectrum was infectious disease, including tuberculosis and herpes virus infection. Lymphokine of Th1 and Th2 existed unbalance in IRIS group and non-IRIS group before HAART. The unbalance tendency in IRIS group was more obvious. All lymphokines had the trend to recover balance. IL-2, INF-γ significantly increased and IL-10 significantly decreased, which might involve the occurrence of the IRIS.

Objective To observe the Th17, IL-17 and Tr cells equilibrium state as well as their changes of HIV infected or AIDS suffered patients in one-year HAART treatment. Methods Select 33 HIV/AIDS patients received HAART treatment while 33 healthy volunteers as controls. Flow cytometry was used to analyze Th17 and Tr cells in venous blood at the time of pre-therapy, 6th, 12th month when IL-17 levels in serum are tested by ELISA. Results The ratio of Th17 cells in CD4 cells in HIV/AIDS patients and volunteers were (1.20±0.37)%, (2.50±1.03)%, (3.70±1.56)%, (4.70±1.43)%, respectively; The ratio of Tr cells were (9.16±3.33)%, (7.19±2.91)%, (5.53±1.88)%, (4.43±0.97)%, respectively; The levels of IL-17 in serum were (5.3±2.5) pg/ml, (7.7±2.4) pg/ml, (10.4±3.1) pg/ml, (17.7±6.6) pg/ml respectively. The Th17 cells' level was positively correlative with the amount of CD4 cells, negatively correlate with the count of viral load. However, the Tr cells level is positively correlative with the count of viral load, negatively relate to the quantity of CD4 cells. Conclusion HIV could make IL-17, Th17 cells and Tr cells lost their balance, but the immune equilibrium state may gradually recover after HAART treatment. Which indicates the IL-17, Th17 cells and Treg cells may play an important role in the pathogenesis of AIDS, and they are likely to be the effective indexes to observe the progress of AIDS and the treatment effect of highly active antiretroviral therapy(HAART).

Objective To explore ability of the vpr gene of human immunodeficiency virus type 1 ( HIV-1 vpr) to induce cell G_2 arrest and apoptosis, and the influence when it mutated, the relationship between Vpr-induced G_2 arrest and apoptosis inductions. Methods Fourteen mutant vpr fragments selected from Chinese patients with HIV. Both eukaryotic expression vector pcDNA3.1( + ) and PCR products purified, double-cut by Hind Ⅲ and BamH Ⅰ and the cut products legated and transformed into competent cells JM109. The 14 reconstructed plasmids electronically transfected into Jurkat-cells, and established cells with pcDNA3. 1-vpr , pcDNA3. 1-vpr-Fs and pcDNA3. 1 blank cells, and without pcDNA3. 1 cell. Cells were harvested after 24 h. mRNA expression was detected by RT-PCR, the DNA content and percentage of apoptosis were monitored by flow cytometry. Results Transfected with 14 mutant HIV-1 Vpr protein, cells display different G_2 percentage and apoptosis ratio. HIV-1 vpr induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation, vector pcDNA3.1( + ) and the blank cells can not. The G_2 percentage and apoptosis ratio reduced when transfected with vpr expressing mutating of 70V, 85P, 86G, 94G compared to the wild type. Subtype AE has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Preliminary, we find that the higher G_2 percentage followed the higher ratio of apoptosis. Conclusion HIV-1 vpr can induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation can not. We firstly found that mutated sites of 70V, 85P, 86G, 94G may reduce the ability of Vpr to induce cell cycle G_2 arrest and apoptosis, subtype AE of vpr in Chinese HIV-1 patients has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Analysis of various mutations in the vpr gene revealed that the extent of Vpr-induced G_2 arrest correlated with the levels of apoptosis. And investigate the pathegenesis of HIV vpr. This can also make a good foundation for further study on gene therapy.

Objective To investigate the different radioprotective effects of total flavonoids of Astragalus (TFA) on human normal mesenchymal stem cells(hMSCs) and hepatoma cells injured by 60 Coγ-ray radiation.Methods hMSCs and HepG-2 cells were cultured and randomly divided into TFA-treated and untreated groups.The cells of different groups were irradiated with 60 Co γ-rays at the dose of 6 Gy.MTT method was utilized to detect the survival rates of the hMSCs and HepG-2 cells pretreated or untreated with TFA before irradiation.Cell clone formation test was used to measure the cellular radiosensitivity.The apoptosis rates of different groups were determined by flow cytometer assay.The expression rates of the apoptosis-promoting proteins Fas and Bax and the apoptosis-inhibiting protein Bcl-2 were analyzed by Western blotting.Results MTT showed that the survival rates of hMSCs pretreated by TFA were 1.15-1.95 times higher than that of the pure irradiation group.On the contrary,the survival rates of the TFA pretreated HepG-2 cells were only 0.53-0.23 times that of the pure irradiation group.There was a good dose-effect relationship between the cell survival rate and the TFA concentration.Cell clone formation rate indicated that combined treatment of TFA and radiation inhibited the cell proliferation more effectively than single TFA or pure radiation.Flow cytometry showed that 6,24 and,48 h post-irradiation to 6 Gy,the apoptosis rates of the hMSCs were 23.3% ,11.2% ,and 2.9% ,respectively in the TFA pretreated group and were 29.3% ,24.9% ,and 13.6% in the pure radiation group.However,the apoptosis rates of the HepG-2 cells at 6,24,and 48 h post-irradiation to 6 Gy were 11.6% ,17.3% ,and 20.1% ,respectively in the TFA pretreated group and were 6.9% ,9.3% ,and 15.8% ,respectively in the direct radiation group.Western blotting showed that the expression levels of Fas and Bax proteins in the HepG-2 cells were significantly higher in the TFA pretreated group than in the pure radiation group.On the contrary,the expression level of the apoptosis inhibiting protein Bcl-2 was significantly lower in the TFA pretreated group than in the pure radiation group.Conclusions TFA has obvious effects of radiological protection on human hMSCs and has no effects of radiological protection but effects of apoptosis enhancement on hepatoma cells.The promotion of apoptosis of TFA on hepatoma cells is primarily through increasing the expression of apoptotic proteins such as Fas and Bax and reducing the expression of anti-apoptotic protein Bcl-2.