Protective Effect of Hydroxysafflor Yellow A on Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Rats

Objective: To observe the effect of hydroxysafflor yellow A(HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleomycin(BLM) in rats. Methods: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone(DXM) group. Three doses of HSYA(35.6, 53.3, and 80.0 mg·kg~(–1)·day~(–1)) were intraperitoneally(i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control(n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin(α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. Results: On the 7 th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure(PaO_2) increased(HSYA 80.0 mg·kg~(–1), P0.01) and CO_2 partial pressure(PaCO_2) decreased(HSYA 53.3, 80.0 mg·kg~(–1), P0.05). Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg·kg~(–1) groups than those in the model group(all P0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO_2(HSYA 53.3, 80.0 mg·kg~(–1), P0.01), and decreased PaCO_2(53.3 and 80.0 mg·kg~(–1), P0.05). Further, the mRNA expression of TGF-β1, α-SMA, and collagen Ⅰ as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes(53.3, 80.0 mg·kg~(–1), P0.05). Hematoxylin and eosin and Masson's trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups(53.3, 80.0 mg·kg~(–1), P0.05). Conclusion: HSYA could alleviate acute lung inflammation and chronic pulmonary fibrosis induced by BLM in rats.     

Effects of Senegenin against Hypoxia/Reoxygenation-Induced Injury in PC12 Cells

Objective:To investigate the effect and the potential mechanism of Senegenin(Sen) against injury induced by hypoxia/reoxygenation(H/R) in highly differentiated PC12 cells.Methods:The cultured PC12 cells were treated with H/R in the presence or absence of Sen(60 μmol/L).Four groups were included in the experiment:control group,H/R group,H/R+Sen group and Sen group.Cell viability of each group and the level of lactate dehydrogenase(LDH) in culture medium were detected for the pharmacological effect of Sen.Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate.Moreover,mitochondrial membrane potential(△Ψm),reactive oxygen species(ROS) and intracellular free calcium([Ca~(2+)]i) were measured by fluorescent staining and flow cytometry.Cleaved caspase-3and activity of NADPH oxidase(NOX) were determined by colorimetric protease assay and enzyme linked immunosorbent assay,respectively.Results:Sen significantly elevated cell viability(P0.05),decreased the leakage of LDH(P0.05) and apoptosis rate(P0.05) in H/R-injured PC12 cells.Sen maintained the value of△Ψm(P0.05) and suppressed the activity of caspase-3(P0.05).Moreover,Sen reduced ROS accumulation(P0.05) and[Ca~(2+)]i increment(P0.05) by inhibiting the activity of NOX(P0.05).Conclusion:Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and[Ca~(2+)]_i,thereby suppressing the mitochondrial pathway of cellular apoptosis.     

Protective Effects of Danlou Tablet (丹蒌片) against Murine Myocardial Ischemia and Reperfusion Injury In Vivo

Objective: To observe the in vivo effect of Danlou Tablet (丹蒌片, DLT) on myocardial ischemia and reperfusion (I/R) injury. Methods: DLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group (n=6), I/R group (n=8), IPC group (ischemia preconditioning, n=6) and DLT group (I/R with DLT pretreatment for 3 days, 750 mg?kg-1?day-1, n=8). The effects of DLT were characterized in infarction size (IS) compared with risk region (RR) and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo. Furthermore, the dose-dependent effect of DLT on I/R injury was evaluated by double staining method. Five different concentrations of DLT (0.625, 1.25, 2.5, 5 and 10 g?kg-1?day-1) were chosen in this study, and dose-response curve of DLT was obtained on these data. Results: The ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group (P<0.05 or P<0.01), the ratio of IS to RR was also reduced in the DLT and IPC groups (P<0.01), while there were no differences in RR among the four groups (P>0.05). Experiments showed incidence of arrhythmias was reduced in the DLT group (P<0.01). Furthermore, DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g?kg-1?day-1. Conclusions: Our research concluded that DLT was effective in reducing I/R injury in mice, and provided experimental supports for the clinical use of DLT.     

Protective Effects of Xiongshao Capsule (芎芍胶囊) on Anti-inflammatory Function of High-Density Lipoprotein in An Atherosclerosis Rabbit Model

Objective: To observe the effects of Xiongshao Capsule(芎芍胶囊, XSC) on anti-inflammatory properties of high-density lipoprotein(HDL), myeloperoxidase(MPO) and paraoxonase 1(PON1) in serum of atherosclerosis(AS) rabbit model and explore the anti-inflammatory protective effects of XSC on HDL. Methods: Sixty rabbits were randomized into the control, the model, XSC low-, medium-and high-dose(Rhizoma Chuanxiong + Radix Paeoniae rubra : 0.6+0.3, 1.2+0.6, 2.4+1.2 g·kg-1·day-1, respectively), and simvastatin(1 g·kg-1·day-1) groups. The model rabbits were fed with high-fat diet and respective drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol(TC) and free cholesterol(FC) in aorta wall cells were tested by enzyme linked immunosorbent assay. Results: TC and FC in the model group were significantly higher than those in the control group(P0.01). Compared with the model group, TC and FC in the XSC groups were significantly lower(P0.05 or P0.01), so was simvastatin group(P0.01). There was no significant difference in PON1 level between groups(P0.05), even between model and control groups(P0.05). The serum MPO level in the model group was significantly higher than that in the control group(P0.05), which was significantly lower in XSC groups as well as simvastatin group(P0.05 or P0.01), and no difference was found between XSC groups and simvastatin group(P0.05). Conclusions: XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.     

Relevant Features Selection for Automatic Prediction of Preterm Deliveries from Pregnancy ElectroHysterograhic (EHG) records

In this study, we proposed an approach able to predict whether a pregnant woman with contractions would give birth earlier than expected (i.e., before the 37 ^{t h} week of gestation (WG)). It only processes non-invasive electrohysterographic (EHG) signals fully automatically without assistance of an expert or an additional medical system. We used term and preterm EHG signals of 30-minutes duration collected between the 27 ^{t h} and the 32 ^{n d} WG. Preterm deliveries (<?37W G) had occurred in average 4.00 ± 1.88 weeks since recording dates. Each recording contains three bipolar channels. Using the Huang-Hilbert transform (HHT), we obtained up to twelve intrinsic mode functions (IMFs) for each signal. We found that the most relevant IMFs for both term and preterm records were IMF3 and IMF6. From these two IMFs, we extracted 8 most relevant features targeting EHG signal specificities. We investigated features classifications using support vector machine (SVM) for the 3 single-channels and for all their possible combinations. High discrimination power between term and preterm EHG records was obtained with linear-SVM classifiers. For almost all the cases, mean areas under curves (AUC) exceeded 0.92. A two-channel combination (7 features) achieved the best mean results with A c c u r a c y =?95.70%, S e n s i t i v i t y =?98.40%, S p e c i f i c i t y =?93.00% and A U C =?0.95. Results of the three-channel combination (9 features) were A c c u r a c y =?92.30%, S e n s i t i v i t y =?93.00%, S p e c i f i c i t y =?91.60% and A U C =?0.96. The best single-channel (8 features) gave the mean values: A c c u r a c y =?90.40%, S e n s i t i v i t y =?93.60% and A U C =?0.94. Thus, the advantage of our approach is the high diagnostic performance at low computational cost.     

Salvianolate Reduces Murine Myocardial Ischemia and Reperfusion Injury via ERK1/2 Signaling Pathways in vivo

Objective

To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.

Methods

Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.

Results

There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).

Conclusion

Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.

     

Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats

Objective: To observe the effect of puerarin on methyl-CpG binding protein 2(MeCP2) phosphorylation(pMeCP2) in the hippocampus of a rat model of vascular dementia(VD). Methods: Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table(n=12 per group). The modified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 m L/d of saline, while the puerarin-treated group was given 100 mg/(kg·d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical(IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively. Results: The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group(P0.05), while the puerarin-treated group was obviously shorter than the dementia group(P0.05). Cross-platform times of the dementia group were significantly decreased compared with the sham-operated group(P0.05), while the puerarin-treated group was obviously increased compared with the dementia group(P0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups(P0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was significantly increased compared with the sham-operated group, and the puerarin-treated group was significantly increased compared with the dementia group(both P0.05). Western blot analysis showed no significant difference of MeCP2 expression among 3 groups(P0.05). The expression of pMeCP2 in the dementia group was significantly increased compared with the sham-operated group, while it in the puerarin-treated group was significantly increased compared with the dementia group(P0.05). Conclusion: Puerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.     

Gefitinib plus Fuzheng Kang'ai Formula(扶正抗癌方) in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation:A Randomized Controlled Trial

Objective: To evaluate the effect of Fuzheng Kang'ai Formula(扶正抗癌方, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor(EGFR) mutations. Methods: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage ⅢB/Ⅳ non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib(250 mg/day orally) plus FZKA(250 m L, twice per day, orally); 35 cases] or G group(gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival(PFS)] and secondary endpoints [median survival time(MST), objective response rate(ORR), disease control rate(DCR) and safety] were observed. Results: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months(95% CI 3.30–21.69) vs. 8.4 months(95% CI 6.30–10.50; log-rank P0.01), MST of 21.5 months(95% CI 17.28–25.73) vs. 18.3 months(95% CI 17.97–18.63; log-rank P0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively(P0.05). The most common toxic effects in the GF group and G group were rash or acne(42.8% vs. 57.1%, P0.05), diarrhea(11.5% vs. 31.4%, P0.05), and stomatitis(2.9% vs. 8.7%, P0.05). Conclusion: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.     

Effect of Health Education Based on Integrative Therapy of Chinese and Western Medicine for Adult Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study

Objective: To investigate the effects of health education based on integrative therapy of Chinese and Western medicine for type 2 diabetes mellitus(T2DM) from the aspects of knowledge, attitude and practice(KAP), health-related quality of life(HRQo L), body mass index(BMI) and glucose control. Methods: Patients were individually randomized into intervention group(receiving integrative education, n=120) and control group(receiving usual education, n=120). The primary outcome was the changes in glycosylated hemoglobin A1c(HbA1c) levels after 3, 6, 9 and 12 months from baseline. Hierarchical linear models(HLMs) were used to assess within-group changes in outcomes over time and between-group differences in patterns of change. Secondary outcomes were KAP scores, HRQo L scores and BMI after 6 and 12 months, paired-sample t test was used to assess within-group changes in outcomes in 6 and 12 months, independent-sample t test was used to assess between-group differences in patterns of change. Results: HbA1c decreased statistically from baseline to 3 months, from 3 to 6 months, from 6 to 9 months and from 9 to 12 months in the intervention group(all P0.01); and decreased significantly from baseline to 3 months, and from 3 to 6 months in the control group(P0.01). There were significant between-group differences from baseline to 3 months(P=0.044), from 6 to 9 months(P0.01) and from 9 to 12 months(P0.01). Significant improvements in the intervention group along with significant between-group differences were found in KAP and HRQo L scores respectively(all P0.05). The number in the intervention group of normal weight increased from 56 at baseline to 81(6 months), 94(12 months), the number in the control group were 63(baseline), 69(6 months), 70(12 months), the χ~2 of hierarchical analysis of BMI were 6.93(P=0.075), 10.31(P=0.016), 15.53(P0.01), respectively. Conclusion: Health education based on integrative therapy of Chinese and Western medicine is beneficial to the control of T2DM and should be recommended for T2DM.     

Genetic variants in <Emphasis Type="Italic">CHEK1</Emphasis> gene are associated with the prognosis of thoracic esophageal squamous cell carcinoma patients treated with radical resection

CHEK1 gene is known to play an important role in tumor progression by cell cycle control. However, the association between CHEK1 and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in CHEK1 gene and prognosis of ESCC patients treated with radical resection. A total of 131 thoracic ESCC patients who underwent radical resection were included in this retrospective study and genotyped using the MassArray method. According to the univariate Cox hazard analysis, the GT/TT genotype of CHEK1 rs555752 was shown to be strongly related to a decreased overall survival (OS) (HR=2.560, 95% CI: 1.415–4.631, P=0.002) and disease-free survival (DFS) (HR=2.160, 95% CI: 1.258–3.710, P=0.005). Furthermore, according to the multivariate Cox hazard analysis and multiple testing, patients with the GT/TT genotype of CHEK1 rs555752 had a notably decreased OS (HR=2.735, 95% CI: 1.468–5.096, P=0.002, Pc=0.006) and DFS (HR=2.282, 95% CI: 1.292–4.023, P=0.004, Pc=0.012). In conclusion, genetic variants of the CHEK1 gene are significantly related to OS and DFS of ESCC patients, and may therefore be predictors of the prognosis of thoracic ESCC after surgery.     

Hot Compress with Chinese Herbal Salt Packets Reducing PICC Catheter Complications: A Randomized Controlled Trial

Objective: To explore the preventive effect of applying hot compress with Chinese herbal salt packets(CHSP) to puncture vessels under aseptic conditions during peripherally inserted central catheter(PICC) on postoperative phlebitis. Methods: A total of 720 hospitalized patients undergoing first PICC were assigned to treatment and control groups(360 cases each group) according to a random number table. The control group received conventional catheterization and nursing care. The treatment group was first given hot compress with CHSP(which consisted of honeysuckle 30 g, Semen brassicae 30 g, Salvia miltiorrhiza 30 g, Angelica dahurica 30 g, Semen raphani 30 g, Evodia rutaecarpa 30 g, and coarse salt 20 g) on the punctured vessel under aseptic conditions for 5–10 min before conventional catheterization. The main efficacy indices were the vessel diameters before and during catheterization and the success rate of a single catheter, and the secondary efficacy indiex was the incidence of superficial phlebitis within 1 week after catheterization. Results: The vessel diameter during catheterization of the treatment group was remarkably increased compared with the control group [(7.96±0.42) mm vs.(4.39±0.54) mm, P0.01]. The success rate of the single catheter of the treatment group was significantly higher than that of the control group [94.00%(329/350) vs. 73.72%(244/329), P0.01]. The incidence of superficial phlebitis within 1 week after catheterization in the treatment group was lower than that in the control group(P=0.007). There was no adverse event with CHSP. Conclusion: Hot compress with CHSP during PICC is applicable as it can effectively improve the success rate of a single catheter and reduce the incidence of superficial phlebitis after catheterization(Trial registration No. ChiCTR-ONC-17010498).     

Allicin Improves Cardiac Function by Protecting against Apoptosis in Rat Model of Myocardial Infarction

Objective:To study the effects of allicin on cardiac function and underlying mechanism in rat model of myocardial infarction(MI).Methods:Ninety-four Wistar rats were randomly assigned to 6 groups(n=14–16 per group):sham control group[underwent thoracotomy without left anterior descending(LAD)occlusion and only received an injection of the same amount of citrate buffer],MI control group(subjected to LAD occlusion and only received an injection of same amount of citrate buffer),positive control group(subjected to LAD occlusion and received an injection of diltiazem hydrochloride at the dose of 1.5 mg/kg),and MI+allicin groups(subjected to LAD occlusion and received an injection of allicin at the doses of 1.2,1.8,and 3.6 mg/kg).All of the drugs were administered intraperitoneally daily for 21 days.The infarct area was measured by myocardial staining.Hematoxylin-eosin staining was used to observe the pathological changes.Cardiac function parameters were assessed by echocardiography.The myocardial apoptotic index was estimated by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling staining.The expression of Bax and Bcl-2 were detected by quantificational real-time polymerase chain reaction and Western blot.Results:Treatment with allicin could attenuate the myocardial infarct area(P0.05)and relieve the changes of the myocardium.The left ventricular anterior wall diastolic and systolic thicknesses were increased in the allicin-treated groups(P0.05),while there was no significant difference in the left ventricular posterior wall diastolic and systolic thickness(P0.05).The left ventricular internal diameter in systole,ejection fraction,fractional shortening,and stroke volume were dramatically elevated in allicin-treated rats(P0.05).Allicin dose-dependently reduced creatine kinase and lactate dehydrogenase levels(P0.05).The myocardial apoptotic index was also markedly lowered,and Bax expression was significantly decreased,whereas Bcl-2 expression exhibited an opposite trend in allicin-treated rats(P0.05).Conclusion:Allicin appears to exert a cardioprotective effect that may be linked to blocking Bcl-2/Bax signaling pathway-denpendent apoptosis,further improving cardiac function.     

Antifibrotic Effect of Total Flavonoids of Astmgali Radix on Dimethylnitrosamine-Induced Liver Cirrhosis in Rats

Objective: To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). Methods: Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen Ⅰ, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen Ⅰ, α-SMA, PPARγ, UCP2 and FXR. Results: Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen Ⅰ and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01). Conclusions: TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.     

Study of T Cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART

Objective

To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART).

Methods

Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group). The counts of CD4⁺, CD8⁺, CD8/CD38⁺, and CD8/HLADR⁺ T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline) and in the HIV negative control group. The expression of CD127 on CD3⁺ T cells was measured by flow cytometry at a single time point (after 7 years) in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group.

Results

At baseline CD4⁺ T cell counts of HIV-1-infected patients were lower than that in the control group (p < 0.01), whereas the CD8⁺, CD8/HLADR⁺ and CD8/CD38⁺ T cell counts were higher than those in the control group (p < 0.01). After seven years of effective HAART, the CD4⁺ T cell counts had increased and the CD8⁺ T cell count had decreased, although not to the normal levels (p < 0.05). Both the CD8/HLADR⁺ and CD8/CD38⁺ T cell counts had gradually approached those of the control group (p > 0.05). In the ineffective HAART group, the CD8/CD38⁺ T cell count had not decreased significantly, and CD8/HLADR⁺ T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (p < 0.01). After seven years of effective HAART, IL-7 levels had gradually decreased, but were still higher than in the control group (p < 0.01). The CD127 expression on CD3⁺ CD8⁺ T cells in effective HAART patients was higher than in untreated HIV+ patients (p < 0.05), but was lower than that in the control group (p < 0.05). CD127 expression on CD3⁺ CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group.

Conclusion

After seven years of effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.

     

Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats

Objective: To evaluate the preventive effect of salvianolate(Sal B) on glucose metabolism disorders of dimethylnitrosamine(DMN)-induced cirrhotic rats. Methods: Fifty-five Wistar rats were randomly divided into a control group(n=10) and a cirrhotic group(n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups(n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B(50 mg/kg), metformin(150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test(OGTT), and fasting plasma glucose(FPG), fasting insulin(FINS), hepatic glycogen, hydroxyproline(HYP) and liver function were detected at the end of the treatment. Area under the curve(AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining(HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic expression of α-smooth muscle actin(α-SMA) and collagen(Col Ⅰ) were evaluated by immunohistochemical staining. Results: Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate(GIR), FPG, FINS levels and hepatic glycogen at the end of administration(P0.05 or P0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level(P0.05 or P0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col Ⅰ in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis(P0.05). Metformin increased insulin sensitivity more potently than Sal B(P0.05). Conclusions: Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.     

Jinmaitong(筋脉通)Alleviates the Diabetic Peripheral Neuropathy by Inducing Autophagy

Objective:To observe the deregulation of autophagy in diabetic peripheral neuropathy(DPN) and investigate whether Jinmaitong(筋脉通i,JMT) alleviates DPN by inducing autophagy.Methods:DPN models were established by streptozotocin-induced diabetic rats and Schwann cells(SCs) cultured in high glucose medium.The pathological morphology was observed by the improved Bielschowsky's nerve fiber axonal staining and the Luxol fast blue-neutral red myelin staining.The ultrastructure was observed by the transmission electron microscopy.Beclinl level was detected by immunohistochemistry and Western blot.The proliferation of cultured SCs was detected by methylthiazolyldiphenyl-tetrazolium bromide.Results:Diabetic peripheral nerve tissues demonstrated pathological morphology and reduced autophagic structure,accompanied with down-regulation of Beclinl.JMT apparently alleviated the pathological morphology change and increased the autophagy[in vivo,Beclinl integral optical density(IOD) value of the control group 86.6±17.7,DM 43.9±8.8,JMT 73.3 ±17.8,P0.01 or P0.05,in vitro Beclinl IOD value of the glucose group 0.4710.25 vs the control group 0.88 ±0.29,P0.05].Consequently,inhibition of autophagy by 3-methyladenine resulted in a time- and concentrationdependent decrease of the proliferation of SCs(P0.05,P0.01).Conclusions:Down-regulation of autophagy in SCs might contribute to the pathogenesis of DPN.JMT alleviates diabetic peripheral nerve injury at least in part by inducing autophagy.     

Chinese Medicine for Idiopathic Parkinson's Disease: A Meta Analysis of Randomized Controlled Trials

Objective:To evaluate the efficacy of Chinese medicine(CM) adjunct to conventional medications for idiopathic Parkinson's disease(PD).Methods:Electronic English and Chinese databases including PubMed,Cochrane Library,Web of Science,Chinese Medical Current Contents,China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Med Database,and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy.The extracted data was analyzed by the Review Manager 5.0.Results:Twelve trials involving 869 participants were included in the meta-analysis.Unified PD Rating Scale(UPDRS) I,Ⅱ,Ⅲ,Ⅳ scores and UPDRS Ⅰ-Ⅳ total scores were used to be the primary outcomes,Parkinson Disease Question-39(PDQ-39) and Scores of Chinese Medical Symptoms were the secondary outcomes.CM adjunct therapy had greater improvement in UPDRS Ⅰ[2 trials;standardized mean difference(SMD)-0.40,95%confidence interval(CI)-0.71 to-0.09;Z=2.49(P=0.01)],Ⅱ[5 trials;SMD-0.47,95%CI-0.69 to-0.25;Z=4.20(P0.01)],Ⅲ[5 trials;SMD-0.35,95%CI-0.57 to-0.13;Z=3.16(P=0.002)],Ⅳ scores[3 trials;SMD-0.32,95%CI-0.60 to-0.03;Z=2.17(P=0.03)],UPDRS Ⅰ-Ⅳ total scores[7 trials;SMD-0.36,95%CI-0.53 to-0.20;Z=4.24(P0.05)].PDQ-39 and Chinese medical symptoms compared to the conventional medication only.Conclusion:CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.     

Preferred Revascularization Strategies in Patients with Ischemic Heart Failure: A Meta-Analysis

Clinically, coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is generally used to treat patients with ischemic heart failure. However, the optimal treatment strategy remains unknown. This study examined the efficacy of the two coronary revascularization strategies for severe ischemic heart failure by using a meta-analysis. Studies comparing the efficacy of CABG and PCI were obtained from PubMed, EMBASE, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL). The quality of each eligible article was evaluated by Newcastle-Ottawa Quality Assessment Scale (NOS), and the meta-analysis was performed using Stata version 12.0 software. Eventually, 12 studies involving 9248 patients (n=4872 in CABG group; n=4376 in PCI group) were subject to the meta-analysis for subsequent pooling calculation. The pooled hazard ratio (HR) [HR=0.83, 95% CI (0.76, 0.90), P<0.001; heterogeneity, P=0.218, I²=22.9%] of CABG compared with that of PCI revealed a statistical superiority of CABG to PCI in terms of the long-term mortality. Furthermore, CABG showed more advantages over PCI with respect to the incidence of myocardial infarction [HR=0.51, 95% CI (0.39, 0.67), P<0.001; heterogeneity, P=0.707, I²=0%] and repeat revascularization [HR=0.40, 95% CI (0.27, 0.59), P<0.001; heterogeneity, P<0.001, I²=80.1%]. It was concluded that CABG appears to be more advantageous than PCI for the treatment of ischemic heart failure in the given clinical setting.     

Contribution of Water and Lipid Soluble Substances in the Relaxant Effects of Tymus Vulgaris Extract on Guinea Pig Tracheal Smooth Muscle in Vitro

Objective:To examine the relaxant effects of hydro-ethanolic,macerated aqueous(MA) and lipidfree macerated aqueous(LFMA) extract of Tymus vulgaris on tracheal chains of guinea pigs.Methods:The relaxant effects of five cumulative concentrations of each extract(0.4,0.8,1.2,1.6 and 2.0 g/100 mL) were compared with saline as negative control and five cumulative concentrations of theophylline(0.1,0.2,0.4,0.6 and 0.8 mmol/L) on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCI(group 1) and 10 μmol/L methacholine(group 2,n=6 for each group).Results:In group 1 all concentrations of theophylline,three higher concentrations of hydro-ethanolic,two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline(P0.05 or P0.01).Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline(P0.05 or 0.01).In group 2 experiments,all concentrations of theophylline,hydro-ethanolic,MA and LFMA extracts showed significant relaxant effects compared to that of saline(P0.05 or P0.01).In both groups,the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others(P0.05 or P0.01).The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments(all P0.01).There were significantly positive correlations between the relaxant effects and concentrations for theophylline and ail extracts in both groups(P0.05 or P0.01).Conclusion:Hydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.