ObjectiveAnalyze the mechanism of traditional Chinese medicine Salvia miltiorrhiza in treating coronary heart disease (CHD).MethodsThe animal experiment using actual research, namely the selection of rat isolated heart perfusion model, rat model of myocardial ischemia and ventricular tachycardia in rabbits model, then the effects of different animal groups in hemodynamics, coronary flow, serum superoxide dismutase (SOD) content, malondialdehyde (MDA) the results of the content.ResultsAfter treatment, the content of SOD was significantly increased and the content of MDA was significantly decreased in the treatment group, and the difference between the two groups was statistically significant (P<0.05).ConclusionTraditional chinese medicine Salvia miltiorrhiza has significant effect on the treatment of coronary heart disease, which is beneficial to the recovery of patients' condition, and is worthy of clinical application.

Targeting cell apoptosis is currently the most promising therapy for cancer treatment. The BH3-only protein, which is a member of Bcl-2 family, can bind to the pro-survival members of the family and neutralize their functional activities to induce apoptosis (ie, to isolate pro-apoptotic members of the Bcl-2 family). BH3 mimetics, a kind of small molecule compounds, has the ability to mimic the BH3-only protein to induce apoptosis. The prototype of BH3 mimetics is ABT-737, who can selectively targets on BCL-XL, BCL-2 and BCL-W (but not MCL-1 and A1). ABT-263, a derivative of ABT-737, has a better performance of inducing apoptosis and inhibiting the growth of tumor in clinical trials. At this stage, some presumably BH3 mimetics has entered the clinical stage, while a large part of them is still being characterized and tested. Basing on the mechanism of BH3-only protein, this review summarize a variety of BH3 mimetics which have been widely recognized, and show the latest developments of newly diagnosed BH3 mimetics in the field.

BACKGROUND:Autologous conditioned serum (ACS) is a new and safe biological therapy method mainly used for osteoarthritis, rheumatoid arthritis and other similar diseases. OBJECTIVE:To explore the purification method and cytokine profile of ACS. METHODS:Blood obtained equipment (containing 3 mm of glass beads) was used to collect peripheral blood samples that were mixed uniformly and then placed in a 37℃ thermostatic incubator for 24 hours, finally filtered to obtain ACS. The quantitative determination of interleukin (IL)-1Ra, IL-6, IL-8, and IL-1β was conducted, and the 36 kinds of cytokines were semi-quantitatively detected by cytokine antibody array. RESULTS AND CONCLUSION: The levels of various cytokines in ACS were obviously increased, among which, IL-1Ra level (important for alleviating osteoarthritis) was increased from 140.25 ng/L to 1125 ng/L(increased by above 8 times); IL-6 level was increased from 389.5 ng/L to 2802 ng/L; IL-8 level was not detected firstly and finally increased to 2822 ng/L. Cytokine antibody array results showed that at least 10 kinds of cytokines in ACS were changed, and most of cytokines were on a rise, and few in decline. These results indicate that the ACS contains IL-1Ra and a variety of cytokines, and some chemokines in the ACS recruit more immune cells to the inflammation sites and accelerate the inflammatory process, further exerting therapeutic effects.

Aim To evaluate the inhibitive effects of celastrol on LDL oxidation and HAEC cell oxidative damage. Methods The Cu2+-induced LDL oxidation model was employed to evaluate celastrol inhibitive effect on LDL oxidation in vitro, the oxidative reaction kinetic curves were determined, and the AUC, lag time,TBARS value were assayed. The AAPH-induced HAEC damaging cellular model was employed to evalu-ate the effect of celastrol on oxidative cellular damage. The safe dose of celastrol on normal cells was deter-mined by MTT method, and the effects of celastrol on HAEC oxidative damage were evaluated at the range of this safe dose. The LDH leakage,ROS level,SOD and GPX enzymatic activity,Nrf2 and HO-1 mRNA expres-sion were determined. Results At the dose range of 100 nmol · L-1 to 1 μmol · L-1 , celastrol effectively extended the lag time of LDL oxidative process induced by Cu2+, reduced the AUC of oxidative reaction kinet-ic curve and reduced the generation of lipid peroxide in the LDL oxidative process. In the cellular experiment, celastrol effectively reduced the LDH leakage induced by AAPH, increased the integrity of cell membrane and nucleus, enhanced the antioxidative enzyme activi-ties of cellular SOD,GPX and increased the expressions of Nrf2,HO-1 mRNA, celastrol also maintained the in-tegrity of cellular structure. Conlusion Celastrol can effectively inhibit LDL oxidation induced by Cu2+, and can inhibit HAEC cell oxidative damage induced by AAPH at the dose range of 100 to 400 nmol·L-1 .

Objective To observe the therapeutic efficacy and safety of the glucagon-like peptide-1 ( GLP-1 )analogue combined with isulin for treating obese or overweight type 2 diabetes.Methods 40 cases with obese or overweight type 2 diabetic patients( body mass index(BMI) ≥24) who have previously used human insulin,and experienced poor glycemic control( ≥7.5％ ) were selected.They were randomly divided into two groups.A group treated by GLP-1 analogue liraglutide plus insulin,and B group by continuous adjustment of insulin.12 weeks later,fasting blood glucose(FBG),2-hour plasma glucose (2hPG),hemoglobin A 1 C (HbA1c),body weight were observed and the incidence of hypoglycemia,insulin dosage were recorded.Results Weight and insulin dosage of group A was significantly lower than those of group B after treatment 12 week( t =2.738,2.865,all P ＜ 0.01 ).Numbers of hypoglycemia events were 6 in group A(30％ ),and 9 in group B(45％ ),but there was no statistical significance between the two groups ( P ＞ 0.05).Conclusion The addition of liraglutide to insulin in patients with obese or overweight type 2 diabetes is associated with reductions in weight and insulin dosage,without increase risk of hypoglycemia.This treatment proved effective and safe.

Objective To evaluate the application of M-mode echocardiography and Doppler echocardiography in diagnosing complete atrioventricular block (CAVB) in fetus. Methods M-mode and Doppler echocardiography were used to screen the fetuses and bradycadia was established as CAVB in 10 cases. Atrial and ventricular rhythm was measured by M-mode echocardiography. Flow of mitral valve, left ventricular in-flow and out-flow tract, venous duct was measured by Doppler echocardiography. The characteristics and prognoses of CAVB fetus were compared and analyzed. Results CAVB was established as independence in rhythm of atrium and ventricle. The rhythm of atrium could be in normal range, while the rhythm of ventricle should be slower than normal. Enlarged chambers were observed in 6 cases, cardiac dysfunction in 5 cases, and pericardial effusion in 7 cases. Tricuspid regurgitation and mitral regurgitation existed in 5 and 1 case, respectively. All of the CAVB fetus in this study underwent abortions. Conclusions Fetal echocardiography is proven to be a useful tool to diagnose CAVB, which greatly influenced the cardiac function in fetuses. Clear diagnosis as early as possible is crucial to the treatment of CAVB fetus.

Objective To investigate the efficacy of transverse insertion of thick needles into the Du meridian in treating rat ischemic facial paralysis and preliminarily explore the possible mechanism by which it produces a therapeutic effect. Methods Sixty Wistar rats were randomly allocated to groups A (transverse insertion of thick needles), B (basic Western drugs), C (blank control) and D (sham operation), 15 rats each. A rat model of ischemic facial paralysis was made using a modified vascular occlusion method in all the rats. Facial nerve deficits were scored in every group of rats during treatment. At 1 day after model making, group A was treated by transverse insertion into point Shendao and 4-hour retention of needle, once daily, for a total of 14 days; group B was treated by an oral gavage of prednisone and intraperitoneal injection of vitamine B12, once daily, for a total of 14 days. Groups C and D were not treated. In 4 rats randomly chosen at 3, 7 or 14 days after model making, facial nerve concomitant intrinsic vascular tissue HIF-1αprotein was measured by an immunohistochemical method; serum NO, by enzyme-linked immunosorbent assay; serum ET content, by radioimmunoassay.Results After 7 days of treatment, the neurological deficit score increased gradually in groups A and B and there was a statistically significant difference compared with after model making in the two groups (P<0.01). After 7 days of treatment, there was a statistically significant difference in the neurological deficit score in groups A and B compared with groups C and D (P<0.05) and between groups C and D (P<0.05). After 14 days of treatment, there was a statistically significant difference in the neurological deficit score between group A or B and group C (P<0.05) and between group B or C and group D (P<0.05). In group A, there was a statistically significant difference in the neurological deficit score after 14 days of treatment compared with after 7 days of treatment (P<0.05). After 3, 7 and 14 days of treatment, there was a statistically significant difference in HIF-1αMOD value in groups A , B and C compared with group D (P<0.01). After 3 and 7 days of treatment, there was a statistically significant difference in HIF-1αMOD value between group A or B and group C (P<0.05). In groups A and B, there was a statistically significant difference in HIF-1αMOD value after 3 and 14 days of treatment compared with after 7 days of treatment (P<0.05). After 3 and 7 days of treatment, there was a statistically significant difference in serum NO content between group A or B and group D (P<0.01). In groups A and B, there was a statistically significant difference in serum NO content after 7 days of treatment compared with after 3 days of treatment (P<0.05). After 3 and 7 days of treatment, there was a statistically significant difference in serum ET content in groups A , B and C compared with group D (P<0.05). In groups A and B, there was a statistically significant difference in serum ET content after 7 days of treatment compared with after 3 days of treatment (P<0.05).Conclusions Transverse insertion of thick needles into the Du meridian can effectively promote rat’s recovery from ischemic facial paralysis. The mechanism by which it produces a therapeutic effect may be regulating the expression of tissue HIF-1α and the NO and ET contents of serum.

Objective To investigate the effect of total flavones of Rhizoma Drynariae on femur distraction osteogenesis in the rabbits. Methods Thirty-two healthy rabbits were randomly divided into treatment group and control group, 16 rabbits in each group. The femoral fracture was treated with unilateral femoral distraction and was fixed with a self-made distraction instrument. After 7-day intermittent period, the fractured femur was distracted at a rate of 1 mm/d, twice a day for 10 continuous days. The treatment group was fed with total flavones of Rhizoma Drynariae from the first post-operative day to the end of the experiment. And then all of the animals were sacrificed after fixation for 28 days. The bone specimens were used for histological observation and immunohistochemical detection. Results The area of mature bone in the newborn bone tissue of the treatment group was increased, and osteoblasts number and the percentage of trabecular bone area were significantly higher than those of the control group . The bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) were stained brown deeply, the staining degree being stronger than that of the control group. Conclusion Rhizoma Drynariae total flavones can effectively accelerate the formation and maturation of newborn bone tissue during bone distraction.

Objective To establish a Chinese hamster model of babesia infection, to find the changing pattern of organs and biochemical parameters in Chinese hamster infected with Babesia, and to promote the detection and treatment of babesiosis.Methods Healthy 5-week old Chinese hamsters were infected by intraperitoneal injection of blood containing Babesia.Blood samples were collected at 0, 2, 4, 6, 8, 10, 12, 14, 16, 23, 30, and 37 days after infection from 5 hamsters at each time point.Blood smears were prepared to detect the parasites using Giemsa staining.ELISA assay was employed to test the IL-2 concentration.The blood biochemical indexes were detected using an automatic biochemical analyzer.DNA was extracted from the whole blood and REAL-TIME RCR was performed to determine the reproduction of Babesia.Aftert the animals were sacrificed, the heart, lung, spleen, liver, and kidney were taken to analyze the changes of organ coefficients.Results The highest level of Babesia in the hamsters occurred on day 4 after the Babesia injection, and then showing a decreasing tendency.However, there was a transient increase on the 12th day after infection.The liver and spleen displayed most extensive response to the infection showing hepatomegaly and splenomegaly, but the variation of heart and kidneys coefficients was within the norm.There were prominent changes of blood cells, especially leucocytes, with two peaks at day 10 and 23 after the Babesia infection.The peak changes of blood biochemical indexes occurred at day 12 after infection.The concentration of serum IL-2 reached a peak on the 10th day after infection.Conclusions The Chinese hamsters display typical characteristics of tick-borne diseases such as hepatomegaly and splenomegaly.The immunological system is activated along with the infection and reaches a highest stage in the second week.Afterwards the Babesia can live in the hamster body for a long period of time.The results of this study provide useful information supporting further studies on the detection, treatment and prevention of Babesiosis.

Objective:To investigate the role and mechanism of long non-coding RNA GAS5 in the targeted regulation of miR-29, miR-96, and miR-208 in promoting insulin secretion of pancreatic β-cells.Methods:Q-PCR was used to detect the expression of miR-29, miR-96, and miR-208 in sera of 122 healthy subjects and 88 type 2 diabetic patients; and so of long non-coding RNA GAS5 and miR-208 in the rat islet cell tumor strain ins-1832/13. Effects of silencing and overexpressing GAS5 on insulin secretion of islet β-cells by lentiviral vector construction were observed. Bioinformatics was used to predict that GAS5 had complementary binding sites with miR-29, miR-96, and miR-208, which was further verified by luciferase reporting system. GAS5 siRNA was co-transfected with miR-29, miR-96, and miR-208 inhibitors, and the effect of GAS5 on insulin receptor (INSR), insulin receptor substrate (irs-1) and PI3K levels was detected by the above method, so as to reveal the effect of GAS5 on insulin secretion in islet cells.Results:The expression of GAS5 in serum of T2DM patients was lower than that of healthy control group ( t=4.632, P<0.01), and expression of miR-29, miR-96, and miR-208 were higher than those of healthy control group ( t were 7.832, 9.164, and 12.359, all P<0.01). GAS5 level was negatively correlated with miR-29, miR-96, and miR-208 ( r were -0.50, -0.47, and -0.70, respectively). GAS5 expression was significantly decreased in serum of type 2 diabetic patients compared with that of in healthy subjects. Overexpression of GAS5 by lentivirus resulted in increased glucose-stimulated insulin secretion and increased insulin concentration compared to negative control. In contrast, knockdown of GAS5 led to significant reduction of glucose-stimulated insulin secretion and insulin concentration. GAS5 levels were negatively correlated with miR-29, miR-96, and miR-208 in serum samples of type-2 diabetes patients. GAS5 can negatively regulate the expression of miR-96, miR-29, and miR-208. By bioinformatics tools, we screened miR-29, miR-96 and miR-208 as targets of GAS5, and their interaction was validated with dual luciferase reporter gene assay. shGAS5 significantly decreased the expressions of INSR, IRS-1 and PI3K( P were 0.022, 0.038, and 0.009), while overexpressed GAS5 significantly upregulated the expressions of INSR, IRS-1 and PI3K at both mRNA and protein levels( P were 0.024, 0.045, and 0.016). Conclusion:GAS5 could stimulate insulin secretion of islet cell through its inhibitry regulationor of expressions of miR-29, miR-96, and miR-208, therely up-regulating INSR, IRS-1, and PI3K that may be the potential targets of these miRNAs, and stimulate insulin secretion of islet cells.