Objective To study the efficacy and safety of different dual antiplatelet therapy(DAPT)in patients with acute myocardial infarction(AMI)undergoing percutaneous coronary intervention(PCI)treatment.Methods AMI patients receiving PCI treatment were randomly divided into treatment group and control group.The treatment group was given clopidogrel(50 mg,bid)combined with ticagrelor(90 mg,bid)after PCI,while the control group was given aspirin(100 mg,qd)combined with clopidogrel(75 mg,qd)after PCI.The treatment course for both groups was 6 months.Platelet activation and endothelial function-related indicators were compared between the two groups,and major adverse cardiovascular events(MACE)and adverse drug reactions were followed up during the treatment period.Results During the trial,5 cases dropped out,and finally,98 cases and 97 cases were included in the treatment group and control group,respectively.After treatment,the incidence of stent restenosis in the treatment group and control group were 2.04％(2 cases/98 cases)and 9.27％(9 cases/97 cases),respectively;the incidence of MACE were 4.08％(4 cases/98 cases)and 13.40％(13 cases/97 cases),respectively,with significant differences between the two groups(P＜0.05).After treatment,the inhibition of platelet aggregation(IPA)in the treatment group and control group were(54.97±6.43)％and(52.38±6.12)％,respectively;the serum nitric oxide(NO)levels were(64.29±8.12)and(59.61±8.45)μmol·L-1,respectively;the prostacyclin(PGI2)levels were(42.15±3.94)and(38.46±3.71)ng·L-1,respectively;the maximum platelet aggregation rate(MPAR)were(31.65±3.86)％and(32.97±4.25)％,respectively;the platelet count(PC)were(169.84±36.71)× 109·L-1 and(172.63±38.94)× 109·L-1,respectively;the positive rates of P-selectin(CD62P)were(24.58±5.34)％and(27.13±5.82)％;the positive rates of platelet activated complex-1(PAC-1)were(7.63±2.15)％and(8.45±2.69)％;serum endothelin-1(ET-1)levels were(61.03±5.97)and(65.39±7.14)ng·L-1,which were significantly reduced compared with those before treatment(all P＜0.05).The adverse drug reactions in treatment group were mainly headache,dyspnea and bleeding events,and the adverse drug reactions in control group were mainly dyspnea and bleeding events.The total incidence rates of adverse drug reactions in treatment group and control group were 11.22％(11 cases/98 cases)and 9.28％(9 cases/97 cases),respectively(P＞0.05).Conclusion Cilostazol combined with ticagrelor in patients with AMI after PCI is beneficial to inhibiting the platelet aggregation and activation,relieving the vascular endothelial function injury and reducing the risk of in-stent restenosis and MACE,and it has obvious advantages over aspirin combined with clopidogrel.

Objective:To summarize the clinical characteristics of 4 cases of mixed pituitary adenomas involving growth hormone(GH), prolactin(PRL), and thyroid stimulating hormone(TSH), and explore the standardized management approaches.Methods:The clinical data of four GH/PRL/TSH mixed pituitary adenoma patients diagnosed by Peking Union Medical College Hospital were retrospectively analyzed, including clinical manifestations, biochemical parameters, radiographic characteristics, as well as treatment and prognosis. Then literature review was conducted.Results:Among the 4 patients, 3 were male, with onset ages ranging from 15 to 38 years. All patients presented with coarse facial features as initial symptom. Three patients had visual impairment or visual field defects. All 4 patients had significantly elevated levels of GH and insulin-like growth factor-Ⅰ(IGF-Ⅰ). GH was not inhibited by oral glucose tolerance test. PRL concentration was over 100 ng/mL. Triiodothyronine(T 3)and thyroxine(T 4)were also elevated, while TSH was not inhibited. All pituitary adenomas in four cases were macroadenomas or giant adenomas, all of which were invasive growth, and one case developed pituitary stroke. Except for one patient who did not receive treatment in our hospital due to medical expenses, the remaining three patients underwent a combined treatment of medication and transnasal transsphenoidal pituitary adenoma resection. Among them, one patient had relief of central hyperthyroidism and hyperprolactinemia, but GH/IGF-Ⅰ did not meet the remission criteria. The other two patients had persistent non-resolution of at least 2 hormone axes. Conclusions:Patients with GH/PRL/TSH mixed pituitary adenoma were mainly characterized by coarse facial features, GH/PRL/TSH hyperfunction, large adenoma volume, low biochemical remission after surgery combined with drug treatment, and poor clinical prognosis.

The "triple combination" review system provides an opportunity for the transformation of human use experience into new Chinese drugs. However, there are some methodological and technical limitations in the assessment of human experience. Hence, the efficacy and safety evaluation methods should be established in accordance with the characteristics of Chinese herbs. This study summarized some evidence-based methodology to promote the transformation of human use experience to new Chinese drugs, mainly including the individualized pragmatic randomized controlled trial(RCT), cluster RCT, single-case RCT, single arm RCT with objective performance criteria, and partially nested RCT. As the real world data can be used to support the transformation of human experience, attention should be paid to convenient and efficient collection of data, prudent selection of design types, and adoption of appropriate ana-lysis methods to deal with confounding bias, including multi-factor regression model and propensity score. The newly proposed mixed research method can also be utilized to assess the human use experience, which is suitable for mining the theory of traditional Chinese medicine(TCM) and expert experience from different aspects. Meanwhile, considering the study design requirements and TCM cha-racteristics, this study put forward the common problems and solutions in the development of new Chinese drugs based on human use experience, including how to select the feasible outcome indicators, how to collect prescription data in the case of herb and dosage adjustment, and how to evaluate the comprehensive effectiveness of TCM from the perspective of "combination of disease and syndrome".
China ; Drug Development ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Research Design

Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mecha-nisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with ber-berine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further stan-dardization and widespread application of TCM in many diseases.

To increase the permeation and retention of isopsoralen in skin, and improve its bioavailability.Isopsoralen loaded nanostructure liquid carrier (IPRN-NLC) was prepared by high pressure homogenization andoptimized by orthogonal experiment with the encapsulation efficiency, drug loading and average particle size as the evaluation indexes. The in vitro transdermal permeation of IPRN-NLC was evaluated by Franze diffusion cells.The results showed that solid-liquid lipid ratio of optimum IPRN-NLC formulation was 7∶3,drug-lipid ratio of 1∶30, 1% surfactant. Under these conditions, IPRN-NLC had an average encapsulation of （90.25±0.73）%,drug loading of （1.56±0.27）% and an average particle size of (305±1.57) nm.The in vitro transdermal permeation results showed that IPRN-NLC could increase the amount of IPRN permeated though skin, with 3 times of the epidermal retention as compared with IPRN solution. From the results we can know that the IPRN-NLC prepared by high pressure homogenization can improve the permeation andaccumulation of IPRN in the skin, with wide application prospects in the field of transdermal administration.

?AIM:To compare the coherence and difference on the fundus examination made with two kinds of optical coherence tomography ( OCT): Angio-OCT and fourier domain-optical coherence tomography ( FD-OCT) .?METHODS:Using Angio-OCT and FD-OCT to measure the retinal nerve fiber layer ( RNFL ) thickness, optic parameters, and ganglion cell complexes ( GCC ) thickness from 20 subjects respectively.The coherence was tested with Pearson's correlation coefficient, the difference was tested with paired Student t testing.?RESULTS:The total correlation of the RNFL thickness, optic parameters, GCC thickness made with two kinds of OCT was between 0.7-0.8;the RNFL thickness, optic disk area etc.made with the Angio-OCT were lower than those made with FD-OCT except for the GCC thickness.?CONCLUSION: The results made with two kinds of OCT from the same subject has certain coherence, but cannot be compared directly.

BACKGROUNDIn vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.

METHODSCNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.

RESULTSThe CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R 2 =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001).

CONCLUSIONSThere is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection. The result might provide a useful evaluation of CNV both for the studies using CNV models induced by subretinal injection and human AMD studies.

Animals ; Choroidal Neovascularization ; pathology ; physiopathology ; Disease Models, Animal ; Fluorescein Angiography ; Humans ; Mice ; Mice, Inbred C57BL ; Tomography, Optical Coherence

Objective To explore the relationship between coping styles and childhood abuse in adult patients with depression . Methods A case‐control study was conducted between 80 adult patients with depression and 80 health controls .In general ques‐tionnaire was designed to collect the demo‐graphic information ,Childhood Trauma Questionnaire‐28 Item Short Form (CTQ‐SF) was used to assess childhood trauma and Trait Coping Styles Questionnaire (TCSQ) was assigned to evaluate coping styles .T test , Mann‐Whitney U test ,Spearman Bivariate correlations and Multiple linear regression were employed to explore the characteristics of the major depressive patients′coping styles and the association between childhood abuse .Results (1) The patients with depres‐sion had both statistically significantly higher scores on negative coping style (t=9 .13 ,P<0 .01) and lower scores on positive cop‐ing style (t= -12 .01 ,P<0 .01)than the controls with childhood abuse .The patients with childhood abuse had both statistically significantly higher scores on negative coping style(Z= -6 .134 ,P<0 .01) and lower scores on positive coping style(Z= -5 .452 , P<0 .01) than the controls with childhood abuse .Inside the group of patients with depression ,the patients who had childhood a‐buse gained significantly higher scores in negative coping style than the others who had no early trauma (Z= -2 .159 ,P<0 .05) , however ,no conspicuous differences were found on the positive coping style scores .(2)The childhood abuse was both significantly positive correlated with the passive coping and negative related to the active coping (r=0 .562 ,P<0 .01;r= -0 .333 ,P<0 .05)a‐mong the patients of depression .(3)The total degree of abuse and physical abuse had significant prediction function of 34 .4% (P<0 .01)on the patients′ negative coping .Conclusion The coping styles of patients with depression were prone to be influenced by childhood abuse remarkably ,more severe abuse ,especially with the physical abuse ,more negative the coping styles were .

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; Boraginaceae ; chemistry ; Flavonoids ; pharmacology ; Heart ; Interleukin-6 ; Myocardial Infarction ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Protective Agents ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; Tumor Necrosis Factor-alpha ; bcl-2-Associated X Protein

OBJECTIVETo determine the expressions of endothelial nitric oxide synthase traffic inducer (NOSTRIN) and endothelial nitric oxide synthase (eNOS) in the testis tissue of azoospermia patients, and investigate their correlation with the pathogenesis of azoospermia.

METHODSWe detected the expressions of NOSTRIN and NOSTRIN mRNA by immunohistochemistry and RT-PCR respectively, determined the activity of eNOS by spectrophotometry, and measured the stable metabolic end product NO, NO2- / NO3-, by nitrate reductase assay in the testis tissues of 17 patients with idiopathic azoospermia (the azoospermia group) and 10 normal men (the normal group).

RESULTSNOSTRIN and NOSTRIN mRNA were expressed in the spermatogonia, sertoli cells, stromal cells and vascular endothelial cells, more lowly in the azoospermia than in the normal group (0.312 +/- 0.076 versus 0.793 +/- 0.082, P < 0.01). The activity of eNOS was significantly increased in the idiopathic azoospermia patients ([33.727 +/- 3.58] U/mg) compared with the normal men ([17.69 +/- 3.84] U/mg) (P < 0.01). The level of NO2- / NO3- was significantly higher in the azoospermia than in the normal group ([48.56 +/- 8.49] micromol/L versus [25.37 +/- 9.61] micromol/L, P < 0.01). The expression of NOSTRIN showed a significant negative correlation with the activity of eNOS (r = -0.57, P < 0.01) as well as with the level of NO2- / NO3- (r = -0.61, P < 0.01) in the testis tissue of the idiopathic azoospermia patients.

CONCLUSIONThe expression of NOSTRIN is decreased, while the activity of eNOS and the level of NO2- / NO3- increased in the testis tissue of azoospermia patients, which may be associated with the pathogenesis of azoospermia.

Adult ; Azoospermia ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Male ; Nitrates ; analysis ; Nitric Oxide Synthase Type III ; metabolism ; Nitrites ; analysis ; Spermatogenesis ; Testis ; metabolism