Associations between epidermal growth factor receptor gene mutation and serum tumor markers in advanced lung adenocarcinomas: a retrospective study.

OBJECTIVE: To investigate the associations between epidermal growth factor receptor (EGFR) gene mutations and serum tumor markers in advanced lung adenocarcinomas. METHODS: We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGFR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. RESULTS: EGFR gene mutations were detected in 42 (43%) advanced lung adenocarcinoma patients. Gender (P=0.003), smoking status (P=0.001), and abnormal serum status of carcinoembryonic antigen (CEA, P=0.028) were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation (P=0.046) with an odds ratio of 2.613 (95% CI: 1.018-6.710). However, receiver operating characteristic (ROC) curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma (the area under the ROC curve was 0.608, P=0.069). CONCLUSIONS: EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

HLA-G expression is associated with metastasis and poor survival in the Balb/c nu/nu murine tumor model with ovarian cancer.

Aberrant HLA-G expression is associated with tumor invasiveness and poor clinical prognosis; however, there is a lack of preclinical animal model to address whether HLA-G plays a causal role in the unfavorable prognosis of malignancies. In the current study, ovarian carcinoma cell lines (HO-8910 and Ovcar-3) were transfected with HLA-G gene. HLA-G expression was analyzed with western blot and flow cytometry. Transwell experiment was performed to analyze the cell migration and invasion capability and/or multicellular spheroid formation was investigated with the 3D culture assay in vitro. The effects of HLA-G expression for tumor cell organ metastasis and for mouse survival was analyzed with the Balb/c nu/nu mouse model. Our data showed that HO-8910-G and Ovcar-3-G cells are of higher invasion potential compared with the parental HO-8910 and Ovcar-3 cells. Multicellular spheroid formation exists only in HO-8910-G cells in a 3D culture assay. In Balb/c nu/nu mouse model, widespread metastasis was observed in mice xenografted with HO-8910-G cells, but not in the group with parental cells. Mouse survival was dramatically decreased in HO-8910-G and Ovcar-3-G xenografted mice than that with HO-8910 and Ovcar-3 cells, respectively. In summary, our study provided the first evidence that HLA-G expression is associated with tumor metastasis and with poor survival in an animal model with ovarian cancer.

Correlation between Characteristics of Coronary Plaque and Chinese Medicine Syndromes of Coronary Heart Disease: A Cross-Sectional Study Analysed by Intravascular Ultrasound.

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). CONCLUSIONS: Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

Salvianolic acid A from Danhong Injection induces vasorelaxation by Regulating L-type calcium channel in isolated mouse arteries.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), which is a Chinese clinical prescription consists of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese)(Plant names have been checked with http://www.theplantlist.org on March 1st, 2022), has been mainly used in the clinical therapy of cardiovascular diseases, including hypertension in China for many years. AIM OF THE STUDY: Cardiovascular diseases (CVDs) are the major causes of death all around the world. Due to the various stimulation, a series of vasoconstrictor substances are secreted to regulate the vasoconstriction function and then change blood pressure. The representative substances leading to abnormal vasoconstriction include renin-angiotensin system, endothelin, vasopressin and adrenaline, which act on the corresponding receptors on vascular smooth muscle to constrict blood vessels. Finally, blood pressure increases, followed by a series of cardiovascular diseases, including hypertension. However, little is known about Danhong injection's specific vasodilating mechanisms and active substances. The aims of the study were to determine the vasodilating substances of Danhong injection and explain its molecular mechanism of vasodilation. MATERIALS AND METHODS: The effects of DHI and its active components on vascular tension were measured by myograph system in the aortic or mesenteric rings of mice. Based on this, the pharmacodynamic substances were analyzed and effective molecules were found. Combined with multiple types of vascular myograph experiments and network pharmacological analysis, the molecular pathway was preliminarily determined. With molecular biology experiments, it was verified that the relevant mechanisms were closely related to calcium-mediated vasoconstriction in smooth muscle cells. RESULTS: DHI could relax endothelium-removed aortic rings pre-constricted with PE and 3 possible active vasodilator substances, including salvianolic acid A, salvianolic acid B and danshensu, were screened out by network pharmacology and vascular myograph experiments, among which the effects of salvianolic acid A were dominant. Meanwhile, salvianolic acid A could dilate mesenteric artery in a pressure-dependent manner. Interestingly, salvianolic acid A could still relax the vascular rings under the stimulation of KCl and Bayk8644, two agonists of L-type calcium channel. By contrast, inhibitors of Kir, Kv, Katp and BKCa channels did not block the effect of salvianolic acid A on vasodilation. Salvianolic acid A alleviated Ca2+ transient, referring to changes of intracellular calcium, induced by PE, Bayk8644 and high K+ in the VSMCs. Salvianolic acid A could partially restore the vasodilation function of vascular smooth muscle damaged by AngII and ET-1 induced hypertension situation. CONCLUSIONS: Our results indicate that salvianolic acid A is the major vasodilator substance in DHI and the vasorelaxation pharmacology mechanism involved in inhibiting the L-type calcium channel signaling in smooth muscle cell. Hence, there are potential therapeutic effects of taking salvianolic acid A preparation which may be beneficial to protect cardiovascular system and reduce blood pressure.

Human leukocyte antigen-G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma.

Human leukocyte antigen (HLA)-G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA-G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA-G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA-G (sHLA-G) in plasma was detected with enzyme-linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case-matched lesions and plasma samples) and in 153 normal healthy controls. HLA-G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA-G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA-G expression had a significantly worse survival, and HLA-G could be an independent prognostic factor. sHLA-G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver-operating characteristic (ROC) curve for sHLA-G in plasma was 0.992. However, no significant correlation was found between sHLA-G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA-G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA-G in plasma might be a useful preoperative biomarker for diagnosis.

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers.

Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors (P<0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments.

Effect of aspirin in takotsubo syndrome: protocol of a systematic review and meta-analysis.

INTRODUCTION: Takotsubo syndrome (TTS) is a sudden reversible weakening of the left ventricle function induced by severe stress and resembles many features as acute coronary syndrome. Even though many guidelines had been published about TTS, there is no consensus regarding the long-term treatment. Aspirin is one of the most common prescribed medicines at discharge for patients with the intention to reduce thrombus events and improve the overall prognosis. However, existing studies yielded conflicting results concerning its effects. This study aims to evaluate the impact of long-term maintenance treatment of aspirin in TTS and provides insights in clinical management. METHODS AND ANALYSIS: After searching through electronic databases (PubMed, Embase, Cochrane Library, Web of Science, National Library of Medicine Gateway, CNKI, Wanfang and VIP), grey literatures, conference abstract and trial registries for clinical studies investigating the impact of aspirin on patients with TTS, a systemic review and meta-analysis will be conducted. The search will be limited from inception of each database to 1 August 2020. The outcomes including all-cause death, TTS recurrence, stroke, transient ischaemic attack or myocardial infarction at 30-day and 5-year follow-up will be examined. Risk of bias will be assessed by Newcastle-Ottawa quality assessment scale for observational studies and Cochrane Effective Practice and Organization of Care evaluation tool for interventional studies. Grading of Recommendations Assessment, Development and Evaluations method will be applied to assess the quality of evidence. If available, the effects of aspirin on the above outcomes for patients with TTS will be evaluated using random-effect modelling with relative risk at 95% CIs. Subgroup analysis and sensitivity analysis will also be performed when possible. ETHICS AND DISSEMINATION: Ethics approval was not required due to the retrospective nature of the study. Results of the review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020212729.

Shenzhu Guanxin Recipe Granules () for Improving Exercise Tolerance in Patients with Stable Angina (SERIES Trial): A Protocol of Multicenter, Randomized, Double-Blind, Placebo Parallel Controlled Clinical Trial.

BACKGROUND: Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients. METHODS: A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up. DISCUSSION: This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504).

Systems Pharmacology Dissection of Traditional Chinese Medicine Wen-Dan Decoction for Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) have been recognized as first killer of human health. The underlying mechanisms of CVDs are extremely complicated and not fully revealed, leading to a challenge for CVDs treatment in modern medicine. Traditional Chinese medicine (TCM) characterized by multiple compounds and targets has shown its marked effects on CVDs therapy. However, system-level understanding of the molecular mechanisms is still ambiguous. In this study, a system pharmacology approach was developed to reveal the underlying molecular mechanisms of a clinically effective herb formula (Wen-Dan Decoction) in treating CVDs. 127 potential active compounds and their corresponding 283 direct targets were identified in Wen-Dan Decoction. The networks among active compounds, targets, and diseases were built to reveal the pharmacological mechanisms of Wen-Dan Decoction. A "CVDs pathway" consisted of several regulatory modules participating in therapeutic effects of Wen-Dan Decoction in CVDs. All the data demonstrates that Wen-Dan Decoction has multiscale beneficial activity in CVDs treatment, which provides a new way for uncovering the molecular mechanisms and new evidence for clinical application of Wen-Dan Decoction in cardiovascular disease.

3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH.

Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression.

BACKGROUND: Myocardial infarction (MI) is the main cause of global mortality and morbidity despite the development of therapeutic approaches. ShenZhuGuanXin granules (SG) have been shown to possess cardioprotective effects against coronary heart disease (CHD). However, little is known about its specific mechanism. The present study aimed to investigate the therapeutic effect of SG in cardiac dysfunction and to demonstrate whether SG can promote myocardium angiogenesis by establishing a rat model of myocardial infarction with left anterior descending ligating. METHODS AND RESULTS: Three days after MI, rats were randomly divided into six groups: sham group (sham), MI group (MI), MI + low dose SG (SG-L) group, MI + middle dose SG (SG-M) group, MI + high dose SG (SG-H) group, and MI + compound Danshen dropping pills (CDDP) group as a positive control. Four weeks after administration, rats underwent hemodynamics and echocardiography study. Ventricle tissues were processed for histology and immunohistochemistry studies. Compared with MI group, SG treatment dose-dependently improved cardiac hemodynamic function, attenuated infarct size, increased microvessel density, and increased the expression of PECAM-1/CD31 and VEGF. CONCLUSIONS: SG dose-dependently improved cardiac hemodynamic function and attenuated infarct size by promoting angiogenesis through upregulating PECAM-1/CD31 and VEGF expression.

Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation.

Hyperhomocystinemia (HHcy) is known as an independent risk factor for cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in endothelial progenitor cells (EPCs) remains unknown. In the study, we found that ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100 and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid arteries significantly increased with EPCs transplant, and was even better with Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the action of Rb1 that may have value in prevention of HHcy associated cardiovascular disease.

Effects of Scleroderma sichuanensis Xiao (Hymenoptera: Bethylidae) venom and parasitism on nutritional content regulation in host Tenebrio molitor L. (Coleoptera: Tenebrionidae).

To explore the mechanisms by which the wasp Scleroderma sichuanensis Xiao regulates the physiology and biochemistry of its host, effects of S. sichuanensis venom and parasitism on host the Tenebrio molitor L. pupae were examined. Significant differences in nutritional content were noted between parasitized and non-parasitized pupae and between venom- and phosphate buffered saline-injected pupae. When pupae were injected with venom, the fat body could not be disintegrated into granules; however, when pupae were parasitized, fat-body disintegration occurred. Electrophoresis showed no differences in hemolymph protein content between parasitized pupae and those injected with venom, indicating that the wasp did not have narrow-spectrum peptides. These findings confirmed that S. sichuanensis was a typical idiobiont ectoparasitoid wasp, and that nutrient regulation was similar between idiobiont and koinobiont wasps. The strong similarities between the two treatments suggest that venom injection is a major factor responsible for changes in host nutrient content. The wasp fed mainly on reducing sugars, free amino acids, and fat-body tissues; larval fat bodies were derived from hemolymph and from host tissue. Our findings suggest that lipid catabolism might be accelerated, and that lipid biosynthesis might be inhibited, when host pupae are parasitized or injected with venom. In addition to venom, physiological and biochemical changes that occur during the parasitic process might be caused by venom, ovarian proteins, saliva, or secretions.

Elevation of HLA-G-expressing DC-10 cells in patients with gastric cancer.

DC-10 is a distinct subset of human tolerogenic dendritic cells (DCs) which express high levels of human leukocyte antigen-G (HLA-G). DC-10 could induce adaptive type 1 regulatory T cells through the IL-10 dependent ILT4/HLA-G signaling pathway. However, the significance of DC-10 in malignancies remains unclear. In this study, the frequency and mean fluorescence intensity (MFI) of HLA-G+ DC-10 in the peripheral blood of 124 patients with gastric cancer (GC) and 130 normal controls was analyzed with flow cytometry. Plasma sHLA-G was analyzed with ELISA. Results showed both the percentages of peripheral HLA-G+ DC-10 (median: 0.13% vs 0.01%; p<0.01) and MFI of HLA-G on these cells (median: 310.0 vs 91.5; p<0.01) were dramatically increased in GC patients than in normal controls. The frequency of HLA-G+ DC-10 in GC patients was strongly relative to the tumor grade (p=0.021). sHLA-G levels in GC patients were significantly higher than in healthy controls (median: 85.80U/ml vs 61.20U/ml; p<0.01). There was no significant correlation between the percentage of DC-10 and plasma sHLA-G (p>0.05). However, the increased HLA-G+ DC-10, HLA-G MFI and plasma sHLA-G in patients with gastric cancer could be a diagnostic factor with the area under the ROC curve with 0.947 (p<0.01), 0.882 (p<0.01) and 0.700 (p<0.01) respectively. Given the immune tolerant function of DC-10 could play, the increased DC-10 might play an important role in immune suppression for patients with gastric cancer, while more studies are necessary to illustrate the clinical relevance of DC-10 in cancer patients.

Effect of Shenzhu Guanxin Recipe () on patients with angina pectoris after percutaneous coronary intervention: A prospective, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a combination therapy using Chinese medicine (CM) Shenzhu Guanxin Recipe (, SGR) and standard Western medicine treatment (SWMT) in patients with angina pectoris after percutaneous coronary intervention (PCI). METHODS: Double-blind randomized controlled trial was used in this experimental procedure. One hundred and eighty-seven patients with coronary heart disease receiving SWMT after PCI were randomly assigned to the treatment (SGR) and control (placebo) groups. Outcome measures including angina pectoris score (APS), CM symptom score, and Seattle Angina Questionnaire (SAQ) score were evaluated in 1, 2, 3 and 12 months, and the death rate, restenosis and other emergency treatments were observed. The mixed-effects models were employed for the data analysis. RESULTS: In the treatment group, a larger within-treatment effect size (d=1.74) was found, with a 76.7% reduction in APS from pretreatment to 12-month follow-up assessment compared with the control group (d=0.83, 53.8% symptom reduction); betweentreatment (BT) effect size was d=0.66. CM symptom scores included an 18.3% reduction in the treatment group (d=0.46), and a 16.1% decrease in the control group (d=0.31); d=0.62 for BT effect size. In regard to scores of SAQ, the BT effect size of cognition level of disease was larger in the treatment group (d=0.63), followed by the level of body limitation of activity (d=0.62), condition of angina pectoris attacks (d=0.55), satisfaction level of treatments (d=0.31), and steady state of angina pectoris (d=0.30). Two cardiovascular related deaths and one incidental death were recorded in the control and treatment groups, respectively. No significant difference in any cardiovascular event (including death toll, frequency of cardiovascular hospitalization or emergency room visits) was found between the two groups. CONCLUSION: The combination therapy of SGR and SWMT is effective and safe in patients with angina pectoris after PCI when compared with SWMT alone.

HLA-G1 and HLA-G5 isoforms have an additive effect on NK cytolysis.

The immunotolerant HLA-G could generate seven isoforms including HLA-G1--G7. The suppressive function of either HLA-G1 or HLA-G5 isoform to NK cell cytolysis has been well established. Whether HLA-G1 and HLA-G5 isoform have an additive effect on the cytolysis of NK cells remain to be explored. In this study, effects of expression of HLA-G1 and HLA-G5 isoforms and their combination on NK cytolysis was investigated. NK cell cytolysis was analyzed by detecting the NK cell surface CD107a expression. In this study, data showed that the inhibition capacity is dependent on the level of both HLA-G1 and HLA-G5 expression, but the HLA-G5 isoform has a more potent inhibition effect on the NK cytolysis (p<0.01). Furthermore, HLA-G1 and HLA-G5 have an additive effect on the suppression of NK cell cytolysis. Our study provided further understanding for the roles of HLA-G1 and HLA-G5 isoform expression in target cells immune escaping from NK cells.

Elevation of human leukocyte antigen-G expression is associated with the severe encephalitis associated with neurogenic pulmonary edema caused by Enterovirus 71.

Enterovirus 71 (EV71) infection can develop devastating clinical outcomes such as brain stem encephalitis (BE) and pulmonary edema (PE). Alteration of human leukocyte antigen-G (HLA-G) expression or cytokine production was considered playing important roles in virus-related pathogenesis. However, clinical relevance of HLA-G in EV71 infection remains unknown. In the current study, patients were stratified by disease severity as BE (n = 107) and PE (n = 18). HLA-G expression on peripheral blood monocytes from patients with BE (n = 15), patients with PE (n = 15) and control subjects (n = 31) was analyzed with flow cytometry. Plasma soluble HLA-G (sHLA-G) (in 67 BE, 18 PE and 120 control subjects), IL-6 and IL-10 (in 50 patients with BE, 18 patients with PE and 45 control subjects) were determined with enzyme-linked immunosorbent assay. Data showed that the percentage of HLA-G-positive monocytes (mean 7.76 vs 3.68 %, p < 0.001), levels for sHLA-G (median 129.2 vs 70.6 U/ml, p < 0.001), IL-10 (median 160.5 vs 29.5 pg/ml, p < 0.001) and IL-6 (median 20.50 vs 5.21 pg/ml, p = 0.002) was significantly higher in patients with PE than in patients with BE. Taken together, our findings indicated that elevation of HLA-G expression on monocytes, plasma sHLA-G, IL-10 and IL-6 levels was associated with PE in patients infected with EV71.

NK cytolysis is dependent on the proportion of HLA-G expression.

The suppressive functions of HLA-G to various immune cells have been well established. The proportion of HLA-G expression in malignant lesion cells was found from negative to 100%. However, effects for the different proportion of HLA-G expression on the cytolysis of NK cells remain to be explored. In this study, NK cytolysis to the various proportion of HLA-G1 expression on leukemia cell line K562 was investigated. Analysis of NK cell cytotoxicity was by detecting the NK cell surface CD107a expression. Data showed that NK cell cytolysis could be inhibited by the HLA-G1 expression and in a manner of HLA-G1 expression proportion dependent manner (r = 0.925, p = 0.008). Our study provided further understanding for the roles of HLA-G1 expression in malignant cell immune escaping from NK cells.

Multiple steps of HLA-G in ovarian carcinoma metastasis: alter NK cytotoxicity and induce matrix metalloproteinase-15 (MMP-15) expression.

Previous study showed that aberrant HLA-G expression in cancer cells plays important roles in disease progression and it was associated with tumor metastasis and with poor survival in an animal model with ovarian cancer; however, the mechanisms remain to be explored. In this study, we found that HLA-G expression could dramatically decreased the NK cytotoxicity against the ovarian carcinoma cell line (HO-8910) engineered to express HLA-G (HO-8910-G), and matrix metalloproteinase-15 (MMP-15) expression was up-regulated in HO-8910-G cells. Consistent with this, a strong correlation between HLA-G and MMP-15 expression were observed in a cohort of ovarian cancer samples. Knockdown the HLA-G induced MMP-15 expression by small interfere RNA (siRNA) significantly decreased the HO-8910-G cell migration potential and tumor metastasis. Collectively, our study indicated that HLA-G involved in tumor invasiveness or metastasis may rely on the NK cytotoxicity inhibition and induction of MMP-15 expression in ovarian cancer.

[Effects of venom from Sclerodermus sichuanensis Xiao on pupa of Tenebrio molitor].

To explore the regulatory mechanisms of parasitism of Sclerodermus sichuanensis on Tenebrio molitor, the methods of natural parasitism and venom injection were adopted to investigate the effects of the venom from S. sichuanensis on the pupa of T. molitor in the parasitic process. Under venom injection, the paralytic degree of the pupa had a positive correlation with the concentration of injected venom, and the number of recovered pupa had a negative correlation with the injected venom concentration. The T. molitor pupa was in slight and reversible paralysis when injected with 0.01 VRE (venom reservoir equivalent) of venom, and in non-reversible and complete paralysis when 0.2 VRE was injected. The pupa died massively and appeared a wide range of melanization when injected with soil bacterial suspension alone, but the melanization delayed and the mortality declined significantly when the mixed liquor of bacterium and venom was injected. The bacteriostasis of the venom on Staphylococcus aureus was significantly stronger than that on Escherichia coli. Within a definite range of temperature, the paralytic activity decreased significantly with increasing temperature, the bacteriostasis on S. aureus increased significantly, while that on E. coli was opposite. This study showed that the venom from S. sichuanensis had the effects of paralysis, bacteriostasis, inhibiting exuviations, and delaying melanization.