Objective To explore clinical feature and coronary artery lesion characteristics of non-ST-segment elevation myocardial infarction (NSTEMI).Methods Seventy-three patients of NSTEMI were studied,their clinical data and results of coronary angiography being analyzed.Results Risk factors of coronary artery disease among all the patients were 50(68%) with hypertension,26(35%) with diabetes,34(46%) with hyperlipidemia and 28(38%) with smoking history.There were 52(71%)with angina pectoris before this hospitalization,22(30.6%) with inhospatial angina pectoris,15(20.4%) with severe arrythmias,7(10.2%) with cardiac shock,3(4%) died.52(71%) were with ST-T depression and 21(29%) with normal ECG.Coronary angiography revealed 54(74%) with lesions in more than one vessel and 19(26%) in one vessel (P

ObjectiveTo identify the differential expressed proteins,and to investigate the relationship between altered expression of annexin A4 during window of implantation [ WOI ( at day-6 after ovulatory day )] in infertile patients with endometriosis and endometrial receptivity.MethodsTwo-dimensional fluorescence differential in-gel electrophoresis (2D-DIGE) and matrix-assist laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect protein expression in endometrial WOI in 10 infertile cases with endometriosis as endometriosis group and 10 infertile cases with tubal factors as control group.The semi-quantitative validation of annexin A4 in the eutopic endometrial tissue during WOI was analyzed by western blot.Results By comparing protein profiles,there were 7 meaningful differential proteins during WOI in infertile patients with endometriosis.One protein with an isoelectric point of 5.84 and relative molecular weight of 36 100 were down regulated 348％ in samples of endometriosis group.It was identified as annexin A4 by mass spectrometry.By western blot,relative intensity of annexin A4 in endometriosis group was 7.2 ±0.9,which was lower than 17.8 ± 2.6 in control group significantly (t =7.654,P =0.002 ).ConclusionLower expresssion of annexin A4 during WOI in infertile patients with endometriosis might be associated with the decrease of endometrial receptivity.

AIM: To investigate the influence and mechanism of recombinant macrophage migration inhibitory factor(rMIF) on fibroblasts.METHODS: MRC-5 fibroblasts were divided into two groups: the treated group was treated with rMIF(25-100 ?g/L,12 h,24 h or 48 h) and the control was non-rMIF treatment.The activity of proliferation in both groups was investigated and compared by CCK-8 means.Synthesis of collagen in the culture supernatants was detected by the hydroxyproline.The expression of collagen type I mRNA was examined using RT-PCR analysis.The level of collagen type I protein induced by rMIF was quantified by Western blotting.RESULTS: The production of proliferation ratio of fibroblasts treated with 50 ?g/L and 100 ?g/L rMIF at 24 h or 48 h were increased obviously(P

AIM: To investigate the action of Xingshen Capsule(Tea, Radix Ginseng, etc.) on anti-centre and body fatigue in mice. METHODS: Mice were divided into five groups and were given different dosage once a day for six days, then, their weight, motor activity, roating bar tolerance and the hypnogenetic effects of sodium pentobarbital were observed on the 1 st and 6 th day. RESULTS: Comparing with the negative control, Xingshen Capsule could notably increase the times of motor activity, prolong the persisting time on the roating bar, shorten the sleeping time caused by sodium pentobarbital while prolong its latence. CONCLUSION: Xingshen Capsule may have outstanding effect on refreshing one's nerve and body.

AIM: To evaluate the main pharmacological effect of Wunzhonganwei Soft Capsule. METHODS: Analgesic effect was investigated by hot plate test and writhing test, anti-inflammation effect by auricular swelling test in mice and toe swelling test in rat, anti-diarrhea effect by diarrhea test induced by rhubarb, effect on gastric emptying by phenolsulfonphthalein empty test in mice and effect on small intestine propulsive test by charcol powder propulsive rate test. RESULTS: Wunzhonganwei Soft Capsule enhanced thermal stimulation threshold in mice, decreased the occurrence of writhing caused by glacial acetic acid in mice, inhabited xylene-induced auricular swelling in mice and carrageenan-induced toe swelling in rat, decreased the number of loose stools induced by rhubarb in mice., inhabited the function of gastric emptying induced by metoclopramide or in normal mice, antagonized the inhibitory effect of gastric emptying induced by atropine and inhabited small intestine propulsive movement induced by neostigmineor or in normal mice. CONCLUSION: Wunzhonganwei Soft Capsule has the effect of anti-inflammation, analgesia, antidiarrhea and adjusting the function of gastrointestinal movement.

Objective To observe the activation of anti-viral innate immune response of type Ⅰinterferon and inhibition of hepatitis B virus (HBV)genome replication in mice by HBV-3p-siRNA. Methods HBV-3p-siRNA was designed by targeting specific sequence of HBV S/P mRNA and was generated by in vitro transcription.Negative control siRNA (NC-siRNA)and non-modified HBV-siRNA were used as control groups.Blood samples were collected from tail vein of mice and the model of HBV-infected mice were established by hydrodynamic injection.Forty mice were divided into 4 groups with 10 in each group.The model group was only injected with pGL3.0-HBV1 .2 copy plasmid.The negative control group received peritoneal injection of NC-siRNA.HBV-siRNA group received peritoneal injection of HBV-siRNA and HBV-3p-siRNA group received peritoneal injection of HBV-3p-siRNA.The interferon-β(IFN-β)and hepatitis B surface antigen (HBsAg)in serum were detected by enzyme linked immunosorbent assay (ELISA).The copies of HBV DNA were assessed by fluore scence quantitative polymerase chain reaction (PCR ).The statistical difference between groups was determined using One way-ANOVA analysis by LSD or Dunnett T3.Results Serum level of IFN-β was (12.37±5 .32)pg/mL in model group,(22.61 ±6.29 )pg/mL in negative control group,(26.40±5 .39)pg/mL in HBV-siRNA group and (68.37± 21 .00 ) pg/mL in HBV-3p-siRNA group.The secretions of IFN-β into serum were significantly enhanced by HBV-siRNA and HBV-3p-siRNA compared with model group (F =23.988 and 46.523,respectively,both P <0.01).Serum level of HBsAg was (2 864.86±907.11 )ng/mL in model group,(2 198.86±456.89 )ng/mL in negative control group,(1 049.71 ± 396.28 )ng/mL in HBV-siRNA group and (640.86±383.08)ng/mL in HBV-3p-siRNA group.The expressions of HBsAg were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F = 23.537 and 39.144, respectively;P =0.025 and 0.010,respectively).Serum level of HBV DNA was (2.54 ×104 ±1 .46 × 104 )copy/mL in model group,(2.22×104 ±2.62×103 )copy/mL in negative control group,(3.59×103 ±2.88×103 )copy/mL in HBV-siRNA group and (2.65 ×103 ±1 .46×103 )copy/mL in HBV-3p-siRNA group.Serum level of HBV DNA were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F =15 .013 and 16.741 ,respectively,both P <0.05 ).All of the indicated siRNA used in the experiments showed no apparent effects on the body mass index of the mice models.Conclusion HBV-3p-siRNA,which induces the production of IFN-β and inhibits HBV replication through gene silencing in vivo ,may be a powerful bifunctional antiviral molecule.

AIM: To investigate combination principle of Gegenqinlian Decoction through experiment of anti-diarrhea. METHODS: Propelling rate of mouse's small intestine was selected as index on the condition of ink as colour reagent, diarrhea frequence served as second index for orthoganal design on the basis of mouse's diarrhea induced by senna. RESULTS:Coptis chinensis franch and Glycyrrhiza uralensis fisch and reduce drive rate. Scutellaria baicalensis Georgi and Pueraria lobata(wild) ohwi had counteracter against Coptis chinensis franch's effect, while Glycyrrhiza uralensis fisch could enforce Coptis chinensis franch's effect.as to DI, Coptis chinensis franch had anti-diarrhea effect. Scutellaria baicalensis Georgi had counteracter against Coptis chinensis franch's effect, Pueraria lobata(wild) Ohwi could enforce Scutellari, baicalensis Georgi effect, but Glycyrrhiza uralensis fisch could enforce Coptis chinensis's effect after compounding with Scutellaria baicalensis Georgi. CONCLUSION: ~Among the combinantion of Gegenginlian Decoction, as to the pharmcological effects on anti-diarrhea, the best compound is Coptis chinensis franch and Glycyrrhiza uralensis fisch.

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.
Dimerization ; HEK293 Cells ; Humans ; I-kappa B Kinase ; metabolism ; Interferon Regulatory Factor-3 ; metabolism ; Interferon Type I ; antagonists & inhibitors ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Papain ; metabolism ; Peptide Hydrolases ; chemistry ; metabolism ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases ; metabolism ; SARS Virus ; enzymology ; Signal Transduction ; TNF Receptor-Associated Factor 3 ; metabolism ; Ubiquitination

Objective: To explore the Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia (COVID-19) and their clinical values, and to provide theoretical basis for clinical diagnosis and treatment. Methods: A total of 164 patients, diagnosed with COVID-19 and admitted to Guangzhou Eighth People's Hospital from January to February 2020, were selected as the research group and divided into three groups (ordinary, severe, and critically severe pneumonia) according to the disease severity. Meandwhile 66 non-infected patients during the same period were selected as negative control group. The expressions of WBC, LYM, CRP, SAA, and PCT were retrospective studied and compared between groups. The diagnostic values of WBC, CRP, SAA and the combination of these three markers in all patients with COVID-19 and in different severity groups were analyzed by ROC curve. Results: Compared with control group (WBC count :8.13(6.51,9.42)×10⁹/L, LYM count:2.00(1.28,2.43)×10⁹/L), WBC count [4.94(4.05, 6.67) ×10⁹/L] and LYM count [1.33(0.94, 1.96) ×10⁹/L] of COVID-19 patients were significantly reduced (Z=-7.435, P<0.01; Z=-4.906, P<0.01) . Compared with the control group [CRP: 1.36 (0.57~5.67) mg/ml; SAA:[4.98 (4.80~15.75) mg/mL], CRP [7.93 (2.45~23.98) mg/ml] and SAA [34.13 (4.83~198.40) mg/ml] were increased in research group (Z=-5.72, P<0.01; Z=-4.166, P<0.01) . PCT in the control group and the research group were 0.100 0(0.030 6~0.100 0)ng/ml and 0.044 5(0.031 6~0.077 0)ng/ml, respectively. There was no statistical difference between two groups (Z=-1.451, P=0.147) . The areas under the ROC curve (AUC) of WBC, CRP and SAA in patients with COVID-19 were 0.814, 0.742, 0.673, respectively (P<0.01), while the AUC of the combination of three indexes for COVID-19 diagnosis was 0.882, with 83.33%(55/66) specificity and 84.76% (139/164) sensitivity, P<0.01.The AUCs of WBC, CRP, and SAA for predicting severe and critically severe COVID-19 were 0.799, 0.779, and 0.886 , respectively (P<0.01), and the AUC of the combination of three indexes for the diagnosis of severe and critically severe COVID-19 was 0.924, with 78.67% (118/150) specificity and 14/14 sensitivity (P<0.01). Conclusion Combining detection of WBC, CRP and SAA can improve the specificity and sensitivity of COVID-19 diagnosis, with a high diagnostic value for severe and critically severe COVID-19.

Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 (PLP2-TM) of coronaviruses acts as a novel autophagy-inducing protein. Intriguingly, PLP2-TM induces incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2-TM interacts with the key autophagy regulators, LC3 and Beclin1, and promotes Beclin1 interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclin1 partially reverses PLP2-TM's inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin1, which in turn modulates coronavirus replication and antiviral innate immunity.
Apoptosis Regulatory Proteins ; antagonists & inhibitors ; genetics ; immunology ; Autophagy ; Beclin-1 ; Coronavirus NL63, Human ; genetics ; immunology ; Gene Expression Regulation ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions ; immunology ; Humans ; Immune Evasion ; Immunity, Innate ; Interferon-gamma ; genetics ; immunology ; Lysosomes ; metabolism ; virology ; MCF-7 Cells ; Membrane Fusion ; Membrane Proteins ; antagonists & inhibitors ; genetics ; immunology ; Microtubule-Associated Proteins ; genetics ; immunology ; Papain ; genetics ; immunology ; Phagosomes ; metabolism ; virology ; RNA, Small Interfering ; genetics ; immunology ; Signal Transduction ; Virus Replication