Objective: To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features. Methods: We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled. Results: Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively. Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.

To determine the inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction,the protein-protein interaction between human immunodeficiency virus type 1( HIV-1) integrase and lens epithelial growth factor p75 protein( LEDGF/p75) was used as a target. The homogeneous time-resolved fluorescence( HTRF) technique was used in the inhibitory activity assay. The results showed that eight endophytic fungi with anti-IN-LEDGF/p75 interaction activity were screened out from fifty-three strains with different morphological characteristic. Among them,106 strain showed strong inhibitory activity against HIV-1 IN-LEDGF/p75 interaction with IC50 value of 5. 23 mg·L-1,and was identified as a potential novel species of Magnaporthaceae family by the analyses of ITS-rDNA,LSU and RPB2 sequences data. This study demonstrated that potential natural active ingredients against the HIV-1 IN-LEDGF/p75 interaction exist in the endophytic fungi of D. versipellis. These results may provide available candidate strain resources for the research and development of new anti-acquired immunodeficiency syndrome drugs.
Berberidaceae ; microbiology ; Endophytes ; Fungi ; chemistry ; HIV Integrase ; metabolism ; HIV-1 ; drug effects ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Protein Binding

Background: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. Methods: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. Results: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ² = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. Conclusion: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. Trial Registration NCT01962155; https://clinicaltrials.gov.

Atherothrombosis is the major cause of acute coronary syndromes and cardiovascular deaths. Platelets participate in the processes of forming and extending atherosclerotic plaques. Therefore, antiplatelet therapy is a milestone in the primary and second prevention of atherothrombotic diseases. Along with the longterm use of antiplatelet agents, the safety and drug resistance has become a big concern in clinic and new drugs possessing higher effectiveness and fewer adverse effects are needed. Abundant recent data support that traditional Chinese herbs may be a good alternative and complementary choice of new antiplatelet drugs. This review highlights the progress of antiplatelet effect of active components derived from traditional Chinese herbs based on their chemical structures.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Platelet Activation ; drug effects ; Platelet Aggregation Inhibitors ; chemistry ; pharmacology ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction ; drug effects

OBJECTIVETo investigate the prognostic value of morphology and Hans classification in diffuse large B cell lymphoma（DLBCL）.

METHODSClinical data of 249 patients diagnosed with DLBCL in our hospital and Hangzhou Xixi hospital during Jan 2006 to Dec 2016 were analyzed retrospectively. These patients were classified into 3 groups: immunoblastic variant（IB） group, centroblastic variant（CB） group and others group according to the cell morphology. And DLBCL was also divided into GCB（germinal center B-cell-like）or non-GCB（non-germinal center B-cell-like） group by analyzing the expression of CD10, BCL6 and MUM1 (GCB: CD10 ,BCL6,MUM1/CD10,BCL6,MUM1；non-GCB：CD10,BCL6,MUM1/CD10,BCL6,MUM1).

RESULTSThe univariate analysis displayed that the age，LDH level，IPI，IB，non-GCB，B-symptoms and rituximab all could influence the OS and EFS, the CR rate of CB subtype patients was significantly higher than that of the patients with IB subtype （68.3% vs 38.9%)(P=0.02）. IB subtype was the in dependent prognostic factor for both EFS and OS in the whole study. In multivariate analysis, IPI and IB were the independent prognostic factors for OS and EFS. IB subtype was also an independent prognostic factor in EFS and OS with or without rituximab. The expression of BCL2 and BCL6 was related with prognosis in R-CHOP, but not in CHOP treated patients. Other markers (CD5, CD10, IRF4/MUM1, HLA-DR and Ki-67 proliferation index) were not of the significant prognostic value for DLBCL. When accepted rituximab, the GCB and non-GCB were not different significantly for prognosis. However, the non-GCB group showed a poor prognosis without using rituximab （EFS P=0.020；OS P=0.020）. Multivariate Cox models showed that OS and EFS were not significantly different between GCB and non-GCB group, however, the IB subtype had a very significantly poor prognosis in OS and EFS (P=0.001, P=0.002). When the analysis was restricted to DLBCL with CB morphology only, no prognostic value was observed in Hans classification.

CONCLUSIONThe subtype of immunoblast is a major risk factor in patients treated with CHOP or R-CHOP. There is a significant association between the Hans classification and the morphologic subclassification. Results of this study have supplemented the data for the prognostic factor of DLBCL and demonstrated that the cytomorphologic diagnosis can be reproducible.

Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Humans ; Immunohistochemistry ; Lymphoma, Large B-Cell, Diffuse ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Rituximab

Oligosaccharide isomers were distinguished by electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry ( ECD-FT-ICR-MS ) in combination with utiliZing alkali, alkaline earth, and transition metals ( Na+, Ca2+, Ba2+, Mg2+, Mn2+ and Co2+) as charge carriers in electrospray.Maltoheptaose, mannohexaose and laminarihexaose were taken as examples to investigate influence of metal ions on the extent of oligosaccharide fragmentation.The same types of fragmentation ions ( 0,2 A and 2,4 A) were obtained for barium- and calcium-adducted maltoheptaose.Mg2+ and Mn2+ had the similar influence ( 0,2 A, 2,4 A and 2,5 A ).Three cross-ring cleavage ions ( 1,4 A, 2,4 A and 2,5 A ) were generated in the spectrum of cobalt-associated maltoheptaose.But in the case of doping Na+into maltoheptaose, only 0,2 A ion was detected.It was found that the signals in the spectra of mannohexaose and laminarihexaose were worse than that in the spectrum of maltoheptaose, probably resulting from different numbers of adducted metal ions.The isomers, mannohexaose and laminarihexaose could be distinguished by ECD-MS in conjunction with the addition of Ca2+, Mg2+ or Co2+.The addition of Ca2+ was the best choice for analysis of oligosaccharides.

BACKGROUNDSince 2010, two versions of National Guidelines aimed at promoting the management of ST-segment elevation myocardial infarction (STEMI) have been formulated by the Chinese Society of Cardiology. However, little is known about the changes in clinical characteristics, management, and in-hospital outcomes in rural areas.

METHODSIn the present multicenter, cross-sectional study, participants were enrolled from rural hospitals located in Liaoning province in Northeast China, during two different periods (from June 2009 to June 2010 and from January 2015 to December 2015). Data collection was conducted using a standardized questionnaire. In total, 607 and 637 STEMI patients were recruited in the 2010 and 2015 cohorts, respectively.

RESULTSSTEMI patients in rural hospitals were older in the second group (63 years vs. 65 years, P = 0.039). We found increases in the prevalence of hypertension, prior percutaneous coronary intervention (PCI), and prior stroke. Over the past 5 years, the cost during hospitalization almost doubled. The proportion of STEMI patients who underwent emergency reperfusion had significantly increased from 42.34% to 54.47% (P < 0.0001). Concurrently, the proportion of primary PCI increased from 3.62% to 10.52% (P < 0.0001). The past 5 years have also seen marked increases in the use of guideline-recommended drugs and clinical examinations. However, in-hospital mortality and major adverse cardiac events did not significantly change over time (13.01% vs. 10.20%, P = 0.121; 13.34% vs. 13.66%, P = 0.872).

CONCLUSIONSDespite the great progress that has been made in guideline-recommended therapies, in-hospital outcomes among rural STEMI patients have not significantly improved. Therefore, there is still substantial room for improvement in the quality of care.

Aged ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Hospital Mortality ; Hospitals ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; ST Elevation Myocardial Infarction ; epidemiology ; mortality ; surgery ; Surveys and Questionnaires

The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.

Objective To evaluate the activities of vastus medialis, rectus femoris and vastus lateralis during stair descent in healthy youth. Methods Thirty healthy college students were recruited from the Capital Medical University 2015 admissions in 2016. The electrode was put on the dominant side of the quadriceps. Surface electromyography was used to record muscle activity during stair descent. Results During stair descent, the maximum amplitude and mean amplitude were significantly lower in rectus femoris than in vastus medialis and vas-tus lateralis (P<0.001). No significant difference was found between vastus medialis and vastus lateralis (P>0.05). Conclusion The activa-tion of both vastus medialis and vastus lateralis during stair descent is significantly higher than that of rectus femoris. The coactivation of vastus medialis and vastus lateralis is equal in healthy youth.