Chinese Center for Disease Control and Prevention

About: Chinese Center for Disease Control and Prevention is a government organization based out in Beijing, China. It is known for research contribution in the topics: Population & Acquired immunodeficiency syndrome (AIDS). The organization has 16037 authors who have published 15098 publications receiving 423452 citations. The organization is also known as: China CDC & CCDC.

mapping of H3n2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation

Abstract: One of the primary efforts in influenza vaccine strain recommendation is to monitor through gene sequencing the viral surface protein haemagglutinin (HA) variants that lead to viral antigenic changes. Here we have developed a computational method, denoted as PREDAC, to predict antigenic clusters of influenza A (H3N2) viruses with high accuracy from viral HA sequences. Application of PREDAC to large-scale HA sequence data of H3N2 viruses isolated from diverse regions of Mainland China identified 17 antigenic clusters that have dominated for at least one season between 1968 and 2010. By tracking the dynamics of the dominant antigenic clusters, we not only find that dominant antigenic clusters change more frequently in China than in the United States/Europe, but also characterize the antigenic patterns of seasonal H3N2 viruses within China. Furthermore, we demonstrate that the coupling of large-scale HA sequencing with PREDAC can significantly improve vaccine strain recommendation for China.

Distinct PD-L1 binding characteristics of therapeutic monoclonal antibody durvalumab.

Abstract: Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies (MAbs) to release the anti-tumor activity of preexisting tumor specific T cell immunity has initiated a new era for tumor immunotherapy. Administration of anti-PD-1 MAbs (nivolumab and pembrolizumab) in either monotherapy or in combination with anti-CTLA-4 MAbs or traditional chemotherapy has achieved a tumor regression rate of 30%–50% in dealing with melanoma, non-small cell lung cancer, etc. (Larkin et al., 2015). The approval of anti-PD-L1 atezolizumab and avelumab by US Food and Drug Administration (FDA) since 2016 has provided additional choices in dealing with multiple tumors aside from anti-PD-1 and anti-CTLA-4 MAbs as immunotherapeutic medication. The structures of the two therapeutic anti-PD-1 MAbs, nivolumab and pembrolizumab, complexed with PD-1 have been reported which elucidated the molecular basis of MAb-based anti-PD-1 immunotherapy (Tan et al., 2016a, b; Na et al., 2017; Tan et al., 2017). Complex structures of avelumab and BMS-936559 with PD-L1 were also reported which contributes a better understanding of the molecular basis of MAb-based anti-PD-L1 checkpoint blockade therapy (Lee et al., 2016; Liu et al., 2017). In addition, two additional anti-PD-L1 MAbs are in clinics or phase III trials, atezolizumab and durvalumab. Durvalumab (MEDI4736) is a fully human IgG1 MAb targeting PD-L1 that was developed by AstraZeneca, and has been approved by US FDA very recently. Multiple Phase III clinical trials are still ongoing in non-small cell lung cancer, head and neck cancer, urothelial cancer, etc. (NCT02542293, NCT02369874, NCT02516241, etc.). A Phase Ib report demonstrated that durvalumab is well tolerated and showed promising anti-tumor efficacy in nonsmall cell lung cancer patients (Antonia et al., 2016). However, the molecular basis of durvalumab-based anti-PD-L1 reactivity and binding characteristics compared to the other three MAbs used in clinics has not yet been elucidated. In the present study, weexpressed the two-Ig-domain PD-L1 and single chain Fv fragment (scFv) of durvalumab as inclusion bodies in Escherichia coli cells. Soluble proteins were obtained by in vitro refolding, and the two refolded proteins survived well in gel filtration (Fig. S1). Subsequently, crystal screen was performed with the durvalumab-scFv/PD-L1 complex proteins, and well-diffractable crystals grew in 3.5 mol/L sodium formate, pH 7.0 (See more details in supplementary information). The complex structure of durvalumab-scFv/PD-L1 was determined by molecular replacement at a resolution of 2.3 Å (Table S1). The binding of durvalumab to PD-L1 involves both of its heavy chain (VH) and light chain (VL) (Fig. 1A). All of the three complementarity-determining regions (CDRs) of VH and CDR1 and CDR3 of VL contribute to interactions with PD-L1, leaving LCDR2without any contacts. Previous reports on the anti-PD-1MAbs revealed that the binding of theseMAb ismainly located on the loops of PD-1, i.e., the N-terminal loop of PD-1 for nivolumab interaction and the C’D loop for pembrolizumab. However, the binding of avelumab and BMS936559 is mainly located on the strands of the front-β-sheet face of PD-L1. Here, the binding of durvalumab on PD-L1 was also mainly located on the front β-sheet face which is constituted by A, G, F, C, and C’ strands of the IgV domain of PD-L1. A detailed analysis of the interactions between durvalumab and PD-L1 shows an unbiased contribution from VH and VL of durvalumab in binding to PD-L1. The A, G, and F strands of PD-L1 provide major hydrogen bond interactions with durvalumab (Fig. 1B). D26 of the A strand andR113 of the F strand of PD-L1were occupied by S30 of LCDR1 andE58 of HCDR2, respectively (Table S2). Especially, residues of the G strand (Y123, K124, and R125) provide multiple hydrogen bonds to both VH (F104 of HCDR3 and N51 nearby HCDR2) and VL (Y92 and S94 of LCDR3), which contribute major hydrogen bond interactions to durvalumab, 7 out of 10 hydrogen bonds in all (Table S2). Structural superimposition of the PD-1/PD-L1 complex (PDB: 4ZQK) and the durvalumab-scFv/PD-L1 complex was conducted to elucidate the molecular basis of durvalumabbased PD-1/PD-L1 intervention. The binding of durvalumab to PD-L1 shows a stereo clash with that of PD-1 (Fig. 1C). The binding surface of durvalumab and PD-1 on PD-L1 is highly overlapped that residues of PD-L1, which contributed major hydrogen bond interactions with PD-1 (D26, Y123, K124, and R125), were also occupied by durvalumab (Fig. 1D) (Zak et al., 2015). The competitive binding involves both VH and VL of durvalumab. Thus, the molecular basis of

HIV transmission risk among serodiscordant couples: a retrospective study of former plasma donors in Henan, China

Abstract: Objectives: To estimate the HIV incidence and assess the behavioral, clinical, and quality-of-life risk factors for HIV transmission among serodiscordant couples from Henan Province, China. Methods: Between January 2006 and December 2008, initially seronegative spouses were tested for HIV at 6-month intervals. Retrospectively identified subjects were interviewed through face-to-face questionnaire. Cox proportional-hazards model was used to assess the relationship between risk factors and HIV seroconversion. Results: Of 1927 couples, 84 (4.3%) seroconversions occurred, representing a seroconversion rate of 1.71 per 100 person-years. Seroconversion rates increased over time. Not always using condoms [relative ratio (RR) = 8.42; 95% confidence interval (CI): 4.83 to 14.67], sexual activity ≥4 times per month (RR = 5.24; 95% CI: 2.55 to 10.77), not switching antiretroviral treatment regimen (RR = 1.99; 95% CI: 0.85 to 4.65), and a quality-of-life score <12 on the psychological domain (RR = 2.33; 95% CI: 1.21 to 4.48) were associated with increased risk of seroconversion. Seventy-one percent of index spouses were on antiretroviral therapy. There was no association between rate of HIV seroconversion and last recorded CD4 cell count level of the index spouse. Conclusions: Effective HIV prevention interventions targeting discordant couples should focus on sustaining health education, increasing psychosocial support services, and increasing medication adherence monitoring.

Educational Stress Scale for Adolescents Development, Validity, and Reliability With Chinese Students

Abstract: This article describes the development and initial validation of a new instrument to measure academic stress—the Educational Stress Scale for Adolescents (ESSA). A series of cross-sectional questionnaire surveys were conducted with more than 2,000 Chinese adolescents to examine the psychometric properties. The final 16-item ESSA contains five latent variables: Pressure from study, Workload, Worry about grades, Self-expectation, and Despondency, which together explain 64% of the total item variance. Scale scores showed adequate internal consistency, 2-week test–retest reliability, and satisfactory concurrent validity. A confirmatory factor analysis suggested the proposed factor model fits well in a different sample. For researchers who have a particular interest in academic stress among adolescents, the ESSA promises to be a useful tool.