Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To explore the coverage of influenza and pneumonia vaccination and factors influencing the vaccination in children.Methods:A cross-sectional questionnaire survey was conducted in children's parents in Beijing and Gansu by using two-stage cluster-sampling to investigate the influenza and pneumonia vaccination rates and influencing factors in children.Results:A total of 2 377 parents were included in the study, and the results indicated that the influenza vaccination coverage was 35.93% and the pneumonia vaccination coverage was 16.58% in children in survey areas, the vaccination rate of both vaccines was 11.65%. The top three reasons for vaccination for both vaccines were being aware of severity of the diseases (influenza vaccine: 36.02%; pneumonia vaccine: 49.61%), being required by school or organization (influenza vaccine: 28.76%; pneumonia vaccine: 25.45%) and being aware of the susceptibility of the diseases (influenza vaccine: 26.41%; pneumonia vaccine: 13.88%). The top three reasons for having no vaccinations were personal unwillingness, concern about vaccine and vaccine accessibility. Families with multi children, living in rural areas and lower family income were the negative factors for both types of vaccinations.Conclusions:The influenza and pneumonia vaccination coverage in children need further improvement, and rural families and families with multi children are the key concern groups for expanding vaccination coverage. Health education about influenza and pneumonia vaccinations, coordinating vaccine supply and decreasing vaccine prices play an important role in improving influenza and pneumonia vaccination coverage.

Objective:To explore the clinical characteristics and influencing factors of refractory lupus thrombocytopenia (RLTP) secondary to systemic lupus erythematosus (SLE).Methods:A retrospective analysis of 113 patients with thrombocytopenia secondary to SLE in the outpatient and inpatient Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2015 to June 2018 was carried out. The medical record and laboratory tests of patients were collected, and they were divided them into the refractory group (RLTP, n=25) and non-refractory group (NRLTP, n=88). The clinical manifestations, blood count, biochemical and immunological test of the two groups were analyzed and compared. All data were analyzed by t-test, Mann-Whitney test, χ2 test, Logistic regression analysis and Kaplan-Meier survival analysis. Results:Compared with NRLTP patients, RLTP patients had longer disease course [72(30, 120) months vs 38.5 (8.5, 93) months, H=-2.401, P=0.016), nervous system damage (28% vs 7%, χ2=8.58, P=0.016), higher bleeding risk [(4.6±1.7) vs (3.8±1.3), t=2.548, P=0.012] and higher mortality rate (8% vs 0, χ2=7.167, P<0.01). Meanwhile, the positive rate of anti-GPⅠb/Ⅸ in RLTP group was significantly higher than that in NRLTP group (27% vs 4%, χ2= 8.647, P<0.01). Further unconditional multivariate logistic regression analysis showed that anti-GPⅠb/Ⅸ positive was one of the main influencing factors of RLTP. Kaplan-Meier survival curve analysis revealed that the cumulative survival rate of RLTP group was significantly lower than that of NLTP group ( χ2=7.909, P<0.01). Conclusion:RLTP has a long course of disease, prone to nervous system impairment and positive anti-GPⅠb/Ⅸ antibody, and has a high risk of bleeding. It is necessary to identify these patients early, adjust treatment strategies and improve the prognosis of patients.

The competence of scientific research ethnical review in domestic hospital was inadequate,which was associated with the development of medical ethnics,values of Chinese traditional society,unsound domestic laws and regulations,weak administrative management,unqualified committee of medical ethnics,the drive of scientific deriving interests and restriction of project funds.Aiming at the above problems,countermeasures were carried out to strengthen the construction of laws and regulations,strengthen the constraint of administrative management,standardize the self-construction of ethnic committee,implement the standard operative procedure,thus to provide a reference for the standardized construction of scientific research ethnical review.

Aim To explore new ways for developing anticancer drugs by the separation of pigment from Fu-sarium species JN158 ( Fusarium sp JN158 ) , the iden-tification of its structure, the screening of anticancer components and the study of its partial mechanism. Methods Pigment separation was done by HPLC, structural analysis by UV, IR, NMR, the screening of anticancer activity by MTT. Western blot was used to analyze the protein expression of CyclinD1, NF-κB, VEGF in tumor cells. Results The results showed that the pigment from Fusarium produced a total of six different peaks, of which peak Ⅵ was the anthocya-nins. Its molecular weight is about 382, molecular for-mula is C17 H18 O10 . According to investigation, this pig-ment was probably a new compound, which could in-hibit the proliferation of MCF-7 cells markedly ( IC50:0.011mmol·L-1 ,P<0.05;the control medicine ube-nimex IC50:10 mmol · L-1 ) in a concentration-de-pendent manner, and had no effect on human umbilical cord intravenous endotheliocyte ( HUVEC ) . The influ-ence on the gene expression of CyclinD1, NF-κB, VEGF in MCF-7 cells varied with the concentration of this compound. The Western blot results showed that VI pigment compound inhibited CyclinD1, NF-κB, VEGF gene expression (P<0.05 or 0. 01),compared with the control group. Conclusion The Ⅵ pigment compound from Fusarium sp JN158 could inhibit MCF-7 proliferation by inhibiting CyclinD1, NF-κB, VEGF gene expression. The compound may be a promising compound against breast cancer.