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 compare the clinical efficacies of endovascular treatments in patients with acute basilar artery occlusion (ABAO) caused by large-artery atherosclerosis (LAA) and cardioembolism (CE).Methods:From March 2018 to February 2021, 104 patients with ABAO accepted endovascular treatments in Department of Neurology and Department of Interventional Radiology, Xuyi County People's Hospital of Huaian City were enrolled; these patients were classified into either a LAA group or a CE group according to Trial of ORG 10172 in Acute Stroke Treatment classification (TOAST). The differences in general data, procedure information, and clinical efficacies were compared between the 2 groups. Univariate and multivariate Logistic regression analyses were used to identify the influencing factors for poor prognosis.Results:In these 104 patients, 51 patients (49.0%) were into the LAA group and 53 patients (51.0%) into the CE group. Ninety-six patients (92.3%) acquired successful revascularization, and 35 patients (33.7%) had good prognosis (modified Rankin scale scores of 0-2) 90 d after surgery. LAA group had significantly lower percentage of patients with atrial fibrillation, significantly lower baseline National Institutes of Health Stroke Scale scores, statistically higher percentages of patients with lower and middle basilar artery occlusion and patients accepted rescued stenting, and statistically longer procedure time ( P<0.05). There were no significant differences between the two groups in terms of successful recanalization percentage, symptomatic intracranial hemorrhage incidence, and prognosis 90 d after surgery ( P>0.05). Age ( OR=0.935, 95%CI: 0.891-0.981, P=0.006) and semiquantitative scores of basilar artery based on computed tomography angiography ( OR=1.520, 95%CI: 1.180-1.959, P=0.001) were independent influencing factors for poor prognosis. TOAST etiology (LAA/CE) was not an independent influencing factors for poor prognosis ( OR=1.175, 95%CI: 0.461-2.933, P=0.736). Conclusion:There are differences in risk factors, vascular occlusion sites, endovascular treatment, and procedure time between patients with ABAO caused by LAA and CE; however, no obvious difference in clinical outcomes is noted, and there was no obvious correlation between stroke etiology and prognoses.

Objective To learn the relationship and operating mechanism between medical staff's loyalty and patient satisfaction.Methods Medical staff and inpatients of a tertiary hospital in Nanjing were sampled at a 1:2 ratio for study,with 840 questionnaires released and 269 valid questionnaires recovered;medical staff service quality as perceived by inpatients served as the intermediate variable,with Mplus7.0 used to build a structural formula model for an empirical study of the relationship between staff loyalty and patient satisfaction.Results Staff loyalty exerts certain positive influence on patient satisfaction and staff service quality ( P < 0.001 ); service quality also exerts some positive influence on patient satisfaction (P<0.001);staff loyalty indirectly exerts positive influence(P<0.001)via the service quality as perceived by patients(mediation effect value 0.364 > direct effect value 0.143).Conclusions Structural formula model can reveal the relationship and extent of the influence of staff loyalty on patient satisfaction.This indicates that hospitals should enhance the loyalty,medical competence and communication skills of their medical staff for higher patient satisfaction.

Objective:To observe and assess the hemorheological efficacy of yixinshu capsules in the treatment of"deficiency of both vital energy and yin or blood stasis"chest-spleen-syndrome patients.Method:According to the stand- ard of the diagnosis of coronary heart diseases and deficiency of both vital energy and yin or blood stasis chest-bi-syndrome, 60 cases were collected from Jan.2006 to Feb.2007 in ward and clinic.Each case was treated with yixinshu capsule for four weeks and its hemorheological efficacy and routine blood change were observed and compared before and after the treat- ment.Result:The yixinshu capsules improved various hemorheological indexes more significantly after the treatment than before it (P0.05).Conclusion:Yixinshu capsules are an effective medicine for the chest-spleen-syndrome case,and recommendable for clinical treatment.