Analysis of epidemiological changes and elimination effects for malaria in Handan city, the north China.

The elimination of malaria requires high-quality surveillance data to quickly detect and respond to individual cases. This study aims to analyze the epidemiological characteristics of malaria and ascertain the long-term epidemic trends of malaria by 2020 in Handan China. Case-level data for the period 2011 to 2020 were extracted from Chinese Information System for Disease Control and Prevention. The lamp trap method was used to capture mosquitoes so that the characteristics of mosquitoes can be analyzed. The incidence, accuracy, and timeliness of malaria case diagnosis, reporting and investigation were evaluated at the elimination stage (2011-2020) in Handan City, China. Between 2011 and 2020, 94 malaria cases were reported in Handan City, of which 93 malaria cases were male and all of which were imported from abroad. The annual average incidence decreased from 622.33/100,000 to 0.11/100,000 in the elimination stage. Since the initiation of the National Malaria Elimination Program in 2010, malaria cases have been consistent with the increase in overseas export channels and labor personnel service. There is a need to strengthen malaria surveillance of returning workers from Africa and to conduct timely blood tests to diagnose and treat imported infections. Local authorities ensure that imported malaria cases can be timely diagnosed, reported, treated and investigated at local level.

Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk.

The anti-HER receptor antibodies cetuximab, trastuzumab, and pertuzumab are used widely in clinic to treat metastatic cancer. However, activation of the extensive crosstalk among the HER receptors as well as other RTKs, particularly HER-MET crosstalk, has emerged as a likely source of drug resistance. In this study, we developed two new types of tetra-specific antibodies that recognize EGFR, HER2, HER3, and VEGF. These tetra-specific antibodies, termed FL518 (four-in-one antibody) and CRTB6 (tetra-specific, tetravalent antibody), not only inhibited signaling mediated by these receptors in vitro and in vivo but unexpectedly also disrupted HER-MET crosstalk. When compared with two-in-one antibodies and a series of bispecific antibodies in multiple tumor models, FL518 and CRTB6 were more broadly efficacious. We further showed that tetra-specific antibodies were far more effective than bispecific antibodies in inhibiting the growth of anti-HER-resistant cancer cells, which exhibited elevated levels of MET activation both in vitro and in vivo. Overall, our results establish a new principle to achieve combined HER inhibition and limit drug resistance using a single antibody.

Pin1, endothelial nitric oxide synthase, and amyloid-ß form a feedback signaling loop involved in the pathogenesis of Alzheimer's disease, hypertension, and cerebral amyloid angiopathy.

Although the molecular mechanism has not yet been clarified until now, it is very interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral amyloid angiopathy (CAA) often occur synchronously and possess many similar pathological characteristics. Herein, we hypothesize that a feedback signaling loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid-ß (Aß), may contribute to the interesting pathological phenomenon. First, Pin1 inhibits the production of Aß, and enhances the activity of eNOS. Second, Aß and eNOS form a mutual inhibition system. Third, the well-balanced feedback signaling loop avoids the development of AD, HTN, and CAA by inhibiting the frequent pathological characteristics of these diseases, including Aß deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1 and eNOS not only inhibit Aß production but also accelerate Aß clearance, preventing Aß deposition in cerebral microvessels. On the other hand, Pin1 and eNOS promote vasodilatation and prevent the elevation of blood pressure in brain, alleviating the pathology of cerebral microbleeds. However, once the precise balance is disturbed, it may result in Aß deposition, microbleeds, and elevated blood pressure, possibly leading to the synchronous occurrence of AD, HTN, and CAA. The hypothesis updates the current understanding of the molecular linkage among AD, HTN, and CAA, and lays the ground for developing combined prevention, diagnosis, and treatment of these diseases more efficiently and more economically. Interestingly, biotechnical medicines enhancing the activity of Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting Aß deposition may alleviate the clinical pathologies of these related diseases.