Objective To analyze the incidence,mortality and survival rates of pancreatic cancer in Pudong New Area of Shanghai from 2002 to 2010.Methods The residents in Pudong New Area of Shanghai were recruited in this study during the period 2002 ～ 2010,the incidence,mortality were calculated according to different age groups and genders.The standardized morbidity and mortality of pancreatic cancer were calculated by world standard population.Logarithmic linear regression was used to calculate the annual percentage change (APC) of incidence and mortality.The 1 ～ 5 year survival of pancreatic cancer patients was analyzed by Kaplan-Meier method and COX regression analysis,and the survival of patients with different TNM staging,with or without operation was determined.Results Among 3089 newly occurred pancreatic cancer cases during 2002 ～ 2010,1707 and 1382 cases were males and females,respectively,with an average age of (69 ± 12) and (73 ± 12) years old,the crude incidence for both genders was 13.32/100 000,and it was 14.71/100 000 for males,which was higher than that in females (11.93/100 000).The ratio of male and female for incidence of age standardize was 1.57:1.There were 2963 death in total,including 1627 males and 1336 females,with a crude mortality rate of 12.78/100 000.The crude mortality rate for males was 14.02/100 000,which was higher than that in females (11.53/100 000).The ratio of male and female ASR for mortality was 1.55:1.Both incidence and mortality significantly increased for males aged over 35 and females aged over 40.The peak of morbidity and mortality appeared in male over 80 years old,and in female over 85 years old.The 1 ～ 5 year survival rates of pancreatic cancer patients were 16.59％,7.31％,5.23％,4.33％ and 3.87％,respectively.The differences in 1 ～5 year survival rates between surgical and non-surgical management groups were statistically significant (P ＜ 0.05).The median survival time of TNM 0 ～ Ⅱ,Ⅲ and Ⅳ staging was (250.00 ± 33.37),(224.00 ± 15.82),(86.00 ± 4.52) d.There was a statistically significant difference among the survival of TNM-Ⅳ and TNM 0 ～ Ⅰ,TNM Ⅲ (P ＜ 0.001).Conclusions The incidence and mortality of pancreatic cancer in males are higher than those in females in Pudong New Area of Shanghai.The survival is associated with TNM staging at diagnosis and whether surgical operation is performed.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment