Anemia, Sideroblastic ; genetics ; Calreticulin ; genetics ; Humans ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; genetics ; Phosphoproteins ; genetics ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear ; genetics

Objective To analyze the epidemiological characteristics of annual reported people living with HIV/AIDS (HIV/AIDS) in Qingdao city,Shandong province from 2010 to 2014 and to provide theoretical evidence for strategies on targeted prevention and control.Methods Information on annual reported HIV/AIDS and sentinel surveillance data from 2010 to 2014 was abstracted from the HIV/AIDS Comprehensive Response Information Management System (CRIMS).Statistical analysis was done by SPSS software.Results The number of annual reported HIV/AIDS increased from 2010 to 2014 in Qingdao,with the sex ratio as 10.8.Among all the patients,77.1％ were aged 20-39 years,65.6％ were unmarried,67.6％ graduated from high school or above.Homosexual contact was the major mode of transmission,and the prevalence of MSM increased yearly (P＜0.05).Conclusions MSM appeared the major high risk population for AIDS epidemic in Qingdao.However,surveillance projects should also be strengthened among the female population with multiple sexual partners.Optimal prevention and control measures based on the characteristics of AIDS epidemic should be developed to explore the stem spread and epidemics of the disease,in Qingdao.

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.
Cartilage, Articular/pathology* ; Chondrocytes/metabolism* ; Down-Regulation ; Epigenesis, Genetic ; Humans ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism* ; Osteoarthritis/pathology* ; RNA, Small Interfering/pharmacology*