Macrolide resistance rates of Mycoplasma pneumoniae in the Beijing population were as high as 68.9%, 90.0%, 98.4%, 95.4%, and 97.0% in the years 2008 to 2012, respectively. Common macrolide-resistant mobile genetic elements were not detected with any isolate. These macrolide-resistant isolates came from multiple clones rather than the same clone. No massive aggregation of a particular clone was found in a specific period. Mycoplasma pneumoniae is one of the important pathogens causing human respiratory tract infection, especially in community-acquired pneumonia (1, 2). The major clinical treatment for M. pneumoniae infection is the use of macrolide antibiotics (ML). With the widespread use of the drug, ML-resistant isolates have been reported worldwide (3-5). The resistance mechanism has been identified as a point mutation in the 23S rRNA gene. Other mechanisms of macrolide resistance cannot be excluded and have not been identified. In recent years, ML-resistant M. pneumoniae has become very serious in Asia (6, 7) and has attracted the attention of scientists. Studies on ML-resistant M. pneumoniae in China have only recently been conducted, and the limited reports have been mainly ML resistance analyses of a small number of strains isolated during a few months and from specific populations, such as children or adults (8-11). These reports are lacking continuous full-population surveillance data of M. pneumoniae drug resistance. In view of the above-mentioned information, we have studied drug resistance of 309 M. pneumoniae isolates from a whole population of strains isolated from people with respiratory infections in Beijing, China, from 2008 to 2012, a study which will help us to understand the status of drug-resistant M. pneumoniae in Beijing in recent years.M. pneumoniae strains. A total of 309 M. pneumoniae strains were isolated from 1,183 respiratory infection specimens from Beijing Chao-Yang Hospital, Beijing Children's Hospital, and Beijing Centers for Diseases Control and Prevention. One hundred fifty-six isolates were from 388 pediatric specimens of patients Ͻ14 years of age, and the remaining 153 isolates were collected from 795 adolescent and adult specimens. All 309 isolates were purified, cultured, and identified with a real-time PCR method (12).Detection of macrolide resistance at the gene level. Genomic DNA of 309 M. pneumoniae isolates was extracted using the QIAamp DNA minikit (Qiagen). The extracts were distributed into aliquots and saved at Ϫ20°C. The domain V region of the 23S rRNA gene was amplified by PCR methods described previously (6). The amplification products were sequenced by the Beijing Genomics Institute (BGI). The results showed that there were existing point mutations in domain V of the 23S rRNA gene region of 280 strains in the 309 M. pneumoniae isolates. In 272 of the 280 isolates (97.1%), the mutation was identified as A2063G. Seven of the 280 isolates (2.5%) had the A2064G mutation, one of the 280 isolates (0.4%) had an A2063T mutation, and the remaining 29 isolates did not h...

BackgroundBefore 1986, scrub typhus was only found endemic in southern China. Because human infections typically occur in the summer, it is called "summer type". During the autumn-winter period of 1986, a new type of scrub typhus was identified in Shandong and northern Jiangsu province of northern China. This newly recognized scrub typhus was subsequently reported in many areas of northern China and was then called "autumn-winter type". However, clinical characteristics of associated cases have not been reported.MethodsFrom 1995 to 2006, all suspected scrub typhus cases in five township hospitals of Feixian county, Shandong province were enrolled. Indirect immunofluorescent assay (IFA) was used as confirmatory serodiagnosis test. Polymerase chain reaction (PCR) connected with restriction fragment length polymorphism (RFLP) and sequence analyses were used for genotyping of O. tsutsugamushi DNAs. Clinical symptoms and demography of confirmed cases were analyzed.ResultsA total of 480 scrub typhus cases were confirmed. The cases occurred every year exclusively between September and December with a peak occurrence in October. The case numbers were relatively higher in 1995, 1996, 1997, and 2000 than in other years. 57.9% of cases were in the group aged 21–50. More cases occurred in male (56%) than in female (44%). The predominant occupational group of the cases was farmers (85.0%). Farm work was reported the primary exposure to infection in 67.7% of cases. Fever, rash, and eschar were observed in 100.0%, 90.4%, and 88.5% of cases, respectively. Eschars formed frequently on or around umbilicus, abdomen areas, and front and back of waist (34.1%) in both genders. Normal results were observed in 88.7% (WBC counts), 84.5% (PLT counts), and 89.7% (RBC counts) of cases, respectively. Observations from the five hospitals were compared and no significant differences were found.ConclusionThe autumn-winter type scrub typhus in northern China occurred exclusively from September to December with a peak occurrence in October, which was different from the summer type in southern China. In comparison with the summer type, complications associated with autumn-winter type scrub typhus were less severe, and abnormalities of routine hematological parameters were less obvious.

Osteoarthritis (OA), the most common form of arthritis, is a very common joint disease that often affects middle-aged to elderly people. However, current treatment options for OA are predominantly palliative. Thus, understanding its pathological process and exploring its potential therapeutic approaches are of great importance. Rat chondrocytes were isolated and exposed to hydrogen peroxide (H2O2) to mimic OA. The effects of H2O2 on ubiquitin-specific protease 7 (USP7) expression, reactive oxygen species (ROS) levels, proliferation, inflammatory cytokine release, and pyroptosis were measured. USP7 was knocked down (KD) or overexpressed to investigate the role of USP7 in OA. Co-immunoprecipitation (Co-IP) was used to study the interaction between USP7 and NAD(P)H oxidases (NOX)4 as well as NOX4 ubiquitination. NOX4 inhibitor was applied to study the involvement of NOX4 in USP7-mediated OA development. USP7 inhibitor was given to OA animals to further investigate the role of USP7 in OA in vivo. Moreover, H2O2 treatment significantly increased USP7 expression, enhanced ROS levels, and inhibited proliferation in rat chondrocytes. The overexpression of USP7 enhanced pyroptosis, ROS production, interleukin (IL)-1β and IL-18 levels, and the expression level of NLRP3, GSDMD-N, active caspase-1, pro-caspase-1, matrix metalloproteinases (MMP) 1, and MMP13, which was abolished by ROS inhibition. The USP7 KD protected rat chondrocytes against H2O2-induced injury. Co-IP results showed that USP7 interacted with NOX4, and USP7 KD enhanced NOX4 ubiquitinylation. The inhibition of NOX4 blocked the pro-OA effect of USP7. Moreover, the USP7 inhibitor given to OA animals suppressed OA in vivo. USP7 inhibited NOX4 ubiquitination for degradation which leads to elevated ROS production. ROS subsequently activates NLPR3 inflammasome, leading to enhanced production of IL-1β and IL-18, GSDMD-N-dependent pyroptosis, and extracellular matrix remodeling. Thus, UPS7 contributes to the progression of OA via NOX4/ROS/NLPR3 axis.