Impact of endoplasmic reticulum stress on chondrocyte apoptosis in rat model of DDH.

Developmental dysplasia of the hip (DDH) is a developmental disorder characterized by acetabular dysplasia leading to early osteoarthritis. This study examines the role of endoplasmic reticulum stress (ERS) in chondrocyte apoptosis and cartilage degeneration within a DDH model. In the rat model of DDH, created using a swaddling technique, significant deformities in the femoral head and acetabulum were observed, alongside an upregulation of matrix metalloproteinase-13 in acetabular cartilage. We also noted increased levels of apoptosis and ERS-related factors in the acetabular cartilage of DDH models. Additionally, rat chondrocytes exposed to high-magnitude cyclic tensile strain (CTS, 1 Hz, 10% equibiaxial strain) in vitro exhibited elevated ERS and increased apoptosis. Importantly, treatment with the ERS inhibitor 4-phenylbutyric acid effectively suppressed apoptosis induced by CTS in chondrocytes. Our findings suggest that ERS contributes to the upregulation of apoptosis-related factors in chondrocytes within the DDH model, indicating the potential of ERS modulation as a therapeutic approach for DDH-related cartilage degeneration.

Molecular Evolution and Increasing Macrolide Resistance of Bordetella pertussis, Shanghai, China, 2016-2022.

Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.

Clinical and molecular characteristics of methicillin-resistant Staphylococcus aureus in bone and joint infection among children.

OBJECTIVE: To investigate the characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in bone and joint infection (BJI) among children. METHODS: A total of 338 patients diagnosed with BJI from 2013 to 2022 in Children's Hospital of Fudan University were enrolled. Demographic information, microbiology culture results and laboratory findings, including white blood counts (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) were collected and analyzed. MRSA was confirmed by antimicrobial susceptibility testing. Other MRSA-caused infections were randomly selected for comparison. Twenty-three virulence and antimicrobial resistance (AMR) genes were screened for MRSA strains. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing were performed using PCR amplification and sequencing. RESULTS: Of the identified pathogens in BJI, MRSA accounted for 21.0% (47/224). Patients with BJI had high levels of initial CRP, white blood cell count (WBC) and IL-6. ST59 (43.9%) and t437 (37.6%) were the main MRSA subtypes isolated from the children. The major genotypes in BJI were ST59-t437 (29.8%) and ST22-t309 (14.9%), with high carriage of hemolysins including hla (94.4-100%), hlb (66.2-93.3%), and hld (100%). Notably, Panton-Valentine leukocidin (pvl) had a high prevalence (53.3%) in ST22-t309-MRSA. Other virulence genes including tst, seg and sei were more commonly detected in ST22-t309-MRSA (40.0-46.7%) than in ST59-t437-MRSA (4.2-9.9%). High-carriage AMR genes in MRSA included aph(3')/III (66.7-80%), ermB (57.5-73.3%) and ermC (66.7-78.9%). MRSA presented high-resistance to erythromycin (52.0-100%) and clindamycin (48.0-92.5%), different genotypes displayed variation in their susceptibilities to antibiotics. CONCLUSIONS: The major MRSA genotype in BJI was ST59-t437, followed by ST22-t309, with a higher prevalence of the pvl gene. Continuous surveillance of pvl-positive ST22-t309-MRSA in pediatric BJI infections is thus required.

Emergence and spread of MT28 ptxP3 allele macrolide-resistant Bordetella pertussis from 2021 to 2022 in China.

OBJECTIVES: To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China. METHODS: A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping. RESULTS: Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged <1 year) accounted for 24.7% and presented much more severe symptoms than noninfants. Pertussis was most frequently detected in infants aged 0-6 months (11.3∼14.0%) and children aged >6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx)P3/(pertactin) prn2/ptxC2/ptxA1/(fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP. CONCLUSION: The emergence and spread of MT28 ptxP3-MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3-MRBP to prevent its potential circulation.