Developmental dysplasia of the hip (DDH) is a congenital or developmental deformation or misalignment of the hip joint that is affected by environmental and genetic factors. Recently, polymorphisms in both TGFB1 and IL-6 have been identified as being significantly associated with hip osteoarthritis in Caucasians. In this study, we conducted a case-control study involving 4,206 Han Chinese individuals to investigate the effects of TGFB1 and IL-6 on the disease status and severity of DDH. A total of 32 single-nucleotide polymorphisms (SNPs) were selected to ensure coverage of the two genetic loci. We found SNP rs1800470 in TGFB1 (OR = 1.255, P = 0.0004) and rs1800796 (OR = 0.84, P = 0.0228) in IL-6 to be significantly associated with DDH in this cohort. Further haplotype-based analysis replicated this significant result. Another SNP in IL-6, rs1800796, showed a marginally significant association with DDH. As a non-synonymous SNP, rs1800470 alters the amino acid sequence of the polypeptide encoded by TGFB1; however, bioinformatics analyses revealed that this SNP has limited functional significance. No significant results were obtained in an association study focusing on the severity of DDH and epistasis analysis. Our findings support an important role for TGFB1 in the risk of DDH. Further research is needed to validate the weak association between rs1800796 in IL-6 and DDH.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

Baicalein is a traditional Chinese medicine with multiple pharmacological effects, including anti-inflammatory activity, anti-pathogen activity, antitumor activity and neuroprotective activity. However, due to the limited solubility and poor stability in aqueous solution, its clinical application is greatly compromised. Here, we investigated the solubility and thermodynamic properties of baicalein in a binary system of water and ethanol from 283.15 K to 328.15 K (common temperature in labs and pharmaceutical industry), in order to optimize the extraction and purification process of baicalein. The results showed that the experimental solubility of baicalein increased with the increased ethanol ratio in the binary system and with the rising temperature. Six models, the ideal mixture model, the polynomial empirical equation, the Apelblat equation, the Buchowski–Ksiazczak (λh) equation, the general single model and the combination of Jouyban–Acree and van’t Hoff models, were chosen to correlate with the experimental data. The correlated results of the general single model were in good agreement with the experimentally measured solubility data with root mean square deviations (%) in the range of 0.22–1.06 $\times {10}^{-3}.$ In addition, its thermodynamic property implied that the dissolution process of baicalein under the studied conditions is a non-spontaneous endothermic process.

With the acceleration of global population aging, the incidence of knee osteoarthritis (KOA) has risen significantly, placing unprecedented pressure on healthcare resources and creating an urgent need for automated segmentation technologies to enhance clinical diagnostic efficiency. Therefore, this paper proposes a novel multi-target tissue segmentation network for knee joints, SwMrNet, which integrates improved Swin Transformer units and a proposed multi-scale residual module within the decoder to enhance both segmentation accuracy and robustness. Firstly, a sliding-window mechanism is used to iteratively exchange feature information, allowing for the extraction of global tissue features. Then, features are extracted at multiple scales, with residual connections preserving the fine details of each tissue type. Through the repeated fusion of global and local features, the SwMrNet segmentation performance and robustness are significantly enhanced. Finally, the proposed model was evaluated on a public knee MRI dataset and a local clinical knee MRI dataset. On the public dataset, the model achieved a Dice score of 98.2%, with Dice scores for all segmented tissues exceeding 94%. On the local clinical dataset, the model showed visually consistent segmentation results, suggesting its potential as an efficient multi-tissue segmentation tool for automated knee joint analysis and auxiliary clinical assessment.

Although genome-wide association studies (GWASs) have identified some risk single-nucleotide polymorphisms in East Asian never-smoking females, the unexplained missing heritability is still required to be investigated. Runs of homozygosity (ROHs) are thought to be a type of genetic variation acting on human complex traits and diseases. We detected ROHs in 8,881 East Asian never-smoking women. The summed ROHs were used to fit a logistic regression model which noteworthily revealed a significant association between ROHs and the decreased risk of lung cancer (P < 0.05). We identified 4 common ROHs regions located at 2p22.1, which were significantly associated with decreased risk of lung cancer (P = 2.00 × 10^-4 - 1.35 × 10^-4). Functional annotation was conducted to investigate the regulatory function of ROHs. The common ROHs were overlapped with potential regulatory elements, such as active epigenome elements and chromatin states in lung-derived cell lines. SOS1 and ARHGEF33 were significantly up-regulated as the putative target genes of the identified ROHs in lung cancer samples according to the analysis of differently expressed genes. Our results suggest that ROHs could act as recessive contributing factors and regulatory elements to influence the risk of lung cancer in never-smoking East Asian females.