Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To rapidly and accurately detect volumetric modulated arc therapy (VMAT) plans with potentially inaccurate radiation doses.Methods:The measurement-based dosimetric verification result of 196 VMAT plans obtained using ArcCHECK phantoms were retrospectively collected. Independent dosimetric calculation and verification were conducted for these plans using the ArcherQA system based on a fast Monte Carlo algorithm. The gamma passing rates of dosimetric verification using ArcCHECK phantom and the ArcherQA system were compared, followed by their correlation analysis and linear regression fitting. The ArcherQA system′s gamma passing rate threshold used to detect positive dosimetric verification result obtained using ArcCHECK phantoms, as well as the specificity of the detection, were calculated. Based on this gamma passing rate threshold, another 50 VMAT plans were selected as a test set to assess the ArcherQA system′s ability to detect positive measurement-based dosimetric verification result.Results:The average gamma passing rates for the dosimetric verification of the VMAT plans using the ArcherQA system and ArcCHECK phantoms were 97.28% and 96.57% (3%/3 mm, TH=10%), respectively. Both rates had a correlation coefficient of 0.71 ( P < 0.01) and a linear fitting coefficient of 0.54 ( R2=0.51). When the gamma passing rate for dosimetric verification using ArcCHECK phantoms was set at 90% (3%/2 mm, TH=10%), the gamma passing rate threshold for dosimetric verification using the ArcherQA system should be adjusted to 94.8% to detect all VMAT plans with positive dosimetric verification result obtained using ArcCHECK phantoms, with a specificity of 67.8%. Using this threshold, the ArcherQA system detected all VMAT plans in the test set for which ArcCHECK phantom-based measurement yielded positive dosimetric verification result. Conclusions:By determining an appropriate gamma passing rate threshold, the ArcherQA system can rapidly and accurately detect VMAT plans with potentially inaccurate doses, thus ensuring treatment accuracy and improving work efficiency.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery. Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024. Morphological evaluation, immunohistochemical staining, and next generation sequencing (NGS) targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions. Results All three implanted lesions exhibited morphological similarity to their primary counterparts, but displayed enriched mutational profiles. Case 1: a 13-year-old female. The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma, while the implanted lesion was follicular carcinoma. Both lesions harbored MEN1 mutations, with an additional PTPRT mutation detected in the implanted lesion. Case 2: a 45-year-old male. The primary lesion was bilateral nodular goiter, and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus. No mutations were identified in the primary lesion, whereas the implanted lesion exhibited MEN1, GLIS3, EZH1, and KMT2C mutations. Case 3: a 42-year-old female. The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter. A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively. The primary lesion harbored TERT, GLIS3, and SPOP mutations, while the implanted lesion showed TERT, GLIS3, EIF1AX, and KMT2C mutations. Conclusions Endoscopic thyroid surgery is widely applied in clinical practice, however, implantation dissemination of thyroid lesions along surgical pathways may occur, encompassing both benign and malignant entities. Implanted lesions exhibit pathological similarities to their primary counterparts, but demonstrate mutational enrichment.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery.Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024.Morphological evaluation,immunohistochemical staining,and next generation sequencing(NGS)targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions.Results All three implanted lesions exhibited morphological similarity to their primary counterparts,but displayed enriched mutational profiles.Case 1:a 13-year-old female.The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma,while the implanted lesion was follicular carcinoma.Both lesions harbored MEN1 mutations,with an additional PTPRT mutation detected in the implanted lesion.Case 2:a 45-year-old male.The primary lesion was bilateral nodular goiter,and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus.No mutations were identified in the primary lesion,whereas the implanted lesion exhibited MEN1,GLIS3,EZH1,and KMT2C mutations.Case 3:a 42-year-old female.The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter.A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively.The primary lesion harbored TERT,GLIS3,and SPOP mutations,while the implanted lesion showed TERT,GLIS3,EIF1AX,and KMT2C mutations.Conclusions Endoscopic thyroid surgery is widely applied in clinical practice,however,implantation dissemination of thyroid lesions along surgical pathways may occur,encompassing both benign and malignant entities.Implanted lesions exhibit pathological similarities to their primary counterparts,but demonstrate mutational enrichment.

Objective:To rapidly and accurately detect volumetric modulated arc therapy (VMAT) plans with potentially inaccurate radiation doses.Methods:The measurement-based dosimetric verification result of 196 VMAT plans obtained using ArcCHECK phantoms were retrospectively collected. Independent dosimetric calculation and verification were conducted for these plans using the ArcherQA system based on a fast Monte Carlo algorithm. The gamma passing rates of dosimetric verification using ArcCHECK phantom and the ArcherQA system were compared, followed by their correlation analysis and linear regression fitting. The ArcherQA system′s gamma passing rate threshold used to detect positive dosimetric verification result obtained using ArcCHECK phantoms, as well as the specificity of the detection, were calculated. Based on this gamma passing rate threshold, another 50 VMAT plans were selected as a test set to assess the ArcherQA system′s ability to detect positive measurement-based dosimetric verification result.Results:The average gamma passing rates for the dosimetric verification of the VMAT plans using the ArcherQA system and ArcCHECK phantoms were 97.28% and 96.57% (3%/3 mm, TH=10%), respectively. Both rates had a correlation coefficient of 0.71 ( P < 0.01) and a linear fitting coefficient of 0.54 ( R2=0.51). When the gamma passing rate for dosimetric verification using ArcCHECK phantoms was set at 90% (3%/2 mm, TH=10%), the gamma passing rate threshold for dosimetric verification using the ArcherQA system should be adjusted to 94.8% to detect all VMAT plans with positive dosimetric verification result obtained using ArcCHECK phantoms, with a specificity of 67.8%. Using this threshold, the ArcherQA system detected all VMAT plans in the test set for which ArcCHECK phantom-based measurement yielded positive dosimetric verification result. Conclusions:By determining an appropriate gamma passing rate threshold, the ArcherQA system can rapidly and accurately detect VMAT plans with potentially inaccurate doses, thus ensuring treatment accuracy and improving work efficiency.

As one of the most common mental disorders, depressive disorder mainly manifests as depressed mood and loss of pleasure. The occurrence and development of depressive disorder are influenced and regulated by many factors. Scientific research and clinical practices have shown that estrogen plays a crucial role in the onset and progression of depressive disorder. From adolescence, estrogen fluctuation causes gender differences in the incidence of depressive disorder between male and female patients, and the differences become even more pronounced during menopause. This paper reviewed the research progress of estrogen levels in the pathogenesis and treatment of depressive disorder to provide new directions for further research on the mechanisms of occurrence and development and the clinical treatment of the disorder.

As one of the most common mental disorders, depressive disorder mainly manifests as depressed mood and loss of pleasure. The occurrence and development of depressive disorder are influenced and regulated by many factors. Scientific research and clinical practices have shown that estrogen plays a crucial role in the onset and progression of depressive disorder. From adolescence, estrogen fluctuation causes gender differences in the incidence of depressive disorder between male and female patients, and the differences become even more pronounced during menopause. This paper reviewed the research progress of estrogen levels in the pathogenesis and treatment of depressive disorder to provide new directions for further research on the mechanisms of occurrence and development and the clinical treatment of the disorder.

Background and Objectives: Mesenchymal stem cells (MSCs) have the multipotent capacity to differentiate into multiple tissue lineages as well as to self-renew, which is the main origin of adipocytes. IL6/IL6R pathway exerts a significant role in tissue regeneration and cell differentiation. Whereas, the underlying mechanism between IL6/IL6R pathway and MSCs adipogenesis differentiation remains elusive. Methods: MSCs from healthy donors were cultured in adipogenesis differentiation medium for 0∼14 days, during which their adipogenesis differentiation degree was evaluated by Oil Red O staining. The expression of IL6R was detected in MSCs during adipogenesis differentiation. Knockdown and overexpression of IL6R were respectively performed using siRNA and lentivirus to investigate its effect on MSCs adipogenesis differentiation. The adipogenesis marker genes expression and MAPK pathway activation were detected by Western blotting. The role of P38 pathway in the adipogenesis differentiation of MSCs was determined using the specific inhibitor SB203580. Results: The expression of IL6 and IL6R increased during adipogenesis differentiation in MSCs, which were positively correlated with Oil Red O quantification result. Knockdown and overexpression experiments demonstrated a positive correlation between the expressions of IL6R and MSCs adipogenesis differentiation, accompanied by same trend of P38 phosphorylation. Besides, the specific P38 inhibitor SB203580 markedly inhibited the adipogenesis differentiation potential of MSCs. Conclusions This study reveals IL6R facilitates the adiogenesis differentiation of MSCs via activating P38 pathway.

Objective: To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods: From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay. Results: The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1. Conclusion miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.