PURPOSE: To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI. METHODS: In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05. RESULTS: The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001). CONCLUSION 4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals ; Synovitis/etiology* ; Mice ; Osteoarthritis/etiology* ; Disease Models, Animal ; Male ; Succinates/pharmacology* ; Mice, Inbred C57BL ; X-Ray Microtomography

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

Circadian rhythm refers to the daily rhythmic variations in an organism. The irregular lifestyles of modern humans have led to a high incidence of chronic diseases, highlighting an inseparable relationship between disrupted circadian rhythm and disease development. TCM has long discussed rhythmic variations, with records dating back to the Yellow Emperor's Inner Canon(Huang Di Nei Jing), which laid a rich theoretical foundation for the research on circadian rhythm. Modern medical research has provided a more comprehensive explanation of its molecular mechanisms. This article integrated the current understanding of circadian rhythm in both Chinese and western medicine, emphasizing the crucial relationship between rhythm regulation and disease treatment. By highlighting the interdisciplinary nature of the two fields, it offers new directions for exploring the field of chronomedicine.
Humans ; Medicine, Chinese Traditional ; Acupuncture Therapy ; Circadian Rhythm ; Biomedical Research ; Polygonatum

Objective To explore the clinical effect of the semi-shoulder arthroplasty in the treatment of humeral head necrosis.Methods Twenty patients with head necrosis of the humerus in first hospital affiliated to army medical university from February 2008 to January2018 were collected, including 8 cases of males, 12 cases of females, 7 cases of left shoulder and 13 cases of right shoulder.The patients were aged from 45 to 83 years old, mean (67.40±5.06) years old.All patients were followed up for at least 6 months, the anterior flexion angle, abduction angle, external rotation angle and internal rotation angle of shoulder joint were measured, the function of shoulder joint was evaluated by ASES, UCLA, SST, and VAS, and the imaging examination was conducted.Results All patients were followed up for 6 to 37 months after surgery, with average (18.50±5.31) months, 2 patients presented mild pain during shoulder joint activity, 1 patient presented brachial plexus nerve damage, but returned to normal 3 months after surgery.No complication happened.X-ray reexamination showed good position and angle of the prosthesis during the follow-up period.The preoperative anteflexion angle, angle of outreach, swing angle and swing angle of the shoulder joint were respectively (55.24±8.21) °, (42.58±6.21) °, (12.95±2.74) °, (17.79±3.65) °, the last follow-up were respectively (120.76±13.15) °, (103.08±10.54) °, (33.51±3.14) °, (50.10±7.25) °, the differences were significant (P＜0.01);The preoperative ASES score, UCLA score, SST score, VAS score of the shoulder joint were respectively (38.24±5.21), (12.58±3.93), (3.25±1.42), (6.79±1.65), the last follow-up were respectively (75.74±9.69), (33.08±4.5), (9.11±1.85), (1.45±0.24), the differences were significant (P＜0.01).Conclusion Artificial semi-shoulder replacement for the treatment of humeral head necrosis can significantly improve the range of limb function, relieve the pain symptoms of patients and improve patients'quality of life, which has excellent and good shoulder function rate and fewer complications.

Accessory navicular source flatfoot is one of the foot deformity of clinical common disease,its treatment method is more controversial, differences in clinical efficacy of different surgical methods, according to accessory navicular source flatfoot symptoms of surgical treatment,there is no uniform standard, around a pair of accessory navicular excision how to reconstruct the arch produced a series of operation methods, the clinical curative effect of different operative methods produce also different, how to develop the operation strategy, choose operation method, and after acessory navicular excision whether to rebuild posterior tibial tendon, how to rebuild, the problems such as how to rebuild is the research hotspot and difficulty, looking forward to further research.
Flatfoot ; diagnosis ; surgery ; Foot Diseases ; surgery ; Humans ; Reconstructive Surgical Procedures ; methods ; Tarsal Bones ; abnormalities ; surgery

A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit.
Anaphase-Promoting Complex-Cyclosome ; Bone Neoplasms ; metabolism ; pathology ; Cadherins ; genetics ; metabolism ; Cdc20 Proteins ; Cell Cycle Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Exodeoxyribonucleases ; genetics ; metabolism ; HEK293 Cells ; Humans ; Mitosis ; Osteosarcoma ; metabolism ; pathology ; Ubiquitin-Protein Ligase Complexes ; genetics ; metabolism

Ankle Injuries ; diagnosis ; surgery ; therapy ; Ankle Joint ; surgery ; Humans ; Joint Instability ; diagnosis ; surgery ; therapy

Adult ; Arthroscopes ; Bone Cysts ; surgery ; Bone Neoplasms ; surgery ; Female ; Humans ; Talus ; surgery

OBJECTIVE: To compare protein levels of pro-inflammatory factors and bone formation mediators in the fibrous cap and shoulder region of non-calcified and calcified carotid endarterectomy (CEA) plaques. METHODS: Twenty-two CEA plaques were classified as non-calcified and calcified groups (n=11 each) in accordance with the American Heart Association (AHA) consensus in 1995. To make frozen sections and H&E staining using plaque, the mean percent of carotid stenosis and calcification area was determined by quantitative histomorphometry. The protein levels of pro-inflammatory interleukin-8 (IL-8), monocyte chematactic protein-1 (MCP-1), bone formation mediators bone morphogenetic protein-6 (BMP-6), and osteocalcin in the fibrous cap and shoulder region of plaques were determined by western blot and were quantified using ImageJ software. RESULTS: MCP-1 and IL-8 protein were 1.3 (P>0.05) and 1.5 (P<0.05) folds greater in the non-calcified plaques than those in the calcified plaques. BMP-6 and osteocalcin protein were 1.3 (P>0.05) and 2.1 (P<0.01) folds greater in the calcified plaques compared with those of the non-calcified plaques. CONCLUSION Inflammation is more likely to occur in non-calcified carotid plaques, and calcification in the plaques may be associated with bone formation, which indicates that decreased inflammation may be the beginning of calcification in carotid atherosclerotic plaques.
Atherosclerosis ; complications ; metabolism ; pathology ; Bone Morphogenetic Protein 6 ; metabolism ; Calcinosis ; metabolism ; pathology ; Carotid Stenosis ; etiology ; metabolism ; pathology ; Chemokine CCL2 ; metabolism ; Endarterectomy, Carotid ; Humans ; Inflammation ; metabolism ; pathology ; Interleukin-8 ; metabolism