Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective This study aims to establish a regional digitalized venous thromboembolism(VTE)prevention and control model with the support of the VTE Quality Control Center in Hangzhou to enhance the standardized prevention and re-gional treatment level.Methods The research was carried out from four aspects:constructing organizational structure,formula-ting implementation standards,promoting operational mechanisms,and building intelligent supervision platforms.A statistical a-nalysis was conducted to the data on the intelligent supervision platforms of three medical institutions.Results From January 2022 to June 2023,the VTE risk assessment of inpatients in the three medical institutions gradually became standardized,with an assessment rate exceeding 93％.The rates of VTE risk assessment within 24 hours of admission,dynamic assessment of VTE,and the proportion of VTE with moderate to high risk all showed significantly increasing trends.The standardized prevention rate of VTE remained around 60％.The incidence of relevant VTE within the hospital decreased from 1.82％to 0.41％,with a de-crease rate of over 70％.Conclusion The regional digitalized VTE prevention and control management model contributes to im-proving the standardized prevention and treatment level of VTE and reducing the incidence of hospital-related VTE in the region.

Ferroptosis is a form of programmed cell death characterized by iron metabolic imbalance and lipid peroxidation.Alzheimer disease(AD)is a neurodegenerative condition.Studies have shown that lipid peroxidation through ferroptosis plays a significant role in the progression of AD.Ferroptosis suppressor protein 1(FSP1)/coenzyme Q10(CoQ10)signaling axis serves as a crucial regulatory element in the process of lipid peroxidation associated with ferropto-sis.This review explores the mechanisms of the FSP1/CoQ10 signaling axis in AD,aiming to present a novel therapeutic ap-proach for AD treatment.

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

Objective: To investigate whether grain-sized moxibustion at Xinshu (BL15) and Shenshu (BL23) can alleviate cognitive decline and other pathologic features in early-stage Alzheimer disease (AD) using transgenic mice with 5 familial AD mutations (5XFAD). Methods: The genotype of transgenic mice was detected by polymerase chain reaction. A total of 40 transgenic mice (1.5 months old) were randomly and equally allocated to an AD model group (5XFAD group) or a grain-sized moxibustion group (5XFAD + GM group), with 20 wild-type (WT) mice (C57BL/6J) serving as the normal control group (WT group). Mice in the 5XFAD + GM group were treated by grain-sized moxibustion at bilateral Xinshu (BL15) and Shenshu (BL23). Mice in the WT group and 5XFAD group received no treatment but were restrained to ensure exposure to a similar experimental condition. Cognitive function and memory were assessed with the Morris water maze and Y-maze tests. The amyloid β 40 (Aβ40) and amyloid β 42 (Aβ42) levels in the brain were evaluated by enzyme-linked immunosorbent assay; amyloid plaque deposition in brain tissue sections was detected by thioflavin-S staining; the expression of glial fibrillary acidic protein (GFAP), cluster of differentiation 11b (CD11b), brain-derived neurotrophic factor (BDNF), and choline acetyltransferase (ChAT) in the hippocampus and prefrontal cortex was analyzed by immunohistochemistry. Results: In the Morris water maze test, compared with the 5XFAD group, mice in the 5XFAD + GM group had a shorter escape latency and more target area crossings and spent more time in the target quadrant (P<0.05). In the Y-maze test, compared with the 5XFAD group, the number of training times of the 5XFAD + GM group was significantly decreased (P<0.05), together with more correct responses (P<0.05). Compared with the 5XFAD group, the levels of Aβ40 and Aβ42 in the brain tissue of the 5XFAD + GM group were significantly lower (P<0.05); in the hippocampus and prefrontal cortex, the total number of amyloid β plaque deposition were significantly lower (P<0.05); the expression levels of GFAP and CD11b were significantly reduced (P<0.05); and the expression levels of ChAT and BDNF were significantly increased (P<0.05).Conclusion: Grain-sized moxibustion at Xinshu (BL15) and Shenshu (BL23) greatly improves learning and memory functions, decreases the levels of Aβ40 and Aβ42, inhibits amyloid β plaque deposition, decreases the expression of GFAP and CD11b, and increases the expression of ChAT and BDNF in AD mice to inhibit the progression of AD.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective: To understand the occupational hazard and distribution of silica dust (free SiO₂≥10%) in the workplace environment of the enterprises in Fengxian District, and to provide scientific basis for improving the working environment and protecting the physical and mental health of the workers. Methods: Individual sampling monitoring and on-site labor hygiene investigation were conducted on 421 workers involved in 87 silicon dust enterprises in the jurisdiction from 2014 to 2018, and measured concentration-time weighted average (C_TWA) . Results: The results showed that the range of the C_TWA was (0.021~17.000) mg/m³, the median was 1.600 mg/m³, and the qualified rate of 30.88%. The difference of total dust concentration was statistically significant in different years (Z=38.831, P<0.05) . The qualified rate of small-scale enterprises is higher than that of medium-scale enterprises (χ²=9.472, P<0.05) . The qualified rate of other domestic enterprises is higher than that of private enterprises and foreign enterprises (χ²=10.089, P<0.05) . The acceptance rate of metal products manufacturing is lower than that of general equipment manufacturing and other manufacturing enterprises (χ²=64.626, P<0.05) . The qualification rate of natural ventilation is higher than that of mechanical ventilation (χ²=6.278, P<0.05) . Conclusion The enterprises involved in silicon production in Fengxian District need to further strengthen the production process reform and improve the ventilation and dust removal protection measures. Widely carry out the publicity of occupational disease prevention and control law, conduct targeted pre-job training, improve workers' awareness of self-protection, and protect the occupational health of workers in many ways.

Collagen is the building component of temporomandibular joint (TMJ) discs and is often affected by inflammation in temporomandibular disorders.The macromechanical properties of collagen are deteriorated by chronic inflammation.However,the mechanism by which inflammation influences disc function remains unknown.The relationship between the ultrastructure and nanomechanical properties of collagen in inflamed discs should be clarified.Seven-week-old female Sprague-Dawley rats were randomly divided into two groups.Chronic TMJ inflammation was induced by intra-articular injection of complete Freund's adjuvant,and samples were harvested after 5 weeks.Picrosirius staining revealed multiple colours under polarized light,which represented alternative collagen bundles in inflamed discs.Using atomic force microscopy scanning,the magnitude of Young's modulus was reduced significantly accompanied with disordered collagen fibril arrangement with porous architecture of inflamed discs.Transmission electron microscopy scanning revealed a non-uniform distribution of collagen fibres,and oversized collagen fibrils were observed in inflamed discs.Fourier transform infrared microspectroscopy revealed a decrease in 1 338 cm-1/amide Ⅱ area ratio of collagen in different regions.The peak positions of amide Ⅰ and amide Ⅱ bands were altered in inflamed discs,indicating collagen unfolding.Our results suggest that sustained inflammation deteriorates collagen structures,resulting in thedeterioration of the ultrastructure and nanomechanical properties of rat TMJ discs.

Objective To study the protective effect of human urinary kallidinogenase (HUK) on focal cerebral ischemia-reperfusion injury in rats via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Methods Eighty adult male SD rats were randomly divided into sham-operated group,model group,HUK group and LY294002 group (n=20).The rat focal cerebral ischemia-reperfusion models in the latter three groups were established by suture-occluded method;model group and HUK group were,respectively,injected with sterile saline or HUK 1.0 mL/kg via tail vein 3 h after reperfusion;rats in the LY294002 group accepted intraventricular injection of 10 nmol LY294002 before cerebral ischemia and caudal vein injection of 1.0 mL/kg HUK three h after reperfusion.Twenty-four h after reperfusion,Neurological Deficit Scale was performed,cerebral infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and protein expressions of Akt,phosphorylated (p)-Akt and Caspase-3 were assessed by Western blotting.Results As compared with those in the model group,the Neurological Deficit Scale scores were significantly lower,cerebral infarct volumes were significantly smaller,p-Akt expression was significantly increased,and Caspase-3 expression was significantly decreased in the HUK group (P＜0.05).As compared with those in the HUK group,Neurological Deficit Scale scores were significantly higher,infarction volumes were significantly increased,p-Akt expression was significantly decreased,and Caspase-3 expression was significantly increased in the LY294002 group (P＜0.05).Conclusion HUK has neuro-protective effect through up-regulating p-Akt expression in the PI3K/Akt signaling pathway and down-regulating Caspase-3 expression.