Objective To investigate the effect of fluid flow shear stress(FFSS)on the fluid mechanic threshold of high-mobility group box 1(HMGB1)release by synovial cells and chondrocytes.Moreover,the mechanism of chondro-cyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis.Methods With the approval of the Ethics Committee for Animal Experiments of the hospital,synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley(SD)rats,and synovial cells and chondrocytes were cultured and digested for subsequent experiments.Synovial cells and chondrocytes of 3-4 generations were acquired,and FFSS was applied to sy-novial and cartilage cells using a fluid shear mechanical device.The cells were divided according to the FFSS values of different sizes.Synovial cells were stimulated for 1 h with 1,3,5,or 10 dyn/cm2 of FFSS,and chondrocytes were stimu-lated for 1 h with 4,8,12,or 16 dyn/cm2 of FFSS.Resting cultures(0 dyn/cm2)were used as the control group.Changes in the morphology of the cells were observed.The expression and distribution of HMGB1 and interleukin-1β(IL-1β)were observed by immunohistochemistry.The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELI-SA.The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot.Results With in-creasing FFSS,the synovial cells and chondrocytes gradually swelled and ruptured,and the number of cells decreased.With increasing FFSS,the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm.In synovial cells,compared with those in the control group,the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1,3,5 and 10 dyn/cm2 intervention groups(P＜0.01).In chondrocytes,com-pared with those in the control group,the expression levels of HMGB1 in the supernatant were increased in the 4,12 and 16 dyn/cm2 intervention groups(P＜0.05),and the protein expression levels of HMGB1 were significantly increased(P＜0.01).The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups(P＜0.01);however,the protein expression levels of HMGB1 were significantly decreased.Compared with those in the control group,the expression levels of IL-1β in the supernatant gradually increased in the 4,8,12 and 16 dyn/cm2 intervention groups(P＜0.01).With the exception of those in the 4 dyn/cm2 group,the protein expression levels of IL-1β gradually increased with increasing FFSS(P＜0.05).Conclusion With increasing FFSS,synovial cells and chondro-cytes gradually swelled and burst,and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2,respectively.Therefore,upon stimulation with a mechanical force,synovial damage was damaged before chondrocytes.

Objective:To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further.Methods:Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results:CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm 3]>ADDWR group [(1 747.34±369.42) mm 3]>ADDWoR group [(1 256.29±418.27) mm 3] [ t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm 2]>ADDWR group [(838.23±118.82) mm 2]>ADDWoR group [(669.14±150.26) mm 2] [ t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [ t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [ t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUC CV=0.77, AUC CSA=0.76; AUC SJS=0.76) for the NADP and ADDWoR groups, and (AUC CV=0.80; AUC CSA=0.80; AUC SJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC (NADP-ADDWR)=0.73, and AUC (ADDWR-ADDWoR)=0.69. Conclusions:CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.

Objective The stress variations during the wear process of an artificial knee joint were studied.Then,a signal acquisition system was designed to capture the vibration signals induced by the wear of knee joint prosthesis.The aim was to provide new technical means for online wear monitoring of the artificial knee joint.Methods To effectively collect vibration signals,the optimal installation position of the vibration sensors was determined by analyzing the dynamic model of the knee joint prosthesis during motion and identifying the main distribution areas of the tibial insert contact stress.The dynamic model of the femoral prosthesis was solved using Lagrangian equations.The torque variation curve of the femoral prosthesis was obtained to validate the effectiveness of finite element analysis.The signals collected by the vibration sensors installed at different positions in the friction wear experiments and the surface morphology in different areas were compared to verify the effectiveness of the acquisition system design and finite element analysis results.Results The stress concentration regions of the tibial pad under four degrees of freedom(flexion,internal and external rotation,anterior-posterior displacement,and up-and-down displacement)were obtained based on a dynamic simulation.A stress concentration was evident in the middle and posterior regions of the tibial pad.A vibration signal with a higher amplitude was collected when the vibration sensor was installed at the rear end of the tibial pad.This aided the vibration feature extraction of the knee joint prosthesis.Conclusions The vibration signal acquisition system designed based on the dynamic simulation analysis effectively collected the vibration signals generated by the artificial knee joint during the wear process.This study provides an important means for evaluating the wear mechanisms of artificial knee joints and monitoring their full-life health status.

Objective The stress variations during the wear process of an artificial knee joint were studied.Then,a signal acquisition system was designed to capture the vibration signals induced by the wear of knee joint prosthesis.The aim was to provide new technical means for online wear monitoring of the artificial knee joint.Methods To effectively collect vibration signals,the optimal installation position of the vibration sensors was determined by analyzing the dynamic model of the knee joint prosthesis during motion and identifying the main distribution areas of the tibial insert contact stress.The dynamic model of the femoral prosthesis was solved using Lagrangian equations.The torque variation curve of the femoral prosthesis was obtained to validate the effectiveness of finite element analysis.The signals collected by the vibration sensors installed at different positions in the friction wear experiments and the surface morphology in different areas were compared to verify the effectiveness of the acquisition system design and finite element analysis results.Results The stress concentration regions of the tibial pad under four degrees of freedom(flexion,internal and external rotation,anterior-posterior displacement,and up-and-down displacement)were obtained based on a dynamic simulation.A stress concentration was evident in the middle and posterior regions of the tibial pad.A vibration signal with a higher amplitude was collected when the vibration sensor was installed at the rear end of the tibial pad.This aided the vibration feature extraction of the knee joint prosthesis.Conclusions The vibration signal acquisition system designed based on the dynamic simulation analysis effectively collected the vibration signals generated by the artificial knee joint during the wear process.This study provides an important means for evaluating the wear mechanisms of artificial knee joints and monitoring their full-life health status.

Objective To preliminary investigate the clinical efficacy of whole brain simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in patients diagnosed with brain metastases ( BM) . Methods Fifty-two cases of BM admitted to our hospital from January 2016 to December 2017 were equally recruited and randomly divided into the observation and control groups. Patients in the observation group were treated with SIB-IMRT, and those in the control group received conventional whole brain radiotherapy (WBRT).The clinical efficacy and prognosis were statistically compared between two groups. Results The ORR in the observation group was 77％, significantly higher than 27％ in the control group (P=0. 00).The median survival in the observation group was 384 d,significantly longer compared with 211 d in the control group (P=0. 00).All patients in both groups successfully completed corresponding treatment. Acute adverse reactions were mainly 1-2 grade reactions. Conclusions SIB-IMRT is an efficacious and safe treatment of BM,which yields tolerable adverse events and deserves application in clinical practice.

OBJECTIVE: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD). METHODS: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work. CONCLUSION In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.
Adult ; Age of Onset ; Aged ; China ; Cross-Sectional Studies ; Delayed Diagnosis ; Female ; Hospitals, Public ; Humans ; Immunoglobulin G/analysis* ; Immunoglobulin G4-Related Disease/therapy* ; Lacrimal Apparatus/pathology* ; Male ; Middle Aged ; Referral and Consultation ; Salivary Glands/pathology*

Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.

Objective To investigate the distribution and incidence of hyperuricemia for the Zhoushan island residents in Zhe-jiang province and provide scientific advice for health management.Methods The uric acid reports of island residents were analyzed by a retrospective statistical analysis in the Physical Examination Center of the 413 Hospital from October 2013 to October 2015.The patients with metabolic diseases (such as diabetes,chronic renal failure and other people,etc.)were ex-cluded.According to the different gender and different age groups,the average level of uric acid,hyperuricemia occurrence rate and the difference among the groups were performed statistical analyses.The single factor analysis of variance was used by Microsoft 2003 Excel software.Results The average serum uric acid level of 7 310 island residents was 283±82μmol/L and the incidence of hyperuricemia was 21.2%.The incidence of hyperuricemia was 33.6% in 31~40 years group,and the average level of uric acid was 343±86μmol/L and significantly higher than≤30 years group,significant statistic difference were observed.The incidence of hyperuricemia was more than 15% in≥41 years group,significantly higher than≤30 years group.The population of physical examination was concentrated in the 31~40 years group.The hyperuricemia incidence was 27.9% in 5 214 male residents,and the average serum uric acid level was 368±74μmol/L and higher than the female group (P<0.001).The hyperuricemia incidence was as high as 43.1% in 31~40 years group.But the level of average serum uric acid showed no significant difference with≤30 years group(P>0.05).The level of average serum uric acid level was less in≥61 and 41~50 years group than in ≤30 years group (P<0.05),but the hyperuricemia incidence were higher than ≤30 years group.The incidence of hyperuricemia was 4.6% in 2 096 female residents.The level of average serum uric acid was 257±57μmol/L and lower than the male group in all age groups (P<0.001).The incidence of hyperuricemia was 18.6% in≥60 years old and lower than 10% in the other groups.The incidence of hyperuricemia increased gradually with age.Conclu-sion The hyperuricemia incidence in island residents was higher,and higher in male than in female.The occurrence of hype-ruricemia was significantly younger.Therefore,health education,reasonable diet adj ustment,improvement of lifestyle and eating habits etc.Should be conducted for a long time to prevent the occurrence of hyperuricemia and related diseases.

Objective To observe the effect of homemade ankle-foot orthopedic band on motor function of lower extremities in children with foot drop post spastic hemiplegic cerebral palsy (CP). Methods 24 spastic hemiplegic CP children were randomly divided into observation group (n=12) and control group (n=12). Both groups accepted roution rehabilitation training. The control group accepted walking training, and the observation group accepted walking training wearing the homemade ankle-foot orthopedic band, for 12 weeks. They were assessed with modified Ashworth Scale (MAS) of gastrocnemius, range of motion (ROM) of ankle active dorsiflexion, and D and E domains of Gross Motor Function Measure (GMFM-88) before and after treatment. Results The score of MAS significantly decreased in both groups after treatment (P<0.01), and decreased more in the observation group than in the control group (P<0.05). ROM and scores of D and E domains of GMFM-88 significantly increased in both groups after treatment (P<0.01), and increased more in the observation group than in the control group (P<0.05). Conclusion Walking training with the homemade ankle-foot orthopedic band may further decrease the muscle tone of gastrocnemius, increase the active range of motion of ankle and improve the motor function of lower extremities in children with foot drop post spastic hemiplegic CP.

OBJECTIVE To investigate the blocking activities of a series of potential α1-adrenoceptor (α1-AR) antagonists (Compounds B1 -B9) on α1-AR.METHODS ① A series of potential α1-adrenoceptor (α1-AR) antagonists,indolylpiperidine derivative (IPD) and Compounds B1 -B9,with indolylpiperidine moiety and different substitutes were synthesized through the coupling of indolylpiperidine and piperazine derivatives.② Inotropic responses experiment was used to examine blocking effects of IPD and Compounds B1 - B9 in isolated rat atria by phenylephrine (PE) stimulation.③ Blocking effect of IPD and Compounds B1 - B9 on phosphorylation level of extracellular signal-regulated kinase (ERK) in PE treated HEK293 cells was tested by Western blotting.RESULTS ① Potential α1-adrenoceptor (α1-AR) antagonists with indolylpiperidine moiety and different substitutes were synthesized successfully.② PE caused a dose-dependent inotropic response which was inhibited by pre-incubation of phentolamine (Phen),a non-selective α1-AR antagonist,IPD and Compounds B1,B3,B4,B7,B8 and B9,respectively; IPD and Compounds B4 and B8 caused an obvious rightward shift of inotropic response-curve,the pA2 values for IPD and Compounds B4 and B8 were 6.72 ± 0.21,6.86 ± 0.29 and 6.67 ± 0.19,respectively.③ Phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B1,B2,B3,B5,B6,B7,B8 and B9 or IPD in PE treated α1A-AR stably expressed HEK293 cells; PE-stimulated phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B2,B4,B7 or B8 in α1B-AR stably expressed HEK293 cells.CONCLUSION Compound B4 has a selective blocking activity on α1B-AR,and Compounds B1,B3,B5,B6 and B9 or IPD have a selective blocking activity on the phosphorylation level of ERK1/2.