1.Ferroptosis in bone diseases:therapeutic targets of osteoporosis
Heng XIE ; Ye GU ; Yingchu GU ; Zerui WU ; Tao FANG ; Qiufei WANG ; Yuqin PENG ; Dechun GENG ; Yaozeng XU
Chinese Journal of Tissue Engineering Research 2024;28(16):2613-2618
BACKGROUND:With the aging of the global population,the incidence rate of osteoporosis is also increasing.It is very important to further understand its pathogenesis and propose new therapeutic targets.Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases,such as inflammatory arthritis,osteoporosis and osteoarthritis. OBJECTIVE:To summarize the previous studies on the mechanism of ferroptosis in osteoporosis,so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS:The first author used the computer to search the documents published from 2000 to 2022 in CNKI,WanFang,VIP,PubMed and Web of Science with the key words of"ferroptosis,osteoporosis,osteoblasts,osteoclasts,iron chelators,reactive oxygen species,nuclear factor erythroid 2-related factor 2,heme oxygenase-1,glutathione peroxidase 4,review"in Chinese and English.A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:Ferroptosis is significantly different from necrosis,apoptosis and autophagy.In terms of cell morphology and function,it does not have the morphological characteristics of typical necrosis,nor does it have the characteristics of traditional apoptosis,such as cell contraction,chromatin condensation,the formation of apoptotic bodies and the disintegration of cytoskeleton.Contrary to autophagy,ferroptosis does not form a classical closed bilayer membrane structure(autophagic vacuole).Morphologically,ferroptosis is mainly manifested by obvious contraction of mitochondria,increased membrane density,and reduction or disappearance of mitochondrial cristae,which are different from other cell death modes.Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation,leading to osteoporosis.Iron overload interferes with the differentiation of stem cells to osteoblasts,leading to a weakened osteoblast function and further imbalance of bone metabolism in the body,which eventually leads to osteoporosis.Stimulated by iron overload,osteoclast bone resorption is enhanced and bone loss exceeds new bone formation.Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts.Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation.Antioxidants can prevent reactive oxygen species production and inhibit bone absorption,thus improving bone metabolism and effectively preventing osteoporosis.
2.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
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.
3.Analysis of infection of fungi, bacteria and Demodex in eyelid margin of non-blepharitis and blepharitis
Lulu WANG ; Shengtao SUN ; Xiaofei YU ; Qiufei MA ; Yanting XIE
Chinese Journal of Experimental Ophthalmology 2023;41(10):998-1003
Objective:To observe the distribution characteristics of fungi, bacteria and Demodex in the eyelid margin of patients with blepharitis and without blepharitis at different ages. Methods:A cross-sectional study was conducted.A total of 98 patients diagnosed with anterior blepharitis and 99 patients diagnosed with posterior blepharitis in Henan Eye Hospital from March 2021 to June 2022 were enrolled as anterior blepharitis group and posterior blepharitis, respectively.Additionally, 100 patients with an initial diagnosis of refractive error and 200 patients with vitreous opacity were enrolled during the same period as a non-blepharitis group.All patients underwent examinations for lid margin fungi, bacteria and eyelash Demodex, as well as fungal spores and ciliary Demodex count.The differences in the positive rate and load of palpebral fungi, bacteria and eyelash Demodex were compared between anterior and posterior blepharitis groups, as well as across different ages in non-blepharitis group.This study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[18]).All patients were informed about the purpose and methods of the study.Written informed consent was obtained from each patient. Results:There were significant differences in the positive rates of bacteria, fungi and Demodex and the load of Demodex in the non-blepharitis group at different ages ( χ2=28.34, 10.36, 51.57, H=35.66; all at P<0.01).The positive rates of palpebral bacteria and ciliary Demodex and the load of Demodex were significantly higher and the palpebral fungi positive rate was significantly lower in the ≥60 years old than in the <60 years old (all at P<0.05).There were significant differences in the positive rates of bacteria and fungi among anterior blepharitis, posterior blepharitis and non-blepharitis groups ( χ2=18.99, 6.36; all at P<0.01).The palpebral bacteria positive rate was significantly higher in anterior blepharitis group than in posterior blepharitis and non-blepharitis groups, and the palpebral fungi positive rate was significantly higher in anterior blepharitis and posterior blepharitis groups than in non-blepharitis group (all at P<0.05).There was no significant difference in the ciliary Demodex detection rate among the three groups ( χ2=0.16, P=0.74).The number of palpebral fungi spores and eyelash Demodex counts were higher in anterior and posterior blepharitis groups than in non-blepharitis group, and the differences were statistically significant (all at P<0.05).The positive rate of palpebral margin bacteria in ciliary Demodex-positive group was 45.7%(156/341), which was significantly higher than 25.6%(40/156) in ciliary Demodex-negative group ( χ2=17.20, P<0.01), and there was no significant difference in the positive rate of palpebral margin fungi between them ( χ2=0.11, P=0.70). Conclusions:In the population with normal eyelid margin, the infection of Demodex and bacteria in lid margin increases and fungal infection decreases in the ≥60 years old.Fungal and bacterial infections are the main sources of palpebral infection in patients with blepharitis, and positive detection of Demodex increases the chance of bacterial infection.
4.Advance in research of occlusal dysesthesia
Chinese Journal of Stomatology 2021;56(1):109-112
Occlusal dysesthesia (OD) or phantom bite syndrome refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. OD is a rare condition, and is usually associated with emotional distress and triggered by dental treatments. The diagnosis and management of OD patients still remains a major challenge for dental practitioners and affected patients. This topical review aims to describe the properties, etiologies, diagnosis, managements and prognosis of OD comprehensively.
5.Occlusion variation of posterior implant-supported single crown: a prospective 4-year follow-up study
Qian DING ; Qiang LUO ; Xiaoli LI ; Lei ZHANG ; Qiufei XIE
Chinese Journal of Stomatology 2021;56(3):244-250
Objective:To analyze the longitudinal variation of occlusal force distribution and occlusal contact time in posterior implant-supported single crown with the computerized occlusal analysis system.Methods:Partially edentulous patients who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology between December 2012 and December 2013, and had received implant-supported single crown in the posterior region were enrolled. The participants underwent occlusal examinations with the computerized occlusal analysis system at 2 weeks, 3 and 6 months, 1, 2, 3, and 4 years after implant prosthesis delivery. The relative occlusal force (ROF) of implant prostheses, mesial adjacent teeth, and control teeth (corresponding teeth on the contralateral side) were recorded, and implant prosthesis occlusion time ratios (implant prosthesis occlusion time/occlusion time) were calculated. The interproximal contact between implant prostheses and adjacent teeth was evaluated using metal contact gauge and dental floss. Mechanical complications of implant prostheses were recorded. The paired t test or Wilcoxon signed-rank test was used to compare the implant prosthesis occlusion time ratios and ROF of implant prostheses at 2 different times as a self-control. The differences in ROF between implant prostheses and control teeth in the same participant at the same time were also analyzed using paired t test. Using a complementary log-log model, the correlation between the occurrence of veneering material fracture and ROF of implant prosthesis was analyzed with gender, age and follow-up time as the control variables. Results:Thirty-seven posterior fixed implant-supported single crowns in 33 participants, including 16 men and 17 women aged (42.8±12.9) years (23.9 to 70.0 years) were followed up for 2 weeks to 4 years [(38.3±15.2) months]. The ROF of implant prostheses increased significantly ( P<0.01) from 2 weeks [(7.0±4.2)%] to 3 months [(9.9±6.8)%], whereas those of control natural teeth decreased significantly ( P<0.05) from (13.1±6.1)% to (11.4±5.5)%. The ROF of implant prostheses continued to increase from 6 months to 1 year, from 1 year to 2 years and from 2 years to 3 years, with significant differences ( P<0.05). Implant prosthesis occlusion time ratios also increased significantly between 2 weeks and 3 months and between 3 months and 6 months ( P<0.05). No significant differences were found between other time points ( P>0.05). For comparison between implant prosthesis and control teeth at the same time point, the ROF of the implant prostheses [(7.5±4.2)%] were significantly lower than those of the control teeth [(13.8±6.0)%] at 2 weeks ( P<0.01). While at 4 years, ROF of implant prostheses [16.7% (8.6%, 32.4%)] became significantly higher than those of control teeth [9.5% (4.9%, 18.0%)] ( P<0.05). ROF of the implant prostheses did not differ significantly with those of the control teeth in other follow-up time points ( P>0.05). The 4-year cumulative incidence of proximal contact loss rate was 32% (22/68). The incidences of veneering material fracture and prostheses loosening were 16% (6/37) and 8% (3/37), respectively. Logistic regression showed a significant correlation between veneering material fracture and ROF of implant prostheses ( r=0.26, P<0.05). Conclusions:The occlusal force and occlusal contact time of posterior implant-supported single crown change over time in 4-year follow-up period, which is mainly reflected in the increasing occlusal force and occlusal contact time. The occlusion of posterior implant prostheses should be carefully monitored during follow-up examinations, and occlusal adjustment should be considered when necessary.
6.Adenosine triphosphate induced odontoblastic differentiation of human dental pulp cells in vitro and in vivo
Xiaosong YI ; Yuzhou LI ; Siyi MO ; Qiufei XIE
Chinese Journal of Stomatology 2020;55(6):394-401
Objective:To choose a suitable efficient concentration of adenosine triphosphate (ATP) which can induce human dental pulp cells (HDPC) differentiate into odontoblast successfully, and explore the role of this concentration of ATP in dentin regeneration in vivo. Methods:HDPC were treated with different concentrations (0, 10, 400, 600, 800 μmol/L) of ATP. Then cell counting kit-8 (CCK-8), quantitative real-time PCR, and Western blotting were used to detect the cell proliferation and the expressions of odontoblastic differentiation related markers, dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP). Alizarin red S staining experiment was used to analyze the effect of ATP on the mineralization ability of HDPC. By the above experiments, the suitable effective concentration of ATP was chosen to pretreat the HDPC for 7 days, then cells were seeded on gelfoam, inserted into the root canal fragment, and subsequently transplanted into the subcutaneous space on the back of immunodeficient mice, after three months, the samples were stained with HE for histological analysis.Results:The CCK-8 results in 5 d showed that 10 μmol/L ATP obviously promoted the proliferation of HDPC, while the 600 and 800 μmol/L ATP apparently inhibited the HDPC proliferation, however, the proliferation in 800 μmol/L ATP group was lower than that of 600 μmol/L ATP group ( P<0.05). qPCR and Western blotting results showed that the 600 and 800 μmol/L ATP significantly up-regulated the DMP1 and DSPP expressions ( P<0.05), furthermore, there was no significant difference in the two groups, but no changes were found in other groups ( P>0.05). After 21 days of culturing, there were obvious mineralization nodules in 600 and 800 μmol/L ATP groups, but no mineralization nodules in other groups. Quantitative analysis of the staining results showed the A value in 0, 10, 400, 600, and 800 μmol/L ATP groups were respectively 1.05±0.15, 1.11±0.23, 1.15±0.17, 3.65±0.30, and 3.40±0.43, and the A value in 600 and 800 μmol/L ATP groups were higher than those of other groups; however, there was no difference in 600 and 800 μmol/L ATP groups. The histological analysis showed that 600 μmol/L ATP could induce the HDPC differentiate into dentin-like structure in the root canal fragment. Conclusions:Therefore, the suitable effective concentration of ATP is 600 μmol/L, which could induce HDPC differentiate into odontoblast-like cells, and form the dentin-like structure in vivo.
7. Present situation and future of occlusal splint in treatment of oral diseases
Chinese Journal of Stomatology 2019;54(8):515-521
Occlusal splint is a removable device for the treatment of oral and maxillary diseases with reversible occlusal treatment property. When patients wear the occlusal splint, the occlusal contact state can be changed and the position of the lower jaw may be adjusted, with the improvement of functions of temporomandibular joints and masticatory muscles. There are various types of occlusal splints, among which stabilization splint, soft occlusal splint and repositioning splint are widely used in the treatment of temporomandibular disorders and night bruxism. For the patients requiring occlusal reconstruction, occlusal splint can be used as an important means to adjust and verify the therapeutic jaw position. As a major trend of research in future, the digital design and production of occlusal splint are still in the initial stage and need to be further improved.
8.Influence of occlusal interferences on the activation of trigeminal-spinal nucleus astroglia and microglia in rats
LIU Cunrui ; CAO Ye ; XU Xiaoxiang ; XIE Qiufei
Journal of Prevention and Treatment for Stomatological Diseases 2018;26(12):766-772
Objective:
To investigate the morphological changes in microglia and astroglia before and after the removal of occlusal interferences in rats and to further understand whether astroglia and microglia activation is involved in experimental occlusal interference-induced masticatory muscle pain.
Methods:
Male Sprague-Dawley rats (200-220 g) were used. Crowns of two heights (0.2 mm and 0.4 mm) were bonded to the right maxillary first molars to establish experimental rat models of occlusal interference. The rats were randomly assigned to one of five groups of twelve rats each: sham-occlusal interference control group, 0.4 mm occlusal interference group, 6-day removal of 0.4 mm occlusal interference group, 0.2 mm occlusal interference group, and 6-day removal of 0.2 mm occlusal interference group. The rats were sacrificed by transcardiac perfusion after deep anesthetization on days 3, 5, 7, and 14. Brain stem sections were obtained and processed for immunofluorescence staining of GFAP and OX-42. Expression levels were semiquantitatively analyzed.
Results:
① Based on the markers OX-42 and GFAP, trigeminal-spinal nucleus (Vsp) microglia and astroglia showed no activation in the sham-occlusal interference control group. ② In the 0.4 mm and 0.2 mm occlusal interference groups, Vsp microglia and astroglia showed mild to moderate activation after 3-7 days of occlusal interference. Vsp astroglia remained activated on day 14, but Vsp microglia did not. At the same time point, the 0.4 mm occlusal interference group had greater activation than the 0.2 mm occlusal interference group. ③ In the 6-day removal of 0.4 mm and 0.2 mm occlusal interference groups, microglia and astroglia activation decreased after removal of the occlusal interference. Vsp astroglia remained activated on day 14, but microglia showed no activation.
Conclusion
Microglia and astrocyte activation is induced in the Vsp after experimental occlusal interference. The astrocytes remained activated for longer than the microglia. The glia activation level is closely related to the intensity of occlusal interference.
9.Influence of the occlusal interference time on masticatory muscle mechanical hyperal-gesia in rats
Cunrui LIU ; Xiaoxiang XU ; Ye CAO ; Qiufei XIE
Journal of Peking University(Health Sciences) 2016;48(1):51-56
Objective:To investigate the relationship between the removal time of 0.2 mm occlusal in-terference and the recovery of masticatory muscle mechanical hyperalgesia in rats.Methods:Forty male Sprague-Dawley rats (200-220 g)were randomly assigned to eight groups,with five rats in each group:(1 )nave group:these rats were anesthetized and their mouths were forced open for about 5 min (the same duration as the other groups),but restorations were not applied;(2 )sham-occlusal interference control group:bands were bonded to the right maxillary first molars which did not interfere with occlu-sion;(3 )occlusal interference group:0.2 mm thick crowns were bonded to the right maxillary first molars;(4)2,3,4,5,and 6 d removal of occlusal interference groups:0.2 mm thick crowns were bonded to the right maxillary first molars and removed on days 2,3,4,5,and 6.The nave group and sham-occlusal interference control group were control groups.The other groups were experimental groups. Bilateral masticatory muscle mechanical withdrawal thresholds were tested on pre-application days 1 ,2, and 3,and on post-application days 1 ,3,5,7,1 0,1 4,21 and 28.The rats were weighed on pre-application day 1 and on post-application days 1 ,2,3,4,5,6,and 7.Results:Between the nave group and the sham-occlusal interference control group,there was no significant difference in the mastica-tory muscle mechanical withdrawal threshold of bilateral temporalis and masseters at each time point.No significant difference was detected between the contralateral side and ipsilateral side in experimental groups (P>0.05 ).In the 2,3,4,and 5 d removal of occlusal interference groups,the masticatory muscle mechanical withdrawal thresholds decreased after occlusal interference and increased after removal of the crowns and recovered to the baseline on days 7,1 0,1 4,and 1 4,respectively [the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (1 37.46 ±2.08)g,(1 39.02 ± 2.1 1 )g,(1 40.40 ±0.98)g,(1 38.95 ±0.98)g,respectively].In the 6 d removal of occlusal inter-ference group,the masticatory muscle mechanical withdrawal threshold increased after removal of the crowns and became stable since day 1 4.There was a significant difference between the 6 d removal of oc-clusal interference group and the sham-occlusal interference group on day 28(P<0.05),the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (1 31 .24 ±0.76 ) g and (1 41 .34 ±1 .43)g,respectively.Conclusion:After removal of the 0.2 mm thick crown within 5 days, the mechanical hyperalgesia of the rats could reverse completely.The mechanical hyperalgesia of the rats could only be relieved,but not reverse completely after removal of the 0.2 mm thick crown on day 6.As the time went on,even minor occlusal interference could cause irreversible mechanical hyperalgesia of masticatory muscles.This study suggested that occlusal interference caused by dental treatment should be eliminated as soon as possible,to avoid irreversible orofacial pain.
10.Three-dimensional finite element analysis of influence of occlusal surface height on stress distribution around posterior implant-supported single crown
Xu ZHAO ; Lei ZHANG ; Jian SUN ; Zhenyu YANG ; Qiufei XIE
Journal of Peking University(Health Sciences) 2016;48(1):94-100
Objective:To evaluate the effect of the occlusal surface height of a mandibular posterior implant-supported single crown on stress in bone tissues.Methods:Three-dimensional finite element models of the implant-supported single crown replacing the missing right lower second premolar,mesial and distal natural teeth,periodontal membrane,alveolar bone,loaded rigid body and analog food of almond were established.Using the Federation Dentaire International (FDI)system,the first premolar, the second premolar and the first molar were represented with 44,45,46.Three occlusal surface heights of the crown were studied:(1 )normal height;(2)1 5 μm reduction in height;(3)30 μm reduction in height.The models were loaded by independent loading with maximal occlusal force(44 by 280 N,45 by 360 N,and 46 by 480 N)and average occlusal force(44 by 1 40 N,45 by 1 80 N,and 46 by 240 N)on the single crown;combined loading (maximal occlusal force transformed into uniform load of 3 .7 MPa on top of rigid body,in contact with points on the occlusal surface),and analog almond-like food loading (average occlusal force transformed into uniform load of 1 .67 MPa in simulated food chewing,in contact with points on the occlusal surface).Results:For maximal biting force under independent loading,Von Mises stress peak values in bone tissues around 44,45,and 46 were 82.57 MPa,45.26 MPa and 27.79 MPa;For average biting force,peak values were 41 .28 MPa,22.63 MPa and 1 3.89 MPa.Under com-bined loading,compared with the normal occlusal surface height group,Von Mises stress peak values de-creased 4.6 MPa,by 0.84%;increased 7.52 MPa,by 20.04%,and decreased 1 .8 MPa,by 5.84%, for 45,46,and 44 in the 30 μm infra-occlusion group,respectively.Under food loading,Von Mises stress peak values decreased 0.34 MPa,by 1 .62%;increased 1 .1 1 MPa,by 2.66%;and increased 0.06 MPa,by 0.54%,and for 45,46,and 44 in the 30 μm infra-occlusion group,respectively.Con-clusion:Within the limitation of this study,within 30 μm reduction of the occlusal surface height of im-plant-supported single crown,no significant difference of the peak values was observed.


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