Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Since 1986, the WHO has held ten global health promotion conferences covering various health promotion issues and sustainable development worldwide. These sessions have formed a series of consensus and actions that guide promoting health globally. This study analyzed the declarations, reports, and news materials from the ten conferences that studied health promotion action areas, focal topics, actor networks, partnership relationships, and other significant outcomes. It also explored how these conferences contributed to the construction and advancement of global health promotion consensus and actions. The first Global Conference on Health Promotion identified the concept of health promotion and five key action areas, laying the foundation for subsequent conferences and health promotion actions. Over the years, the ten conferences continuously expanded the essence of health promotion, developed partnership relationships, formulated public health promotion policies, and called for health promotion actions. This process culminated in the formation of global consensus and collective actions. The latter conferences have gained significant attention and influence. The conferences offer valuable insights for future global health promotion endeavors and provide global perspectives and pathways for the development of Healthy China.

Objective:This study analyzed how the 10 Global Conferences on Health Promotion have played a significant role in shaping and promoting a worldwide consensus and actions on health promotion,effectively addressing diverse health challenges that evolved over different periods. Methods:The textual analysis method was used in this study and text encoding was conducted to systematically examine the declarations and reports presented by the 10 Global Conferences on Health Promotion held during 1986-2021.We summarized the themes and key achievements,and key vocabulary in the conference declarations was extracted and analyzed to construct the global health promotion consensus and actions. Results:The fundamental principles of the conferences are to foster consensus and initiate actions in the realm of health promotion on a global scale.The primary purpose and goal are to promote health from regional to global.Significantly,our findings highlight a transition in the primary actors driving health promotion.It underscores a shift in health promotion from being driven primarily by organizations like the World Health Organization,governments,and international bodies,to a more inclusive approach involving non-governmental organizations and the general public.This development implies that health promotion has evolved into a collective global en-deavor,demanding the proactive involvement of various stakeholders,and forging new alliances in public health.Meanwhile,the coronavirus disease 2019(COVID-19)pandemic has further shaped the landscape of health pro-motion,underscoring the need for intensified focus on areas including disease prevention,health education,and the integration of digital health technologies,and emphasizing the importance of a multidimensional,responsive approach in public health initiatives. Conclusions:Sustained collaboration and innovative strategies are pivotal to advancing health promotion globally.Countries,together with public and private entities,should intensify cooperation.Multisectoral collaboration among partners such as healthcare,education,social security,and the industry is vital for health promotion and achieving global health goals.

Objective:Through determination of urinary arsenic metabolites in high water arsenic exposed areas of Jilin and Shanxi provinces, to explore the mode and possible influencing factors of arsenic metabolism in different populations.Methods:From October 2018 to August 2019, a cluster sampling was carried out in villages (arsenic in drinking water ≥0.05 mg/L) of some townships (towns) in Lyuliang City, Shanxi Province and Baicheng City, Jilin Province for epidemiological investigation and general health examination. The residents over 35 years old drinking water from local centralized water supply and small well water sources were selected as arsenic exposure group, and people (nearby low-arsenic water source areas) with the same diet and living habits and similar economic conditions were selected as control group. Urine samples were collected. Liquid chromatography-atomic fluorescence spectrometry(LC-AFS) technology was used to separate and detect 4 species of arsenic compounds, including trivalent inorganic arsenic (iAs Ⅲ), pentavalent inorganic arsenic (iAs Ⅴ), methylated arsine (MMA), and dimethylated arsine (DMA). Total arsenic (tAs), inorganic arsenic percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), primary methylation index (PMI) and the secondary methylation index (SMI) were calculated. The influencing factors of arsenic metabolism were analyzed by multiple linear regression. Results:A total of 1 415 villagers were investigated, including 1 256 in arsenic exposure group and 159 in control group. Compared with the control group, there were no significant differences in age, gender ratio and occupation distribution between arsenic exposure group and control group ( P > 0.05), but there were significant differences in smoking, drinking, body mass index (BMI) and education level distribution ( P < 0.05). The median of urinary tAs, iAs%, MMA%, DMA%, PMI and SMI in control group and arsenic exposure group were 12.86 μg/L, 15.03, 5.23, 76.35, 84.97, 93.68 and 69.68 μg/L, 10.24, 8.37, 79.31, 89.76, 90.65, respectively, the levels of urinary tAs, DMA% and PMI in arsenic exposed group were higher than those in control group, while iAs% and SMI were lower than those in control group, the differences were statistically significant ( U=- 13.87, - 4.30, - 6.64, - 6.64, - 1.99, P < 0.05). After analysis of the factors influencing urinary arsenic metabolism in the population, we found that age and BMI had an impact on iAs% ( β=- 0.08, - 0.08, P < 0.05); gender, drinking, BMI and education level were influencing factors of MMA% ( β =- 0.11, - 0.09, - 0.07, 0.08, P < 0.05); DMA% was mainly affected by age, gender, BMI and education level ( β = 0.06, 0.09, 0.10, - 0.09, P < 0.05); PMI was mainly affected by age and BMI ( β = 0.08, 0.08, P < 0.05); while SMI was affected by gender, drinking, BMI and education level ( β=0.09, 0.08, 0.08, - 0.09, P < 0.05). Conclusions:The urinary arsenic metabolism models of different arsenic exposed groups are different. Age, gender, smoking, drinking, BMI and education level may be influencing factors of different arsenic metabolism models.

OBJECTIVE：To study the potential mechanism of yam protein （DOT） in the prevention and treatment of diabetes-induced erectile dysfunction （DIED）. METHODS ：DIED model was induced by high-glucose and high-fat diet and intraperitoneal injection of streptozotocin （40 mg/kg）. The experiment was set up in the normal control group （normal saline ）， model group （normal saline ），DOT low-dose ，medium-dose and high-dose groups （0.3，0.6，0.9 mg/kg），sildenafil group （positive control ，4.4 mg/kg），with 9 rats in each group. In the stage of successful establishment of diabetes model and initiation of inducing DIED ，rats in each group were given relevant solution intragastrically ，once a day ，for consecutive 11 weeks. Body weight，fasting plasma glucose （FPG），the times and rate of penile erection ，fasting insulin （FINS），insulin resistance index （IR），the contents of endothelial nitric oxide synthase （eNOS）and cyclic guanosine monophosphate （cGMP）in penile cavernous tissue were determined so as to evaluate the intervention effects of DOT on DIED model rats. High-glucose damaged mice cavernous endothelial cells （MCECs）model was induced by 30 mmol/L glucose for 48 h，and then give DOT 125，250，500 μg/mL. The cell viability was detected so as to evaluate the effects of DOT on high-glucose damaged MCECs model. RNA-Seq mail：xingxin0902@163.com technology was adopted to screen the differentially expressed genes between normal MCECs and high-glucose damaged MCECs，high-glucose damaged MCECs and MCECs treated with 250 μg/mL DOT. Gene ontology（GO）function enrichment analysis and KEGG pathway enrichme nt analysis were performed for differentially expressed genes. The common differentially expressed genes between 2 groups were analyzed ，and mRNA expressions of six key genes were validated. RESULTS ：Different doses of DOT could reverse the reduction of body weight ，the increase of FINS and IR ，the reduction of the times and rate of penile erection ，the decrease of eNOS and cGMP contents in penile cavernous tissue of DIED model rats ；above indexes of DIED model rats were reversed significantly after treated with high-dose of DOT（P＜0.05 or P＜0.01）. 125，250，500 μg/L DOT could significantly improve the activity of high-glucose damaged MCECs （P＜0.05 or P＜0.01）. RNA-Seq technology showed that compared with normal MCECs ，a total of 48 differentially expressed genes were found in high-glucose damaged MCECs. Compared with high-glucose damaged MCECs ，a total of 779 differentially expressed genes were found in MCECs treated with DOT. The differentially expressed genes of 2 groups were mainly cellular process in biological process annotation ，cellular part in cell component annotation and binding molecular function in molecular function annotation ，which were mainly enriched in extracellular matrix receptor interaction pathway ，mismatch repair pathway ， phosphatidylinositol 3 kinase-protein kinase B （PI3K-Akt）signal pathway and so on. Among differentially expressed genes of 2 groups，13 common differentially expressed genes such as Aldh1a1，Abcc5，Tac1 were found. DOT could significantly reverse the expression of the above common differentially expressed genes in high-glucose damaged MCECs. After validation ，DOT could significantly reverse the mRNA expression of TGF-β3，Txnip，Aldh1a1，Loxl1，Mt1 and Mt2 in high-glucose damaged MCECs. CONCLUSIONS：DOT could improve the symptom of DIED model rats ，the mechanism of which may be related to biological pathway of inhibiting fibrosis and reducing oxidative stress ，so as to improve the endothelial function of cavernous body.

Objective:To observe the inhibitory effect of berberine (BBR) on the apoptosis of human retinal vascular endothelial cells (hREC) under high glucose environment.Methods:hREC was divided into blank control group (NC group), high glucose group (HG group), BBR treatment group (BN group), and BBR+high glucose treatment group (BH group). The cells of each group were cultured in Dulbecco's modified eagle medium; 5.5 and 30.0 mmol/L glucose were added to the medium of the NC group and HG group, respectively; 5.0 mmol/L glucose and 5.0 mmol/L BBR was added to the BN group; 30.0 mmol/L glucose and 5.0 mmol/L BBR was added to the medium of the BH group. Flow cytometry was used to observe the apoptosis rate of each group. Western blotting was used to detect the relative expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), and Cytochrome C (Cyt-C) and cysteine aspastic acid-specific protease 3 (Caspase-3) proteins in each group of cells. The difference between the two groups was tested by t test, and the difference among multiple groups was analyzed by one-way analysis of variance. Results:The results of flow cytometry showed that compared with the NC group, the apoptosis rate of the HG group significantly increased, and the difference was statistically significant ( P<0.01); compared with the HG group, the apoptosis rate of the BH group significantly reduced, the difference was statistical significance ( P<0.05). Western blot test results showed that, compared with the NC group, the relative expression of Bax and Caspase-3 protein in the HG group increased, and the relative expression of Bcl-2 protein decreased. The difference was statistically significant ( P<0.01). Compared with the HG group, the relative expression of Bax, Cyt-C, and Caspase-3 protein in BH group cells decreased, and the relative expression of Bcl-2 protein increased, and the difference was statistically significant ( P<0.01). Conclusion:BBR can inhibit hREC apoptosis by affecting the expression of apoptotic protein under high glucose environment.

Objective:To explore the clinical value of autoantibodies in patients with liver disease.Methods:We retrospectively analyzed the data of 1 495 outpatients or inpatients with liver disease in Beijing Ditan Hospital of Capital Medical University from August 2020 to April 2021. Indirect immunofluorescence and Western blot were used to detect antinuclear antibody (ANA) and antinuclear antibodies (ANAs).Results:ANA and ANAs were positive in patients with liver diseases of various etiologies. Among 1 495 patients with liver disease, 494 cases were ANA positive, the positive rate was 33.04%; 573 cases were positive for ANAs, the positive rate was 38.33%. The positive rate of ANA in the immune liver disease group (63.37%) was higher than that in the viral, alcoholic, fatty liver, confounding factors and other liver disease groups, and the difference was statistically significant ( P<0.01). The ANA positive rate between the viral, alcoholic, fatty liver, and confounding factor groups was statistically significant ( χ2=19.823, P<0.01), the positive rate of ANAs in the immune liver disease group (80.23%) was higher than that in other liver disease groups, and the difference was statistically significant ( P<0.05). The antibody titer of immune liver disease group was mainly 1∶1000, and other liver disease etiology groups was mainly 1∶100. The two most common fluorescent karyotypes in liver disease groups of different etiologies are cytoplasmic and nuclear granular types. The most common specific antibody in the immune liver disease group was anti-mitochondrial antibody type 2 (anti-AMA-M2) antibody, the most common anti-Ro-52 antibody in viral, drug-induced, complex etiology, and other etiological groups, and the most common anti-SSA antibody in alcoholic liver disease. Anti-SSA antibody (17.44%), anti-SSB antibody (9.30%), anti-CENP-B antibody (22.09%), anti-Ro-52 antibody (41.28%), anti-AMA-M2 antibody (51.74%) were positive in immune liver disease group, The rate was higher than that of other liver disease etiology groups, and the difference was statistically significant ( P<0.01). When the ANA fluorescence karyotype is nuclear granule type, the positive rate of anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody in the immune liver disease group was higher than that in the viral liver disease group ( P<0.01), The positive rate of anti-Ro-52 antibody was higher than that of drug-induced liver disease group ( P<0.05). Conclusions:The ANA titer of autoimmune liver disease was mainly (1∶1 000). ANAs were mainly positive for anti-SSA antibody, anti-SSB antibody, anti-CENP-B antibody, anti-Ro-52 antibody, and anti-AMA-M2 antibody, especially anti-AMA-M2 antibody. When combined with ANA fluorescent karyotype and ANAs for analysis, if the fluorescent karyotype is nuclear particle type, the positive anti-Ro-52 antibody in ANAs is more valuable in distinguishing immunity from viral and drug-induced liver diseases.

The colonization of microorganisms planted on the surface of teeth and restoration materials is the main cause of oral disease and treatment failure. How to improve the antibacterial properties of dental materials is a hot topic in dentistry. Nano-sized antibacterial materials have attracted much attention. Among them, metal and metal oxide nanoparticles are prominent due to their strong and broad-spectrum antibacterial activity. Thus, in recent years, many studies have used metal and metal oxide nanoparticles to develop antimicrobial dental materials for resin restoration, root canal therapy, orthodontic treatment, and implant surface and removable denture repair and have found that the antibacterial properties of nano-sized materials are significantly enhanced. However, the mechanical properties and esthetic properties of the modified materials are affected, so it is still necessary to explore appropriate modification methods. In addition, most of the experiments are carried out in vitro, which cannot accurately simulate the oral environment. Therefore, the antibacterial effect, cytotoxicity and immune response of these materials in vivo still need further research and exploration. This paper reviewed the potential antibacterial mechanisms and the safety of those nanoparticles and their applications in dentistry.

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.