Fluorine is a common chemical element. Excessive intake of fluoride can lead to fluorosis. Fluoride easily passes through the blood-brain barrier and accumulates in different brain regions, causing pathological changes in brain tissue. It leads to adverse effects on neuronal metabolism, enzyme, protein function, neurotransmitters, and redox homeostasis, and subsequently neuronal damage and neurodegenerative diseases in humans and experimental animals. This paper reviewed the effects and important mechanisms of fluoride on neurological function and behavior, involving mitochondrial toxicity, oxidative stress, cell apoptosis and autophagy, and activation of pro-inflammatory factors. It provided a reference for further studying the mechanisms of brain damage induced by fluorosis.

Objective: To analyze the adverse treatment outcome status and spatio temporal characteristics of pulmonary tuberculosis cases among students in Qinghai Province, providing a reference basis for pulmonary tuberculosis prevention and control in schools. Methods: The data of student pulmonary tuberculosis cases during 2013-2023 in Qinghai Province were obtained through the "National Tuberculosis Management Information System", and the treatment outcome was retrospectively analyzed. The Joinpoint model was applied to analyze the adverse outcome rate trend. Global and local spatial autocorrelation analysis, and spatiotemporal scan cluster analysis were conducted on the adverse outcome rate of pulmonary tuberculosis among students in Qinghai Province. Results: During 2013-2023, 488 cases of adverse outcomes were reported among 6 155 students with pulmonary tuberculosis in Qinghai Province, with an adverse outcome rate of 7.93%. The reporting adverse outcome rate of pulmonary tuberculosis among students showed a downward trend from 2013 to 2023 (APC=-16.20, t =-3.89, P <0.05). The results of spatial autocorrelation showed that the adverse outcome rate of pulmonary tuberculosis was Moran s I >0 among students in Qinghai Province. Among them, there was a spatially positive correlation in the adverse outcome rate of pulmonary tuberculosis among students in 2020, 2021 and 2022(all Z >1.96, all P <0.05). The results of clustering and outlier analysis in local spatial autocorrelation showed that the areas with high high aggregation were mainly concentrated in Yushu Prefecture(Zhiduo County, Zaduo County, Nangqian County, Yushu City), Huangnan Prefecture (Zeku County, Henan County) and Hainan Prefecture (Tongde County). The low low concentration areas were distributed in Haidong City, Xining City, Haibei Prefecture (Gangcha County, Qilian County), Haixi Prefecture (Tianjun County, Ulan County), Hainan Prefecture (Gonghe County, Guide County) and Huangnan Prefecture (Tongren City, Jianzha County). The spatio temporal scanning showed that a total of two possible aggregation areas had been detected. Among them, the first level aggregation area composed of 10 counties and districts in Yushu Prefecture and Guoluo Prefecture of Qinghai Province, and the cluster radius was 658.09 km, the RR was 10.58 , and the LLR was 305.91; the second level aggregation area was composed of 16 counties and districts in Hainan Prefecture, Haixi Prefecture, Huangnan Prefecture and Guoluo Prefecture, and the cluster radius was 407.02 km, the RR was 9.83, and the LLR was 152.48 (both P <0.05). Conclusions The reporting rates of adverse treatment outcome of pulmonary tuberculosis cases among students in Qinghai Province remain relatively high and unevenly distribute throughout the province. Supervision should be strengthened to improve cases compliance,and to reduce student pulmonary tuberculosis adverse treatment outcomes incidence.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Purpose To investigate the expression of pro-tein of relevant evolutionary and lymphoid interest domain-con-taining 1(PRELID1)in gastric cancer tissues and to analyze its effect on prognosis,and the mechanism of influencing the prolif-eration and invasion ability of gastric cancer cells.Methods Using TCGA data and clinical data of 111 patients with gastric cancer,we analyzed the relationship between the expression of PRELID1 and clinicopathological parameters and the impact on clinical prognosis.The biological function of PRELID1 was pre-dicted by bioinformatics,and further verified by in vitro and in vivo experiments.Lentivirus was applied to regulate the level of PRELID 1 in gastric cancer cell line(MGC803)in vitro,and its effect on the proliferation,migration,and invasion of gastric cancer cells was observed.The nude mouse subcutaneous tumor-igenesis was used to observe the effect of PRELID1 on the growth of gastric cancer tissue in vivo.Results The expression of PRELID1 was significantly higher in gastric cancer tissues than that in the adjacent tissues(P＜0.001)and was positively cor-related with the cell proliferation indicator Ki67(P＜0.001).Cox regression model analysis showed that the high expression of PRELID 1 was an independent risk factor affecting the 5-year survival rate after radical gastrectomy(HR=2.336;95％CI=1.354-4.029).Gene enrichment results showed that the func-tion of PRELID1 was related to proliferation and JAK/STAT sig-naling.CCK-8 and Transwell experiments found that up-regula-tion of PRELID1 promoted the proliferation(P=0.016),mi-gration(P=0.016)and invasion(P=0.025)of gastric cancer cells,while down-regulation inhibited the proliferation(P=0.026),migration(P=0.048)and invasion(P=0.029).Subcutaneous tumor formation experiments in nude mice found that up-regulation of PRELID1 promoted the growth of gastric cancer tissue(P=0.047),while down-regulation was the oppo-site(P=0.005).Western blot detecting gastric cancer cells and gastric cancer tissues found that up-regulation of PRELID1 promoted the expression of JAK and STAT proteins(all P＜0.05),while down-regulation inhibited them(all P＜0.05).Conclusion The high expression of PRELID1 associated with poor prognosis may regulate the proliferation,migration and in-vasion of gastric cancer cells by up-regulating JAK/STAT signa-ling in gastric cancer.

Decline of immunity is an epidemiological feature of opioid addicts.Recent work reveals a landscape of peripheral immune microenvironment in opioid addicts.Opioid addicts exhibit a significant expansion of fragile-like regulatory T cells(Tregs)and enhanced Treg-derived interferon-y(IFN-γ)expression.IFN-γ signaling reshapes synaptic morphology in nucleus accumbens(NAc)neurons,modulating subsequent withdrawal symptoms.Treg fragility transformation from WT Tregs is primarily due to opioid-induced global hypoxia during acute withdrawal period.Opioids increase the expression of neuron-derived C-C motif chemokine ligand 2(Ccl2)and disrupt blood-brain barrier(BBB)integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7(Fabp7),both of which trigger peripheral Treg infiltration into NAc.Recent studies suggest that subtle homeostatic changes in the peripheralimmune milieu may also contribute to modulating synapses that are responsible for addictive behaviors,which may lead to the development of new therapeutic strategies.

Objective To study the mechanical response of tibial prostheses and the distal tibial cancellous bone after implantation of radial and axial functionally graded materials(FGM)into the ankle joint.Methods Three FGM were used:titanium alloy-bioactive glass composite FGM(FGM-Ⅰ),titanium(Ti)alloy-ideal bone elastic composite FGM(FGM-Ⅱ),and Ti alloy-hydroxylapatite composite FGM(FGM-Ⅲ).A three-dimensional finite element model of total ankle arthroplasty(TAA)was established,and the simulation software ABAQUS was used for secondary development based on Fortra.By changing the volume fraction,the mechanical properties of the FGM tibial prosthesis can be adjusted both axially and radially.The stress distributions of the tibial prosthesis and cancellous bone after FGM axial and radial tibial component implantation in the standing position were analyzed.Results Compared with Ti alloy tibial prosthesis,three kinds of FGM could effectively reduce the stress concentration on the tibial prosthesis,and the overall effect of FGM-Ⅲ tibial prosthesis was better than that of FGM-Ⅰ and FGM-Ⅱ tibial prosthesis;the radial distribution of FGM could effectively reduce the maximum von Mises stress of the prosthesis.For the tibial cancellous bone,the three types of FGM radial tibial prostheses and FGM-Ⅲ axial tibial prostheses could effectively increase the distal stress,thus,relieving the stress shielding on the cancellous bone;the FGM-Ⅲ radial tibial prosthesis was the most effective in improving the stress level of the cancellous bone.Conclusions FGM-Ⅲ radial ankle prosthesis can effectively reduce the stress concentration phenomenon and the stress shielding effect on the prosthesis to prolong its life,with potential application prospects.

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3(GATA3)and forkhead protein P3(Foxp3)in peripheral blood.Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method.The control group was given conventional diet before operation,and the observation group was given enteral nutrition support before operation.The two groups were compared in terms of nutritional support.Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume(FEV1/FVC)(P<0.05),FVC(P<0.05),FEV1(P<0.05)and the levels of peripheral blood GATA3(P<0.05),Foxp3 mRNA(P<0.05)expression compared with those at admission(P<0.05),but no significant differences in pulmonary function(P>0.05),peripheral blood GATA3(P>0.05),and Foxp3 mRNA(P>0.05)expression between them at 1 week postoperatively.Both groups exhibited significantly lower levels of albumin,prealbumin,haemoglobin,transferrin,PNI and body mass and body mass index at admis-sion as compared to those at one week after surgery(P<0.05).The observation group showed significantly higher levels of albumin,prealbumin,haemoglobin,transferrin,and PNI at 1 week postoperatively(P<0.05),but no significant differences in ventilation time,defecation time,drain retention time,hospitalisation time,and compli-cation rate as compared to the control group(P>0.05).Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status,and ren-ders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression.

Thrombospondin 2(THBS2)is a matrix cell calcium-binding glycoprotein that interacts with a variety of growth factors,receptors,matrix molecules or proteases on the extracellular matrix and cell surface.THBS2 can be activated by N6-methyladenosyl RNA methylase,and mediates tumor proliferation,migration and invasion by re-modeling the tumor microenvironment and participating in multiple cell signaling pathways.THBS2 could be used as a diagnostic and prognostic indicator for a variety of tumors,and is expected to become a new target for malignant tumor treatment.