Development and application of Chinese customized total temporomandibular joint prosthesis

Alloplastic total joint replacement is one of the effective methods for temporomandibular joint (TMJ) reconstruction. As the first choice for TMJ reconstruction, alloplastic total joint replacement has the advantages of no need to open up a second operative area, short operation duration and immediate functional restoration, compared with autogenous bone graft. The customized prosthesis has the edge over the stock prosthesis due to its excellent suitability and less intraoperative bone trimming. However, there are no commercialized counterparts in China yet. Hence, it is urgent to develop a Chinese customized total TMJ prosthesis for Chinese patients. Since 2009, the authors′ team has begun to develop the customized total TMJ prostheses suitable for Chinese anatomical features independently. Through three generations of products, the team gradually realized the stable connection of porous titanium alloys and ultra-high molecular weight polyethylene (UHMWPE), and finally achieved a key technological breakthrough in 2017. The third generation of customized total TMJ prosthesis was successfully developed by friction stir welding technology. The mechanical properties of Chinese customized prostheses have prevailed over its international counterparts, with satisfactory short-term follow-up results based on its preliminary clinical application. Furthermore, in order to ensure high efficiency and accuracy of the procedures from design and manufacture to clinical application, the authors′ team has developed a relatively mature standardized process, and improved the surgical procedures. This review systematically summarizes the research and development of Chinese customized total TMJ prosthesis system in the past decade, and looks forward to the future development of Chinese customized prosthesis system

Non-vitamin K Antagonist Oral Anticoagulants and Cognitive Impairment in Atrial Fibrillation: Insights From the Meta-Analysis of Over 90,000 Patients of Randomized Controlled Trials and Real-World Studies

Background: The relationship between the use of non-vitamin K antagonist oral anticoagulants (NOACs) and the impairment of cognition in atrial fibrillation (AF) remains unknown.Methods: A comprehensive database search of Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website was performed for randomized controlled trials (RCTs) reporting cognitive impairment events and observational nationwide database studies reporting adjusted hazard ratio (HR) in AF patients with NOACs. The primacy outcome was a composite of any cognitive impairment. Summary of HRs and 95% confidence intervals (95%CI) were calculated using the fixed- and random-effects models. Subgroup analyses were undertaken according to the individual NOACs, study types, and duration of follow-up.Results: Finally, eight studies including 97,595 patients (77,643 patients in 6 RCTs and 19,952 patients in 2 observational database studies) met the inclusion criteria, among which 55,337 (56.7%) patients were receiving NOACs and 42,258 (43.3%) patients were receiving vitamin K Antagonists (VKAs) or acetylsalicylic acid. The results showed a borderline significant association between the use of NOACs and the lower risk of cognitive impairment when compared with VKAs/ acetylsalicylic acid (HR: 0.80, 95%CI: 0.63–0.98 for fixed-effects model; HR: 0.77; 95%CI: 0.53–1.01 for random-effects model), with no significant heterogeneity between the studies (I2 = 39.4%, P = 0.12). The results were consistent across the key subgroups (Pinteraction > 0.05 for each).Conclusions: The results indicated that the use of NOACs might lower the tendency on the risk of cognitive impairment in comparison to VKAs/acetylsalicylic acid, and further RCTs and real-world studies are required on an urgent basis to obtain a robust result

Development of lifetime comorbidity in the world health organization world mental health surveys

CONTEXT: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. DESIGN: Nationally or regionally representative community surveys. SETTING: Fourteen countries. PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study

Unraveling the role of NLRP3 inflammasome in allergic inflammation: implications for novel therapies

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1β and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1β, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3’s specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases

Carbocisteine Improves Histone Deacetylase 2 Deacetylation Activity via Regulating Sumoylation of Histone Deacetylase 2 in Human Tracheobronchial Epithelial Cells

Histone deacetylase (HDAC) 2 plays a vital role in modifying histones to mediate inflammatory responses, while HDAC2 itself is commonly regulated by post-translational modifications. Small ubiquitin-related modifier (SUMO), as an important PTM factor, is involved in the regulation of multiple protein functions. Our previous studies have shown that carbocisteine (S-CMC) reversed cigarette smoke extract (CSE)-induced down-regulation of HDAC2 expression/activity in a thiol/GSH-dependent manner and enhanced sensitivity of steroid therapy. However, the mechanism by which S-CMC regulates HDAC2 is worth further exploring. Our study aimed to investigate the relationships between HDAC2 sumoylation and its deacetylase activity under oxidative stress and the molecular mechanism of S-CMC to regulate HDAC2 activity that mediates inflammatory responses in human bronchial epithelial cells. We found that modification of HDAC2 by SUMO1 and SUMO2/3 occurred in 16HBE cells under physiological conditions, and CSE induced SUMO1 modification of HDAC2 in a dose and time-dependent manner. K462 and K51 of HDAC2 were the two major modification sites of SUMO1, and the K51 site mediated deacetylation activity and function of HDAC2 on histone H4 that regulates IL-8 secretion. S-CMC inhibited CSE-induced SUMO1 modification of HDAC2 in the presence of thiol/GSH, increased HDAC activity, and decreased IL-8 expression. Our study may provide novel mechanistic explanation of S-CMC to ameliorate steroid sensitivity treatment in chronic obstructive pulmonary disease