Functional therapy and adenotonsillectomy clinical trial for class II malocclusion (FACT-II): protocol for a randomised controlled trial.

INTRODUCTION: Class II malocclusion with mandibular retrognathia is a common complication of paediatric obstructive sleep apnoea (OSA), often accompanied by transverse maxillary deficiency. In early orthodontic treatment, a twin block (TB) is a regular functional appliance for correcting this malocclusion. For paediatric OSA, the most common risk factor is adenotonsillar hypertrophy (AHT). Untreated AHT may lead to the persistence and worsening of obstructive sleep-disordered breathing traits, including habitual mouth breathing. Additionally, the clockwise mandibular rotation associated with AHT-induced pharyngeal crowding can undermine the effectiveness and stability of TB treatment. Adenotonsillectomy (T&A) is currently the first-line treatment for paediatric OSA. This proposed trial will investigate the impact of T&A surgery timing on the efficacy and stability of TB functional treatment in children with class II mandibular retrognathia and ATH. METHODS AND ANALYSIS: This will be a single-centre, parallel-group, superiority randomised controlled trial with participants randomised to intervention (T&A followed by TB treatment) or control arms (TB treatment followed by T&A) in a 1:1 ratio. A total of 40 patients aged 8-14 years, diagnosed with class II mandibular retrognathia and co-existing ATH-induced OSA, and indicated for both T&A surgery and TB treatment, will be recruited at the School and Hospital of Stomatology, Wuhan University. The primary outcomes will be the changes in the apnoea-hypopnoea index and the point A-nasion-point B angle from baseline to postorthodontic treatment between the two groups. Secondary outcomes will include other dental, skeletal, upper airway and soft tissue changes, as well as subjective sleep-related and oral-related quality of life. Outcome changes within each group and between groups will be analysed. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of the School and Hospital of Stomatology, Wuhan University (no. 2022-D07). The research findings will be faithfully disseminated through scientific conferences or published articles. TRIAL REGISTRATION NUMBER: ChiCTR2200061703 (https://www.chictr.org.cn).

Abstracts of randomized controlled trials in pediatric dentistry: reporting quality and spin.

BACKGROUND: Abstracts provide readers a concise and readily accessible information of the trials. However, poor reporting quality and spin (misrepresentation of research findings) can lead to an overestimation in trial validity. This methodological study aimed to assess the reporting quality and spin among randomized controlled trial (RCT) abstracts in pediatric dentistry. METHODS: We hand-searched RCTs in five leading pediatric dental journals between 2015 and 2021. Reporting quality in each abstract was assessed using the original 16-item CONSORT for abstracts checklist. Linear regression analyses were performed to identify factors associated with reporting quality. We evaluated the presence and characteristics of spin only in abstracts of parallel-group RCTs with nonsignificant primary outcomes according to pre-determined spin strategies. RESULTS: One hundred eighty-two abstracts were included in reporting quality evaluation. The mean overall quality score was 4.57 (SD, 0.103; 95% CI, 4.36-4.77; score range, 1-10). Only interventions, objective, and conclusions were adequately reported. Use of flow diagram (P < 0.001) was the only significant factor of higher reporting quality. Of the 51 RCT abstracts included for spin analysis, spin was identified in 40 abstracts (78.4%), among which 23 abstracts (45.1%) had spin in the Results section and 39 in the Conclusions Sect. (76.5%). CONCLUSIONS: The reporting quality of RCT abstracts in pediatric dentistry is suboptimal and the prevalence of spin is high. Joint efforts are needed to improve reporting quality and minimize spin.

Astrocytes in the spinal cord contributed to acute stress-induced gastric damage via the gap junction protein CX43.

Rat restraint water-immersion stress (RWIS) is a compound stress of high intensity and is widely used to study the pathological mechanisms of stress gastric ulcers. The spinal cord, as a part of the central nervous system, plays a dominant role in the gastrointestinal tract, but whether the spinal cord is involved in rat restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of spinal astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, connexin 43 (Cx43), and p-ERK1/2 during RWIS by immunohistochemistry and Western blotting. In addition, we intrathecally injected the astrocytic toxin L-a-aminoadipate (L-AA), gap junction blocker carbenoxolone (CBX), and ERK1/2 signaling pathway inhibitor PD98059 to explore the role of astrocytes in the spinal cord in RWIS-induced gastric mucosal damage and its possible mechanism in rats. The results showed that the expression of GFAP, c-Fos, Cx43, and p-ERK1/2 was significantly elevated in the spinal cord after RWIS. Intrathecal injection of both the astrocyte toxin L-AA and the gap junction blocker CBX significantly attenuated RWIS-induced gastric mucosal damage and decreased the activation of astrocytes and neurons induced in the spinal cord. Meanwhile, the ERK1/2 signaling pathway inhibitor PD98059 significantly inhibited gastric mucosal damage, gastric motility and RWIS-induced activation of spinal cord neurons and astrocytes. These results suggest that spinal astrocytes may regulate the RWIS-induced activation of neurons via CX43 gap junctions and play a critical role in RWIS-induced gastric mucosa damage through the ERK1/2 signaling pathway.

'Spin' among abstracts of randomised controlled trials in sleep medicine: A research-on-research study.

STUDY OBJECTIVES: 'Spin', using reporting strategies to distort study results, can mislead readers of medical research. This study aimed to evaluate the prevalence and characteristics of 'spin' among randomised controlled trial (RCT) abstracts published in sleep medicine journals, and to identify factors associated with its presence and severity. METHODS: The search for RCTs published between 2010 and 2020 were conducted in seven reputable journals of sleep medicine. Abstracts of RCTs with statistically nonsignificant primary outcomes were included and analysed for 'spin', according to pre-determined 'spin' strategies. Chi-square tests or logistic regression analyses were performed to detect the association between characteristics of included abstracts and the presence and severity of 'spin'. RESULTS: A total of 114 RCT abstracts were included in this study, of which 89 (78.1%) were identified as having at least one type of 'spin' strategy. Sixty-six abstracts (57.9%) had 'spin' in the Results section, 82 (71.9%) abstracts presented with 'spin' in the Conclusions section. The presence of 'spin' varied significantly among RCTs based on the different categories of research area (P=0.047) and the statistician involvement (P=0.045). Furthermore, research area (P=0.019) and funding status (P=0.033) were significant factors associated with the severity of 'spin'. CONCLUSIONS: The prevalence of 'spin' is high among RCT abstracts in sleep medicine. This raise the need for researchers, editors and other stakeholders to be aware of the issue of 'spin' and make joint efforts to eliminate it in future publications.

Abstracts of randomized controlled trials in the field of dentofacial trauma: Reporting quality and spin.

BACKGROUND/AIM: Abstracts of randomized controlled trials (RCTs) provide a summary of the entire trial report. Their transparent, detailed, and accurate reporting is essential for clinical decision-making and evidence-based dental practice. The aim of this study was to assess the reporting quality and prevalence of spin in abstracts of RCTs in the field of dentofacial trauma. MATERIALS AND METHODS: The PubMed database was searched to identify RCT reports published between 2017 and 2021 in the field of dentofacial trauma. The reporting quality of abstracts was assessed according to the 16-item CONSORT for Abstracts checklist and measured with an overall quality score (OQS, range: 0-16). Linear regression analyses were used to identify factors associated with reporting quality. Among the included RCTs, parallel-group RCTs with non-significant primary outcomes were selected for spin assessment using predefined spin strategies. RESULTS: One hundred and twelve eligible abstracts were identified and included. The mean OQS was 4.51 (SD, 1.35; 95% CI, 4.26-4.76). Abstracts with more than 250 words (p = .004) and a structured format (p = .032) had significantly better reporting quality. Of the 30 abstracts that were eligible for spin assessment, spin was identified in 23 (76.7%). Among these, spin was observed in the Conclusions sections of 22 abstracts (73.3%) and the Results sections of 9 abstracts (30.0%). CONCLUSIONS: Among RCT abstracts in the field of dentofacial trauma, the reporting quality was sub-optimal and the prevalence of spin was relatively high. Strict adherence to the CONSORT for Abstracts guidelines is needed to ensure complete and transparent reporting. Relevant stakeholders need to make concerted efforts to avoid spin.

Alpha5 nicotinic acetylcholine receptor mediated immune escape of lung adenocarcinoma via STAT3/Jab1-PD-L1 signalling.

BACKGROUND: Immunotherapy has proven to be an emerging treatment for non-small-cell lung cancer in recent years. Notably, smokers show higher programmed cell death ligand-1 (PD-L1) expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Genome-wide association studies show that the CHRNΑ5 encoding α5-nicotinic acetylcholine receptor (α5-nAChR) is especially relevant to lung cancer and nicotine dependence. Jab1 is a key regulatory factor and promotes the stabilization of PD-L1. Our previous study reported that α5-nAChR mediates lung adenocarcinoma (LUAD) epithelial-mesenchymal transition (EMT) and metastasis via STAT3/Jab1. However, the link between α5-nAChR and PD-L1 is unclear in LUAD. METHODS: We used various bioinformatics databases to analyze the expression of related genes and their correlations. Expression and clinicopathologic significance of α5-nAChR and PD-L1 were detected by immunohistochemistry in a tissue microarray. α5-nAChR regulated LUAD cell immune escape by targeting the STAT3/Jab1-PD-L1 signalling by Western-blotting and ChIP in vitro. We used T cell coculture, flow cytometry, ELISA, CCK8 assay and crystal violet staining to detect the expression of regulatory T cell (Tregs), IFN-γ, IL-2 and the ability of T cell-mediated tumour cell killing respectively. IF assays were performed in both cancer cells and tumour xenograft paraffin sections to analyze the protein expression. The in vivo experiments in mouse model were performed to show the α5-nAChR-mediated immune escape via PD-L1 pathway. RESULTS: The expression of α5-nAChR was correlated with PD-L1 expression, smoking status and lower survival of LUAD in vivo. In vitro, the expression of α5-nAChR mediated phosphorylated STAT3 (pSTAT3), Jab1 and PD-L1 expression. STAT3 bound to the Jab1 or PD-L1 promoter and mediated PD-L1 expression. Jab1 stabilized PD-L1 expression in LUAD cells. Furthermore, in primary T cell cocultured system, downregulation of α5-nAChR suppressed the function of CD4+CD25+FOXP3+ Tregs, enhanced IFN-γ secretion, and increased T cell-mediated killing of LUAD cells. In the Jurkat T cells and LUAD cells coculture assay, inhibition of α5-nAChR increased IL-2 secretion. In tumour xenograft tissues, α5-nAChR expression was related to PD-L1, Jab1, pSTAT3, CD4 and granzyme B expression (GB). CONCLUSIONS: Our results suggest that the novel α5-nAChR/STAT3-Jab1-PD-L1 axis is involved in LUAD immune escape, which could lead to potential therapeutic strategies for cancer immunotherapy. Video abstract.

CLEC3B is a novel causative gene for macular-retinal dystrophy.

PURPOSE: Macular degeneration is the leading cause of blindness worldwide. In this study, we aimed to define a new subtype of macular-retinal dystrophy and its genetic predisposition in 5 families. METHODS: Exome sequencing was performed to determine the putative disease-causing genes in patients with inherited macular disorders confirmed through comprehensive ophthalmic examinations. To validate its functional consequence, adeno-associated virus-mediated mutant gene was delivered into the murine retina, and both structural and functional tests were performed to investigate its pathological effects in vivo. RESULTS: In total, 5 multigenerational families diagnosed with autosomal dominant maculoretinopathy were found to carry a pathogenic variant in a new gene, CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Consistent with the disease phenotypes of patients, mice that received subretinal injections with the CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. Moreover, the optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in these mice. CONCLUSION: We have presented a new subtype of macular-retinal dystrophy in 5 families as well as a new pathogenic gene, CLEC3B, providing new insights into maculoretinopathy etiology.

Outcomes used in trials regarding the prevention and treatment of orthodontically induced white spot lesions: A scoping review.

INTRODUCTION: The objective was to identify and summarize the outcomes and evaluation methods used in clinical trials regarding the prevention and treatment of orthodontically induced white spot lesions (WSLs). METHODS: Three electronic databases were searched to identify studies that were (1) clinical trials on prevention and/or treatment of orthodontically induced WSLs, (2) reported in English, and (3) published between January 2010 and October 2019. At least 2 authors assessed the eligibility and extracted the characteristics, outcomes, and evaluation methods from included studies. All disagreements were resolved through discussion. RESULTS: Among 1328 studies identified, 51 were eligible and included. A total of 48 different outcomes and 11 different evaluation methods were used in these studies. The most frequently used outcomes were WSLs clinical visual examination scores (n = 22, 43.1%), DIAGNOdent values (n = 14; 27.5%), fluorescence loss measured with quantitative light-induced fluorescence (QLF) (n = 10; 19.6%), and lesion area measured with QLF (n = 10; 19.6%). The most frequently used evaluation methods were clinical examination (n = 25; 49.0%), visual inspection by photographs (n = 15; 29.4%), DIAGNOdent (n = 14; 27.5%), and QLF (n = 10; 19.6%). None of the included studies reported data on quality of life. CONCLUSIONS: Substantial outcome heterogeneity exists among studies regarding the prevention and treatment of orthodontically induced WSLs. Most of the identified outcomes are aimed to assess morphologic changes of WSLs and may not reflect patient perspectives. REGISTRATION: The Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) project was registered in the COMET Initiative database (No. 1399).

The presence and characteristics of 'spin' among randomized controlled trial abstracts in orthodontics.

OBJECTIVES: To identify the presence and characteristics of spin (using reporting strategies to distort study results and mislead readers) within randomized controlled trial (RCT) abstracts published in orthodontic journals, and to explore the association between spin and potentially related factors. METHODS: A manual search was conducted to identify abstracts of RCTs with statistically non-significant primary outcomes published in five leading orthodontic journals between 2015 and 2020. Spin in the Results and Conclusions sections of each included abstract was evaluated and categorized according to pre-determined spin strategies. Logistic regression analyses were employed to explore the association between spin and relevant factors. RESULTS: A total of 111 RCT abstracts were included, of which 69 (62.2 per cent) were identified with spin. In the Results section, 47 (42.3 per cent) abstracts had spin, and 'focusing on significant within-group comparison for primary outcomes' was the most frequent spin strategy. In the Conclusions section, 57 (51.4 per cent) abstracts presented spin, with the most common strategy being 'claiming equivalence or non-inferiority for statistically nonsignificant results'. According to multivariable logistic regression analysis, a significantly lower presence of spin was found in studies with international collaboration (odds ratio [OR]: 0.331, 95 per cent confidence interval [CI]: 0.120-0.912, P = 0.033) and trial registration (OR: 0.336, 95 per cent CI: 0.117-0.962, P = 0.042). CONCLUSION: The prevalence of spin is high among RCT abstracts in orthodontics. Clinicians need to be aware of the definition and presence of spin. Concerted efforts are needed from researchers and other stakeholders to address this issue.

The Impact of the COVID-19 Epidemic on Orthodontic Patients in China: An Analysis of Posts on Weibo.

Background: During the COVID-19 pandemic, many dental care services including orthodontic practice were suspended. Orthodontic patients turned to social media platforms to communicate, share experiences, and look for solutions. Our study aimed to investigate the attitudes and perspectives of orthodontic patients during the COVID-19 epidemic in China by analyzing orthodontics-related posts on Sina Weibo (a Chinese counterpart of Twitter). Materials and Methods: Potentially eligible posts on Sina Weibo platform were collected between December 30, 2019, and April 18, 2020. Posts related to both orthodontics and COVID-19 were included and then coded and classified into specific appliances and themes. Geographic and temporal distributions of the included posts were analyzed. In addition, time-lagged cross correlation was performed to explore the association between the number of daily posts and daily new COVID-19 cases/deaths in China. Chi-square tests were employed to compare the differences between fixed appliances and aligners in problems/difficulties and feelings during the epidemic. Results: Of the 28,911 posts identified, 4,484 were included in the analysis. The most frequently mentioned themes were appointments (n = 2,621, 58.5%), negative feelings (n = 2,189, 48.8%), and problems/difficulties (n = 1,155, 25.8%). A majority of posts were tweeted in regions with high levels of economic development and population density in eastern China and from February to March. The number of daily posts had a significantly positive correlation with daily new COVID-19 cases/deaths in China (P < 0.05). Compared with clear aligners, patients with fixed appliances reported more problems/difficulties (P < 0.001) and negative feelings (P < 0.001), but fewer positive feelings (P < 0.001). Conclusions: The analysis of Weibo posts provided a timely understanding of the impact of COVID-19 on orthodontic patients. Delayed appointments were their greatest concern, and negative feelings and untreated orthodontic problems increased during the suspension of dental care services. However, patients with clear aligners reported fewer negative feelings and problems than those with fixed appliances. The findings highlighted the need to consider both treatment- and psychology-related issues of orthodontic patients and how to handle them appropriately during the epidemic.