HELQ deficiency impairs the induction of primordial germ cell-like cells.

Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Genomic analysis of Cobetia sp. D5 reveals its role in marine sulfur cycling.

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle.

Study on time-frequency features of induced charge signals during the damage and failure process of coal medium.

Monitoring and preventing coal-rock dynamic disasters are vital for safe mining. To investigate the time-frequency features of induced charge signals with coal damage and failure of roadways, the generation mechanism of free charge in loaded coal is analyzed and the induced charge monitoring test is conducted. According to the stress-induced charge-time curves, the time-domain features of charge signals at each loading stage are obtained. The wavelet threshold denoising approach and generalized Morse wavelet transform method are applied to denoise the raw signals and study the frequency-domain features. Further, the quantitative relationship between the de-noised induced charge signals and the degree of coal damage is established. The results show that the event number, amplitude and fluctuation degree of available induced charge signals are all at a low level in the compaction and elastic stages of the coal, which are mainly generated by the piezoelectric effect and predominantly represent discreteness. When entering the plastic and failure stages, the available signals are primarily produced by the crack propagation and triboelectric effects, with a significant increase in the event number, amplitude, and fluctuation degree. Then the induced charge signals gradually transit from discrete to continuous. Generally, the dominant frequency of the available induced charge signals during the coal damage process is concentrated at 0 ~ 11 Hz. The available induced charge is positively correlated with the degree of coal damage, which can perform the damage degree of coal mass, providing a new approach to evaluate the stability of roadway surrounding rocks.

IDN5706 inhibits synovial inflammation via inducing M2 polarization of synovial macrophages in osteoarthritis rats.

INTRODUCTION: IDN5706 is a tetrahydro derivative of hyperforin. In this study, we aimed to explore the effect of IDN5706 on synovial macrophages in osteoarthritis (OA) rats, and the underlying mechanisms. METHODS: OA rats were employed for the in vivo experiments, and RAW264.7 cells were employed for the in vitro experiments. Histopathological changes in synovium were examined using hematoxylin and eosin (HE) staining; Cell apoptosis in synovium was assessed by TUNEL staining; Macrophages polarization was determined by immunohistochemical analysis and flow cytometry; The mRNA expression and protein level of genes were detected by qRT-PCR and western blot; The efferocytosis of macrophages was assessed by flow cytometry. RESULTS: IDN5706 reversed the increased CD86-positive cells (M1 macrophages) and decreased CD206-positive cells (M2 macrophages), both in synovium and synovial fluid of OA rats. The in vitro experiments further confirmed the promotion effect of IDN5706 on M2 macrophages, accompanied by the elevated Arg-1 and reduced iNOS. Also, the up-regulated p-mTOR in synovium and synovial fluid of OA rats were reversed by IDN5706, and the decreased M1 macrophages and increased M2 macrophages induced by IDN5706 were reversed by mTOR activator. IDN5706 enhanced the efferocytosis of IL-4 treated RAW264.7 cells, and the animal experiments further revealed the involvement of efferocytosis in the improvement of OA by IDN5706. CONCLUSIONS: IDN5706 enhanced the efferocytosis of synovial macrophages by inducing M2 polarization via inhibiting p-mTOR, thus suppressing synovial inflammation and OA development, providing a theoretical basis for IDN5706 as a clinical drug for inflammatory diseases.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

LanGui tea, an herbal medicine formula, protects against binge alcohol-induced acute liver injury by activating AMPK-NLRP3 signaling.

BACKGROUND: LanGui tea, a traditional Chinese medicine formulation comprising of Gynostemma pentaphyllum (Thunb.) Makino, Cinnamomum cassia (L.) J. Presl, and Ampelopsis grossedentata (Hand-Mazz) W.T. Wang, has yet to have its potential contributions to alcoholic liver disease (ALD) fully elucidated. Consequently, the objective of this research is to investigate the protective properties of LanGui tea against binge alcohol-induced ALD and the mechanisms underlying its effects. METHODS: An experimental model of acute alcohol-induced liver disease was performed to assess the protective effects of extract of LanGui tea (ELG) at both 50 and 100 mg.kg-1 dosages on male C57BL/6 mice. Various parameters, including hepatic histological changes, inflammation, lipids content, as well as liver enzymes and interleukin 1ß (IL-1ß) in the serum were measured. The pharmacological mechanisms of ELG, specifically its effects on adenosine monophosphate-(AMP)-activated protein kinase (AMPK) and NLR family pyrin domain containing 3 (NLRP3) signaling, were investigated through Western blotting, qRT-PCR, ELISA, immunohistochemistry, immunofluorescence analyses, and by blocking the AMPK activity. RESULTS: ELG demonstrated a mitigating effect on fatty liver, inflammation, and hepatic dysfunction within the mouse model. This effect was achieved by activating AMPK signaling and inhibitingNLRP3 signaling in the liver, causing a reduction in IL-1ß generation. In vitro studies further confirmed that ELG inhibited cell damage and IL-1ß production in ethanol-induced hepatocytes by enhancing AMPK-NLRP3 signaling. Conversely, the pharmacological inhibition of AMPK activity nearly abrogated such alteration. CONCLUSIONS: Thus, LanGui tea emerges as a promising herbal therapy for ALD management involving AMPK-NLRP3 signaling.

Raman spectrum combined with deep learning for precise recognition of Carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) is a major pathogen that poses a serious threat to human health. Unfortunately, currently, there are no effective measures to curb its rapid development. To address this, an in-depth study on the surface-enhanced Raman spectroscopy (SERS) of 22 strains of 7 categories of CRE using a gold silver composite SERS substrate was conducted. The residual networks with an attention mechanism to classify the SERS spectrum from three perspectives (pathogenic bacteria type, enzyme-producing subtype, and sensitive antibiotic type) were performed. The results show that the SERS spectrum measured by the composite SERS substrate was repeatable and consistent. The SERS spectrum of CRE showed varying degrees of species differences, and the strain difference in the SERS spectrum of CRE was closely related to the type of enzyme-producing subtype. The introduced attention mechanism improved the classification accuracy of the residual network (ResNet) model. The accuracy of CRE classification for different strains and enzyme-producing subtypes reached 94.0% and 96.13%, respectively. The accuracy of CRE classification by pathogen sensitive antibiotic combination reached 93.9%. This study is significant for guiding antibiotic use in CRE infection, as the sensitive antibiotic used in treatment can be predicted directly by measuring CRE spectra. Our study demonstrates the potential of combining SERS with deep learning algorithms to identify CRE without culture labels and classify its sensitive antibiotics. This approach provides a new idea for rapid and accurate clinical detection of CRE and has important significance for alleviating the rapid development of resistance to CRE.

Prediction of freshwater ecotoxicological hazardous concentrations of major surfactants using the QSAR-ICE-SSD method.

Synthetic surfactant products are continuously released into the aquatic environment in large quantities, posing a burden on ecosystems as a "pseudo-persistent" organic pollutant. Threshold derivation for protecting aquatic ecosystems is challenging due to the various homologous components of surfactants. In this study, five commercially available products were chosen as representative major types of surfactants. Corresponding quantitative structure-activity relationships (QSAR) were screened and subsequently combined with interspecific correlation estimation (ICE) to develop species sensitivity distributions (SSDs) for each component. Then, the 5th percentile hazard concentrations (HC5s) were calculated. The results indicated that the developed QSAR-ICE models demonstrated good toxicity prediction performance. The HC5 of each component showed a negatively correlation with alkyl chain length and a positive correlation with the amount of ethylene oxide. The HC5s of surfactants correlate with variations in their charged properties. Quaternary ammonium compounds (QAC) exhibited the lowest HC5s (8.5 ± 18.3 µg/L), followed by alcohol ethoxylates (AE), linear alkylbenzene sulfonates (LAS), and alcohol ethoxylated sulfates (AES); and alkyl oxide (AO) exhibited the highest HC5s (15784.2 ± 21552.6 µg/L). For cationic surfactants, the HC5s in the invertebrates were significantly lower than those in the fish; conversely, for anionic surfactants, the opposite was true, indicating a difference in the toxic mechanisms of surfactants with different charged properties across species taxa. Additionally, among invertebrates, shellfish demonstrated heightened sensitivity to surfactants, owing to their high accumulation and low metabolism of pollutants. Salmoniformes were the most sensitive among all species, indicating the necessity of prioritizing these species for aquatic ecological conservation in surfactant-contaminated waters.

Pd-catalyzed ortho-C-H arylation of free anilines with arylboric acids forming o-amino biaryls.

We report a Pd-catalyzed ortho-C-H arylation of free anilines with arylboric acids. Under the reaction conditions, a wide range of arylboric acids can couple with free anilines to produce the corresponding o-amino biaryls in moderate to good yields with good functional group tolerance. This reaction can be conducted on the gram scale. The products can be easily further functionalized via transformation of the free amino group. These results indicate the potential synthetic value of this new reaction in organic synthesis.

Hearing aid wear time and its impact on vocabulary in preschoolers with moderately severe to profound hearing loss.

OBJECTIVE: This study aimed to explore how the consistency of hearing aid (HA) use impacts vocabulary performance in children with moderately severe to profound hearing loss and determine the amount of HA use time associated with better vocabulary outcomes. DESIGN: Personal wear time percentage (WTP) was an indicator of HA use consistency, and the information on HA wear time was collected from both parent reports and datalogs. Pearson's correlations were performed to investigate the associations between hearing loss severity, WTP and vocabulary performance. Standard vocabulary scores among children below and above three WTP cutoff values (80%, 85%, and 90%) were examined to determine the WTP amount that yielded significantly better vocabulary outcomes. STUDY SAMPLE: Forty-seven children aged 36-79 months and their caregivers. RESULTS: Both parent reports and datalogs WTP significantly correlated with vocabulary outcomes. Parent-reported WTP were found to be predictive of datalogs WTP. Apart from hearing thresholds, HA fitting age and maternal education level, datalogs WTP was a significant independent predictor of vocabulary performance. Children with ≥ 90% WTP were more likely to perform better on vocabulary tests than those with < 90% WTP. CONCLUSION: The findings support the potential benefits of consistent HA use for vocabulary development.

A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

PURPOSE: Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. METHODS: In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. RESULTS: The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. CONCLUSION: The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.

NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer's Disease.

Oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD), which is linked to reactive oxygen species (ROS), lipid peroxidation, and neurotoxicity. Emerging evidence suggests a role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a major source of antioxidant response elements in AD. The molecular mechanism of oxidative stress and ferroptosis in astrocytes in AD is not yet fully understood. Here, we aimed to investigate the mechanism by which Nrf2 regulates the ferroptosis of astrocytes in AD. We found decreased expression of Nrf2 and upregulated expression of the ROS marker NADPH oxidase 4 (NOX4) in the frontal cortex from patients with AD and in the cortex of 3×Tg mice compared to wildtype mice. We demonstrated that Nrf2 deficiency led to ferroptosis-dependent oxidative stress-induced ROS with downregulated heme oxygenase-1 and glutathione peroxidase 4 and upregulated cystine glutamate expression. Moreover, Nrf2 deficiency increased lipid peroxidation, DNA oxidation, and mitochondrial fragmentation in mouse astrocytes (mAS, M1800-57). In conclusion, these results suggest that Nrf2 deficiency promotes ferroptosis of astrocytes involving oxidative stress in AD.

Anti-inflammatory response-based risk assessment in acute type A aortic dissection: A national multicenter cohort study.

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (ß -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

[Comparative study of orthopaedic robot-assisted minimally invasive surgery and open surgery for limb osteoid osteoma].

Objective: To compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma. Methods: A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively. Results: Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05). Conclusion: Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.

Study protocol for the validation of a new pictorial functional scale in patients with knee osteoarthritis: the functional activity scoring tool (FAST).

BACKGROUND: Patient-reported outcome measures (PROMs) are required for patient-centred care. There are limited PROMs with good psychometric properties, and limitations to any language-based scale are often constrained by the written words or numerals used. Therefore, we developed the Functional Activity Scoring Tool (FAST), a self-reporting pictorial scale. FAST measures the impact of knee osteoarthritis on essential activities of daily living (ADL) and the significant changes in the self-perceived functional status over time. OBJECTIVES: This study aims to (1) develop FAST with adaptation from the Wong-Baker FACES pain rating scale, (2) validate FAST against the Patient-Specific Functional Scale (PSFS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) and (3) establish the reliability, validity and responsiveness of FAST in individuals with knee osteoarthritis. METHODS AND ANALYSIS: The prospective study protocol investigates the validity, responsiveness and reliability of FAST. The PSFS and KOOS will be gold standard comparisons. Participant recruitment will occur at four public polyclinics that offer physiotherapy outpatient services in Singapore. Onsite physiotherapists familiar with the study eligibilities will refer potential participants to the investigators after the routine physiotherapy assessment. After providing written consent, eligible participants will complete outcome measurements with FAST, the PSFS and KOOS during baseline and follow-up assessments. The Global Rating of Change (GROC) scale will determine how the participant's knee status was changed compared with the beginning of the physiotherapy intervention. ETHICS AND DISSEMINATION: SingHealth Centralised Institutional Review Board approved the study (CIRB reference number: 2022/2602). The final results will be published via scientific publication. FAST will benefit the evaluation and management of those who suffer knee osteoarthritis regardless of English proficiency or language barriers. TRIAL REGISTRATION NUMBER: NCT05590663.

Application of Botulinum Toxin at the Yonsei Point for the Treatment of Gummy Smile: A Randomized Controlled Trial.

BACKGROUND: Demand for less-invasive procedures for treating gummy smile, such as botulinum toxin A injections, has increased substantially over the years. Meanwhile, the optimal injection site for botulinum toxin A injection is debated. The authors aimed to investigate the efficacy of botulinum toxin A injection at the Yonsei point for treating gummy smile. METHODS: In this double-blind, single-site, randomized clinical trial, healthy participants with a gummy smile (anterior gingival exposure of ≥3.0 mm) were enrolled and randomized (1:1 ratio) into two groups. The experimental group was administered 6 U of botulinum toxin A at the Yonsei point (a single-site injection of 3 U to the right Yonsei point and 3 U to the left Yonsei point), and the control group received the same dose in the bilateral levator labii superioris alaeque nasi muscle sites. The patients were assessed at baseline and 4, 12, 24, and 48 weeks after the first injection using a digital vernier caliper. RESULTS: A total of 49 participants were enrolled. Anterior and bilateral posterior gingival exposure were reduced at 4, 12, and 24 weeks ( P ≤ 0.05) and returned to baseline at 48 weeks in both groups; there was no difference between the groups at these time points. The increase in satisfaction among patients was significant, and few adverse events were observed. CONCLUSION: Both the Yonsei point and the levator labii superioris alaeque nasi muscle site can be used as botulinum toxin A injection sites for treating gummy smile. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.