Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile.

Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Aesthetic evaluation of nasolabial reconstruction using abbe flap in bilateral cleft lip patients with secondary deformities.

BACKGROUND: The Abbe flap is a common technique frequently utilized in secondary surgery for bilateral cleft lip deformities, but objective indications for the Abbe flap remain unclear, and postoperative aesthetic evaluations are limited. METHODS: The study group consisted of 92 bilateral cleft lip patients with secondary deformities aged 7-39 years, and the control group consisted of 33 people aged 19-35 years. Thirteen objective nasolabial aesthetic parameters were selected to evaluate patients' nasolabial aesthetics. RESULTS: Minor secondary deformities were characterized by a smaller lip height index than severe deformities, as well as a smaller columellar angle compared with moderate and severe deformities (P < 0.05). For all patients, significant differences were found between preoperative and postoperative values of intercanthal distance/medial upper vermilion height ratio, intercanthal distance/medial upper lip height ratio, lip height index, lip vermilion height index, lip protrusion angle, columellar-labial angle, and nasal tip angle (P < 0.05). For patients with minor deformity, intercanthal distance/philtrum width ratio and intercanthal distance/medial cutaneous upper lip height ratio showed no significant change postoperatively (P > 0.05), and labial protrusion angle was smaller than the control group (P < 0.05). CONCLUSIONS: Patients undergoing secondary surgery using an Abbe flap achieved good nasolabial aesthetics. Intercanthal distance/medial upper vermilion height ratio, intercanthal distance/medial upper lip height ratio, lip height index, columellar-labial angle, nasolabial angle, nasal tip angle, and columellar angle are the objective aesthetic indicators for Abbe flap selection. Intercanthal distance/philtrum width ratio, intercanthal distance/medial cutaneous upper lip height ratio, and labial protrusion angle are reference parameters for choosing an Abbe flap for secondary bilateral cleft lip revision.

Serum 25-Hydroxyvitamin D Is Differentially Associated with Early and Late Age-Related Macular Degeneration in the United States Population.

BACKGROUND: Age-related macular degeneration (AMD) has been the leading cause of irreversible blindness in industrialized countries. Emerging data suggest that serum vitamin D levels may be associated with AMD but show mixed results. National-level population data on the relationship between vitamin D and AMD severities are still lacking. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. Retinal photographs were taken and graded for AMD stage. The odds ratio (OR) of AMD and its subtype was calculated after adjusting for confounding factors. Restricted cubic spline (RCS) analyses were used to explore potential non-linear relations. RESULTS: A total of 5041 participants with a mean age of 59.6 years were included. After adjusting for covariates, participants with higher level of serum 25-hydroxyvitamin D [25(OH)D] had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08-2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09-0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was present in the <60 years group (OR, 2.79; 95% CI, 1.08-7.29), whereas a negative relation between the level of serum 25(OH)D and late AMD was detected in the ≥60 years group (OR, 0.24; 95% CI, 0.08-0.76). CONCLUSIONS: A higher level of serum 25(OH)D was related to increased risk of early AMD in those <60 years and decreased risk of late AMD in those ≥60 years.

A bibliometric analysis of systematic reviews and meta-analyses in ophthalmology.

Background: Bibliometric analysis is a quantitative method which applies mathematical and statistical tools to evaluate the inter-relationships and impacts of publications, authors, institutions and countries in a specific research area. Systematic reviews and meta-analyses (SRMAs) are summaries of the best available evidence to address a specific research question via comprehensively literature search, in-depth analysis and synthesis of results. To date, there have been several studies summarizing the publication trends of SRMAs in research specialties, however, none has conducted specifically in ophthalmology. The purpose of this study is to establish the scientometric landscape of SRMAs published in the field of ophthalmology over time. Methods: We retrieved relevant ophthalmological SRMAs and the corresponding bibliometric parameters during 2000 to 2020 from Web of Science Core Collection. Bibliometric analysis was performed using bibliometrix package. Pre-registration and guideline compliance of each article was independently assessed by two investigators. Results: A total of 2,660 SRMAs were included, and the average annual growth rate was 21.26%. China and the United States were the most productive countries, while Singapore was the country with the highest average citations per document. Wong TY was not only the most productive, but also the most frequently cited author. The most productive affiliation was National University of Singapore (n = 236). Systematic reviews and meta-analyses output in most subspecialties had steadily increased with retina/vitreous (n = 986), glaucoma (n = 411) and cornea/external diseases (n = 303) constantly as the most dominant fields. Rates of pre-registration and guideline compliance had dramatically increased over time, with 20.0 and 63.5% of article being pre-registered and reported guideline in 2020, respectively. However, SRMAs published on ophthalmology journals tended to be less frequently pre-registered and guideline complied than those on non-ophthalmology journals (both p < 0.001). Conclusion: The annual output of SRMAs has been rapidly increasing over the past two decades. China and the United States were the most productive countries, whereas Singapore has the most prolific and influential scholar and institution. Raising awareness and implementation of SRMAs pre-registration and guideline compliance is still necessary to ensure quality, especially for ophthalmology journals.

Recent Advances and Challenges in Uveal Melanoma Immunotherapy.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4-5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.

Photochemical deposition of amorphous MoSx on one-dimensional NaNbO3-CdS heterojunction photocatalysts for highly efficient visible-light-driven hydrogen evolution.

A novel ternary MoSx-CdS-NaNbO3 (MoSx-CN) photocatalyst was successfully fabricated through a two-step method (hydrothermal synthesis and photo-deposition step). The results demonstrated that CdS nanoparticles and amorphous MoSx uniformly dispersed on one-dimensional (1D) NaNbO3 nanowires, thus forming multi-junctions (CdS-NaNbO3, CdS-MoSx and NaNbO3-MoSx) that could increase the migration efficiency of photo-excited charge carriers. In addition, an abundance of unsaturated sulfur atoms in MoSx led to a strong attraction to H+, thus providing active sites for water splitting. Consequently, the optimized composite sample (MoSx-CN-100) exhibited a hydrogen (H2) evolution efficiency of 2.386 mmol g-1 h-1, which was about 125.58 and 11.93 times that of NaNbO3 and CdS, respectively. Moreover, the ternary photocatalyst also exhibited excellent stability in the long-term hydrogen production process compared with the binary and single samples. Our work provided new insight into the rational design of multi-heterojunction photocatalysts with high efficiency for H2 evolution under visible light irradiation.