Better efficacy, lower recurrence rate and decreased CD8+TRM with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China.

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis.

BACKGROUND: Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE: This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS: A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS: The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS: This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

BNIP3L/NIX-mediated mitophagy alleviates passive stress-coping behaviors induced by tumor necrosis factor-α.

Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.

Insulin Resistance Impairs Biological Agents Response in Moderate-to-Severe Plaque Psoriasis: Insights from a Prospective Cohort Study in China.

BACKGROUND: Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. OBJECTIVE: The objective of this study was to investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. METHODS: This project was based on a prospective cohort study design. Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using the triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. RESULTS: A total of 290 patients were included in the analysis. Based on the median TyG-BMI, the patients were divided into two groups: High and Low. The High group exhibited a higher prevalence of diabetes, higher BMI, fasting blood glucose, and triglyceride compared with the Low group. Further analysis of the treatment efficacy revealed that the High group had lower response rates for PASI 75, PASI 90, and PGA 0/1 after 12 weeks of treatment. In the Low group, 81.94% of patients achieved PASI 75, 58.33% achieved PASI 90, and 75.69% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the High group. The impairment in response to PGA 0/1 was more significant in the High group, indicated by lower odd ratios. Subsequent subgroup analysis and sensitivity analysis produced consistent results. CONCLUSION: IR is associated with lower effectiveness of biologics in patients with psoriasis. CLINICAL TRIAL REGISTRATION: [www.chictr.org.cn], identifier [ChiCTR2000036186].

Quality of Life Benefit and Clinical Predictors of Complete Skin Clearance in Psoriasis: A Multicenter, Prospective, Real-World Study.

BACKGROUND: Newer biologics, such as interleukin (IL)-17 inhibitors, make it possible to achieve complete skin clearance (CSC) in patients with moderate-to-severe psoriasis. However, the clinical meaningfulness and predictive factors of CSC in daily practice have not yet been fully investigated. OBJECTIVE: The study was conducted to, first, assess the impact of CSC on quality of life (QoL) improvements compared with treatment responses without clearance and, second, identify clinical parameters as predictors of CSC response in psoriasis patients treated with ixekizumab. METHODS: Patients attending 26 dermatology centers across China were recruited into this real-world setting between August 2020 and May 2022. Prospective cohort study in which response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI). The absolute DLQI score and DLQI (0) response at week 12 were compared between groups achieving various levels of skin clearance. A stepwise logistic regression analysis was applied to identify which baseline clinical characteristics were predictive factors for CSC. RESULTS: After 12 weeks of treatment, 226 of 511 (44.2%) patients achieved CSC, defined as 100% improvement in PASI score (PASI-100). A significantly higher proportion of patients with CSC versus almost clear skin (PASI 90-99) achieved DLQI score of 0, corresponding to the experience of no impairment on QoL (54.4% vs. 37.7%, p = 0.001). Females patients were more likely than males to achieve CSC response (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.24-2.70), while previous biologic treatment (OR = 0.43; 95% CI: 0.24-0.81) and joint affected (OR = 0.61; 95% CI: 0.42-0.89) were significantly associated with less CSC response. CONCLUSIONS: This study highlights the fact that clinical parameters are important in determining CSC response in psoriasis. In daily practice, achieving CSC represents a clinically meaningful treatment goal, especially from the patient perspective.

Improvement of parents' oral health knowledge by a school-based oral health promotion for parents of preschool children: a prospective observational study.

BACKGROUND: Parents of preschool children have inadequate oral health knowledge in Hong Kong. Parents play a critical role in preschool children's dietary patterns and oral health behaviors. A school-based oral health promotion (OHP) for parents of preschoolers was developed and investigated. OBJECTIVES: The objective of this study was to evaluate effects of the school-based OHP for parents of preschool children on parents' oral health knowledge and preschool children's early childhood caries (ECC). MATERIALS AND METHODS: This was a quasi-experimental study. Parents of preschool children were divided into the intervention group (IG) and the control group (CG) according to their own selection. Parents in the IG participated in a structured school-based OHP workshop, while those in the CG did not attend the OHP workshop. Parents in both groups were invited to complete a questionnaire assessing their oral health knowledge before (T0), one month after (T1), and twelve months after (T2) the OHP workshop. Preschool children's caries was examined via dmft score at T0 and T2. RESULTS: Parents' oral health knowledge was negatively correlated with preschool children's dmft scores (R = -0.200, P < 0.001). Oral health knowledge was significantly improved in IG (P < 0.001) but not in CG (P = 0.392) at T1. Both groups experienced a significant improvement in oral health knowledge from T0 to T2 (P < 0.001). Parents' oral health knowledge in the IG was significantly higher compared to the CG at T1 (P < 0.001), but difference in the scores at T2 between the two groups showed no significant difference (P = 0.727). No significant difference was found in changes in children's dmft score from T0 to T2 between the IG and CG (p = 0.545). CONCLUSION: Preschool children's high ECC is associated with the limited oral health knowledge of their parents. The school-based OHP workshop for parents increased parents' oral health knowledge within one month. This positive effect was maintained for twelve months and can be extended to a larger scale in the school setting.

Erythrokeratodermia variabilis et progressiva due to a novel mutation in GJB4.

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare genodermatosis of clinical and genetic heterogeneity, characterized by the manifestations of localized or disseminated persistent hyperkeratotic plagues and stationary to migratory transient erythematous patches. The majority of EKVP cases display an autosomal dominant mode of inheritance with incomplete penetrance, although recessive transmission has also been described. Mutations associated with EKVP have been primarily detected in connexin (Cx) genes. We herein reported a Chinese sporadic case of late-onset EKVP with a novel heterozygous missense mutation c.109G>A (p.V37M) in GJB4 (Cx30.3) gene, which resulted in a significant reduction of GJB4 expression in the epidermis of the patient. In accordance, while wild-type GJB4 localized at the cell membrane of HeLa cells forming intercellular junctions and intracellular puncta, V37M mutant variant was diffusely expressed within HeLa cells at a considerably lower level. Our findings reveal an essential role of GJB4 in the pathogenesis of EKVP and provides insights into the therapeutic potential of the disease.

The efficacy and safety of dupilumab for the treatment of atopic dermatitis among Chinese patients in clinical practice: A single-center retrospective study.

Little real-work data regarding the efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) is available at present. To assess the efficacy and safety of dupilumab at 12 weeks in the treatment of AD in clinical routine clinical practice. A retrospective, single-centre study of adult patients with moderate to severe AD treated with dupilumab for 12 weeks in China. In total, 60 patients (48 male, 12 female; mean age: 53.2 ± 15.6) were enrolled in this retrospective study. These patients exhibited a mean AD disease course of 10.6 years (6.0), 30% exhibited a family history of allergies, and 31 (51.7%) had one or more allergic comorbidities. Following dupilumab treatment for 12 weeks, 83.3% and 42% of patients had achieved EASI-50 and EASI-75, respectively. Overall, adverse events (AEs) were reported by 15% of patients, with the most common being conjunctivitis, injection site reactions, and herpes simplex virus infections. Laboratory testing after 12 weeks revealed pronounced decreases in both circulating eosinophil counts (from 0.6 (0.1-2.8) to 0.3 (0.1-9.7) 109 /L) and total IgE concentrations (from 327 (2.46-2500) to 230 (47.6-2200) U/ml) in these patients. These real-world data reaffirm the safety and efficacy of dupilumab as a treatment for moderate-to-severe AD among Chinese patients in clinical practice.

Integrated bioinformatic analysis of key biomarkers and signalling pathways in psoriasis.

BACKGROUND AND AIMS: Psoriasis is a relatively common autoimmune inflammatory skin disease with a chronic etiology. Since psoriasis is still incurable, it is necessary to identify the molecular mechanisms of psoriasis. The present study was designed to detect novel biomarkers and pathways associated with psoriasis incidence, and provide new insights into treatment of psoriasis. METHODS AND RESULTS: Differentially expressed genes (DEGs) associated with psoriasis in the Gene Expression Omnibus (GEO) database were identified, and their functional roles and interactions were then annotated and evaluated through GO, KEGG, and gene set variation (GSVA) analyses. In total 197 psoriasis-related DEGs were identified and found to primarily be associated with the NOD-like receptor, IL-17, and cytokine-cytokine receptor interaction signalling pathways. GSVA revealed significant differences between normal and lesional groups (P < 0.05), while PPI network analyses identified CXCL10 as the hub gene with the highest degree value, whereas IRF7, IFIT3, OAS1, GBP1, and ISG15 were promising candidate genes for the therapeutic treatment of psoriasis. CONCLUSION: The findings of the present integrated bioinformatics may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis.

3-Dimensional simulations and student learning in orthodontic education.

INTRODUCTION: The electronic dental model (e-model) is an example of a digital 3-dimensional technology to support inquiry-based learning in undergraduate dental education. As student perceptions of and engagement with e-models vary, it is uncertain whether these perceptions have implications for their learning processes and outcomes. MATERIALS AND METHODS: Third-year dental students (N = 40) completed a questionnaire to identify their perceptions of and preferences for model modalities. They were divided into three groups based on their preference: Preferring plaster models (Group 1); Preferring e-models (Group 2); No preference (Group 3). Students from three groups (N = 9) attended a hands-on digital occlusion evaluation workshop, and then completed a case-based diagnostic evaluation test using digital occlusion evaluation software. Camtasia Studio™ recorded real-time and on-screen data of the number of mouse-clicks and time spent. RESULTS: Students reported positive feedbacks on the use of e-models, and 72.5% of the students preferred combination use of e-models and plaster models. After attending the hands-on digital dental occlusion evaluation workshop, Group 2 scored higher on the diagnostic evaluation test (p < .05) and registered more mouse-clicks than Group 1 when evaluating the arch symmetry (p < .05). Group 2 registered fewer mouse-clicks than Group 3 during tooth size measurement (p < .05). There was no significant difference regarding the time used to answer the knowledge questions amongst the three groups. CONCLUSION: Undergraduate dental students indicated a generally high acceptance of e-models for their learning in orthodontics, and more prefer a blended approach. Students preferring e-models presented higher performance outcomes, which supports cognitive load theory regarding prior exposure to simulation-based environments.

A randomized prospective study of different dose regimens using the 308-nm excimer laser in the treatment of palmoplantar pustulosis.

The objective of this study was to evaluate optimal treatment regimen of 308-nm excimer laser for palmoplantar pustulosis (PPP). 77 patients with PPP were randomly assigned to receive low dose (2-fold of MED as initial dose), medium dose (4-fold of MED as initial dose) and high dose group (6-fold of MED as initial dose) and the MED of each patient depended on the ultraviolet light sensitivity of individual's skin which ranged from 0.1 to 0.25 J/cm2 . All group received 308-nm excimer laser treatment three times weekly for 8 weeks. Clinical evaluation based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PP-PASI) and Dermatology Life Quality Index (DLQI) score. All treatment groups achieved satisfied efficacy at the end of the treatment period with more obvious reduction of PP-PASI score in high dose group (16.05 ± 4.26) than low and medium dose group (23.67 ± 7.16, p < 0.01; 22.04 ± 5.74, p < 0.01). Improvement of DLQI score was greatest at week 4 for all patients in each group, while DLQI improved more quickly in high/medium dose group than low dose group. Adverse effects of erythema, blistering and erosions were more common with the higher dose regimen. High dose of 308-nm excimer laser could achieve a better efficacy in PPP treatment, reduce the severity of the disease in patients and improve the life quality of patients. Meantime, the incidence of adverse reactions should be aware of and it's necessary to evaluate the skin and lesion type before the dose selection.

Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis.

Many studies confirm that circular RNA (circRNA) plays an important regulatory role in the malignant progression of cancer, including melanoma. However, the role of a novel circRNA, circ_0079593, in melanoma is unclear. The expression levels of circ_0079593 and miR-516b were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured by cell counting kit-8 (CCK-8) assay, and cell migration and invasion were evaluated using transwell assay. Meanwhile, western blot (WB) analysis was employed to determine the levels of proliferation and metastasis-related proteins, as well as metabotropic glutamate receptor 3 (GRM3) protein. Furthermore, cell apoptosis was tested by detecting the cell apoptosis rate and Caspase-3 activity. The glucose consumption and lactate production of cells were measured to evaluate cell glucose metabolism. Moreover, dual-luciferase reporter assay and biotin-labeled RNA pull-down assay were used to confirm the interaction between miR-516b and circ_0079593 or GRM3. In addition, mice xenograft models were constructed to explore the effect of circ_0079593 on melanoma tumor growth in vivo. Our results discovered that circ_0079593 was highly expressed in melanoma, and its silencing suppressed melanoma cell proliferation, migration, invasion, glucose metabolism and promoted apoptosis. Moreover, we found that circ_0079593 could serve as a sponge of miR-516b, and miR-516b could target GRM3 in melanoma. The rescue experiments revealed that both miR-516b inhibitor and GRM3 overexpression could reverse the inhibition effect of circ_0079593 knockdown on melanoma progression. Additionally, in vivo experiments also revealed that circ_0079593 interference suppressed melanoma tumor growth. Our study concluded that circ_0079593 accelerated melanoma progression via upregulating GRM3 by sponging miR-516b, which suggested that circ_0079593 had the potential to be a new therapeutic biomarker for melanoma.

Efficacy and survival of infliximab in psoriasis patients: A single-center experience in China.

Psoriasis is a chronic, systemic disease that requires long-term management. Biologic agents have been used widely against psoriasis, such as infliximab. We analyzed the survival and discontinuation rates of infliximab when treating psoriasis under real-world conditions in China. Patients with moderate-to-severe psoriasis treated with infliximab in Shanghai Skin Disease Hospital from January 2015 to April 2020 were included in our retrospective study. Information from their medical records (clinical characteristics, Psoriasis Area Severity Index [PASI] score, laboratory results, and time of discontinuation) was collected through the Shanghai Skin Disease Hospital database. The survival of infliximab was assessed with Kaplan-Meier plots and multivariate Cox regression. Forty-two patients who underwent treatment were assessed retrospectively (38.1% had been diagnosed with psoriatic arthritis [PsA]). The discontinuation rate was 57.1%, the mean survival time of discontinuation was 57 weeks for patients with PsA vs 69 weeks for those without PsA (P = .5993). The cholesterol level (P = .003) and lymphocyte percentage (P = .010) were associated with longer survival of infliximab according to Cox regression analysis. Our study revealed that infliximab had a similar drug survival as previous studies, the high cholesterol level and lymphocyte percentage might function as negative predictor for infliximab persistence.

Local reinfusion of B10 cells is effective in the treatment of pustular psoriasis.

Psoriasis is a common chronic skin disease characterized by epidermal proliferation and inflammation. Pustular psoriasis (PP) is one of the most serious and refractory. The number, differentiation, and function of B10 cells in patients with PP were analyzed, and the relationship between B10 cells and PP, an autoimmune disease, was explored. We established an Imiquimod psoriasis mouse model and subcutaneously injected B10 cells as treatment. We found that the proportion of B10 cells in the peripheral blood of patients with PP was lower than that of the normal controls. However, the number of B10 precursor cells increased. B10 cells in the peripheral blood may be mobilized to effector sites, such as the skin. In patients with PP, B10 cells do not display evident developmental disorders under the CD40 and TLR9 pathways. Normal human B10 cells were found to inhibit the secretion of IFN-γ and TNF-α by lymphocytes significantly. Whereas the function of B10 cells in patients with PP is impaired, and the inhibition is not apparent. Treatment with a B10 cells injection displays a certain therapeutic effect on PP. This study enriched the etiology and pathogenesis of PP. It provides a foundation for cell therapy for the treatment of autoimmune diseases.

miR-214-3p Targets ß-Catenin to Regulate Depressive-like Behaviors Induced by Chronic Social Defeat Stress in Mice.

ß-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of ß-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons. We demonstrated that the levels of miR-214-3p, which targets ß-catenin transcripts were significantly increased in the medial prefrontal cortex (mPFC) of CSDS mice. Antagomir-214-3p, a neutralizing inhibitor of miR-214-3p, increased the levels of ß-catenin and reversed the depressive-like behavior in CSDS mice. Meanwhile, antagomir-214-3p increased the amplitude of miniature excitatory postsynaptic current (mEPSC) and the number of dendritic spines in mPFC of CSDS mice, which may be related to the elevated expression of cldn1. Furthermore, intranasal administered antagomir-214-3p also significantly increased the level of ß-catenin and reversed the depressive-like behaviors in CSDS mice. These results may represent a new therapeutic target for MDD.

Miliaria crystallina secondary to herbal remedies-induced toxic epidermal necrolysis: A case report.

Miliaria crystallina is a skin disorder that often erupts in the process of febrile diseases or under hot and humid climatic conditions. Toxic epidermal necrolysis (TEN) is a rare, acute, and life-threatening mucocutaneous disease with a mortality rate of 25-35%. There has been no inevitable connection between the two diseases among previously reported cases, but we observed a case of secondary miliaria crystallina a woman with herbal remedies-induced TEN during the therapeutic process.

The role of traditional Chinese medicines in osteogenesis and angiogenesis.

The article aims to review various Traditional Chinese Medicines (TCMs) with both osteogenic and angiogenic effects, alone and in combination, and to consider whether these TCMs promote osteogenesis via angiogenesis and vascular endothelial growth factor (VEGF). Each of the TCMs involving in osteogenesis was searched through PubMed and CBMdisc using its Latin name and English name, and keywords such as 'osteogenesis', 'bone', 'osteoblast', 'angiogenesis', 'VEGF' were used. A total of 241 articles were screened from PubMed and CBMdisc. The articles were only chosen if they discussed the relationship of the TCMs with bone formation and/or angiogenesis. Twenty-seven articles were chosen, of which 16 were in English and 11 were in Chinese with English abstract. As a result, the TCMs (Danshen or Salvia miltiorrhiza Bunge, Danggui or Angelica sinensis, Astragalus membranaceus Bunge or Huangqi, and Ge Gan or Puerarin radix) that have a relationship with both osteogenesis and angiogenesis were screened out. It is found that the aforementioned TCMs enhance angiogenesis and osteogenesis. They show a positive effect on bone formation, and the possible mechanisms may be related to their ability to promote angiogenesis via an effect on substances such as VEGF.