OBJECTIVES: Verrucous epidermal nevus (VEN), seborrheic keratosis (SK), verruca plana (VP), verruca vulgaris (VV), and nevus sebaceous (NS) are common verrucous proliferative skin diseases with similar clinical appearances, often posing diagnostic challenges. Dermoscopy and reflectance confocal microscopy (RCM) can aid in their differentiation, yet their specific features under these tools have not been systematically described. This study aims to summarize and analyze the dermoscopic and RCM features of VEN, SK, VP, VV, and NS. METHODS: A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled. Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions. RESULTS: Under dermoscopy, the 5 diseases displayed distinct characteristics: VEN typically showed gyriform structures; SK was characterized by gyriform structures, comedo-like openings, and milia-like cysts; VP and VV featured dotted vessels and frogspawn-like structures; NS presented as brownish-yellow globules. RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases. Specific features included gyriform structures and elongated rete ridges in VEN; pseudocysts and gyriform structures in SK; evenly distributed ring-like structures in VP; vacuolated cells and papillomatous proliferation in VV; and frogspawn-like structures in NS. CONCLUSIONS These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM. The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.
Humans ; Dermoscopy/methods* ; Diagnosis, Differential ; Microscopy, Confocal/methods* ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Keratosis, Seborrheic/pathology* ; Young Adult ; Warts/diagnosis* ; Child ; Aged ; Skin Diseases/pathology* ; Nevus, Sebaceous of Jadassohn/diagnosis* ; Skin Neoplasms/diagnosis* ; Child, Preschool

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

Objective To understand the molecular epidemiological characteristics of Norovirus outbreaks and the genome evolution of Norovirus epidemic strains in Hainan Province from 2020 to 2022.Methods The information and samples have been collected from the norovirus outbreaks from 2020 to 2022.Norovirus was detected by using the real-time PCR in these samples,then the detected sequences were amplified the analyzed.The Norovirus se-quences of 8 strains had been amplified and analyzed.Results From 2020 to 2022,39 gastroenteritis outbreaks were reported,and 25 outbreaks caused by Norovirus which mainly occurred in childcare institutions and schools(20/25,80％).The Norovirus outbreaks were mainly concentrated in counties around Haikou(northeast),which including Ding'an(5 cases),Wenchang(4 cases),Chengmai(4 cases),and Lingao(3 cases);following by western regions which included Baisha(2 cases),Ledong(2 cases),and Dongfang(3 cases).1 case was in Wanning in the southeast.Among individuals aged 2-17,the positive proportion of Norovirus in males was higher than that in females.Among individuals aged over 55,the proportion of Norovirus positive in females was higher than that in males.The gender of positive samples among individuals aged 18-40 was related to their profession.According to RT-PCR typing and sequencing,GⅡ group Norovirus were classified in13 outbreaks.There were 4 genotypes detected.GⅡ.2[P1 6]was the main epidemic strain with 60％(9/13),and the other three genotypes were GⅡ.4 Sydney[P31](15.4％,2/13)GⅡ.4 Sydney[P16](7.7％,1/13)and GⅡ.3[P12](7.7％,1/13).Further genic analysis of 8 Norovirus strains showed that all of them were still in the same branch as the previ-ous strain,and all exhibited a certain amount of amino acid variation.Conclusion Norovirus is the main pathogen of gastroenteritis outbreaks in Hainan province,and the main epidemic strain is GⅡ.2[P16].It is necessary to continue to strengthen the monitoring that provides scientific evidence for the prevention and control of norovirus out-breaks in Hainan region.

Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.

With the aging population in China,health issues among the elderly are becoming increasingly prominent,leading to a rapidly growing demand for health interventions for the elderly.Exergames are one of the important emerging methods in the field of health interventions for the elderly,widely used and yielding positive results.While research on exergames is well-established abroad,it is still in its infancy in China,lacking reports on the types,interaction forms,intervention content,application status,and effectiveness of exergames.Exergames are suitable for widespread use among the elderly in China,and there is a need to accelerate the development and application of exergames in the field of health interventions for the elderly in China.

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases. Methods:The two-sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P＜5×10-8).Causal effect estimates were generated using the inverse-variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed. Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease(OR=1.444,95％CI 1.199 to 1.738,P＜0.001)and ulcerative colitis(OR=1.002,95％CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema. Conclusion:Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Objective:To investigate the efficacy of acidified aliphatic ester in the treatment of atopic dermatitis (AD) in mouse models, and to preliminarily explore its mechanisms of action.Methods:Twenty female BALB/c mice aged 6 to 8 weeks were randomly divided into 2 groups: 5 mice in the blank control group were topically treated with absolute ethanol on both ears (14.3 μl per ear) every day, and 15 mice in the model group were topically treated with calcipotriol liniment (14.3 μl per ear) and 20 g/L ovalbumin (25 μl per ear) on both ears every day for 10 consecutive days to establish AD-like mouse models. From day 11, 15 mice in the model group were randomly divided into 3 groups (5 mice in each group), including AD model group, aliphatic ester group, and acidified aliphatic ester group; in the forenoon, all the 3 groups continued to be topically treated with calcipotriol liniment and ovalbumin to maintain AD-like models; in the afternoon, the aliphatic ester group and acidified aliphatic ester group were topically treated with aliphatic ester and acidified aliphatic ester respectively (10 μl per ear), and no treatment was given to the AD model group. Changes in body weight, ear thickness, ear skin lesion scores, and scratching frequency were observed. Ear skin swabs were obtained from the mice on days 10 and 14 for 16S rRNA gene - based microbial diversity tests. On day 14, mice were sacrificed after reflectance confocal microscopy examinations of the ear skin, ear tissues were resected for hematoxylin and eosin staining, mast cell staining, and real-time fluorescence-based quantitative PCR (RT-qPCR), and blood samples were collected for detection of serum IgE levels. One-way analysis of variance was used for analysis of data that met homogeneity of variance criteria, and least significant difference- t test for multiple comparisons. Results:On day 14, the severity of mouse ear lesions was the highest in the AD model group, followed in turn by the aliphatic ester group, acidified aliphatic ester group, and blank control group; compared with the AD model group, the acidified aliphatic ester group showed significantly decreased mouse ear thickness ( F = 897.50, P < 0.001), skin lesion scores ( F = 268.80, P < 0.001), scratching frequency ( F = 64.36, P < 0.001), and epidermal thickness ( F = 256.20, P < 0.001). In addition, RT-qPCR indicated that the expression of inflammatory factors such as interleukin (IL) -33, thymic stromal lymphopoietin, IL-4, and tumor necrosis factor-α in lesional areas, and the degree of mast-cell infiltration were all significantly lower in the acidified aliphatic ester group than in the AD model group ( F = 3.38, 8.70, 41.73, 44.30, 134.30, P = 0.049, = 0.001, < 0.001, < 0.001, <0.001, respectively). Microbial diversity tests showed that the acidified aliphatic ester treatment could inhibit the colonization of Staphylococcus spp. in the ears of AD-like mouse models, and the Shannon index and Simpson index significantly differed among the 4 groups ( F = 9.00, 7.92, P = 0.001, 0.002, respectively) . Conclusion:Acidified aliphatic ester could improve skin lesions of AD-like mouse models, possibly by regulating immunity, suppressing inflammation, and restoring skin microecological diversity.

OBJECTIVE To study the effects of isoliquiritigenin （ISL） regulating gut microbiota and repairing gut barrier function in model mice with non-alcoholic fatty liver disease （NAFLD）， and to clarify its mechanism for improving NAFLD. METHODS Thirty male C57BL/6J mice were randomly divided into the normal （ultrapure water）， model group （ultrapure water）， ISL group （100 mg/kg）， with 10 mice in each group. Model group and ISL group were fed with high-fat diet for 19 weeks to establish NAFLD model； at the same time， the mice were given relevant medicine/ultrapure water intragastrically. The changes of body weight in mice were recorded， and liver index， white fat index and brown fat index were calculated. The pathological changes of liver tissue and colon tissue as well as lipid accumulation were observed in mice. The levels of total cholesterol （TC）， triglyceride （TG）， aspartate aminotransferase （AST） and alanine aminotransferase （ALT） E-mail：xiangshj3@mail.sysu.edu.cn in serum or liver were measured； the serum levels of interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） and the levels of IL-6， IL-1β and TNF-α mRNA expression in liver tissue were detected. Fecal samples underwent 16S rDNA sequencing analysis， and the effects of ISL on gut microbiota structure of mice were investigated. The expressions of gut mucosal barrier-related proteins （Claudin-4， Occludin and ZO-1） were determined in the colon tissue of mice. RESULTS Compared with model group， the body weight， liver index， the levels of TC in liver tissue and serum， the levels of AST and ALT in serum， the levels of IL-6， IL-1β and TNF-α in serum， and the mRNA expression of TNF-α in liver tissue were all decreased significantly in ISL group， while brown fat index was increased significantly. The inflammation and damage of liver tissue were significantly improved， and the NAFLD activity score and the proportion of lipid staining area were significantly reduced （P＜0.05）. ISL could significantly up-regulate the relative abundance of beneficial microbiota （norank_f_Muribaculaceae， Odoribacter， Ruminiclostridium， etc.） and the expressions of intestinal barrier function- related proteins， but could significantly down-regulate the relative abundance of harmful bacteria （Desulfovibrio， norank_f_Lachnospiraceae， unclassified_p_Firmicutes）， and could repair intestinal barrier. CONCLUSIONS ISL could significantly delay the progress of NAFLD， the mechanism of which may be associated with regulating gut microbiota and improving gut barrier function.