Acquired perforating dermatosis: A clinicopathologic study, and the features of dermoscopy and reflective confocal microscopy of 37 cases.

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.

Fulvic Acid Attenuates Atopic Dermatitis by Downregulating CCL17/22.

The main pathogenic factor in atopic dermatitis (AD) is Th2 inflammation, and levels of serum CCL17 and CCL22 are related to severity in AD patients. Fulvic acid (FA) is a kind of natural humic acid with anti-inflammatory, antibacterial, and immunomodulatory effects. Our experiments demonstrated the therapeutic effect of FA on AD mice and revealed some potential mechanisms. FA was shown to reduce TARC/CCL17 and MDC/CCL22 expression in HaCaT cells stimulated by TNF-α and IFN-γ. The inhibitors showed that FA inhibits CCL17 and CCL22 production by deactivating the p38 MAPK and JNK pathways. After 2,4-dinitrochlorobenzene (DNCB) induction in mice with atopic dermatitis, FA effectively reduced the symptoms and serum levels of CCL17 and CCL22. In conclusion, topical FA attenuated AD via downregulation of CCL17 and CCL22, via inhibition of P38 MAPK and JNK phosphorylation, and FA is a potential therapeutic agent for AD.

A novel model of myocardial infarction based on atherosclerosis in mice.

RATIONALE: Coronary artery ligation to induce myocardial infarction (MI) and ischemia injury in mice is typically performed in normal mice, but This is not consistent with disease progression. There should be atherosclerosis (AS) first, followed by MI. OBJECTIVE: We tried a novel model to induce MI that was established on atherosclerosis in mice. This approach was much more consistent with disease progression. METHODS: In this study, Mice lacking apolipoprotein E (ApoE-/-) were randomly divided into four groups. The mice of the control and MI groups were fed normal diet for 24-weeks, while the mice of AS and AS + MI groups were fed high-fat diet (HFD). After 23 weeks, the mice of MI and AS + MI groups were ligated with coronary arteries. A week later, after echocardiography, analysis of plaque and myocardium were conducted on aortic and heart, then the serum, aorta and heart tissues were further detected. RESULTS: Our results showed that AS model mice exhibited significant body weight gain, dyslipidemia and atherosclerotic lesions formation which were in accordance with the pathological changes of AS. Co-treatment with AS and MI led to higher operative mortality and heart pathological were in accordance with the pathological changes of MI. In addition, Echocardiography and NT pro-BNP revealed co-treatment with AS and MI led to deterioration of cardiac function. AS also aggravated myocardial inflammatory cell infiltration and fibrosis post-MI. CONCLUSIONS: Together, it is feasible to establish myocardial infarction model based on atherosclerosis model.

Glycogen phosphorylase B promotes cell proliferation and migration through PI3K/AKT pathway in non-small cell lung cancer.

OBJECTIVE: Glycogen phosphorylase B (PYGB), the rate-determining enzyme in glycogen degradation, plays a critical role in progression of various tumors. The present study focused on the potential molecular mechanism toward PYGB in non-small cell lung cancer (NSCLC) progression. METHODS: Expression of PYGB in NSCLC tissues and cell lines was evaluated via quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. Cell viability, proliferation and apoptosis were investigated using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-bromo-2-deoxyuridine (BrdU) and flow cytometry, respectively. Cell migration and invasion ability were detected by wound healing and transwell invasion assays, respectively. The in vivo effect of PYGB on NSCLC tumor growth was determined via subcutaneous xenotransplanted tumor model. RESULTS: PYGB was upregulated in NSCLC tissues and cell lines, suggesting a poor prognosis in NSCLC patients. In vitro functional assays indicated that knockdown of PYGB suppressed cell viability, proliferation, migration and invasion, while promoted cell apoptosis in NSCLC. Mechanistically, we found that overexpression of PYGB could activate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, while these effects were effectively reversed by knockdown of PYGB. In vivo tumorigenesis and PI3K/AKT signaling pathway were also inhibited by PYGB knockdown. CONCLUSIONS: Knockdown of PYGB suppressed NSCLC progression, suggesting PYGB as a novel biomarker and potential molecular therapeutic target for further investigation in NSCLC.

Acquired Perforating Dermatosis Induced by PD-1 Inhibitor: A Case Report.

ABSTRACT: Acquired perforating dermatoses (APDs) are a group of diverse skin disorders in patients with systemic disease, most commonly chronic renal failure and diabetes mellitus. APD induced by medication has seldom been reported. Anti-PD-1 monoclonal antibody has recently been used as a broad-spectrum, effective, durable, and relatively safe antitumor therapy for various malignancies. Thus far, known side effects involving skin have included rash, pruritus, and vitiligo. Here, we present a rare case of a unilateral linear eruption with histopathologic features of APD in a 36-year-old man during treatment with Terepril monoclonal antibody. To the best of our knowledge, APD induced by the PD-1 inhibitor has not been described in the medical literature.

Chlamydial Plasmid-Encoded Protein pGP3 Inhibits Development of Psoriasis-Like Lesions in Mice.

BACKGROUND The anti-microbial protein cathelicidin LL-37 plays an important role in the pathogenesis of psoriasis by inducing inflammation. Our previous study showed that the chlamydial plasmid-encoded protein pGP3 forms a stable complex with LL-37 to neutralize its pro-inflammatory activity. Here, we explored whether pGP3 can inhibit the development of lesions in mice with imiquimod-induced psoriasis. MATERIAL AND METHODS The protein pGP3 was expressed in bacteria and purified using glutathione-conjugated agarose beads and a precision protease. The ability of the purified pGP3 to block chemotaxis mediated by LL-37 was tested in vitro using bone marrow-derived neutrophils. The ability of the protein to inhibit the development of psoriasis-like lesions was tested by topically or subcutaneously administering pGP3 in doses of 10 or 50 µg to mice previously treated with imiquimod. Mouse skin was evaluated using the psoriasis area and severity index (PASI) score and photography. Skin biopsies were taken on day 8 and analyzed histologically. RESULTS Purified pGP3 inhibited LL-37-mediated chemotaxis. Mice treated with 50 µg pGP3 showed clinical improvement with less severe erythema, infiltration, and scales; these mice also showed thinner dermis and less hyperkeratosis, parakeratosis, and inflammatory cell infiltration than mice treated with without 10 µg pGP3. CONCLUSIONS PGP3 can inhibit the development of psoriasis-like lesions in mice, possibly through its ability to bind LL-37. Future work should examine the mechanisms underlying this therapeutic effect.

Congenital Blaschkoid Angiolymphoid Hyperplasia With Eosinophilia of the Anogenital Region.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic vascular disorder. It manifests as dermal or subcutaneous red to brown papules or nodules, most commonly on the head and neck; other less common sites include the trunk, extremities, genitalia, lips, and oral mucosa. Although ALHE is a benign disease, lesions are often persistent and difficult to eradicate. ALHE occurs more frequently in Asian young and middle-aged women. Histologically, it is characterized by a florid vascular proliferation with hobnail epithelioid endothelial cells surrounding by lymphocytic and eosinophilic infiltrate. Here, we reported congenital ALHE in a 2-year-old girl. Unilateral lesions had a blaschkoid segmental distribution in the anogenital region and were successfully treated with the Nd:YAG laser.

Primary Cutaneous Interdigitating Dendritic Cell Sarcoma: A Case Report and Review of the Literature.

Interdigitating dendritic cell sarcoma (IDCS) is defined as a neoplastic proliferation of spindle to ovoid cells with phenotypic features similar to those of interdigitating dendritic cells, which are present in the T cell-rich areas of lymphoid organs and participate as antigen-presenting cells responsible for initiating primary T lymphocyte immune response. IDCS usually presents with lymphadenopathy. Solitary lymph node involvement is often seen. Extra nodal presentation has been described as well. Cutaneous lesions are extremely rare, and less than 10 cases have been previously documented in medical literature. Here, the authors describe another primary cutaneous IDCS in a 42-year-old patient and review the literature.

Panfolliculoma and histopathologic variants: a study of 19 cases.

Panfolliculoma (PF) is an uncommon benign follicular neoplasm exhibiting differentiation toward all components of a hair follicle. Several pathologic manifestations have been described in a limited number of cases. We studied 19 cases of PF to summarize the clinical parameters and to classify this unique neoplasm histopathologically. A study of the largest sample series of PF has been performed here. The lesions affect both genders after age 20. The head is the most common site of PF of all types. On microscopic examination, all cases demonstrated advanced follicular differentiation by showing cell components of infundibulum, isthmus, stem, bulb, and mesenchymal papilla. Based on the findings and various patterns in histopathology, we classified PF into 3 subtypes: nodular, superficial, and cystic. The superficial and cystic variants account for most of the cases in our study. The histopathologic differential diagnosis is also discussed for each subtype.

Exenatide-induced eosinophilic sclerosing lipogranuloma at the injection site.

Sclerosing lipogranuloma is a granulomatous reaction to the injection of a high-viscosity fluid in the tissues for the cosmetic purpose of improving body contour; lesions on the extremities and buttocks are commonly the results of injections of therapeutic agents in oily vehicles. Exenatide, once-weekly injection, is a therapeutic method for patients with type 2 diabetes. Here, we describe a case of exenatide once weekly induced eosinophilic sclerosing lipogranuloma at the injection site of a 62-year-old patient. To the best of our knowledge, the histopathologic features of this adverse event have not been reported in the medical literature.

Far-infrared radiation alleviates steatohepatitis and fibrosis in metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a disease that causes an abnormal accumulation of fat in the liver, triggering inflammation and fibrosis, the mechanism of which is not fully understood and for which there is a lack of specific drug therapy. Far-infrared radiation (FIR) has demonstrated evident therapeutic efficacy across various diseases, and novel nanomaterial graphene patches can emit it through electric heating. This study aimed to investigate the potential protective effects of FIR against MAFLD. Mice were fed with a MCD diet to mimic MAFLD progression, and histopathology analysis, biochemical analysis, RT-qPCR, and Western blotting analysis were performed to assess the effect of FIR on MAFLD in vivo. The effect of FIR treatment on MAFLD in vitro was investigated by biochemical analysis and gene expression profiling of hepatocytes. Mice subjected to the MCD diet and treated with FIR exhibited reduced hepatic lipid deposition, inflammation, fibrosis and liver damage. The therapeutic effect exerted by FIR in mice may be caused by the enhancement of AMPK phosphorylation and inhibition of the TGFß1-SMAD2/3 pathway. Besides, FIR intervention alleviated MAFLD in hepatocytes in vitro and the results were verified by gene expression profiling. Our results revealed a promising potential of FIR as a novel therapeutic approach for MAFLD.

Roles of gut microbiota in androgenetic alopecia: insights from Mendelian randomization analysis.

Background: Androgenetic alopecia (AGA) is the most common type of androgen-associated hair loss. Previous studies have indicated an association between the gut microbiota and AGA. To delve deeper, we executed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between the gut microbiota and AGA. Methods: A two-sample MR investigation was utilized to delve into the intricate interplay between gut microbiota and AGA. Information regarding 211 gut microbial taxa was sourced from the MiBioGen consortium. The summary statistics of the genome-wide association studies (GWAS) for AGA were obtained from the FinnGen biobank, which included 195 cases and 201,019 controls. Various analytical approaches, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed to evaluate the causal impact of gut microbiota on AGA. Sensitivity analyses were subsequently conducted to affirm the robustness of the findings. Results: A two-sample MR investigation unveiled the genus Olsenella, genus Ruminococcaceae UCG-004, and genus Ruminococcaceae UCG-010 were identified as risk factors associated with AGA. In contrast, the family Acidaminococcaceae and genus Anaerofilum, along with the genus Ruminiclostridium 9, demonstrated a protective effect. The sensitivity analyses provided additional assurance that the findings of the current study were less susceptible to the influence of confounding variables and biases. Conclusion: The MR study has established a link between specific gut microbiota and AGA, offering evidence for the identification of more precisely targeted probiotics. This discovery has the potential to aid in the prevention, control, and reversal of AGA progression.

Atopic dermatitis is associated with abnormal stool form: a population-based cross-sectional study in college students.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Bristol Stool Form Scale (BSFS) is a widely used stool scoring method that could indirectly reflect intestinal function. OBJECTIVES: To evaluate the associations of AD with BSFS. METHODS: This was a population-based cross-sectional study of freshmen in five universities of China. AD diagnosis was performed by dermatologists according to the guideline from the American Academy of Dermatology. BSFS and covariates were collected through an online questionnaire survey. Chronic itch scores were assessed by the numeric rating scales and grouped into quartiles (Q). Mixed logistic regression models were used. Subgroup analysis was conducted by covariates. P value < 0.05 was considered statistically significant. RESULTS: The prevalence of hard stools and loose stools were 8.9% and 7.6%, respectively (20,049 participants). After adjusting covariates, AD was significantly associated with hard stools (OR = 1.38, P < 0.001) and loose stools (OR = 1.24, P = 0.037). In subgroup analysis of hard stool, a stronger effect was observed in intake of milk (> 3 days/week), yogurt (> 3 days/week), pork (< 1 day/week), and higher itch scores (Q4). CONCLUSION: This study found the relationship between AD and abnormal stool forms, and the association with hard stools might be modified by dietary factor.

Association of exposure to artificial light at night with atopic diseases: A cross-sectional study in college students.

The impact of artificial light at night (ALAN) exposure on health has become increasingly prominent. However, little is known about the effect of ALAN exposure on atopic diseases. In this study, a cross-sectional analysis of incoming students was conducted in 5 geographically disperse universities which locate in Changsha (south), Wuhan (central), Xiamen (east), Urumchi (west), and Hohhot (north), respectively. All incoming students who consented to participate were recruited, followed by a health examination and a questionnaire survey. Prevalent atopic diseases were diagnosed by clinicians. Mean ALAN (nanoWatts/cm2/sr) during their adolescence was obtained from the remote sensing observed nighttime light data matching with their residence information, which was obtained from survey. Mixed generalized linear models (log-binomial) were used to estimate the associations, in terms of prevalence ratio (PR) with 95% confidence interval (CI). A total of 20106 participants were included in the analysis. Based on previous work, we chose factors including socioeconomic status, behavioural factors, major air pollutants, and air climatic parameters for adjustment. After full adjustment, the PR for atopic diseases was 1.35 (95% CI: 1.27-1.42; P < 0.001). The effect size of ALAN was the largest for asthma (PR = 1.80; 95% CI: 1.48-2.19; P < 0.001), followed by atopic rhinitis (PR = 1.42; 95% CI: 1.33-1.51; P < 0.001), and atopic dermatitis (PR = 1.20; 95% CI: 1.06-1.35; P = 0.003). Subgroup analyses by covariates showed consistent results. This study revealed that exposure to ALAN during adolescence may contribute to a higher risk of atopic diseases in young adulthood.

Helianthus Annuus L. Alleviates High-Fat Diet Induced Atherosclerosis by Regulating Intestinal Microbiota, Inhibiting Inflammation and Restraining Oxidative Stress.

Helianthus Annuus L. (HAL) is composed of flavonoids and polysaccharides. Flavonoids have demonstrated beneficial effects on atherosclerosis (AS). The objective of this study was to investigate the anti-atherosclerosis effect and the related mechanism of HAL. In this study, the AS model induced by high-fat diet (HFD) mice that lacked apolipoprotein E (Apoe[Formula: see text] received feed containing 5% HAL for 24 weeks. After administration, the analysis of plaque on aorta was conducted, and the possible mechanisms were further explored. With HAL treatment, the size of atherosclerotic lesions in HFD-induced AS model mice was reduced. HAL ameliorated dyslipidemia and decreased the combined ratio. HAL up-regulated concentrations of superoxide dismutase (SOD), nitric oxide (NO) and glutathione peroxidase (GSH-Px) and down-regulated concentrations of malondialdehyde (MDA) in the aorta. In addition, 16S rRNA analysis showed that HAL also reduced diversity of the intestinal microbiota, decreased the Firmicutes-to-Bacteroidetes ratio, and increased the relative abundance of probiotics such as Akkermansia muciniphila and Lactobacillus. In the end, HAL decreased the permeability of intestine by increasing the levels of occludin and tight junction protein 1 (ZO-1) in the colon, consequently decreasing concentration of interleukin (IL)-6, IL-1[Formula: see text] and tumor necrosis factor-alpha (TNF-[Formula: see text] in serum and mRNA expressions in the aorta. Data showed that HAL alleviates AS by restraining oxidative stress, regulating intestinal microbiota, decreasing intestinal permeability and inhibiting inflammation. Our findings provided novel insights into the role and mechanism of anti-atherogenic potential of HAL.

Behavior of Nutritional Supplements Use in Association With Inflammatory Skin Diseases in Chinese College Students.

Objectives: It is understudied how frequently adolescents use nutritional supplements (NS) and whether the corresponding behavior is associated with skin diseases that may cause unpleasant symptoms and disfigurement. The current study aimed to investigate the prevalence of NS use in Chinese college students and its association with inflammatory skin diseases. Methods: This was a university-based epidemiologic investigation that included 20,138 students who underwent dermatological examinations. A questionnaire survey was conducted to inquire about the use of NS along with related information. Skin diseases were diagnosed by dermatologists during the health examination. Logistic regression models were used for analysis. Adjusted odds ratios (aORs) were presented as the effect size. Results: Survey responses from a total of 20,138 participants were analyzed. Specifically, 18.3% of the participants reported the use of NS in the past year. The use of vitamin C was most frequently reported, accounting for a proportion of 12.9%, followed by vitamin B and mineral supplements. The use of NS was found to be associated with female sex, Han ethnicity, higher annual household income, and a series of healthy lifestyles such as more physical activity, less second-hand smoke exposure, less alcohol consumption, and higher intake of milk and yogurt (p < 0.001). Participants with chronic urticaria (aOR = 1.3; 95% CI, 1.0-1.7), atopic dermatitis (aOR = 1.4; 95% CI, 1.2-1.6), or acne (aOR = 1.17; 95% CI, 1.04-1.31) were more likely to use NS, especially herbs (aOR = 2.7; 95% CI, 1.2-3.7), followed by vitamin B (aOR = 1.6; 95% CI, 1.2-2.0) and mineral supplements (aOR = 1.4; 95% CI, 1.0-2.0). Conclusion: College students with inflammatory skin diseases are more likely to use NS.

Association of antibiotics use in preschool age with atopic and allergic skin diseases in young adulthood: a population-based retrospective cohort study.

BACKGROUND: Overuse and misuse of antibiotics is a public health problem in low-income and middle-income countries. Although the association of antibiotics with atopic and allergic diseases has been established, most studies focused on prenatal exposure and the occurrence of disease in infants or young children. OBJECTIVE: To investigate the association of preschool use of antibiotics with atopic and allergic skin diseases in young adulthood. DESIGN: Population-based retrospective cohort. SETTING AND PARTICIPANTS: The first-year college students (n=20 123) from five universities were investigated. The sampled universities are located in Changsha, Wuhan, Xiamen, Urumqi and Hohhot, respectively. METHODS: We conducted a dermatological field examination and a questionnaire survey inquiring the participants about the frequency of upper respiratory tract infection (URTI) and the preschool antibiotics use (prior to 7 years old). The two-level probit model was used to estimate the associations, and adjusted risk ratio (aRR) and 95% CI were presented as the effect size. RESULTS: A total of 20 123 participants with complete information was included in the final analysis. The frequent antibiotics use intravenously (aRR 1.36, 95% CI 1.14 to 1.62) and orally (aRR 1.18, 95% CI 1.01 to 1.38) prior to 7 years old was significantly associated with atopic dermatitis in young adulthood. Similar trends could be observed in allergic skin diseases among those who use antibiotics orally and intravenously, with RRs of 1.16 (95% CI 1.01 to 1.34) and 1.33 (95% CI 1.13 to 1.57), respectively. CONCLUSIONS: Preschool URTI and antibiotics use significantly increases the risk of atopic and allergic skin diseases in young adulthood.

Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare neoplasm of apocrine gland-bearing skin. It is known that over-expression of survivin and human telomerase reverse transcriptase (hTERT) correlates with malignancies. We investigated the expression of hTERT and survivin by Paget's cells and their role in the tissue invasion and recurrence of EMPD. METHOD: Forty-two patients were enrolled into the study. Expression of survivin and hTERT were analyzed by immunohistochemistry and in situ hybridization techniques. The variables including the expression level of survivin and hTERT, gender, age, lesion location, invasion level and number of surgeries were statistically analyzed using Fisher's exact test. RESULTS: Survivin was positively stained in 18 of 22 cases (81.8%), and hTERT in 18 of 29 cases (62.1%). Significantly higher level of survivin expression was detected in patients with multiple surgeries than those with single one (p = 0.0458). Expression of hTERT was significantly higher in the patients with micro-invasive and invasive lesions than those with non-invasive lesions (p = 0.0478). CONCLUSIONS: Over-expression of survivin and hTERT correlated strongly with recurrence and local invasion of EMPD lesions. EMPD has male gender predominance in Oriental population.