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BACKGROUND Acne vulgaris (acne) is a common inflammatory skin disorder prevalent among all ethnic groups. This review aimed to investigate the current literature regarding the potential benefit of over-the-counter (OTC) adjuncts (eg, moisturizers, cleansers) for acne patients focusing on Asian phenotypes. METHODS An online procedure was employed to review the role of adjunctive OTC acne treatment. A panel consisting of dermatologists with expertise in treating Asian acne patients participated in a pre-meeting survey that collected information regarding their recommendation habits for OTC products in acne patients. Recommendations on using OTC products as an adjunct for treating acne in Asians are based on the pre-meeting survey results, evidence from literature presented during a series of plenary lectures, and discussions conducted during a stepwise program of sessions. RESULTS Many topical treatments have been associated with adverse events (AEs) (eg, skin dryness, erythema, scaling, stinging, burning, pruritus). Multiple studies on topical acne treatments have found that Asians display greater sensitivity and less tolerability than Caucasians to acne treatment. Skincare as an adjunct to acne treatment may reduce dryness or irritation, particularly important in Asians with acne. CONCLUSIONS Advisors agreed that cleansers and moisturizers should be considered for their beneficial adjunctive role in the armamentarium of acne treatment and maintenance strategies. J Drugs Dermatol. 2021;20(11): 1213-1221. doi:10.36849/JDD.6259.

The c.194+2 TC variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear.Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively.Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3.The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.

Background There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. Methods A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients’ sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. Results There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12–18) vs. 21 (16–25), P P P P P > 0.05). Conclusion Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated.To explore the clinical features and prognosis of young and middle-aged adults with SAC.Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study.Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history.An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.

Preclinical and clinical studies support cannabidiol (CBD)'s antioxidant and anti-inflammatory effects, which are linked to its skin protective effects, but there have been limited mechanistic studies reported. Herein we evaluated CBD's protective effects against hydrogen peroxide (H2O2)-induced oxidative stress in human keratinocyte HaCaT cells and explored its possible mechanism(s) of action. CBD (10 μM) protected HaCaT cells by alleviating H2O2 (200 μM)-induced cytotoxicity (by 11.3%) and reactive oxygen species (total- and mitochondrial-derived). Several NLRP3 inflammasome-related genes including CASP1 and IL1B were identified as potential molecular targets for CBD's antioxidant effects by multiplexed gene and network pharmacology analyses. CBD treatment down-regulated the mRNA expression levels of CASP1 and IL1B (by 32.9 and 51.0%, respectively) and reduced IL-1β level (by 16.2%) in H2O2-stimulated HaCaT cells. Furthermore, CBD inhibited the activity of caspase-1 enzyme (by 15.7%) via direct binding to caspase-1 protein, which was supported by data from a biophysical binding assay (surface plasmon resonance) and a computational docking experiment. In addition, CBD mitigated H2O2-induced pyroptosis (capase-1-mediated cell death) and apoptosis by 23.6 and 44.0%, respectively. The findings from the current study suggest that CBD exerts protective effects in human keratinocytes via the modulation of the caspase-1-IL-1β axis, supporting its potential skin health applications.

Rosacea is a facial chronic inflammatory skin disease with almost 5.5% prevalence. Although there are various scales of rosacea, they are objective and discordant among different dermatologists. Noninvasive objective measurements such as VISIA system might play essential roles in the diagnosis and evaluation of rosacea. Here, we intended to reveal the effectiveness of VISIA system in rosacea.A number of 563 participants diagnosed with facial rosacea were enrolled in study. They all received both full-face image-shoot by VISIA system with quantitative analysis software and physician's assessment via five different scales, including investigator global assessment (IGA), clinician erythema assessment (CEA), numerical score, the National Rosacea Society (NRS) grading system and telangiectasis.Absolute score and percentile of red area had significant correlations with IGA and CEA, whereas red area had no significant correlation with numerical score, NRS and telangiectasis. Red area in erythematotelangiectatic rosacea patients demonstrated the highest correlation with IGA and CEA, especially in those aged between 51 and 60. Besides red area, pigmentation parameters in VISIA system (brown spot) also showed significant correlation with IGA and CEA.VISIA system might be an effective measurement in the assessment of rosacea severity.

Although the MAPK pathway is aberrantly activated in triple-negative breast cancers (TNBCs), the clinical outcome of MEK-targeted therapy is still poor. Through a genome-wide CRISPR-Cas9 library screening, we find that inhibition of PSMG2 sensitizes TNBC cells BT549 and MB468 to the MEK inhibitor AZD6244. Mechanistically, PSMG2 knockdown impairs proteasome function, which in turn activates autophagy-mediated PDPK1 degradation. The PDPK1 degradation significantly enhances AZD6244-induced tumor cell growth inhibition by interrupting the negative feedback signals toward the AKT pathway. Consistently, co-targeting proteasomes and MEK with inhibitors synergistically suppresses tumor cell growth. The autophagy inhibitor chloroquine partially relieves the PDPK1 degradation and reverses the growth inhibition induced by combinatorial inhibition of MEK and proteasome. The combination regimen with the proteasome inhibitor MG132 plus AZD6244 synergistically inhibits tumor growth in a 4T1 xenograft mouse model. In summary, our study not only unravels the mechanism of MEK inhibitor resistance but also provides a combinatorial therapeutic strategy for TNBC in clinics.

CAR-T cells therapy can give rise to most common and concerning two side effects – cytokine release syndrome (CRS) and neurotoxicity. But in our CD19 CAR-T cells therapy clinical trial, we observed 1 out of 17 patients with B-cell acute lymphoblastic leukemia (B-ALL) developed acute myelofibrosis(AMF) after grade IV CRS post to the CD19 CAR-T cells therapy. This finding suggests that the CAR-T cells therapy may have rare and serious AMF, which we should pay important attention to. Trial registration:NCT02968472. Registered 18 November 2016 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02968472

Neuropilin-1 regulated by miR-320a participates in the progression of cholangiocarcinoma by serving as a co-receptor that activates multiple signaling pathways. The present study sought to investigate upstream lncRNAs that control the expression of miR-320a/neuropilin-1 axis and dissect some of the underlying mechanisms. Here we report lncRNA TTN-AS1 (titin-antisense RNA1) acts as a sponging ceRNA to downregulate miR-320a and is highly expressed in human cholangiocarcinoma tissues and cells. The expression of the above three molecules is correlated with the clinicopathologic parameters of cholangiocarcinoma patients. In this study, multiple bioinformatics tools and databases were employed to seek potential lncRNAs that have binding sites with miR-320a and TTN-AS1 was identified because it exhibited the largest folds of alteration between cholangiocarcinoma and normal bile duct epithelial cells. The regulatory role of TTN-AS1 on miR-320a was further evaluated by luciferase reporter and RNA pulldown assays, coupled with in situ hybridization and RNA immunoprecipitation analyses, which showed that TTN-AS1 bound to miR-320a through an argonaute2-dependent RNA interference pathway in the cytoplasm of cholangiocarcinoma cells. Knockdown and overexpression assays showed that the regulatory effect between TTN-AS1 and miR-320 was in a one-way manner. TTN-AS1 promoted the proliferation and migration of cholangiocarcinoma cells via the miR-320a/ neuropilin-1 axis. The function of TTN-AS1 on tumor growth and its interaction with miR-320a were confirmed in animal models. Further mechanistic studies revealed that TTA-AS1, through downregulating miR-320a, promoted cell cycle progression, epithelial–mesenchymal transition, and tumor angiogenesis by upregulating neuropilin-1, which co-interacted with the hepatocyte growth factor/c-Met and transforming growth factor (TGF)-β/TGF-β receptor I pathways. In conclusion, the present results demonstrate that lncRNA TTA-AS1 is a sponging ceRNA for miR-320a, which in turn downregulates neuropilin-1 in cholangiocarcinoma cells, indicating these three molecules represent potential biomarkers and therapeutic targets in the management of cholangiocarcinoma.

Pancreatic cancer is a malignancy of the digestive system characterized by poor prognosis. A number of prognostic messenger RNA (mRNA) signatures have been identified by using the high-throughput expression profiles. MicroRNAs (miRNA) play a critical role in regulating multiple cellular functions. However, no such integrated analysis of miRNAs and mRNAs for studying the prognostic mechanisms of pancreatic cancer has been reported. In this study, we first identified prognostic mRNAs and miRNAs based on The Cancer Genome Atlas datasets, and then performed an enrichment analysis to explore the underlying biological mechanisms involved in pancreatic cancer prognosis at the mRNA level. Furthermore, we performed an integrated analysis of mRNAs and miRNAs to identify prognostic subpathways, which were closely associated with pancreatic cancer genes and tumor hallmarks and involved in hypoxia, oxidative phosphyorylation and xenobiotic metabolisms. Meanwhile, we performed a random walk algorithm based on global network, prognostic mRNAs and miRNAs, and identified top risk mRNAs as the prognostic signature. Finally, an independent testing set was used to confirm the predictive power of the top mRNA signature, and most of these genes involved were known oncogenes. In conclusion, we performed a series of integrated analyses by comprehensively exploring pancreatic cancer prognosis and systematically optimized the prognostic signature for clinical use.

The rise in the incidence of androgenetic alopecia (AGA) in China has increased the inclination toward hair transplantation. To calculate the optimum density of hair follicles needed covering both the hairless area and the safe donor area (SDA), 119 male patients with AGA were recruited into this multicenter investigation. We evaluated the mean diameter and the number of hair follicles (HFs) and follicular units (FUs) in the SDA of AGA. The mean density of HFs was 137.45 ± 30.11 hair/cm

Context Dendrobium officinale Kimura et Migo (Orchidaceae) is a naturally occurring precious traditional Chinese medicine (TCM) originally used in treating yin-deficiency diseases. The main active substances of Dendrobium officinale are polysaccharides (DOP). Recent findings highlighted the potential of DOP as a promising natural material for medical use with a diversity of pharmaceutical effects. Objective In this review, we provide a systematic discussion of the current development and potential pharmacological effects of Dendrobium officinale polysaccharides in dermatology. Methods English and Chinese literature from 1987 to 2019 indexed in databases including PubMed, PubMed Central, Web of Science, ISI, Scopus and CNKI (Chinese) was used. Dendrobium officinale, Dendrobium officinale polysaccharides, phytochemistry, chemical constituents, biological activities, and pharmacological activities were used as the key words. Results Dendrobium officinale polysaccharides have been found to possess hair growth promoting, skin moisturising and antioxidant effects, which are highly valued by doctors and cosmetic engineers. We highlighted advances in moisturising and antioxidant properties from in vivo and in vitro studies. Dendrobium officinale polysaccharides exhibited strong antioxidant effects by decreasing free radicals, enhancing antioxidant system, inhibiting nuclear factor-kappa B and down-regulating inflammatory response. Conclusions Our review is a foundation to inspire further research to facilitate the application of Dendrobium officinale polysaccharides in dermatology and promote active research of the use of TCM in dermatology.

Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for the treatment of port-wine stain (PWS) in China. However, no research on its efficacy for treating PWS lesions of Sturge-Weber syndrome (SWS) has been made. To assess the efficacy and safety of HMME-photodynamic therapy (PDT) in the treatment of SWS and simple large segmental facial PWS. Medical records of patients with SWS and large segmental facial PWS were reviewed. Efficacy was evaluated according to color blanching and graded as excellent (≥75%), good (50%-74%), fair (25%-49%), and poor (≤24%). Adverse events were analyzed. Nineteen patients with SWS and 33 patients with large segmental facial PWS were analyzed. 52.6% SWS and 69.7% PWS patients (p .05) achieved at least 25% improvement. Common adverse events included short-term pain, edema, pruritus, exudation, and scab. No severe adverse event occurred. HMME-PDT was effective and safe for SWS and large segmental facial PWS.

This phase III study aimed to compare the efficacy, safety, and immunogenicity of SCT630 with the reference adalimumab.A total of 367 Chinese patients with moderate-to-severe plaque psoriasis were randomly assigned to receive 80 mg of SCT630 or adalimumab subcutaneously at week 1, 40 mg at week 2, then 40 mg biweekly. At week 16, those with 50 % or more improvement in psoriasis area and severity index (PASI) were eligible to enter an extension period up to week 52. Patients on SCT630 continued the same treatment, whereas patients receiving adalimumab were re-randomized at a ratio of 1:1 to adalimumab or SCT630 group. The primary endpoint was percentage improvement in PASI at week 16. Other endpoints included PASI 50/75/90/100, Physician's Global Assessment, Dermatology Life Quality Index, safety, and immunogenicity.PASI improvement at week 16 was 85.07 % for SCT630 and 84.82 % for adalimumab. The mean difference (3.10 %, 95 % CI: -1.875 %, 8.066 %) was within the equivalence interval. Other efficacy endpoints, safety and immunogenicity profiles were similar across the two groups. There were no safety or immunogenicity difference between switched/continued groups.This phase III study demonstrated the equivalences in efficacy, safety and immunogenicity of SCT630 to adalimumab in patients with moderate to severe psoriasis.

Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)-induced psoriasis-like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro-inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ-triggered skin inflammation in mice. Single-cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ-induced psoriasis-like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)-but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll-like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF-κB-mediated skin inflammation. Importantly, Tlr7 point-mutant knock-in mice showed an attenuated psoriasis-like phenotype compared to wild-type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.

Acquired resistance to sorafenib greatly limits its therapeutic efficiency in the treatment of hepatocellular carcinoma (HCC). Increasing evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the resistance to anti-cancer drugs. The present study aims to explore the involvement of lncRNA SNHG1 (small nucleolar RNA host gene 1) in sorafenib resistance and how SNHG1 is associated with overexpressed microRNA-21 (miR-21) and the activated Akt pathway, which have been demonstrated to mediate this resistance in HCC cells.Sorafenib-resistant HCC (SR-HCC) cells were generated and their sorafenib-resistant properties were confirmed by cell viability and apoptosis assays. Potential lncRNAs were screened by using multiple bioinformatics analyses and databases. The expression of genes and proteins was detected by qRT-PCR, Western blot and in situ hybridization. Gene silencing was achieved by specific siRNA or lncRNA Smart Silencer. The effects of anti-SNHG1 were evaluated in vitro and in experimental animals by using quantitative measures of cell proliferation, apoptosis and autophagy. The binding sites of miR-21 and SNHG1 were predicted by using the RNAhybrid algorithm and their interaction was verified by luciferase assays.The Akt pathway was highly activated by overexpressed miR-21 in SR-HCC cells compared with parental HCC cells. Among ten screened candidates, SNHG1 showed the largest folds of alteration between SR-HCC and parental cells and between vehicle- and sorafenib-treated cells. Overexpressed SNHG1 contributes to sorafenib resistance by activating the Akt pathway via regulating SLC3A2. Depletion of SNHG1 enhanced the efficacy of sorafenib to induce apoptosis and autophagy of SR-HCC cells by inhibiting the activation of Akt pathway. Sorafenib induced translocation of miR-21 to the nucleus, where it promoted the expression of SNHG1, resulting in upregulation of SLC3A2, leading to the activation of Akt pathway. In contrast, SNHG1 was shown to have little effect on the expression of miR-21, which downregulated the expression of PTEN, leading to the activation of the Akt pathway independently of SNHG1.The present study has demonstrated that lncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and its nuclear expression is promoted by miR-21, whose nuclear translocation is induced by sorafenib. These results indicate that SNHG1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.

Multifunctional and stimulus-sensitive intelligent nanodrug delivery systems (NDDSs) can significantly optimize the effectiveness of theranostic agents for cancer treatment. In this study, redox and pH dual-responsive nanocarriers (CPNPs) were prepared through molecular assembly by utilizing the Schiff base interactions of cystamine (Cys), PEG-NH

Cannabidiol (CBD) has emerged as a phytocannabinoid with various beneficial effects for the skin, including anti-photoaging effects, but its mechanisms of action are not fully elucidated. The study assessed CBD’s photoprotective effects against acute ultraviolet B (UVB)-induced damage in HaCaT human keratinocyte cells and murine skin tissue. CBD (8 μM) alleviated UVB-induced cytotoxicity, apoptosis, and G2/M cell cycle arrest in HaCaT cells. The contents of γH2AX and cyclobutane pyrimidine dimers were decreased after CBD treatment. CBD reduced the production of reactive oxygen species and modulated the expression of antioxidant-related proteins such as nuclear factor erythroid 2-related factor 2 in UVB-stimulated HaCaT cells. Furthermore, CBD mitigated the UVB-induced cytotoxicity by activating autophagy. In addition, a cream containing 5% CBD showed effectiveness against UVB-induced photodamage in a murine model. The CBD cream improved the skin’s condition by lowering the photodamage scores, reducing abnormal skin proliferation, and decreasing expression of the inflammation-related protein cyclooxygenase-2 in UVB-irradiated skin tissue. These findings indicate that CBD might be beneficial in alleviating UVB-induced skin damage in humans. The photoprotective effects of CBD might be attributed to its modulatory effects on redox homeostasis and autophagy.

Janus kinase (JAK) inhibitors are novel treatment approaches for atopic dermatitis (AD). This study was aimed to compare the efficacy of JAK inhibitors for AD treatment. The database of PubMed, EMBASE, Web of Science, and Cochrane Library were searched until March 28, 2021, for randomized control trials (RCTs) of AD patients treated with JAK inhibitors. Baseline and follow-up data were extracted. Efficacy of JAK inhibitors was evaluated using 50% improvement in Eczema Area and Severity Index (EASI-50). A Bayesian multiple treatment network meta-analysis with fixed effects was performed. Odds ratio (OR) with 95% credibility interval (CrI) were used for comparing the efficacy of JAK inhibitors with placebo for AD. A total of seven RCTs of JAK inhibitors with 2530 patients were included for analysis. After excluded one study with high risk of bias, a total of six JAK inhibitors with 17 different formulations and doses were analyzed. The severity of atopic dermatitis of included patients was almost moderate to severe (93.4%). Compared with placebo, all JAK inhibitors had higher EASI-50 at 4 weeks of treatment, except for baricitinib with 1 mg once daily (QD) (OR: 1.4, 95% Crl: 0.9-2.1), ruxolitinib with 0.15% QD (OR: 2.3, 95% Crl: 0.8-11.4), and ruxolitinib with 0.5% QD (OR: 3.4, 95% Crl: 0.9-18.1). Among all included, upadacitinib had the highest probability of being the best treatment (SUCRA value of 0.936). In topical JAK inhibitors, delgocitinib 3% twice a day (BID) had the highest probability of being the best treatment (SUCRA value of 0.849). JAK inhibitors had promising treatment efficacy for AD patients. Upadacitinib with 30 mg QD had the best efficacy among all included JAK inhibitors, and delgocitinib 3% BID showed superior efficacy over other topical JAK inhibitors for AD treatment.

Topical Janus kinase (JAK) and phosphodiesterase-4 (PDE4) inhibitors are novel treatment approaches for atopic dermatitis (AD). This study aimed to compare the efficacy and safety of JAK and PDE4 inhibitors for AD treatment. The databases of PubMed, EMBASE, Web of Science, and Cochrane Library were searched until June 2021 for eligible studies of AD patients treated with topical JAK and PDE4 inhibitors. Baseline and follow-up data were extracted. Efficacy of JAK inhibitors was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear", with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA response"). A Bayesian multiple treatment network meta-analysis with fixed effects was performed. Odds ratio (OR) with 95% credibility interval (CrI) were used for comparing the efficacy of JAK and PDE4 inhibitors with placebo for AD. A total of 10 randomized controlled trials of topical JAK and PDE4 inhibitors with 4689 patients were included for analysis. A total of three topical JAK inhibitors and two topical PDE4 inhibitors were included. Compared with placebo, all JAK and PDE4 inhibitors had higher IGA response at 4 weeks of treatment. Notably, with similar safety profile, tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d., and delgocitinib 3% b.i.d. showed favorable IGA response compared with topical tacrolimus and corticosteroids. Ranking analysis suggested that among all included JAK and PDE4 inhibitors, tofacitinib 2% b.i.d. had the highest probability of achieving IGA response (SUCRA = 0.880). Besides, JAK and PDE4 inhibitors showed non-inferior safety profile with placebo. This study confirmed that topical JAK and PDE4 inhibitors had promising treatment efficacy and safety for AD patients. Tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d. and delgocitinib 3% b.i.d. showed superior efficacy over other JAK and PDE4 inhibitors.

To assess the efficacy of 595 nm pulsed dye laser (PDL) in the treatment of facial and neck port-wine stains (PWSs), and to explore the main factors affecting the efficacy.A total of 259 PWS cases who were treated with 595 nm PDL were retrospectively enrolled and their clinical information was analyzed in the study. Before- and after-treatment comparison of individual patient was done by comparing patient photographs taken before and after PDL treatment of the PWSs in order to assess the treatment efficacy, using mild purpura as the endpoint of the PDL treatment. A total of 82 male and 177 female cases were included, with patient age ranging between 1 month and 63 years. Univariate analysis was done to select factors influencing the treatment efficacy. Then, ordered multivariate logistic regression analysis was performed to evaluate the main factors affecting the efficacy. Statistics of adverse reaction of patients were also collected.Of the 259 patients covered in the study, 57 (22%) had achieved complete clearing of PWS, 106 (40.9%) showed significant improvement, and 68 (26.3%) showed moderate improvement, amounting to a total of 231 effective treatment cases, indicating a 89.2% overall rate of effective treatment. There were 28 ineffective treatment cases (10.8%). Ordered multivariate logistic regression analysis showed that the color of PWS, the area of PWS, anatomical sites of PWS and the number of treatment sessions were the main factors affecting the therapeutic efficacy, while proliferation did not affect the therapeutic efficacy. Red-type PWS had better treatment efficacy than that of the purple-type PWS (odds ratio [Patients with PWS located on the neck, red-type PWS and area ≤10 cm

Loss of α6 and β4 integrin expression caused by germ line mutations in ITGA6 and ITGB4 usually leads to junctional epidermolysis bullosa (JEB) with pyloric atresia (PA) (JEB-PA; Online Mendelian Inheritance in Man #226730). However, recent studies have suggested that integrin-associated JEB may occur without PA but with other symptoms of the epithelial tissues. Here, we present a case of a Chinese woman with JEB without PA but with profound urinary symptoms. Mutation analysis revealed that the patient carried compound heterozygous mutations in the ITGB4 gene: a frameshift mutation c.600dupC (p.Phe201Leufs*15) and a novel missense mutation c.599C>G (p.Pro200Arg). Our report not only raises the question of whether the designation JEB-PA is appropriate, but also expands our current knowledge of the ITGB4 mutation spectrum.

Background Recent insights showed the possibility of using JAK inhibitors for the treatment of alopecia areata (AA). Most of the previous articles evaluated the overall efficacy of existing JAK inhibitors rather than evaluating one of them alone. Currently, the benefit and risk profile of tofacitinib for the treatment of AA is still not clear. Objective To estimate the safety and efficacy of tofacitinib in patients with AA based on summarizing the clinical outcomes. Methods The systematic review and meta-analysis was performed according to PRISMA guidelines. ROBINS-I (Risk of Bias in Non-randomized Studies-of Interventions) was used for quality assessment. Results We enrolled 14 studies including six clinical trials and eight observational studies with 275 patients. The result of meta-analysis showed that tofacitinib has reasonable effectiveness in patients with AA. The pooled good/complete hair regrowth rate of tofacitinib treating patient with AA was 54.0% (95% CI: 46.3%-61.5%), and the pooled rate of partial response in patients with AA taking tofacitinib was 26.1% (20.7-32.2%). Approximately a quarter of patients had experience of relapse, most of which was reported due to discontinuation of tofacitinib. In terms of toxicity, reported adverse effects included only mild symptoms. Upper respiratory infection, headache and acne were the most common adverse events. Conclusion Tofacitinib seems to be a promising drug for the treatment of AA with only mild adverse effects. More thorough larger sized randomized clinical trials are required to further assess the safety and clinical efficacy of tofacitinib for the treatment of AA.

Background Riehl's melanosis is a chronic, refractory disorder, which can adversely affect patient's quality of life. Intense pulse light, neodymium-doped yttrium aluminum garnet laser, hydroquinone, tranexamic acid have been reported to treat this disease, but there have been few reports on the effectiveness of other treatments. Aim To assess the efficacy and safety of triple combination therapy with salicylic acid chemical peels, oral glycyrrhizin compound, and vitamin C for Riehl's melanosis. Patients/methods Three patients diagnosed with Riehl's melanosis were enrolled. All patients were treated with glycyrrhizin compound (150 mg/d), vitamin C (100 mg/d), and salicylic acid 30% peels once every 2 weeks. Clinical photographs and VISIA were used to assess the efficacy. Results All patients received obvious improvement and reported no obvious side effects. Conclusion Triple combination therapy with salicylic acid peels, oral glycyrrhizin compound, and vitamin C is a safe and effective modality for Riehl's melanosis.

Objective: To investigate the risk factors affecting the survival of patients with gastrointestinal stromal tumors (GISTs) in different age groups. Methods: Information on 6089 GIST patients was screened from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factor analysis was performed using a chi-square test (univariate analysis). Survival analysis was performed using the Kaplan-Meier method (log-rank test) and the COX proportional hazard model. p Value 60 years). Risk factors such as primary location, tumor diameter, and mitotic index varied significantly between the different age groups. Conclusions: Age, gender, race, and surgical treatment are independent risk factors that influence the prognosis in patients with GISTs. Some risk factors affecting prognosis are age dependent.

The current study analyzed the clinical and genetic characteristics of a family with familial myeloproliferative neoplasms (MPNs). Whole-exome sequencing was conducted, and a germline heterozygous mutation in lysine methyltransferase 2A (KMT2A, also known as MLL1), G3131S (c.9391G > A, p.Gly3131Ser, rs150804738), was identified. Somatic DNA and germline DNA were collected from 8 family members, 120 healthy donors (somatic DNA), and 30 healthy donors (germline DNA). Using Sanger sequencing, the KMT2A G3131S mutation was analyzed. Four individuals, the proband (II-1), his sister (patient II-2), and family members II-3 and III-1 (somatic DNA and germline DNA), tested positive for the KMT2A G3131S mutation. We did not observe the KMT2A G3131S mutation in healthy donors (somatic DNA and germline DNA), indicating that this is not a SNP. Bioinformatics analysis of KMT2A G3131S suggested that protein structure changes could be caused by this mutation. To further elucidate the function of KMT2A G3131S, the CRISPR-Cas9 technique was applied to generate a KMT2A G3131S heterozygous K562 cell line. The colony formation potency, apoptosis, and cell cycle of KMT2A G3131S mutant K562 cells were analyzed. The results demonstrated that KMT2A G3131S mutant K562 cells showed increased proliferation and colony formation ability. Immunophenotyping was performed using flow cytometry to analyze the surface marker expression of gene-edited KMT2A G3131S mutant K562 cells. A significant increase in CD11b and mild increases in CD61 and CD235a were observed in KMT2A G3131S mutant K562 cells, suggesting that the KMT2A G3131S mutant could cause an increase in myeloproliferation. May-Giemsa staining showed that the morphological changes in KMT2A G3131S mutant K562 cells were consistent with the flow cytometry analysis. To verify which downstream genes were affected by the KMT2A G3131S mutant, we performed real-time PCR to evaluate the expression of previously reported KMT2A-related genes and found that C-MYB expression was significantly decreased. Western blotting was applied to investigate the expression of Kmt2a and C-myb proteins, and the results showed that in KMT2A G3131S mutant K562 cells, the expression of C-myb was decreased. Our findings suggested that KMT2A G3131S could affect the myeloproliferation of K562 cells and decrease C-myb expression. In conclusion, KMT2A G3131S could be considered a novel genetic susceptibility gene in familial MPN.

Importance Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH. Objective To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy. Design, Setting, and Participants This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020. Interventions Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment. Main Outcomes and Measures The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score. Results Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, −4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, −5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups. Conclusions and Relevance In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy. Trial Registration ClinicalTrial.gov Identifier:NCT02342275

Wound tension plays a key role in the process of wound healing and scar formation. Tension offloading devices have been reported to reduce post-surgical scar formation. This study aims to determine whether the application of a tension offloading device pre-operatively would result in superior attenuation of scar genesis in comparison to traditional methods. Randomized, controlled trials were performed on 12 patients, 4 patients were treated both pre- and post-operatively, while the other 4 were treated only post-operatively. The remaining 4 patients didn't receive any sort of intervention. The overall performance was analyzed over 6 months period. The skin elasticity coefficient improved significantly with the application of a tension-offloading device. Compared with control group, patients who received treatment via the device displayed a better result in scar width and regression of color. It was also shown that the use of a device in the group with twin pre- and post-op intervention resulted in a reduction of the wound healing period in comparison to the post-op group. Application of a tension-offloading device pre-operatively can reduce tensile forces acting on the incision, thereby resulting in faster wound healing and enhanced efficacy on post-surgical reapplication. The effectiveness of the device in preventing hypertrophic scar is likely to be improved by long-term application after operation. This article is protected by copyright. All rights reserved.

Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, anti‑inflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPS‑induced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPS‑mediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit‑8, JC‑1 fluorescence, Hoechst 33258 staining assays, respectively. IL‑1β, IL‑6 and TNF‑α mRNA expression and protein levels were measured by performing reverse transcription‑quantitative PCR and ELISAs, respectively. Bcl‑2, Bax, cleaved caspase‑3, cleaved caspase‑7, cleaved caspase‑9, phosphorylated (p)‑IκB‑α, p‑IκB‑β, p‑NF‑κB‑p65 and total NF‑κB p65 protein expression levels were determined via western blotting. NF‑κB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPS‑induced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL‑1β, IL‑6, TNF‑α, Bax, cleaved caspase‑3, cleaved caspase‑7, cleaved caspase‑9 and p‑NF‑κB‑p65, but upregulated the expression levels of Bcl‑2, p‑IκB‑α and p‑IκB‑β in LPS‑induced HUVECs. Moreover, PB2 markedly inhibited LPS‑induced NF‑κB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl‑2 and NF‑κB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.

Excessive reactive oxygen species (ROS) can cause oxidative stress of tissues and adversely influence homeostasis of the body. Epigallocatechin gallate (EGCG) with an antioxidative effect can effectively eliminate the ROS, but an evident weakness associated with it is the relatively poor cytocompatibility. Combining with other biomacromolecules such as human hair keratin (KE) and using nanotechnology to prepare nanoparticles can improve this situation. By covalent bonding, we assembled KE and EGCG into KE-EGCG nanoparticles (NANO) with size of about 50 nm and characterized them by DLS, UV, FTIR, NMR, and XPS. Free radical scavenging experiments show that antioxidant properties of the obtained NANO are superior to that of vitamin C. Cell culture experiments also show that the NANO can effectively protect the proliferation of L929 cells and HUVEC cells. In addition, we also used RAW264.7 cells to establish a H2O2-induced cell injury model and an lipopolysaccharide-induced cellular inflammatory model to evaluate the antioxidant and anti-inflammatory properties of NANO. The results show that the NANO can effectively prevent cells from oxidative damage and reduce inflammatory expression of the cells, indicating that the NANO have a good antioxidative and anti-inflammatory effect on cells which can be applied to many diseases related to oxidative stress.

Topical anesthesia is widely used in many dermatological and cosmetic procedures. Nevertheless, the stratum corneum serves as the skin barrier, impedes the transdermal drug delivery greatly, and results in insufficient analgesia. Cold atmospheric plasma (CAP) has been researched as a transdermal drug delivery promoter with ex vivo experiments for a few years, while clinical trials are scarce.To assess the efficacy and safety of CAP as a pretreatment to improve the transdermal absorption of topical anesthetic cream before the COTwenty patients, seeking full facial laser treatment for atrophic acne scars, underwent a randomized split-face study. One side of the face was pretreated by CAP before topical anesthetic cream was applied, and the other side was applied with topical anesthetic cream only as control. After that, the subjects went through full-face fractional COThe VAS score of the treated side was statistically lower (5.1 ± 2.1) compared with the nontreated side (6.3 ± 1.9), with a mean difference of 1.3 (95% confidence interval [CI], 0.6-1.9; P .0001). No severe adverse event was reported, and all the disturbing sensations and symptoms (pain, heat, and edema) were evaluated as mild with no mean score surpassing 4.0.Plasma pretreatment of 5 minutes before topical anesthetic cream application gives significant pain reduction during the laser procedures, showing the potential effects of CAP on promoting transdermal drug delivery, with no obvious adverse effects reported.

Little is known about the cellular signals that organize synapse formation. To explore what signaling pathways may be involved, we employed heterologous synapse formation assays in which a synaptic adhesion molecule expressed in a nonneuronal cell induces pre- or postsynaptic specializations in cocultured neurons. We found that interfering pharmacologically with microtubules or actin filaments impaired heterologous synapse formation, whereas blocking protein synthesis had no effect. Unexpectedly, pharmacological inhibition of c-jun N-terminal kinases (JNKs), protein kinase-A (PKA), or AKT kinases also suppressed heterologous synapse formation, while inhibition of other tested signaling pathways—such as MAP kinases or protein kinase C—did not alter heterologous synapse formation. JNK and PKA inhibitors suppressed formation of both pre- and postsynaptic specializations, whereas AKT inhibitors impaired formation of post- but not presynaptic specializations. To independently test whether heterologous synapse formation depends on AKT signaling, we targeted PTEN, an enzyme that hydrolyzes phosphatidylinositol 3-phosphate and thereby prevents AKT kinase activation, to postsynaptic sites by fusing PTEN to Homer1. Targeting PTEN to postsynaptic specializations impaired heterologous postsynaptic synapse formation induced by presynaptic adhesion molecules, such as neurexins and additionally decreased excitatory synapse function in cultured neurons. Taken together, our results suggest that heterologous synapse formation is driven via a multifaceted and multistage kinase network, with diverse signals organizing pre- and postsynaptic specializations.

Accumulating evidence has showed the possibility of using NK1R antagonists for the treatment of chronic pruritus. However, the benefit and risk profile of NK1R antagonists-serlopitant and aprepitant for the treatment of pruritus remains unclear. To assess the efficacy and safety of NK1R antagonists-serlopitant and aprepitant in patients with pruritus based on analysis of clinical trials. The current systematic review and meta-analysis was performed according to PRISMA guidelines. A total of 10 randomized clinical trials including 631 patients were enrolled. Four randomized controlled trials investigated the comparative treatment effect of serlopitant on pruritus. Our results showed that serlopitant had reasonable anti-pruritic effectiveness in patients, with mild toxicities. The overall proportion of 4-point improvement of NRS and VAS in serlopitant-treatment group were both significantly higher relative to placebo group (OR 2.345, 95%CI 1.557 to 3.531, P .001; OR 3.308, 95% CI 1.949 to 5.616, P .001). Serlopitant treatment was also found to be associated with a significant reduction in NRS score as compared with placebo (SMD -0.381, 95%CI -0.599 to -0.164, P = .001). Six clinical trials reported the treatment effect of aprepitant on pruritus. The meta-analysis result of fixed-effect model showed that there was no significant difference between aprepitant and controlled treatment in terms of improved pruritus VAS score (SMD -0.088, 95%CI -0.384 to 0.207, P = .558). There is promising high-quality evidence regarding the efficacy of serlopitant on pruritus. More large-sample randomized controlled trials with appropriate treatment regimen are urgently needed to further evaluate the effectiveness of aprepitant in pruritus.

Background Rosacea is a complex, chronic, and recurrent dermatologic condition that adversely affects quality of life and self-esteem. However, clinical relevance and molecular mechanisms underlying NEAT1 influence in rosacea remain unclear. Objective The present study aims to investigate the dynamics and influences of lncRNAs, miRNAs, and mRNAs in rosacea patients, and to explore the impacts of NEAT1 treatments on miR-196a-5p and S100A9 expression in LL37-treated HaCaT cells. Methods RNA-sequencing of skin tissues from rosacea patients and integrative analyses facilitated comprehensive exploration of lncRNA, mRNA, and miRNA networks. We identified differentially expressed lncRNAs in paired rosacea afflicted and non-lesioned tissues by hub lncRNAs in the ceRNA network. The role of NEAT1 in LL37-treated HaCaT cells was identified by in vitro experiments. Results There were 237 lncRNAs, 38 miRNAs, and 1784 mRNAs in lesioned skin compared to non-lesioned skin in six rosacea patients. NEAT1 was upregulated in rosacea skin and in LL37-treated HaCaT cells. Moreover, inflammatory damage was able to be reduced in vitro after knockdown of NEAT1. Finally, NEAT1 was able to directly interact with miR‐196a-5p, and downregulating miR‐196a-5p was efficient in reversing the influence of NEAT1 siRNA on S100A9. Conclusion We have completed the first genome-wide lncRNA profiling of paired lesioned and non-lesioned samples from rosacea afflicted patients. The NEAT1/miR-196a-5p/S100A9 axis may have played an important role in the dynamics underlying inflammatory responses of rosacea. NEAT1 may have functioned as a competing endogenous RNA which regulated inflammatory responses in rosacea by sponging miR-196a-5p and upregulating S100A9 expression.

BackgroundFibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) is a form of tumor progression of dermatofibrosarcoma protuberans (DFSP) with an increased risk of metastasis and recurrence. Few studies have compared the clinicopathological features of FS-DFSP and conventional DFSP (C-DFSP).ObjectivesTo better understand the epidemiological and clinicopathological characteristics of FS-DFSP.MethodsWe conducted a cohort study of 221 patients diagnosed with DFSP and built a recognition model with a back-propagation (BP) neural network for FS-DFSP.ResultsTwenty-six patients with FS-DFSP and 195 patients with C-DFSP were included. There were no differences between FS-DFSP and C-DFSP regarding age at presentation, age at diagnosis, sex, size at diagnosis, size at presentation, and tumor growth. The negative ratio of CD34 in FS-DFSP (11.5%) was significantly lower than that in C-DFSP (5.1%) (P = 0.005). The average Ki-67 index of FS-DFSP (18.1%) cases was significantly higher than that of C-DFSP (8.1%) cases (P ConclusionsThe clinical manifestations of FS-DFSP and C-DFSP are similar but have large differences in immunohistochemistry. The classification accuracy and feasibility of the BP neural network model are high in FS-DFSP.

Objectives There are no cohort studies of chronic lymphedema in patients with kaposiform hemangioendothelioma (KHE). We sought to characterize the incidence, clinical features, risk factors and management of chronic lymphedema in patients with KHE. Methods We conducted a multicenter retrospective analysis of patients who had a minimum of 3 years of follow-up after the onset of KHE and/or Kasabach–Merritt phenomenon (KMP). Clinical features were reviewed to determine the possible cause of chronic lymphedema. The degree of lymphedema, risk factors and management strategies were analyzed. Results Among the 118 patients, chronic lymphedema was confirmed by lymphoscintigraphy 1 year after the onset of KHE and/or KMP in 13 patients. In 8 patients with lymphedema, extremity swelling was evident in the presence of KHE and/or KMP. In all patients with lymphedema, a unilateral extremity was affected, along with ipsilateral KHE. Most (84.6%) patients reported moderate lymphedema. Lymphedema was more common in patients with larger (≥ 10 cm) and mixed lesions involving the extremities (P P > 0.05). Overall, 76.9% of patients received sirolimus treatment after referral, including 53.8% who presented extremity swelling before referral. Seven (53.8%) patients received compression therapy. Five (38.5%) patients reported lymphedema-associated decreased range of motion at the last follow-up. Conclusions Chronic lymphedema is a common sequela of KHE and can occur independently of KMP and sirolimus treatment. Patients with large and mixed KHE involving extremities should be closely monitored for this disabling complication.

This meta-analysis aimed to evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in identifying lymphazdenopathy. PubMed, Web of Science, Embase and the Cochrane Library were searched for relevant articles through September 2020. A total of 16 articles, which included 1787 participants, were analyzed. The summary sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio of CEUS for diagnosing lymphadenopathy were 0.88 (0.86-0.90), 0.90 (0.88-0.92), 6.04 (3.67-9.95), 0.15 (0.10-0.21) and 47.38 (23.45-95.66), respectively. The summary receiver operating characteristic (SROC) area under the curve (AUC) was 0.9405. After omitting outliers identified in a bivariate box plot and forest plot, heterogeneity was decreased, and the pooled sensitivity and specificity were 0.87 (0.84-0.90) and 0.87 (0.84-0.90), respectively. Furthermore, the SROC AUC was 0.9327. In conclusion, CEUS has the potential to be a valuable tool for characterizing lymphadenopathy and could provide clinical decision support.

The 755 nm picosecond Alexandrite laser has been demonstrated to be effective and well tolerated in patients with acne scars. In this split-face, investigator-blinded study, 16 patients with post-inflammatory erythema (PIE) and acne scars were randomized to receive laser treatment on half the face, with the other half serving as a control. The treatment side demonstrated a significant improvement in both PIE and scars compared to the baseline and also when compared to the control side. Treatment was well-tolerated, with only transient and mild erythema and edema reported as side-effects. In our study the picosecond Alexandrite laser was safe and effective in the treatment of PIE and acne scars. Comprehensive treatment outcomes should be taken into consideration when deciding on which device to use. This article is protected by copyright. All rights reserved.

To analyze the clinical manifestations and neuroimaging characteristics of Sturge-Weber syndrome (SWS), to describe the manifestations of facial port-wine stains (PWS) of SWS, and to explore the screening opinions for SWS.A retrospective analysis was performed on the general condition, clinical manifestations, and neuroimaging results of 24 SWS patients from the dermatology department of West China Hospital of Sichuan University between 2017 and 2019. Three different facial PWS distribution methods (traditional anatomical distribution, facial trigeminal nerve distribution, and facial embryological vasculature distribution) in SWS patients were Analysed.Among the 24 patients, 50% were male and 50% were female, with an average age of (18.9±14.0) years (range 1 to 54 years old). 12 cases were SWS type Ⅰ, and the other 12 cases were type Ⅱ. All patients had facial PWS at birth, and the facial PWS of 13 cases (54.2%) were thickened. According to the anatomical division, all the PWS involved the upper and middle face (above the oral commissure); according to the trigeminal nerve distribution, 100% (24/24) patients involve the V2 area; according to the distribution of facial embryological vasculature, 95.8% (23/24) of the patients involved frontal region. 22 patients had ophthalmic abnormalities, the most common was glaucoma (70.8%), and 4 patients had a history of epilepsy. The typical neuroimaging presentations of SWS include leptomeningeal enhancement, cortical calcification, enlarged choroid plexus, focal cerebral atrophy, abnormal intracranial vessels, and local thickening of the skull.Early intervention is recommended for facial PWS in patients with SWS , and ophthalmological screening should be performed on children with PWS found in any part of the upper and middle face after birth. Moreover, neuroimaging examination (MRI) for patients with high suspicion of SWS should be performed after 1 year old, and regular ophthalmological examination and intraocular pressure measurement is necessary.

Abdominal ultrasonography has been proposed to screen for infantile hepatic hemangioma (IHH) in patients with multiple cutaneous infantile hemangiomas (IHs).The aim of this study was to establish the optimal cutoff point for the number of cutaneous IHs needed to screen for IHH.We performed a prospective, multicenter study to screen for IHH in patients younger than 9 months who had multiple cutaneous IHs (n ≥ 3) on ultrasonography. For comparison, a group of patients with 1 or 2 focal cutaneous IHs was also recruited.In total, 676 patients with at least 3 cutaneous IHs and 980 patients with 1 or 2 focal cutaneous IHs were enrolled. Thirty-one patients were found to have IHH. A higher number of cutaneous IHs was associated with an increased risk of IHH (R = 0.973; P .001). Receiver operating characteristic curve analysis showed that 5 cutaneous IHs was the optimal cutoff point to screen for IHH, with an area under the curve of 0.872 (P .001; 95% confidence interval, 0.789-0.955).This was an uncontrolled study.Screening for IHH is recommended in patients younger than 9 months who present with 5 or more cutaneous IHs.

Background. Rosacea is a common inflammatory skin disorder. Several studies, but not all, have suggested a high prevalence of cardiovascular diseases (CVDs) in rosacea patients. This study is aimed at investigating the association between rosacea and CVDs and related risk factors. Methods. We performed a literature search through PubMed, Embase, and Web of Science databases, from their respective inception to December 21, 2019. Two reviewers independently screened the articles, extracted data, and performed analysis, following the PRISMA guidelines. Odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes. The included studies’ quality was evaluated using the Newcastle Ottawa Scale (NOS). Results. The final meta-analysis included ten studies. The pooled analysis found no association between rosacea prevalence and the incidence of CVDs (OR 0.97; 95% CI 0.86-1.10). Rosacea was found to be significantly associated with several risk factors for CVDs (OR 1.17; 95% CI 1.05-1.31), including hypertension (OR 1.17; 95% CI 1.02-1.35), dyslipidemia (OR 1.34; 95% CI 1.00-1.79), and metabolic syndrome (OR 1.72; 95% CI 1.09-2.72). However, no association was found between rosacea and diabetes mellitus (OR 0.98; 95% CI 0.82-1.16). Among the biological parameters, a significant association was found between rosacea and total cholesterol (SMD=0.40; 95% CI=−0.00, 0.81; p<0.05), low-density lipoprotein cholesterol (SMD=0.28; 95% CI=0.01, 0.56; p<0.05), and C-reactive protein (CRP) (SMD=0.25; 95% CI=0.10, 0.41; p<0.05). We found no association between rosacea and high-density lipoprotein cholesterol (SMD=0.00; 95% CI=−0.18, 0.18; p=0.968) or triglycerides (SMD=0.10; 95% CI=−0.04, 0.24; p=0.171). Conclusions. Although no significant association was found between rosacea and CVDs, rosacea was found to be associated with several of related risk factors. Patients with rosacea should pay more attention to identifiable CVD risk factors, especially those related to inflammatory and metabolic disorders.

Antibody-based near-infrared photoimmunotherapy (NIR-PIT) is an attractive strategy for cancer treatment. Tumor cells can be selectively and efficiently killed by the targeted delivery of an antibody-photoabsorber complex followed by exposure to NIR light. Glycoprotein A33 antigen (GPA33) is highly expressed in most human colorectal cancers (CRCs) and is an ideal diagnostic and therapeutic target. We previously produced a single-chain fragment of a variable antibody against GPA33 (A33scFv antibody). Here, we investigate the efficacy of NIR-PIT by combining A33scFv with the NIR photoabsorber IR700 (A33scFv-IR700). In vitro, recombinant A33scFv displayed specific binding and delivery of an NIR dye to GPA33-positive tumor cells. Furthermore, A33scFv-IR700-mediated NIR-PIT was successful in rapidly and specifically killing GPA33-positive colorectal tumor cells. NIR-PIT treatment induced the release of lactate dehydrogenase from tumor cells, followed by cell necrosis, rather than apoptosis, through the promotion of reactive oxygen species accumulation in tumor cells. In mice bearing LS174T tumor grafts, A33scFv selectively accumulated in GPA33-positive tumors. Following only a single injection of the conjugate and subsequent illumination, A33scFv-IR700-mediated NIR-PIT induced a significant increase in therapeutic response in LS174T-tumor mice compared with that in the non-NIR-PIT groups (p < 0.001). Because the GPA33 antigen is specifically expressed in CRC tumors, A33scFv-IR700 might be a promising antibody fragment-photoabsorber conjugate for NIR-PIT of CRC.

The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. Insertion of a short alternatively-spliced region within TENs abolishes the TEN-LPHN interaction and switches TEN function to specify inhibitory synapses. How alternative-splicing regulates TEN-LPHN interaction remains unclear. Here, we report the 2.9 Å resolution cryo-EM structure of the TEN2-LPHN3 complex, and describe the trimeric TEN2-LPHN3-FLRT3 complex. The structure reveals that the N-terminal lectin domain of LPHN3 binds to the TEN2 barrel at a site far away from the alternatively spliced region. Alternative-splicing regulates the TEN2-LPHN3 interaction by hindering access to the LPHN-binding surface rather than altering it. Strikingly, mutagenesis of the LPHN-binding surface of TEN2 abolishes the LPHN3 interaction and impairs excitatory but not inhibitory synapse formation. These results suggest that a multi-level coincident binding mechanism mediated by a cryptic adhesion complex between TENs and LPHNs regulates synapse specificity., The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs) promotes excitatory synapse formation. Here authors report the high resolution cryo-EM structure of the TEN2-LPHN3 complex, describe the trimeric TEN2-LPHN3-FLRT3 complex and show how alternative-splicing regulates the TEN2-LPHN3 interaction.