Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma.

Several clinical studies observed a surprising beneficial effect of obesity on enhancing immunotherapy responsiveness in patients with melanoma, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here, we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug commonly used to treat diabetes by sequestering fatty acids in metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-programmed cell death protein 1 (PD-1) treatment in YUMMER1.7 tumor-bearing mice, an initially immunotherapy-sensitive murine melanoma model. We observed a transition from high to intermediate PD-1 expression in tumor-infiltrating CD8+ T cells. Moreover, TZD inhibited PD-1 expression in mouse and human T cells treated in vitro. In addition to its direct impact on immune cells, TZD also decreased circulating insulin concentrations, while insulin induced T cell exhaustion in culture. In TZD-treated mice, we observed higher fatty acid concentrations in the tumor microenvironment, with fatty acids protecting against exhaustion in culture. Together, these data are consistent with an indirect mechanism of TZD inhibiting T cell exhaustion. Finally, we analyzed imaging data from patients with melanoma before and after anti-PD-1 treatment, confirming the beneficial effect of increased subcutaneous fat on anti-PD-1 responsiveness in patients. We also found that the expression of peroxisome proliferator-activated receptor gamma (PPARγ), the canonical activator of lipid uptake and adipogenesis activated by TZD, correlated with overall survival time. Taken together, these data identify a new adjuvant to enhance immunotherapy efficacy in YUMMER1.7 melanoma mice, and discover a new metabolism-based prognostic marker in human melanoma.NEW & NOTEWORTHY Zhang et al. demonstrate that the diabetes drug rosiglitazone improves the efficacy of immunotherapy in mouse melanoma. This effect is both direct and indirect: TZD directly reduces PD-1 expression in CD8+ T cells (i.e., reduces exhaustion), and indirectly reduces exhaustion by lowering insulin levels and increasing local fat. Finally, they demonstrate that hallmarks of TZD action (such as PPARγ expression and subcutaneous fat content) correlate with improved immunotherapy efficacy in humans with melanoma.

Analysis of Population Representation Among Willed Whole-Body Donors to Facilitate the Construction of a Body Donation Program in China: From the Perspective of Medical Students and Anatomists.

The body donation program of Peking Union Medical College was established in May 1999. From May 1999 to December 2017, a total of 5,576 registrants registered and 1,459 donors donated their bodies. Demographic and medical characteristics of the donors were analyzed. The top four causes of death were neoplasms, heart diseases, respiratory diseases, and cerebrovascular diseases. Age at death among donors who died of neoplasms were significantly lower than other causes of death (all p < .05), and the interval between registration and donation among donors who died of neoplasms was significantly shorter than that among donors with other causes (all p < .001). The age of donors when they registered (p < .001) and donated (p < .001) was significantly older than that of general Beijing population. This study may provide a guide for medical colleges or research institutions to establish or enhance their own body donation programs.

Public interest in Raynaud's phenomenon: A Google Trends analysis.

Raynaud's phenomenon is a common disorder affecting body extremities and other vascular beds. As infodemiological methods have developed, online search tools could be used to explore the public interest of the disease. The study aimed to determine the annual trend, seasonal pattern, and associated topics of Raynaud's phenomenon. Google Trends was used to collect the data. "Raynaud syndrome" was selected as the search term. Data on monthly relative search volume (RSV) were collected from four selected countries (United States, United Kingdom, Australia, and New Zealand) and globally. Related topics were obtained, and annual-related topics were also collected for analysis. The maximum RSV appeared in January 2019, and the minimum value was observed in August 2011. The peak for RSV occurred in winter, and the bottom appeared in summer. In top related topics, "Maurice Raynaud" was the most related. In rising related topics, disease manifestations and autoimmune connective diseases were highly concerned. For annual-related topics, associated diseases were attracting more attention over time. The population is interested in related diseases, pathogenesis, and treatment. There was a peak in winter for searching and supported the importance of season variation on the impact of Raynaud's phenomenon.

Cutaneous manifestations of the Coronavirus Disease 2019 (COVID-19): A brief review.

COVID-19, first appeared in December 2019 in Wuhan, China, has been spreading quickly throughout the world. We reviewed the evidence on cutaneous manifestations of COVID-19 based on PubMed database. The searching strategy was (COVID* or coronavirus*) and (dermatol* or skin* or cutaneous*). The publication time was limited to 2019 onward. After independent review by two authors, 14 studies with 228 confirmed cases were included in the analysis. A total of 60 patients developed skin rashes, and the age ranged from 8 to 84. Exanthematous eruptions potentially related to COVID-19 infection were highly variable and heterogeneous. Skin lesions mainly appeared erythematous, urticarial, and vesicular (chicken pox-like or varicelliform). Petechiae rash, livedo reticularis, and reactivation of oral HSV-1 were also observed in single cases. Newly reported eruptions like vascular lesions and peculiar (perniosis-like) skin lesions caused concern among dermatologists. Exanthems were widely distributed and were primarily located on the trunk. Associated symptoms, latency time, treatment, and prognosis were also carefully summarized. This study reviewed the recently published COVID-19 studies with skin manifestations, which may pave the way for further research.

Contributions of dermatologists to COVID-19 research: A brief systematic review.

Coronavirus disease 2019 (COVID-19) has been declared a pandemic. We conducted a systematic review to reveal the contribution of dermatologists in COVID-19 research. Two hundred and ninety-eight articles were included and classified into cutaneous manifestations of COVID-19, operating experience against COVID-19, mechanisms and treatment of COVID-19, disinfection and personal protective equipment (PPE)-related skin diseases, and other topics. The value of these articles and their impact on clinical impact were discussed and we hope that dermatologists can have a better understanding of these areas from this study.

The top 100 most-cited articles citing human brain banking from 1970 to 2020: a bibliometric analysis.

Many articles involving human brain banks have been published. Bibliometric analysis can determine the history of the development of research and future research trends in a specific field. Three independent researchers retrieved and reviewed articles from the Web of Science database using the following strategy: "TS = (((brain OR cerebral) AND (bank* OR biobank*)) OR brainbank*)." The top 100 most-cited articles were identified and listed in descending order by total citations. Web of Science was used to identify ten recent articles describing bank construction. GeenMedical ( https://www.geenmedical.com/ ) was used to identify ten recent articles from journals with an impact factor (IF) > 20. The top 100 most-cited articles citing human brain banks were published between 1991 and 2017. Fifty-two percent of the articles focused on a specific type of neurodegenerative disease, and 16% discussed the construction and development of human brain banks. Articles using brain tissue had more total and annual citations than those on bank construction. Ten articles with high IFs were published from 2017 to 2019, and they were primarily studies using novel research techniques such RNA sequencing and genome-wide association studies. Most studies were published in journals specializing in neurology or neuroscience such as Movement Disorders (10%), and had been conducted in the United States (52%) by neurologists (62%). The top 100 most-cited articles and recent publications citing human brain banks and their bibliometric characteristics were identified and analyzed, which may serve as a useful reference and pave the way for further research.

Energy transfer mechanism dominated by the doping location of activators in rare-earth upconversion nanoparticles.

Research on the energy transfer mechanism of rare-earth-doped upconversion nanoparticles (UCNPs) has been an important area due to the increasing demand for tuning multicolor emission and enhancing the upconversion efficiency; however, because of large energy mismatch, many lanthanide activators, such as Eu3+, cannot realize highly efficient near infrared-to-visible upconversion by simple codoping of Yb3+. Therefore, introduction of other ions to assist the energy transfer process is required. Herein, we prepared core-shell nanoparticles with different doping locations to investigate the upconversion energy transfer mechanism. The upconversion luminescence (UCL) of core-shell nanoparticles was investigated by steady-state luminescence and time-resolved luminescence spectra. The UCL behaviors in these different multi-activator core-shell nanoparticles were observed. The results revealed different energy transfer channels influenced by the doping location of activators. This study may open up new avenues of structure design for fine-tuning of multicolor UCL for specific applications.

Pregnancy in adult-onset dermatomyositis/polymyositis: A systematic review.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) in pregnancy is uncommon but may result in complications for both mother and the fetus. AIM: In this systematic review, we summarized the current literature investigating outcomes of pregnancy related to the dermatomyositis/polymyositis (DM/PM) process. CONTENT: We searched PubMed, Embase, Cochrane Library, and Web of Science databases and included 61 studies reporting the disease course, pregnancy outcomes, and management of both pregnancy and DM/PM in the final analysis.The specific information of 221 pregnancies was extracted and these pregnancies were divided into three distinct forms: pregnancies after disease onset (n = 159), pregnancies with new disease onset (n = 37), and pregnancies followed by postpartum onset (n = 25). In most cases, DM/PM disease activity remained stable or improved throughout pregnancy (80.2%) and the postpartum period (83.9%). Active DM/PM during pregnancy significantly increased the risk of stillbirth or neonatal death (12% vs. 1%, P = .005) and preterm birth (34.7% vs. 11%, P < .001). The rates of other poor outcomes (total fetal loss, low birth weight, and intrauterine growth retardation) were also increased in pregnancies with active disease. Mainstay treatments for active DM/PM during pregnancy are glucocorticoids and intravenous immunoglobins. IMPLICATIONS: The present results underline the importance of good control of myopathy in optimizing the pregnancy outcomes of women with DM/PM.

An Updated Review of Recent Advances in Neurosyphilis.

Neurosyphilis is caused by Treponema pallidum invading the central nervous system, of which the incidence is increasing worldwide. Due to its variable clinical manifestations, diagnosis of neurosyphilis remains challenging, especially the asymptomatic form. This review focuses on recent advances in neurosyphilis, including epidemiology, clinical manifestations, laboratory findings, comorbidities, diagnosis, treatment, prognosis, and basic research. The expansion of men who have sex with men and the infection of human immunodeficiency virus mainly accounted for the increasing incidence of neurosyphilis. The rate of some historically described forms of neurosyphilis in the pre-antibiotic era declined significantly; atypical features are more prevalent. Neurosyphilis, regarded as a great mimicker for neuro-ophthalmic, audio-vestibular, and psychiatric disorders, often presents concomitantly with other diseases, including metabolic disorders. Studies on long non-coding RNAs, miRNAs, chemokines, and metabolites in peripheral blood and cerebrospinal fluid may facilitate exploring the pathogenesis and identifying novel biomarkers of neurosyphilis. The drug resistance of Treponema pallidum to penicillin has not been reported; ceftriaxone was proposed to be more effective than penicillin, whereas few randomized controlled trials supported this view. This study may pave the way for further research, especially the diagnosis and treatment of neurosyphilis.

Topical calcineurin inhibitors as a double-edged sword in rosacea: A systematic review.

BACKGROUND: Rosacea is a chronic inflammatory disease mainly with skin or ocular manifestations. Topical calcineurin inhibitors, pimecrolimus and tacrolimus, can be used to treat rosacea. However, they can also induce rosacea-like eruptions. AIMS: This study systematically reviewed the double-edged sword effects of pimecrolimus and tacrolimus on rosacea. METHODS: Four databases were retrieved to search for articles on the effects of pimecrolimus and tacrolimus on rosacea, including Cochrane Library, Embase, PubMed, and Web of Science. Only English articles were included in the systematic review. Relevant data were collected, and the levels of evidence were evaluated. RESULTS: 28 articles published between 2001 and 2016 were included. 11 articles were about pimecrolimus as the treatment of rosacea, 4 articles were about the pimecrolimus-induced rosacea, 9 articles were about tacrolimus as the treatment of rosacea, and 4 articles were about tacrolimus-induced rosacea. Participants for each study ranged from 1 to 200. Several types of outcome measurements were used for these publications. CONCLUSIONS: Both pimecrolimus and tacrolimus might have double-edged sword effects on rosacea. Pimecrolimus and tacrolimus could be effective for rosacea. However, both of them could also induce rosacea. Larger, randomized, controlled studies on pimecrolimus and tacrolimus as the treatment of rosacea and studies on the mechanisms of pimecrolimus and tacrolimus in treating or inducing rosacea are needed. This systematic review emphasized the double-edged sword role of topical calcineurin inhibitors in rosacea, which may pave the way for future research.

Murine models of rosacea: a review.

Rosacea is a chronic inflammatory disease characterized by facial flushing, erythema, telangiectasia, papules, and pustules. Its pathogenesis has not been fully understood. In 2017, the global ROSacea COnsensus (ROSCO) panel updated the diagnosis, classification, and assessment of rosacea. Phenotype-based treatments and long-term managements have also been recommended. Murine models are a powerful tool in unveiling and dissecting the mechanisms of human diseases. Here, we summarized murine models of rosacea developed or used in previous research, including LL-37 intradermal injection model, KLK-5-induced inflammation model, croton oil inflammation model, 12-O-Tetradecanoylphorbol-13-acetate inflammation model, arachidonic acid inflammation model, RTX-induced vasodilation model, and UVB-induced model. LL-37 injection model has become the most intensively used model in rosacea research. Each model could show the pathophysiological and clinical features of rosacea to some extent. However, no model can show the full picture of the characteristics of rosacea. Improving existed murine models, developing new murine models, and applying them to pathogenesis and treatment research on rosacea are highly warranted in the future.

The Relationship Between Alzheimer's Disease and Skin Diseases: A Review.

Alzheimer's disease is the most common type of dementia placing a heavy burden on the healthcare system worldwide. Skin diseases are also one of the most common health problems. Several skin diseases are associated with Alzheimer's disease through different mechanisms. This review summarizes the relationship between Alzheimer's disease and several types of skin diseases, including bullous pemphigoid, hidradenitis suppurativa, psoriasis, skin cancer, and cutaneous amyloidosis, and provides suggestions based on these associations. Neurologists, dermatologists, and general practitioners should be aware of the relationship between Alzheimer's disease and skin diseases. Dermatology/neurology consultation or referral is necessary when needed.

Clinical Characteristics and Management of Patients With Clinical Amyopathic Dermatomyositis: A Retrospective Study of 64 Patients at a Tertiary Dermatology Department.

Background: Clinical amyopathic dermatomyositis (CADM) represents a subtype of 5-20% of patients with dermatomyositis (DM), which can be categorized into amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). The characteristics of patients with CADM are still limited in English literature. Objective: To investigate clinical features, cutaneous findings, diagnostic accuracy, and treatment regimen of CADM patients. Methods: Sixty-four patients diagnosed with CADM at Peking Union Medical College Hospital by dermatologists were retrospectively analyzed. Data were recorded in the electronic database at each offline clinical consultation and directly extracted from medical records. 2017 EULAR/ACR criteria for idiopathic inflammatory myositis (IIM) classification was used to identify and classify patients with CADM. Published studies were searched to extract relevant data of CADM patients. Results: This cohort included 38 ADM patients and 26 HDM patients. 2017 EULAR/ACR criteria classified 67.2% of patients with CADM into probable or definite DM. Antimalarials were given to a majority of CADM patients (72.6%, n = 45). However, 68.8% (31 out of 45) required at least one aggressive agent combined with hydroxychloroquine due to insufficient response or side effects. The median of systemic treatments in HDM was significantly higher than ADM (p = 0.007). The number of ADM patients using antimalarials as monotherapy was significantly higher than that of HDM patients (p = 0.031), while the number of HDM patients receiving steroids combined with immunosuppressants was significantly higher (p = 0.025). The median of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score improvement was 11.5 and 10.5 for ADM and HDM after a median follow-up of 31.5 and 32.5 months, respectively. Six patients with normal muscle strength developed muscle weakness after a median of 10.5 months (IQR 9-13), and elevated inflammatory markers at initial visit might indicate their muscle weakness development. Conclusions: 32.8% of patients may be overlooked using the three skin variables of 2017 EULAR/ACR criteria. The response rate to single hydroxychloroquine in our cohort was 68.8%. Detailed treatment modalities were different among ADM and HDM. Long-term monitoring for the development of myositis in patients with CADM, especially those with elevated inflammatory markers at initial visit, may be warranted.

Stigmatization in Patients With Psoriasis: A Mini Review.

Psoriasis is a chronic and recurrent immune-related skin disease that often causes disfigurement and disability. Due to the visibility of lesions in patients and inadequate understanding of dermatology knowledge in the general public, patients with psoriasis often suffer from stigma in their daily lives, which has adverse effects on their mental health, quality of life, and therapeutic responses. This review summarized the frequently used questionnaires and scales to evaluate stigmatization in patients with psoriasis, and recent advances on this topic. Feelings of Stigmatization Questionnaire, Questionnaire on Experience with Skin Complaints, and 6-item Stigmatization Scale have been commonly used. The relationship between sociodemographic characteristics, disease-related variables, psychiatric disorders, quality of life, and stigmatization in patients with psoriasis has been thoroughly investigated with these questionnaires. Managing the stigmatization in patients with psoriasis needs cooperation among policymakers, dermatologists, psychologists, psychiatrists, researchers, and patients. Further studies can concentrate more on these existing topics, as well as other topics, including predictors of perceived stigmatization, stigmatization from non-patient groups, influence of biologics on stigmatization, and methods of coping with stigmatization.

Botulinum toxin in treating Hailey-Hailey disease: A systematic review.

BACKGROUND: Hailey-Hailey disease is a rare disorder characterized by recurrent painful blistering, erosions, maceration in the intertriginous regions. Botulinum toxin has been used in the treatment of Hailey-Hailey disease. AIMS: This study aimed to examine all published articles on botulinum toxin in the treatment of Hailey-Hailey disease, and to evaluate its efficacy and safety. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were used to identify eligible articles on August 8, 2020. The searching strategy was "(Hailey Hailey or Hailey-Hailey or pemphigus) and botulinum." RESULTS: Sixteen articles including 38 patients described the use of botulinum toxin in treating Hailey-Hailey disease. Only one case had no response, while the other patients all had partial or complete remission. No side effects were reported. Nine articles including 10 patients mainly described other treatment options, and the patients were only treated with botulinum toxin previously. Their responses to botulinum toxin were limited: one was mild improvement, one was partial response, and the other eight failed. CONCLUSION: Botulinum toxin is not almighty, but a promising alternative option. We recommend botulinum toxin as an adjuvant or supplemental treatment modality for severe and recalcitrant Hailey-Hailey disease. Larger studies are warranted to confirm its efficacy, safety, long-term effects, and cost performance.

Circular RNA as a Potential Biomarker for Melanoma: A Systematic Review.

Circular RNAs (circRNAs) are newly discovered RNAs with covalently looped structures. Due to their resistance to RNAase degradation and tissue-specific expression, circRNAs are expected to be potential biomarkers in early diagnosis and target treatment of many diseases. However, the role of circRNAs in melanoma still needs to be systematically reviewed for better understanding and further research. Based on published articles in PubMed, Embase, Cochrane Library, and Web of Science database, we systematically reviewed the implications and recent advances of circRNAs in melanoma, focusing on function, mechanism, and correlation with melanoma progression. According to inclusion and exclusion criteria, a total of 19 articles were finally included in this systematic review. Of the 19 studies, 17 used human samples, including melanoma tissues (n = 16) and blood serum of patients with melanoma (n = 1). The sample size of the study group ranged from 20 to 105 based on the reported data. Several studies explored the association between circRNAs and clinicopathological characteristics. circRNA dysregulation was commonly observed in melanoma patients. circRNAs function in melanoma by miRNA sponging and interaction with RNA binding proteins (RBP), ultimately controlling several important signaling pathways and cancer-related cellular processes, including proliferation, migration, invasion, metastasis, apoptosis, and glucose metabolism. circRNA expression could be associated with prognostic factors and drug responses, consolidating the potential clinical value in melanoma. Herein, we clarified the functional, prognostic, and predictive roles of circRNAs in melanoma in this systematic review, providing future directions for studies on melanoma-associated circRNAs.

Inpatient Dermatology Consultations in a General Surgery Ward in a Tertiary Hospital in China: A Retrospective Study of 251 Patients.

INTRODUCTION: Dermatologists play essential roles in providing dermatology consultations to inpatients admitted to hospital for care in another speciality ward. Data on dermatology consultations provided to inpatients admitted to general surgery wards are limited. The aim of this study was to analyze the reasons for and diagnoses of consultations provided by dermatologists to hospitalized patients in a general surgery ward and compare the provisional diagnoses by surgical residents and the final diagnoses by dermatologists. METHODS: Electronic health records were retrieved for patients admitted to a general surgery ward who received dermatology consultations while inpatients in Peking Union Medical College Hospital between 1 September 2015 and 31 August 2020. Sex, age, surgical diagnosis, reason for dermatology consultation, provisional diagnosis by surgical residents, and final diagnosis by dermatologists were reviewed. RESULTS: A total of 262 dermatology consultations for 251 patients (n = 251, 123 women and 128 men) were identified, of whom 240 (95.6%) required only one consultation and 11 (4.4%) required two. Dermatology consultations were classified into three categories: preoperative consultation (n = 45, 17.9%), postoperative consultation (n = 65, 25.9%), and consultation unrelated to general surgery diseases or treatments (including surgery) (n = 141, 56.2%). For consultations falling in the category preoperative consultation, common reasons for the consultation were: to evaluate whether the current treatment plan for previously diagnosed skin diseases needed to be changed; to evaluate and manage skin problems that emerged after admission; to evaluate syphilis; and to evaluate whether previously diagnosed skin diseases would affect surgical incision or wound healing. Drug eruption, dermatitis/eczema, infectious skin disorders, and urticaria were the most common skin diseases in the hospitalized general surgery patients. Only 32 (12.7%) provisional diagnoses were made, of which 25 (78.1%) were correct and seven (21.9%) were incorrect. Surgical residents mainly had difficulty distinguishing herpes zoster, drug eruption, and infectious skin disorders from dermatitis/eczema. CONCLUSION: Our results facilitate the understanding of inpatient dermatology consultations in general surgery wards and may help in the design of future educational materials and/or management guidelines.

Use of Botulinum Toxin in Treating Rosacea: A Systematic Review.

BACKGROUND: Rosacea is a chronic skin disorder characterized by erythema, flushing, telangiectasia, papules and pustules, phymatous changes, and ocular involvement. The aim of this study was to examine all published research articles in which botulinum toxin was used to treat rosacea and to evaluate the efficacy and safety of this treatment. METHODS: PubMed, Embase, Cochrane Library, and Web of Science database were used to identify articles eligible for systematic review on March 26, 2021. Prospective or retrospective studies which directly used botulinum toxin to treat rosacea were included and reviewed. RESULTS: Nine studies were included in this systematic review. Two were randomized controlled trials, graded as Level 2 for the quality of evidence. The total number of participants was 130, and the number of participants in each study ranged from 1 to 25. The improvement was observed in all studies in signs and symptoms compared with baseline. Adverse events were transitory and self-limited. CONCLUSION: Botulinum toxin could have overall satisfying efficacy and safety in the treatment of rosacea, though limited by small sample size, imperfect study design, and short follow-up visits.

Rosacea Treatment: Review and Update.

Rosacea is a chronic and inflammatory skin disease characterized by flushing, nontransient erythema, papules/pustules, telangiectasia, and phymatous changes. Secondary manifestations, such as itching, burning, or stinging, are often observed in patients with rosacea. In 2017, a phenotype-based approach for diagnosis and classification was recommended. With the update of the diagnosis and classification of rosacea, treatment options for patients with rosacea have attracted the attention of dermatologists. Here, we summarize the latest advances in rosacea treatment, including skin care and cosmetic treatments, topical therapies, oral therapies, laser- and light-based therapies, injection therapies, treatments for specific types of rosacea, treatments for systemic comorbidities, and combination therapies. The impact of the phenotype-based approach on rosacea treatment and future directions are also discussed.