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Atopic dermatitis (AD) is a common disease clinically characterized by chronic recurrent eczematous lesions, dry skin, and pruritus. AD can negatively impact patients’ quality of life. The prevalence of AD in China has been increasing during the past few decades. Based on the most recent advances in the treatment of AD, we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition, epidemiology, pathogenesis, clinical classification, diagnosis, prevention, and treatment of AD.

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development.Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls.Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively).Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.

Introduction:. Erosive pustular dermatosis of the scalp (EPDS) is an uncommon condition with unknown etiology. The clinical exclusive diagnosis needs to be differentiated from similar diseases. Here, we present a case of EPDS after surgical treatment of scalp squamous cell carcinoma. Case presentation:. A 68-year-old woman presented with an eight-month history of a chronic scalp eruption. She had been diagnosed as squamous cell carcinoma by biopsy nine months ago, and had been treated by surgical excision and skin grafting. One month later, she was referred for evaluation of the newly enlarged lesion which was observed at the skin grafting site. She was diagnosed of EPDS based on characteristics of lesions, clinicopathological findings and laboratory data. The condition had clinically improved with systemic steroid therapy and topical tacrolimus for two weeks. Relapses occurred after complete withdrawal of both treatments. After repeating the above therapy and applying topical tacrolimus as maintenance therapy, the condition was well controlled at the one-year follow-up. Discussion:. EPDS is an uncommon inflammatory dermatosis with main incidence rate of elderly patients and female predominance. The diagnosis of EPDS cant be made only by histopathological examination, which is helpful for differential diagnosis. Microbiological investigations commonly remain negative. For the high risk of relapse, it is important for clinicians to be aware of maintenance treatment and a long- term management. Conclusion:. It should be recognized by clinicians that EPDS is an uncommon and relapse disease, leading to serious cosmetic problems. The treatment lacks evidence-based medicine data, clinician should choose the appropriate therapy according to the condition of patients.

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74–0.87)] and 0.71 (95% CI: 0.56–0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39–0.68) and denileukin diftitox 0.56 (95% CI: 0.35–0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42–0.68) and 0.42 (95%CI: 0.29–0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16–0.51) and denileukin diftitox 0.37 (95% CI: 0.24–0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.

This study aimed to evaluate the variability of dabigatran plasma concentration and the association with clinical events in Chinese patients treated with dabigatran etexilate (DE) for non-valvular atrial fibrillation (NVAF). The steady-state concentration of dabigatran (the active metabolite of DE) was determined at trough and peak. The effect of dabigatran concentration variability and related factors on clinical outcomes were explored. Data from 86 patients receiving a fixed dose of 110 mg showed that dabigatran trough concentration varied remarkably. Age, BMI and history of heart failure were identified as important covariates for dabigatran trough concentration. Dabigatran trough concentration (P = 0.002) and history of hypertension (P = 0.012) scores were identified as key factors for predicting the risk of bleeding events. Dabigatran trough concentration, affected by Age, BMI and history of heart failure, may serve as an independent risk factor for bleeding events in Chinese patients treated with DE for NVAF.

Clown nose-like lesion refers to the manifestation of a reddish or skin-colored bulge on the tip of the nose or the manifestation of bulbous tip of the nose. More and more clinical cases show that clown nose-like lesion can also be the indication of some genetic syndromes, not just the manifestation of metastatic visceral tumor as it initially proposed. However, the clinical features of clown nose-like lesion indicated by metastatic malignancies, genetic cancer predisposition syndromes or primary diseases involving the nasal tip are lacking. In this study, patients with clown nose-like lesion in our clinical practices and from published literatures were collected and reviewed. We found that clown nose-like lesions caused by metastatic malignancies including lung cancer are often solitary and more common in male (24/31) older individuals (average age 62.3, ranging 40–78 years old). In addition, they usually appear for a short time, and are prone to be misdiagnosed as primary nasal diseases, leading to a poor prognosis (all patients with data available died within 4 months). Clown nose-like lesions associated with genetic cancer predisposition syndromes usually develop at a young age (mean age 15.3) with female preference (9/10). They are accompanied by multiple-systemic involvements, including low hair volume, developmental delay, cancer predisposition or neurological diseases. They show slow development and often positive family history (6/10). These two kinds of clown nose-like lesions are often asymptomatic, which delays the diagnosis and treatment of underlying malignancies or syndromes. In brief, the term of clown nose-like lesion is underrecognized, and should be updated. Clown nose-like lesions can serve as indicators to at least three categories of clinical issues: metastatic visceral tumors, genetic syndromes, and primary diseases involving the nasal tip. Increased awareness of clinical features of updated clown nose-like lesions can alert physicians to these underlying malignancies or syndromes, render earlier detection of associated medical issues, and allow for genetic counseling of family members.

Predicting disease progression remains a particularly challenging endeavor in chronic degenerative disorders and cancer, thus limiting early detection, risk stratification, and preventive interventions. Here, profiling the spectrum of chronic myeloproliferative neoplasms (MPNs), as a model, we identify the blood platelet transcriptome as a proxy strategy for highly sensitive progression biomarkers that also enables prediction of advanced disease via machine learning algorithms. Using RNA sequencing (RNA-seq), we derive disease-relevant gene expression in purified platelets from 120 peripheral blood samples constituting two time-separated cohorts of patients diagnosed with one of three MPN subtypes at sample acquisition - essential thrombocythemia, ET (n=24), polycythemia vera, PV (n=33), and primary or post ET/PV secondary myelofibrosis, MF (n=42), and healthy donors (n=21). The MPN platelet transcriptome reveals an incremental molecular reprogramming that is independent of patient driver mutation status or therapy and discriminates each clinical phenotype. Differential markers in each of ET, PV and MF also highlight candidate genes as potential mediators of the pro-thrombotic and pro-fibrotic phenotypes in MPNs. In ET and PV, a strong thromboinflammatory profile is revealed by the upregulation of several interferon inducible transmembrane genes (IFITM2, IFITM3, IFITM10, IFIT3, IFI6, IFI27L1, IFI27L2), interleukin receptor accessory kinases/proteins (IRAK1, IL15, IL1RAP, IL17RC) and several solute carrier family genes (SLC16A1, SLC25A1, SLC26A8, SLC2A9) as glucose and other metabolic transport proteins, and coagulation factor V (F5). In MF, fibrosis-specific markers were identified by an additional focused comparison of MF patients versus ET and PV, showing increased expression of several pro-fibrotic growth factors (FGFR1, FGFR3, FGFRL1), matrix metalloproteinases (MMP8, MMP14), vascular endothelial growth factor A (VEGFA), insulin growth factor binding protein (IGFBP7), and cell cycle regulators (CCND1, CCNA2, CCNB2, CCNF). Also, focusing on the JAK-inhibitor ruxolitinib/RUX-specific signatures, we not only confirm previous observations on its anti-inflammatory and immunosuppressive effects (e.g. downregulation in our RUX-treated cohort of IL1RAP, CXCR5, CPNE3, ILF3) but also identify new gene clusters responsive to RUX - e.g. inhibition of type I interferon (e.g. IFIT1, IFIT2, IFI6), chromatin regulation (HIST2H3A/C, HIST1H2BK, H2AFY, SMARCA4, SMARCC2), epigenetic methylation in mitochondrial genes (ATP6, ATP8, ND1-6 and NDUFA5), and other proliferation, and proteostasis-associated markers as putative targets for MPN-directed therapy. Mechanistic insights from our data highlight impaired protein homeostasis as a prominent driver of MPN evolution, with a persistent integrated stress response. Preliminary ex vivo data on MPN patient bone-marrow-derived CD34+ cells and cultured megakaryocytes validate a proteostasis-focused subset of our peripheral platelet RNA-seq signatures. Further leveraging this substantive dataset, and in particular a progressive expression gradient across MPN, we develop a machine learning model (Lasso-penalized regression) predictive of the advanced subtype MF at high accuracy and under two conditions of validation: i) temporal Stanford internal (AUC-ROC of 0.96) and ii) geographic external cohorts (AUC-ROC of 0.97, using independently published data of an additional n=25 MF and n=46 healthy donors). Lasso-derived signatures offer a robust core set of < 5 MPN progression markers. Together, our platelet transcriptome snapshot of chronic MPNs demonstrates a methodological avenue for disease risk stratification and progression beyond genetic data alone, with potential utility in a wide range of age-related disorders. Part of the work contributing to this abstract has been posted as a preprint at this link: https://www.biorxiv.org/content/10.1101/2021.03.12.435190v2 Figure 1 Figure 1. Disclosures Gotlib: Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Kartos: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaEssentia: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cogent Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair for the Eligibility and Central Response Review Committee, Research Funding; Allakos: Consultancy.

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of α1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63–0.85; p ≤ 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65–0.84; p ≤ 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03–0.94; p = 0.028) compared to matched controls not on any α1-AR antagonist at the time of admission. These findings suggest that use of α1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.

Background The involvement of the nerve in psoriasis development was suggested by sporadic case reports. Objectives To provide multiple evidence for the nerve in psoriasis development with a retrospective case review, a literature review and a mouse-based experimental experiment. Methods Psoriatic patients who had concomitant nerve injuries and such cases from literatures were reviewed. And, on wild-type mouse level, unilateral denervation surgery was performed on the dorsal skin before and after the induction of psoriasiform dermatitis, respectively. Lesion visual scores were calculated, and biopsies were taken for hematoxylin-eosin (HE) staining, immunofluorescence analysis, and RNA sequencing & bioinformatics analysis before denervation surgery and the 2nd, 4th, 6th, 8th day after the surgery. Results All clinical cases (20/20) showed that local lesions under the control of injured nerves relieved spontaneously or even cleared/spared, and only about 1/3 experienced partial recurrence. Next, mouse psoriasiform experiments demonstrated that unilateral denervation prior to imiquimod application attenuated the enhancement of inflammatory reactions (e.g. adaptive immune response and Th17 cell differentiation pathway) and the induction of ipsilateral psoriasiform dermatitis. On the other hand, unilateral denervation after psoriasiform dermatitis induction promoted the regression of inflammatory reactions (e.g. T cell activation, TNF signaling, and Th17 cell differentiation pathway) and ipsilateral dermatitis recovery. Conclusion Our study based on both retrospective clinical case review and wild-type mouse experiments provides multiple evidence for the involvement of the nerve in psoriasis development. Regulation of immune events, including TNF signaling and Th17 cell differentiation, may be the mechanisms of the nerve in psoriasis.

Background There is an obvious need for more prompt and specific biomarkers of bacterial infections in generalized pustular psoriasis patients. Objective The aim of this study was to evaluate the diagnostic properties and define appropriate cut-off values of procalcitonin and C-reactive protein in predicting bacterial infection in generalized pustular psoriasis patients. Methods Sixty-four generalized pustular psoriasis patients hospitalized from June 2014 to May 2017 were included in this retrospective study. The values of procalcitonin, C-reactive protein, details of infection, and other clinical parameters were analyzed. Results Receiver operating characteristic curve analysis generated similar areas (p = 0.051) under the curve for procalcitonin 0.896 (95% CI 0.782–1.000) and C-reactive protein 0.748 (95% CI 0.613–0.883). A cut-off value of 1.50 ng/mL for procalcitonin and 46.75 mg/dL for C-reactive protein gave the best combination of sensitivity (75.0% for procalcitonin, 91.7% for C-reactive protein) and specificity (100% for procalcitonin, 53.8% for C-reactive protein). Procalcitonin was significantly positively correlated with C-reactive protein levels both in the infected (r = 0.843, p = 0.040) and non-infected group (r = 0.799, p = 0.000). Study limitations The sample size and the retrospective design are limitations. Conclusions The serum levels of procalcitonin and C-reactive protein performed equally well to differentiate bacterial infection from non-infection in generalized pustular psoriasis patients. The reference value of procalcitonin and C-reactive protein applied to predicting bacterial infection in most clinical cases may not be suitable for generalized pustular psoriasis patients. C-reactive protein had better diagnostic sensitivity than procalcitonin; however, the specificity of procalcitonin was superior to that of C-reactive protein.

These are viral warts on the eyebrows of a woman in her late 20s (black arrows, fig 1), caused by inoculation with human papillomavirus 18 (HPV18). Fig 1 The patient presented with a four month history of …

To explore HIV-related facial skin disorders among HIV-positive outpatients and the role in identifying HIV infection and/or AIDS. We retrospectively evaluated records from all HIV-positive patients who initially presented at our Dermatology and Venereology Department (Southwest Hospital, Chongqing, China) between January 2009 and March 2016. We also compared the prevalences of facial skin disorders among HIV-positive and HIV-negative outpatients. We identified 827 HIV-positive patients, who included 150 patients who initially presented with 1 of 14 different facial skin disorders. Noninfectious/inflammatory dermatosis was the most common diagnosis (109/150, 72.7 %), and infectious dermatosis was diagnosed in 41 cases (27.3 %). Most facial skin disorders exhibited a higher proportion of HIV-positive patients, compared to HIV-negative patients. Herpes zoster was the most common disorder, and psoriasis and eczema or neurodermatitis were secondary disorders. Some disorders, such as seborrheic dermatitis, exhibited a severe and refractory clinical manifestation. Photosensitive dermatoses were significantly more common among HIV-positive patients, compared to HIV-negative patients (1.9 % vs. 0.0 %). No malignancies were diagnosed. There is a wide spectrum of facial skin disorders among HIV-positive patients in southwest China, and some of these disorders may provide the first clinical indication of HIV infection and/or AIDS. However, these findings require confirmation using immunological data.

Background Medical students will encounter cutaneous lesions associated with systemic disorders during their training and career. However, there are no chapters in Chinese undergraduate medical textbooks regarding these lesions. Objective The objective of the present study was to evaluate the impact of an additional learning module about cutaneous lesions associated with systemic disorders for Chinese undergraduates. Methods In this medical course, we introduced a case-based clinical learning module. This module was evaluated with a pre-/postcourse questionnaire and a final multichoice examination. Results After learning, more students agreed that some skin lesions could serve as "windows" to hidden systemic diseases, and it was more important to learn how to distinguish lesions associated with systemic diseases from simplex ones. We found that the group that was provided conventional teaching plus this module scored significantly better (52.75 ± 23.96) than the conventional teaching group (40.53 ± 21.43; t = 2.370, p = 0.020) in the final multichoice examination. Conclusion Introducing this additional learning module may offer an early opportunity to explore systemic diseases from a dermatological view and is likely to lay the foundations for interdisciplinary collaboration in the future practice for medical students.

// An-Chuan Li 1,2,* , Wei-Wei Xiao 1,* , Guan-Zhu Shen 1,* , Lin Wang 1 , An-An Xu 1,3 , Yan-Qing Cao 1,4 , Shao-Min Huang 1 , Cheng-Guang Lin 1 , Fei Han 1 , Xiao-Wu Deng 1 and Chong Zhao 1 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China 3 Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, Guangzhou, China 4 Department of Radiation Oncology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Fei Han, email: // Xiao-Wu Deng, email: // Chong Zhao, email: // Keywords : nasopharyngeal carcinoma, distant metastasis, intensity-modulated radiotherapy, chemotherapy Received : March 24, 2015 Accepted : May 22, 2015 Published : May 28, 2015 Abstract Purpose: To report the distant metastasis (DM) risk and patterns for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to analyze the benefits of chemotherapy based on DM risk. Materials and Methods: 576 NPC patients were analyzed. The DM rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences. The patients were divided into different risk subclassifications according to DM hazard ratios. Results: 91 patients developed DM after treatment, with bone as the most common metastatic sites. 82.4% of DMs occurred within 3 years of treatment. Patients were classified as low-risk, intermediate-risk and high-risk, and the corresponding 5-year DM rates were 5.1%, 13.1% and 32.4%, respectively ( P < 0.001). Chemotherapy failed to decrease the DM rate in the low-risk subclassification, but decreased the DM risk in the intermediate-risk subclassification ( P = 0.025). In the high-risk subclassificaiton, the DM rate was 31.9% though chemotherapy was used, which was significantly higher than that of other two subclassifications. Conclusions: DM is the dominant treatment failure in NPC treated by IMRT, with similar occurrence times and distributions to those that occurred in the era of conventional radiotherapy. Further studies on treatment optimization are needed in high-risk patients.

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1 %. N2–3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm3, haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0–2), intermediate risk (3–4) and high risk (5–8). The 5-year DM rates were 4.6, 21.8 and 50.8 %, respectively (P

Background: Medication adherence is essential for psoriasis management. Although studies have determined the prevalence and correlative factors of non-adherence, as far as we know, there has been no study specifically addressing them in China. Methods: Anonymous 23-item questionnaires were distributed to 324 psoriatic patients from June 2012 to June 2013. χ2 test, normality test, Student's t test or Mann-Whitney U test, Bonferroni correction and the binary logistic regression model were applied. Results: Self-medication of psoriasis was high in China (82.4%). Joint involvement, absence of communication with families and short communication duration with doctors were the three top factors affecting adherence. Besides low efficacy (16.0%) and recurrence frustration (27.0%), we found that patients' deception by sham advertisings (24.1%) is an non-negligible issue. Conclusion: Psoriasis self-medication in China was high. Improvement of patients' communication with families and/or doctors were suggested to be crucial to enhance adherence. Meanwhile, extermination of sham advertisings by administrative agencies is of great concern.

Objective Investigation was conducted to understand the mechanism of action of diacylglycerol acyltransferase 1 (DGAT1) using small molecules DGAT1 inhibitors, compounds K and L. Design and Methods Biochemical and stable-label tracer approaches were applied to interrogate the functional activities of compounds K and L on TG synthesis and changes of carbon flow. Energy homeostasis and gut peptide release upon DGAT1 inhibition was conducted in mouse and dog models. Results Compounds K and L, dose-dependently inhibits post-prandial TG excursion in mouse and dog models. Weight loss studies in WT and Dgat1-/- mice, confirmed that the effects of compound K on body weight loss is mechanism-based. Compounds K and L altered incretin peptide release following oral fat challenge. Immunohistochemical studies with intestinal tissues demonstrate lack of detectable DGAT1 immunoreactivity in enteroendocrine cells. Furthermore, 13C-fatty acid tracing studies indicate that compound K inhibition of DGAT1 increased the production of phosphatidyl choline (PC). Conclusion Treatment with DGAT1 inhibitors improves lipid metabolism and body weight. DGAT1 inhibition leads to enhanced PC production via alternative carbon channeling. Immunohistological studies suggest that DGAT1 inhibitor's effects on plasma gut peptide levels are likely via an indirect mechanism. Overall these data indicate a translational potential towards the clinic.

There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66–0.83), 0.49 (95% CI, 0.37–0.64), 0.69 (95% CI, 0.65–0.76), 0.62 (95% CI, 0.54–0.69), and 0.56 (95% CI, 0.42–0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists.

Summary Purpose To analyze the prevalence and significance of FOXP3+ infiltration into (pre)malignant skin carcinomas following ultraviolet radiation (UVR) exposure. The possible pathways that UVR impacts on FOXP3 are to be discussed. Background FOXP3+ regulatory T cells (FOXP3+ Tregs) are correlated to cutaneous squamous tumor progression. However, there is no information describing the prevalence of FOXP3+ infiltration in cutaneous premalignant and malignant squamous carcinomas with UVR exposure. Methods We investigated the prevalence of FOXP3+ infiltration in 14 patients with Bowen's disease, 40 squamous cell carcinoma SCC patients and 21 patients with basal cell carcinoma (BCC) by immunohistochemistry. Results The percentages of FOXP3+ vs. total peri-neoplasm infiltration cells (FOXP3+ PCT) were significantly higher in Bowen's disease and well-differentiated SCC that were exposed to UVR than these diseases not exposed to UVR (t = 3.5776, P = 0.0038; t’ = 5.9214, P

Uric acid is the end product of nucleic acid catabolism for humanity. Serum uric acid level has been suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aims to examine the association between serum uric acid levels and NAFLD in subjects of different ages. A cross-sectional study was performed among the patients of different ages with NAFLD (abnormal group) or without NAFLD (normal group) in Lianyungang, Jiangsu, China. The levels of serum uric acid, total cholesterol, triglyceride, and low density lipoprotein in the abnormal group were significantly higher than those in the normal group, while the level of high density lipoprotein in the abnormal group was significantly lower than that in the normal group (p < 0.05). The serum uric acid prevalence, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein in the abnormal group was significantly higher than those in the normal group (p < 0.05). The serum uric acid, total cholesterol, triglyceride, and low density lipoprotein levels and prevalence rates in elderly patients were higher than younger and middle aged patients. Serum uric acid level is highly associated with NAFLD in patients of different ages.

This study was designed to determine the optimal treatment frequency with the 308-nm excimer laser for vitiligo and identify key clinical variable(s) associated with treatment efficacy at the optimal frequency.Optimal clinical parameters for excimer laser treatment of vitiligo have not been fully determined. Data about the influence on treatment frequency of different clinical variables of vitiligo are needed to facilitate effective treatment regimens.A total of 187 patients were treated with the 308-nm excimer laser for 20 sessions at different frequencies (0.5, 1.0, 2.0, and 3.0 per week). The repigmentation rate was graded on a six-point scale and was blindly evaluated by independent physicians.The final percentage of repigmentation for group 0.5 was statistically lower than those for group 1.0, 2.0, and 3.0, and percentages of final levels of repigmentation among these three groups were not statistically different. The clinical variables showed no statistical differences in the final repigmentation effect. Repigmentation occurred fastest with treatment frequencies of 2.0 and 3.0 and there was no statistically significant difference between them. The onset of repigmentation correlated with the area of vitiliginous patches treated, not with the other clinical variables.The 308-nm excimer laser is effective for therapy to treat vitiligo on the face and neck. The ultimate laser-induced repigmentation effect does not correlate with treatment frequency and repigmentation occurs faster with treatment frequencies of 2.0 and 3.0 than that of 1.0. It appears that the onset of repigmentation correlates with the total area of vitiliginous patches and the optimal treatment frequency. Monitored studies on a larger population with long-term follow-up would be needed to confirm and extend our findings.

The efficacy of methotrexate (MTX) varies in the treatment of psoriasis.We sought to identify an indicator from routine pretreatment tests to predict MTX efficacy in the treatment of psoriasis.In a retrospective analysis of 77 psoriatic patients, the correlation between MTX efficacy and pretreatment routine test results was analyzed with Spearman correlation. The potential risks were further evaluated with a linear regression model. Receiver operating characteristic analysis was performed to examine the effectiveness of serum total calcium (tCa) to predict the effect of MTX on psoriasis. The highest Youden index was used to determine the cutoff point, with which the positive and negative predictive values were calculated. Synergistic effects of MTX and calcium on keratinocyte growth and psoriasis-like mouse model were also investigated.The pretreatment tCa level exhibited the closest association with MTX efficacy. The relative psoriasis improvement with tCa was 61.07% (95% confidence interval, 42.85-79.29; P.001) and better improvements were observed in patients with higher tCa (r = 0.588; P.002). MTX inhibited keratinocyte growth, which was enhanced synergistically by calcium. In a psoriasis-like mouse model, MTX strongly inhibited epidermis proliferation in the high-calcium group.One limitation of our study is the relatively small sample size.Pretreatment tCa level has the highest correlation with MTX efficacy, which might be useful in predicting beneficial treatment results in psoriasis. Larger studies are required to confirm our findings.

Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by alpha-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp(-/-)) mice to examine the physiological role of AgRP. Agrp(-/-) mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp(-/-) mice display normal responses to starvation, diet-induced obesity, and the administration of exogenous leptin or neuropeptide Y (NPY). In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin, Mc3r, Mc4r, or NPY mRNAs in Agrp(-/-) mice. As AgRP and the orexigenic peptide NPY are coexpressed in neurons of the arcuate nucleus, we generated AgRP and NPY double-knockout (Agrp(-/-);Npy(-/-)) mice to determine whether NPY or AgRP plays a compensatory role in Agrp(-/-) or NPY-deficient (Npy(-/-)) mice, respectively. Similarly to mice deficient in either AgRP or NPY, Agrp(-/-);Npy(-/-) mice suffer no obvious feeding or body weight deficits and maintain a normal response to starvation. Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.

The serum total protein levels of the elderly possibly decrease gradually with aging. However, serum total protein levels are not suitable as a uniform reference standard for the elderly at different ages and genders. Thus, we investigated the total serum protein distribution in different gender and age groups of 11,453 elderly individuals aged ≥60 years and without liver or renal disease from Lianyungang, Jiangsu, China. The total protein levels (TPL) of these individuals exhibited normal distribution (Z = 1.206, P = 0.109), whereas the reference range (95% CI) was 54.1 g/L to 82.3 g/L. TPL was higher in females than in males for those aged between 60 and 75 years, whereas no significant difference was observed for those aged between 80 and 95 years. TPL was negatively correlated with age in males (r = -0.1342, P

Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant.

Paragonimiasis, caused by the lung fluke of the genus Paragonimus, affects an estimated 22 million people yearly worldwide. Humans acquire these parasites mostly by ingestion of raw or poorly cooked freshwater crustaceans (second intermediate hosts), or by eating raw meat from wild animals.1 Paragonimiasis is closely associated with some special eating habits or incomplete sanitary systems in developing countries. Cutaneous features are reported rarely and may occur without pleuropulmonary involvement. Certain microenvironmental stressors of the host are likely the main triggers that lead to the migration of parasites. Here we report a case in which a migratory parasite was found to exit from the patient's body. This was most likely triggered by regional anesthesia or a surgical procedure.

Diacylglycerol acyltransferase-1 (DGAT1) is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4) inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

Genetic syndromes with dermatologic findings and multisystemic involvement (e.g., visceral cancer predisposition) are underrecognized. Patients may have incomplete penetrance and variable expressivity; some patients may solely exhibit subtle skin signs, which create a diagnostic challenge for physicians. Interdisciplinary diagnostic knowledge is required for the early diagnosis and monitoring of patients with these syndromes. Cutaneous changes in the face—one of the most highly exposed areas—can be easily noticed by patients themselves, their families and friends, and physicians; these changes may serve as early indicators of genetic syndromes with malignancies. In this article, we present examples of genetic syndromes with malignancies for which a thorough faciocutaneous examination is helpful in establishing a diagnosis. These examples include lentiginosis-related syndromes (e.g., Peutz-Jeghers syndrome, Carney complex), photosensitivity-related syndromes (Bloom syndrome, Rothmund-Thomson syndrome), and hamartoma-related syndromes (Cowden syndrome, multiple endocrine neoplasia syndrome, tuberous sclerosis complex, Gardner syndrome, Muir-Torre syndrome). The characteristics of these faciocutaneous clues are summarized and discussed. Objective evaluation of these faciocutaneous clues in combination with other clinical information (e.g., family history, histopathological findings, combination with other concomitant faciocutaneous lesions) is emphasized to narrow the diagnosis. The list of genetic syndromes with faciocutaneous manifestations is still expanding. Increased awareness of faciocutaneous markers can alert physicians to underlying syndromes and malignancies, render earlier screening and detection of associated medical issues, and allow for genetic counseling of family members.

Background Cronkhite-Canada syndrome (CCS) is a rare multiple gastrointestinal polyposis. Up till now, many complications of CCS have been reported in the literature, but rib fracture is not included. Case Presentation We report a case of a 58-year-old man who was admitted to our hospital with a 6-month history of frequent diarrhea, intermittent hematochezia and a weight loss of 13 kg. On admission, physical examination revealed alopecia of the scalp, hyperpigmentation of the hands and soles, and dystrophy of the fingernails. Laboratory data revealed hypocalcaemia and hypoproteinemia. Esophagogastroduodenoscopy, video capsule endoscopy and colonoscopy revealed various sizes of generalized gastrointestinal polyps. Histological examination of the biopsy specimens obtained from the stomach and the colon showed adenomatous polyp and inflammatory polyp respectively. Thus, a diagnosis of CCS was made. After treatment with corticosteroids for 24 days and nutritional support for two months, his clinical condition improved. Two months later, he was admitted to our hospital for the second time with frequent diarrhea and weight loss. The chest radiography revealed fractures of the left sixth and seventh ribs. Examinations, including emission computed tomography, bone densitometry test, and other serum parameters, were performed, but could not identify the definite etiology of the rib fractures. One month later, the patient suffered from aggravating multiple rib fractures due to the ineffective treatment, persistent hypocalcaemia and malnutrition. Conclusions This is the first case of a CCS patient with multiple rib fractures. Although the association between CCS and multiple rib fractures in this case remains uncertain, we presume that persistent hypocalcaemia and malnutrition contribute to this situation, or at least aggravate this rare complication. Besides, since prolonged corticosteroid therapy will result in an increased risk of osteoporotic fracture, CCS patients who accept corticosteroid therapy could be potential victims of rib fracture.

Objective To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on rats with cirrhosis based on the method of differential proteomics. Methods Wistar male rats (n=48) were randomly divided into normal control group (n=12) and model-making group (n=36). Rat cirrhosis model was established by intraperitoneal injection of 50% carbon tetrachloride (CCl4) plus olive oil solution (1 mL/kg, twice weekly for 9 weeks). After 3- and 6-week injection, 6 rats each time were sacrificed for dynamic observation before medicine intervention, and the 24 remained rats were randomly divided into untreated group (n=12) and Yiguanjian Decoction group (n=12) at the first day of the 7th week. All animals were sacrificed by the end of the 9th week, and total protein of liver tissue was isolated by two-dimensional gel electrophoresis (2-DE); some differentially expressed protein spots were analyzed and identified by matrix-assisted laser desorption/ionization two-stage time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and database querying. Protein expressions of Cu/Zn superoxide dismutase (Cu/Zn SOD) and DJ-1 were validated by Western blot and immunohistochemical methods. Results 2-DE maps with high resolution and good repeatability were obtained. In all 50 protein spots identified by MALDI-TOF/TOF-MS and database querying, there were 5 protein spots related to oxidative stress named Cu/Zn SOD, DJ-1, glutathione synthetase, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 respectively. Compared with the normal control group, expressions of Cu/Zn SOD, DJ-1, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 in the untreated group were decreased significantly. Expressions of Cu/Zn SOD and aldo-keto reductase family 7, A2 were decreased time-dependently. Compared with the untreated group in 9th week, protein expressions of Cu/Zn SOD, DJ-1, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 in the Yiguanjian Decoction groups were increased significantly while expression of glutathione synthetase was decreased notably. Western blot and immunohistochemical results of Cu/Zn SOD and DJ-1 expressions coincided with proteomics results. Conclusion Anti-oxidative depression is a key pathological change of cirrhosis induced by CCl4 in rats, and increasing expression of proteins related to anti-oxidative stress may be a major mechanism of Yiguanjian Decoction in treating cirrhosis induced by CCl4 effectively.

Nuclear factor kappa-beta (NF-kappaB) is a critical transcription factor modulating the expression of many genes involved in the pathogenesis of psoriasis. SUMO4 is a negative regulator of NF-kappaB in the cell-signaling pathway. Two functional polymorphisms of the NFKB1 and SUMO4 genes have been found to be associated with the risks of some autoimmune-related diseases, but no published study has investigated the role of these polymorphisms in the etiology of psoriasis in the Chinese population. In this hospital-based, case-control study of 519 Chinese psoriasis vulgaris patients and 541 matched controls, we genotyped the NFKB1-94 ins/delATTG and the SUMO4 rs237025 AG polymorphisms and assessed their respective associations with psoriasis vulgaris risk. We found that the genotype distribution of NFKB1-94 ins/delATTG polymorphism was statistically different between psoriasis patients and controls (P = 0.031). But the difference was not still statistically significant after correction for multiple comparisons. The frequency of wild WW genotype in psoriasis patients was statistically higher than that in controls (35.8 vs. 29.0%, respectively, P = 0.021). The W allele frequency in cases was also significantly higher than that in controls (59.7 vs. 54.1%, P = 0.008). Compared with the DD genotype, a significantly increased psoriasis risk was associated with the NFKB1 WW genotype (adjusted OR = 1.57, 95% CI = 1.10-2.24). In addition, the WW genotype frequency was also statistically higher in the psoriatic subgroups of onset ageor=40, PASI20, male patients and sporadic patients than that in controls. But, no associations of the SUMO4 rs237025 AG polymorphism with the susceptibility of psoriasis were detected. In conclusion, we found a marginal association between the NFKB1-94 ins/delATTG WW genotype and the increased psoriasis vulgaris risk and the association was more evident in the subgroups of onset ageor=40, PASI20, male patients and sporadic patients in Chinese.

To investigate the effects and mechanism of qi-tonifying and stasis-eliminating (QTSE) therapy on the expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the brains of intracerebral hemorrhagic (model) rats. One hundred and eighty Sprague-Dawley rats were randomly divided into six groups: the normal group (n=5), the sham-operative (SO) group (n=35), the model group (n=35), the QTSE group (n=35), the QT group (n=35) and the SE group (n=35). All the rats except those in the normal group and SO group were established into an intracerebral hemorrhage(ICH) model by intracerebral injection of collagenase type VII and the latter three were orally administered with Buyang Huanwu Decoction (补阳还五汤, a classical recipe for QTSE) or with some of its components for qi-tonification and for stasis-elimination, respectively. To the other three groups, normal saline solutions were given instead. Behavioral tests were carried out in the animals randomly chosen from each group on days 1, 2, 4, 7, 14, 21 and 28 after modeling. The expressions of VEGF, Flk-1 and Flt-1 were determined by immunohistochemistry and the number of vascular segments with positive expression in the injured brain area of the rats was calculated. From day 7 onwards, the asymmetric forelimb use rate in the QTSE group recovered more significantly than that in the other model groups. In the model group, the expressions of VEGF, Flk-1 and Flt-1 appeared on day 1 and reached a peak on day 21, then weakened gradually. In the QTSE group, as compared with the other model groups, a higher level of VEGF expression was shown from day 7 (P

Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus, which plays an important role in regulating energy balance. To elucidate the physiological role of MCH in obesity development, the present study examined the effect of a selective MCH1 receptor (MCH1R) antagonist in the diet-induced obesity mouse model. The MCH1R antagonist has high affinity and selectivity for MCH-1R and potently inhibits intracerebroventricularly injected MCH-induced food intake in Sprague Dawley rats. Chronic intracerebroventricular infusion of the MCH1R antagonist (7.5 μg/d) completely suppressed body weight gain in diet-induced obese mice during the treatment periods and significantly decreased cumulative food intake, by 14%. Carcass analysis showed that the MCH1R antagonist resulted in a selective decrease of body fat in the diet-induced obese mice. In addition, the MCH1R antagonist ameliorated the obesity-related hypercholesterolemia, hyperinsulinemia, hyperglycemia, and hyperleptinemia. These results indicate that MCH has a major role in the development of diet-induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent.

Mch1r-deficient (Mch1r(-/-)) mice are hyperphagic, hyperactive, lean, and resistant to diet-induced obesity. To examine whether the MCH1R is involved in regulating activity-based energy expenditure, we investigated voluntary wheel running (WR) activity of wild-type (WT) and Mch1r(-/-) mice basally, in response to diets with different caloric density and with different feeding schedules. We also evaluated WR activity of mice with ablation of the prepro-MCH gene (Pmch(-/-) mice). Dark cycle WR activity of Mch1r(-/-) mice fed low fat (LF) chow was increased significantly relative to WT mice. Transition to moderate high-fat (MHF) diet was associated with an increase in nocturnal WR activity in both genotypes. Both Mch1r(-/-) and WT mice exhibited food anticipatory activity (FAA) before the daily scheduled feeding time, indicating that MCH1R is not required for FAA. Naloxone (3 mg/kg, i.p.) suppressed WR activity of both genotypes, suggesting opioid regulation of locomotor activity. WR increased nocturnal dynorphin mRNA levels in Mch1r(-/-) brain. Importantly, Pmch-deficient mice had significantly enhanced WR activity relative to WT controls. These results suggest that endogenous MCH plays an inhibitory role in regulating locomotor activity. In summary, we demonstrated enhanced WR activities in mice lacking either MCH or its cognate receptor.

Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.

This study observes the hypocholesterolemic effects of Mixture Da Huai — a drug of enhancing monocyte macrophage system — on experimental rats, and the treatment of a homozygous familial hypercholesterolemia (FH) child. The results show that TC, VLDL-C and LDL-C in Mixture Da Huai group were significantly reduced and HDL-C was significantly increased. Fractional clearance rates for 125I-GLC-LDL, and the 125I-GLD-LDL uptake of rat peritoneal macrophages were significantly increased. Excretions of total sterol and acidic sterol in feces were also increased. After treatment for 3 months, serum TC and LDL-C of a homozygous FH child were significantly decreased. Tendon and cutaneous xanthomas were limited. This study indicates that by promoting the monocyte macrophage system to degrade LDL, a promising prevention and treatment of hypercholesterolemia and atherosclerosis might be provided, especially in the treatment of homozygous FH.

Bombesin receptor subtype 3 (BRS-3) is a G protein coupled receptor whose natural ligand is unknown. We developed potent, selective agonist (Bag-1, Bag-2) and antagonist (Bantag-1) ligands to explore BRS-3 function. BRS-3-binding sites were identified in the hypothalamus, caudal brainstem, and several midbrain nuclei that harbor monoaminergic cell bodies. Antagonist administration increased food intake and body weight, whereas agonists increased metabolic rate and reduced food intake and body weight. Prolonged high levels of receptor occupancy increased weight loss, suggesting a lack of tachyphylaxis. BRS-3 agonist effectiveness was absent in Brs3(-/Y) (BRS-3 null) mice but was maintained in Npy(-/-)Agrp(-/-), Mc4r(-/-), Cnr1(-/-), and Lepr(db/db) mice. In addition, Brs3(-/Y) mice lost weight upon treatment with either a MC4R agonist or a CB1R inverse agonist. These results demonstrate that BRS-3 has a role in energy homeostasis that complements several well-known pathways and that BRS-3 agonists represent a potential approach to the treatment of obesity.