[Clinical and Neuroimaging Analysis of 24 Cases of Sturge-Weber Syndrome].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Port-wine stains associated with large vestibular aqueduct syndrome caused by mutations in GNAQ and SLC26A4 genes: A case report.

Port-wine stains (PWS) are capillary malformations associated with mutation in the GNAQ (NM_000441.1) gene. Large vestibular aqueduct syndrome (LVAS), caused by mutation in the SLC26A4 (NM_002072) gene, is an inner ear malformation that can lead to hearing loss. To our knowledge, LVAS in PWS patients has never been reported. Here, we describe a case of a 9-year-old female patient diagnosed with PWS on the face and neck, coexisting with large vestibular aqueduct syndrome. Further analyses revealed a somatic mutation in GNAQ and a compound heterozygous mutation in the SLC26A4 gene. Some PWS patients have associated abnormalities, such as glaucoma and choroidal hemangioma, leptomeningeal angiomas and atrophy or hypertrophy of bone and soft tissue. We present here the first case that reveals the possibility that capillary malformations are associated with inner ear malformation. More case reports and further studies are needed to determine whether these conditions coexist in other patients.

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes.

Acne vulgaris is a prevalent cutaneous disease characterized by a multifactorial pathogenic process including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and Propionibacterium acnes (P acnes) overgrowth. Salicylic acid (SA), a beta-hydroxy acid, is frequently used in the treatment of acne. SA has been found to decrease skin lipids and to possess anti-inflammatory properties. However, few studies have elucidated the mechanisms and pathways involved in such treatment of acne. In this study, we initially investigated the anti-acne properties of SA in human SEB-1 sebocytes. Treatment with SA decreased sebocyte lipogenesis by downregulating the adenosine monophosphate-activated protein kinase (AMPK)/sterol response element-binding protein-1 (SREBP-1) pathway and reduced inflammation by suppressing the NF-κB pathway in these cells. Salicylic acid also decreased the cell viability of SEB-1 by increasing apoptosis via the death signal receptor pathway. Subsequently, histopathological analysis of a rabbit ear acne model after application of SA for three weeks confirmed that SA suppressed the levels of cytokines and major pathogenic proteins around acne lesions, which supports the mechanisms suggested by our in vitro experiments. These results initially clarified that therapeutic activities of SA in acne vulgaris treatment could be associated with the regulation of SREBP-1 pathway and NF-κB pathway in human SEB-1 sebocytes.

From pathogenesis of acne vulgaris to anti-acne agents.

Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes (C. acnes) and inflammation. The main hormones responsible for the development of acne vulgaris include androgens, insulin and insulin-like growth factor-1. Other factors involved in this process are corticotropin-releasing hormone, α-melanocyte-stimulating hormone and substance P. Wnt/ß-catenin signaling pathway, phosphoinositide 3-kinase (PI3K)/Akt pathway, mitogen-activated protein kinase pathway, adenosine 5'-monophosphate-activated protein kinase pathway and nuclear factor kappa B pathway participate in the modulation of sebocyte, keratinocyte and inflammatory cell (e.g. lymphocytes, monocytes, macrophages, neutrophils) activity. Among all the triggers and pathways mentioned above, IGF-1-induced PI3K/Akt/Forkhead box protein O1/mammalian target of rapamycin (mTOR) C1 pathway is the most important signaling responsible for acne pathogenesis. Commonly used anti-acne agents include retinoids, benzoyl peroxide, antibiotics and hormonal agents (e.g. spironolactone, combination oral contraceptive and flutamide). New approaches including peroxisome proliferator-activated receptor γ modifier, melanocortin receptor antagonists, epigallocatechin-3-gallate, metformin, olumacostat glasaretil, stearoyl-CoA desaturase inhibitor omiganan pentahydrochloride, KDPT, afamelanotide, apremilast and biologics have been developed as promising treatments for acne vulgaris. Although these anti-acne agents have various pharmacological effects against the diverse pathogenesis of acne, all of them have a synergistic mode of action, the attenuation of Akt/mTORC1 signaling and enhancement of p53 signal transduction. In addition to drug therapy, diet with no hyperglycemic carbohydrates, no milk and dairy products is also beneficial for treatment of acne.

Prognostic significance of neutrophil-to-lymphocyte ratio in patients with malignant pleural mesothelioma: a meta-analysis.

Systemic inflammation responses can be reflected by peripheral blood count and combine index like the neutrophil-to-lymphocyte (NLR). The NLR has been reported to be a poor prognostic indicator in cancer recently. However, the prognostic effect of the NLR in patients with malignant pleural mesothelioma (MPM) still unclear yet. We conducted this meta-analysis aiming to evaluate the pooled value of NLR in prognosis as well as clinical characteristics in malignant pleural mesothelioma. A total of 11 studies with 1533 patients were included in this meta-analysis, in which 10 studies investigated the prognosis role of NLR using hazard ratio (HR) and 95% confidence intervals (95% CI). The elevated NLR was detected to be associated with a poor overall survival (OS)(HR=1.48, 95%CI=1.16-1.89, P < 0.001). The significant prognostic roles of NLR were also indicated in subgroup analyses. NLR level was also associated with histology instead of gender, stage or performance status (PS) score. These findings suggested that the elevated NLR could be a potential prognostic factor for malignant pleural mesothelioma patients and might be associated with histology as an efficient clinical index to stratify patients.

Increased platelet-lymphocyte ratio closely relates to inferior clinical features and worse long-term survival in both resected and metastatic colorectal cancer: an updated systematic review and meta-analysis of 24 studies.

Colorectal cancer (CRC) is one of the most common cancers worldwide. However, the prognostic and clinical value of platelet-lymphocyte ratio (PLR) in colorectal cancer was still unclear, which attracted more and more researchers' considerable attention. We performed a systematic review and meta-analysis to investigate the relationship between PLR and survival as well as clinical features of CRC update to September 2016. The hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were calculated to access the association. We included 24 eligible studies with a total of 13719 patients. Elevated PLR predicted shorter overall survival (OS) (HR=1.47; 95%CI, 1.28-1.68; p<0.001), poorer disease-free survival (DFS) (HR=1.51; 95% CI, 1.2-1.91; p=0.001), and worse recurrence-free survival (RFS) (HR=1.39; 95% CI, 1.03-1.86; p=0.03), but had nothing to do with Cancer-specific survival (CSS) (HR=1.14; 95% CI, 0.92-1.42; p=0.223). After trim and fill method, the connection between PLR and DFS disappeared (HR=1.143; 95%CI, 0.903-1.447; p=0.267). By subgroup analyze, we found that increased PLR predicated a worse OS and DFS in patients who underwent surgery, and this prognostic role also shown both in metastatic and nonmetastatic patients. In addition, elevated PLR was associated with poorly differentiated tumor (OR=1.51; 95% CI, 1.26-1.81; p<0.001), higher tumor stage (OR=1.25; 95% CI, 1.05-1.49; p=0.012), lymphovascular invasion (LVI) (OR=1.25; 95% CI, 1.09-1.43; p=0.001), and the recurrence of CRC (OR=2.78; 95% CI, 1.36-5.68; p=0.005). We indicated that pretreatment PLR was a good prognostic marker for CRC patients. High PLR was related to worse OS, RFS and poor clinical characteristics.