Inhibitory Effects of Rap1GAP Overexpression on Proliferation and Migration of Endothelial Cells via ERK and Akt Pathways

Rapl is expressed in human umbilical vein endothelial cells （HUVECs）. Rapl-GTPase activating protein （RaplGAP）, with its specific target, Rapl, has been shown to be important in the regulation of many physiological and certain pathological processes. In this study, we investigated the effect of RaplGAP expression on endothelial cell function, or, more specifically, proliferation and migration of endothelial cells. HUVECs were transfected with pcDNA3.1 （empty vector）, pcDNA3.1 containing Flag-tagged-RaplGAP or Myc-tagged-RaplN17. The proliferation, migration and tube formation were examined and compared among the 3 groups. Expression of Rapl, RaplGAP, extracellular signal-regulated kinase （ERK）, phospho-ERK, Akt, phosphor-Akt was detected by Western blotting. The results showed that the proliferation, migration and tube formation were significantly reduced in RaplGAP- and RaplN17-transfected HUVECs as compared with empty vector-transfected control. These changes were coincident with increased expression of Rap 1GAP and decreased expression of activated Rap l, phospho-ERK and -Akt. After treatment of Rap l GAP-transfected HUVECs with a stimulator of Rapl guanine-nucleotide-exchange factor （RaplGEF） 8CPT-2＇OMe-cAMP, it was found that Rapl activity was decreased as compared with empty vector-transfected control. Pretreatment of HU- VECs with an ERK inhibitor PD98059 or a PI3K inhibitor LY294002 prior to stimulation not only blocked 8CPT-2＇OMe-cAMP-induced phosphorylation of ERK and Akt, but also significantly reduced cell proliferation and migration. Finally, we examined the effect of vascular endothelial growth factor （VEGF） on HUVECs overexpressing RaplGAP. VEGF-stimulated Rapl activity, phosphorylation of ERK and Akt, cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing RaplGAP as compared to empty vector-transfected Control. Taken together, our findings demonstrate that RaplGAP/Rapl and their downstream effectors regulate proliferation and migration of HUVECs via ERK and Akt pathways.

Biology of chronic graft-vs-host disease:Immune mechanisms and progress in biomarker discovery

Chronic graft-vs-host disease(c GVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cG VHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage. An array of cytokines and chemokines produced by different types of immune cells also mediate tissue inflammation and damage of cG VHD target tissues such as the skin and oral cavity. Many of these same immune regulators have been studied as candidate cG VHD biomarkers. Recent studies suggest that some of these biomarkers may be useful for determining disease prognosis and planning long-term clinical followup of cG VHD patients.

Review of allergic contact dermatitis: Scratching the surface

Contact dermatitis-including allergic contact dermatitis(ACD)-n and results in over four million lost work days per year in the United States alone. ACD is a classic example of a type IV delayed hypersensitivity reaction, and represents a significant burden on the health system, economy, and patient quality of life. Thorough history taking, clinical examination, histologic evaluation, and patch testing are keys to diagnosing contact dermatitis. Patch testing, especially with comprehensive and customized panels based on the patient's exposure history, is particularly useful in identifying potential allergens inthe case of allergic contact dermatitis. ACD management requires a combination of direct medical intervention, patient education, and appropriate environmental modification to prevent exposure to offending allergens in the home or workplace. Continuing advances in the study of ACD has led to an increased understanding of the disease processes, new methods for diagnosis, and improved management. This article reviews ACD-aiming to connect recent investigational data with the current clinical understanding of disease pathophysiology, diagnostic techniques, and management strategies.

Application of 4% formaldehyde under electronic colonoscope as a minimally invasive treatment of chronic hemorrhagic radiation proctitis

BACKGROUND: To investigate the effectiveness of topical application of 4% formaldehyde as a minimally invasive treatment of rectal bleeding due to chronic radiation proctitis(CRP) under direct vision of electronic colonoscope.METHODS: The clinical data of 13 CRP patients complicated with ≥ grade Ⅱ bleeding admitted to our hospital between January 2003 and December 2018 were retrospectively analyzed. Under the guidance of electronic colonoscope,4% formaldehyde combined with 5-aminosalicylic acid(5-ASA) suppositories was topically applied. Patients were followed up for two months after treatment,and the therapeutic effectiveness was observed and analyzed.RESULTS: The rectal bleeding due to CRP was markedly reduced after topical application of 4% formaldehyde under colonoscope in all 13 patients. The bleeding stopped after one treatment session in 11 patients and after the second session in 2 patients. 5-ASA was also applied along with the use of 4% formaldehyde. The therapeutic effectiveness was satisfactory during the 1-and 2-month follow-up period.CONCLUSION: Topical application of 4% formaldehyde under the direct vision of colonoscope as a minimally invasive treatment for CRB-induced bleeding is a simple,effective,affordable,and repeatable technique without obvious complications,which deserves further exploration and promotion.

Review of the cutaneous manifestations of autoimmune connective tissue diseases in pediatric patients

Autoimmune connective tissue diseases are chronic inflammatory disorders associated with complex genetic and environmental interplay resulting in a variety of cutaneous and systemic manifestations. Pediatric onset of these disorders carries a unique diagnostic pressure for the clinician due to the potential years of disease burden and complications. Mortality and morbidity from these disorders has fallen dramatically over the past fifty years due to increasing awareness of these disease sequelae and utilization of systemic treatment modalities when necessary. This review highlights the clinicalfeatures that are unique to pediatric presentations of lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, juvenile onset systemic sclerosis and morphea. Each of these disorders has a distinct appearance corresponding to a particular cutaneous and systemic clinical course and prognosis. Awareness of the associated potential systemic complications can also alert the clinician to make astute management decisions when confronted with a probable rheumatologic case. Cutaneous symptoms may predate onset of systemic symptoms and by keeping the rheumatologic differential diagnoses in mind, the dermatologist can play a key role in potentially offsetting autoimmune disease burden in children.

Hair Transplantation into the Nape of the Neck

Background: Hair loss at the nape of the neck causes embarrassment and psychological stress in a number of patients due to a variety of causes including acne keloidalis nuchae and traction alopecia. Objectives: To report a case of hair transplantation into the nape of the neck as a treatment option for scarring resulting from acne keloidalis nuchae. Methods: 700 grafts where transplanted from the occipital donor area and transplanted by follicular unit extraction (FUE) into the nape area of a male patient with recurrent scarring folliculitis in that area. Results: Hair Restoration was successful with natural looking results. More tumescence than usual and skin traction was necessary to stabilize the skin during graft insertion due to soft skin in the nape area. Conclusions: Hair Restoration Surgery into the nape of the neck is an option for patients with hair loss in that area. FUE is the best method of hair transplantation allowing the selection of 1 and 2 hair FUE grafts in order to achieve a natural looking result in the nape area.

Cutaneous Manifestations of Sickle Cell Disease

Sickle cell disease is an inherited erythrocyte disorder affecting multiple organ systems. As individuals are living well into middle age due to advances in diagnosis and treatment, further disease-related complications are being recognized. This article reviews the cutaneous manifestations of sickle cell disease including leg ulcers and acquired pseudoxanthoma elasticum.

Rapid Visible Improvements in Onychomycosis: An Open-Label Clinical Investigation of Kerasal Nail^TM

Traditional treatments for onychomycosis, a fungal disease primarily affecting the toenails, are associated with poor tolerability or inadequate efficacy. Moreover, because many patients find onychomycosis embarrassing, achieving rapid cosmetic improvements is desirable. Kerasal NailTM is a marketed topical treatment containing propylene glycol, urea and lactic acid. The ability of Kerasal Nail to improve the appearance of an affected nail was investigated in a 4-week open-label study. Patients aged ≥21 years and with 25% to 75% of a big toenail or thumbnail (the “target” nail) affected by clinically suspected onychomycosis (n = 65) were instructed to apply Kerasal Nail to all their affected nails once daily for 4 weeks. After 1, 2 and 4 weeks of treatment, they assessed the appearance of the target nail on a 4-point scale, with a score of ≥2 indicating a minimum of some improvement. They also assessed the nail for improvements in thickening, discoloration, brittleness and softness. Adverse events (AEs) occurring between administration of the first dose of Kerasal Nail and the end of the 4-week treatment period were recorded. 85% of patients (95% confidence interval [CI] 74 to 92) achieved some improvement in the target nail at 4 weeks. Improvement of the target nail was reported by 65% of patients (95% CI 52 to 76) after 1 week of treatment and by 82% of patients (95% CI 70 to 90) after 2 weeks. 55% of patients achieved some improvement in discoloration in the first week of treatment. After 4 weeks of treatment, discoloration, thickening, brittleness and softness were each improved in more than half of patients. Treatment-related AEs were limited to two cases of administration site pain. Overall treatment compliance was 99%. In summary, Kerasal Nail produced very rapid improvements in nail appearance in patients with onychomycosis and was well tolerated.

Monkeypox presenting as a chancre-like rash:A case report

BACKGROUND Since May 2022,outbreaks of monkeypox have occurred in many countries around the world,and several cases have been reported in China.CASE SUMMARY A 38-year-old man presented with a small,painless,shallow ulcer on the coronary groove for 8 d.One day after the rash appeared,the patient developed inguinal lymphadenopathy with fever.The patient had a history of male-male sexual activity and denied a recent history of travel abroad.Monkeypox virus was detected by quantitative polymerase chain reaction from the rash site and throat swab.Based on the epidemiological history,clinical manifestations and nucleic acid test results,the patient was diagnosed with monkeypox.CONCLUSION Monkeypox is an emerging infectious disease in China.Monkeypox presenting as a chancre-like rash is easily misdiagnosed.Diagnosis can be made based on exposure history,clinical manifestations and nucleic acid test results.

Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the Pub Med database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals(including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agentseither as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.

RBBP4 promotes colon cancer malignant progression via regulating Wnt/β-catenin pathway

BACKGROUND Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis.However,the potential biological function of RBBP4 in colon cancer is still unknown.AIM To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression.METHODS Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines.The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining.The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown.Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells.Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer.The nuclear translocation ofβ-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown.The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/β-catenin activation.The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown.RESULTS We found that RBBP4 was highly expressed in colon cancer cell lines.The 5-ethynyl-2’-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation.RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition.Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis.Mechanistically,the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway.Meanwhile,RBBP4 knockdown suppressed nuclear translocation ofβ-catenin.With Wnt/β-catenin activator,rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION RBBP4 promotes colon cancer development via increasing activity of the Wnt/β-catenin pathway.RBBP4 may serve as a novel therapeutic target in colon cancer.

Liver involvement in the drug reaction,eosinophilia,and systemic symptoms syndrome

First described in 1996,the drug reaction,eosinophilia,and systemic symptoms syndrome(DReSS) is considered,along with Stevens-Johnson syndrome and toxic epidermal necrolysis,a severe cutaneous drug reaction. It is characterized by the presence of a maculopapular erythematous skin eruption,fever,lymphadenopathy,influenza-like symptoms,eosinophilia,and visceral involvement such as hepatitis,pneumonitis,myocarditis,pericarditis,nephritis,and colitis. The prognosis of patients with DReSS is related to the severity of visceral involvement. The mortality ranges from approximately 5% to 10%,and death is mainly due to liver failure,which is also the organ most commonly involved in this syndrome. Although it was previously hypothesized in 1994,DReSS syndrome can lead to reactivation of one or more human herpesvirus family members. Now being included as diagnostic criteria in a proposed diagnostic score system,this reactivation can be detected up to 2-3 wk after DReSS syndrome onset. Other causes of mortality in DReSS syndrome include myocardial or pulmonary lesions and hemophagocytosis. We reviewed the literature of previously reported case-series of DReSS and liver involvement,highlighting the pattern of liver damage,the treatment used,and the outcome.

Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer

BACKGROUND Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer(CRC).Accumulating evidence suggests that intestinal microbiota is correlated with anastomotic healing.AIM To explore the microbiota structural shift in margin-surrounding mucosa and evaluate the predictive ability of selected bacterial taxa for impaired anastomotic healing.METHODS Margin-surrounding mucosa samples derived from 37 patients were collected to characterize the microbial community structure by 16 s r RNA gene sequencing.The patients were divided into two groups according to the healing status of anastomoses:well-healing group(n=30)and impaired-healing group(n=7).Statistic differences in bacteria taxa were compared by Wilcoxon test and chisquared test.The predictive ability of the selected bacterial taxa for the healing status of anastomoses was evaluated by the area under the receiver operator characteristic curve.RESULTS Community structure shifts were observed in the impaired-healing group andwell-healing group.Six bacterial species were found to be significantly correlated with anastomotic healing,and among these species,Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis were considered as the predictive factors.Taking the known risk factor age into consideration,Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis improved predictive ability for the healing status of anastomoses.CONCLUSION These data show that Alistipes shahii,Dialister pneumosintes,and Corynebacterium suicordis could be considered as supplementary factors in the prediction of anastomosis healing status in patients after CRC radical resection.

奥马佐单抗治疗顽固性特应性皮炎

Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.

Acne Vulgaris in Jeddah Medical Students: Prevalence, Severity, Self-Report, and Treatment Practices

Acne is a common skin disorder of teenagers and continues into adulthood. Research has been limited regarding acne prevalence, perception and health care utilization in Saudi Arabia. The objective of this study was to assess acne prevalence in final year female medical students in Jeddah, Saudi Arabia using the global acne grading system (GAGS) compared with student’s self-report of their acne. This is a cross-sectional study conducted among 151 students during 2016, in which students were interviewed subjectively and examined objectively by a trained physician. This study showed that acne was reported subjectively by 83.4% of female students compared to 98% of students assessed objectively by the global acne grading system. 14.6% of students claimed having no acne while it was objectively present, which was statistically significant (Χ2 = 15.4, P 2 months in 39.1% of students. Acne was present in 41.1% of the students parents compared to 83.4% in their siblings. A total of 41.7% of student had trunk acne. 60.9% of students had scarring and 72.8% of them had pigmentation. Moderate to severe acne students had higher siblings acne history of 95.2% (Χ2 = 5.85, P 2 = 4.05, P 2 = 4.87, P < 0.05) which was statistically significant. Our study confirms that acne is very common in female medical students in Jeddah, Saudi Arabia with a prevalence rate of 98%. Knowledge regarding acne treatment was inadequate demonstrating the need for educational and awareness programs about early treatment that will prevent suffering from acne scarring or pigmentation.

Editor-in-Chief Characteristics of Dermatology Journals

Dear Editor,Editors-in-chief(EICs)hold respected leadership positions that help shape the publication landscape of their fields.A diverse editorial board can enrich the quality and diversity of the scientific literature.Investigating thefactors that may influence the appointments of EICs canuncover ways for prospective editors to advance in theircareer.

Allergic Contact Dermatitis Syndrome Due to Tocopherol Acetate, in Addition to Glycyrrhetinic Acid

Natural vitamin E is suggested to have an antioxidant function. However, the synthetic form of vitamin E, DL-tocopherol, which has been widely used in topical ointments, may cause allergic contact dermatitis. Here, we report a case of allergic contact dermatitis with erythema multiforme-like eruption caused by a topical ointment. Patch testing indicated a positive allergic reaction to an anti-inflammatory ointment the patient had been using and its ingredient, DL-alpha-tocopheryl acetate (vitamin E). In addition, a positive reaction to glycyrrhetinic acid was observed. Both vitamin E and glycyrrhetinic acid are useful ingredients of topical applications. However, the possibility that both can cause contact dermatitis, albeit rarely, should be considered.

夫妻共患变异性蕈样肉芽肿病:病毒感染和环境暴露在皮肤T细胞淋巴瘤发展中的未知作用

The etiology of mycosis fungoides (MF) is uncertain, although infectious agents and other environmental exposures have been implicated. We describe what appears to be the first case inwhich both a husband and his wife were diagnosed with large cell transformation of MF. After 10 years of having stage I MF,the wife developed tumors that showed sheets of large transformed cells with dysplastic nuclei on skin biopsies, leadingto a diagnosis of transformed MF. Her husband was diagnosed 14 months later with transformed MF following a biopsy of his right arm and leg after a 15-year history of presumed psoriasis. The fact that this rare occurrence happened in a couple who had been married for more than 25 years points to a common environmental exposure. Future studies should aim to clarify the potential role of infectious agents, such as human T-lymphotropic virus I and II, cytomegalovirus, Epstein-Barr virus, and other environmental exposures, in the development of MF.

肿胀性红斑狼疮

Background. Lupus erythematosus tumidus (LET) is a rare form of chronic cutaneous lupus erythematosus that characteristically presents as a succulent, erythematous plaques on sun-exposed areas. The histopathological change that primarily distinguishes LET from other variants of cutaneous lupus erythematosus is the lack of alterations of the dermo-epidermal junction and epidermis. Our purpose was to describe 15 cases of LET from Thailand. Methods. The records of 15 patients diagnosedwithLETatSrinagarindHospitalMedicalSchoolbetween 1995 and 2002 were reviewed on the following aspects: clinical manifestation, laboratory investigation, direct immunofluorescence study, phototesting, histopathological findings, clinical course, and treatment. Results. All 15 patients consisted of 10 females and five males. The mean age at onset was 38.8 years. The lesions more commonly affect the face and trunk. One patient had concomitant discoid lupus erythematosus and two developed systemic involvement 4 and 6 months after LET. Direct immunofluorescence studies all showed negative results. Positive phototest reactions were detected in five of 10 tested patients: four with ultraviolet A and B and one with ultraviolet A only. Most patients responded well to chloroquine phosphate and the remainder successfully improved with methotrexate, topical and systemic corticosteroids. Conclusion. Our data demonstrate the features of LET that are repeatable and characteristic. Lupus erythematosus tumidus in this study was more common in women, and photosensitivity reactions of the patients were seen less frequently compared with those in the earlier report of Kuhn et al. Furthermore, two of 15 patients exhibited systemic involvement in the course of their disease.