Diagnostic significance of TCR gene clonal rearrangement analysis in early mycosis fungoides

Mycosis fungoides(MF),the most common type of cutaneous T-cell lymphoma,has various unspecific clinical and histological characteristics.Its early diagnosis is challenging.The application of T-cell receptor(TCR) gene clonal rearrangement to the diagnosis of MF has been widely studied.In this study,we used polymerase chain reaction(PCR) to investigate the diagnostic significance of detecting TCR-γ and-β gene clonal rearrangement in the early diagnosis of mycosis fungoides.PCR for TCR-γ and TCR-β gene rearrangement was performed on 19 patients with suspected early MF,6 with typical MF,and 6 with chronic dermatitis.Of the 19 patients with suspected early MF,13 had TCR-γ gene clonal rearrangement,whereas none had TCR-β gene clonal rearrangement.All patients with typical MF had TCR gene clonal rearrangement,in which 4 showed TCR-γ clonal rearrangement,1 showed TCR-β gene clonal rearrangements,and 1 showed both.No patients with chronic dermatitis had TCR gene clonal rearrangement.These results indicate that TCR gene clonal rearrangement analysis is a useful tool in diagnosing early MF.TCR-γ gene is recommended to the routine analysis,whereas TCR-β gene has potential in combination toward intractable cases.

Psoriasis: A Comprehensive Review on the Aetiopathogenesis and Recent Advances in Long-Term Management of Patients with Plaque Psoriasis

Immense changes have been introduced in psoriasis treatment, including successful systemic treatment of inflammation and education of psoriatic patients. The focus of this review is the latest developments in the understanding of the aetiopathogenesis of psoriasis, the significance of its comorbidities, treatment possibilities and long-term management using the latest insight provided by pharmacogenetics and identification of biomarkers. The successful control of the disease leads to reduction of myocardial infarction and long-term cardiovascular risk but is usually achieved after various therapeutic attempts until the best-matched treatment for the individual is identified. There is a high unmet medical need for revealing biomarkers associated with disease prognosis, comorbidities, response to therapy and adverse effects. More studies have to be performed for identification and validation of biomarkers and implementation of personalized medicine into clinical practice.

Efficacy and Safety of Travoprost and Timolol Fixed Combination Compared to Travoprost in Patients with Primary Open Angle Glaucoma and Ocular Hypertension

Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma and ocular hypertension. Methods: In this prospective, multicentre clinical trial, 62 patients received travoprost 0.004% (n = 31) or travoprost 0.004% and beta-blocker 0.5% fixed combination (n = 31). Efficacy and safety were compared across treatment groups over 2 years. IOP reduction and adverse events were examined at 3, 6, 12 and 24 months for each group. Results: Mean IOP at the first visit in the travoprost 0.004% group was 26.4 (SD ± 2.1), and travoprost 0.004%/timolol 0.5% group was 26.3 (SD ± 2.1). Mean IOP after 24 months in the travoprost 0.004% group was 20.5 (SD ± 1.5) and travoprost 0.004%/timolol 0.5% group was 18.5 (SD ± 1.5). There were statistically significant differences in IOP in both eyes after third visit (after 1 year) and fourth visit (after 2 years). Conclusion: After 2 year of treatment, travoprost 0.004%/timolol 0.5% produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by travoprost 0.004% alone.

Translational medical mycology guides clinical and laboratory practice on fungal diseases

Patients with fungal infection having skin lesions may consult a dermatologist, which is a diagnostic and therapeutic challenge. Dermatologists take samples from the lesion to check the fungal elements under a microscope by KOH preparation and then treat the patient. This model has advanced from bedside to bench and from bench to bedside(B to B to B), which is defined as Translational Medical Mycology. Dermatologists have an advantageous position in finding, isolating and identifying the pathogenic fungi and treating the patient with antifungal drugs. Samples should be cultured in different media with or without chloramphenicol and cycloheximide and incubated at room temperature or 37 ℃. Non-culture techniques such as polymerase chain reaction based molecular identification, transmission electron microscopy, scanning electron microscopy, biochemistry tests and histopathology are also necessary to confirm the identification of the species, especially when the routine culture is negative. We start treatment upon obtaining evidence of fungal infection,i.e., positive KOH examination. Antifungal drugs such as itraconazole, fluconazole, terbinafine and amphotericin B can be used alone or in combination based on the fungal species and the location of the lesion. Practice on fungal infection includes screening of the patient, merging all of the laboratory techniques and methods from the microbiologists, pathologists, molecular researchers, identification of the pathogen and determination of the optimum antifungal drug.

Interleukin-2 and Interleukin-6 in Recurrent Genital Herpes Patients

Objective: To study the cellular immunity status of patients with recurrent genital herpes. Methods: Serum levels of interlukin-2 and its soluble receptor and interlukin-6 were measured by ELISA in 34 patients with recurrent genital herpes. Results: Serum levels of IL-2 and IL-6 were significantly decreased in patients compared to healthy controls (P<0.01),and the level of sIL-2R was significantly increased in patients with recurrent genital herpes (P<0.01). There were nosignificant differences in all variables amongst patients regarding relapse stage and remission stage (P >0.05). Conclusion: There was a cellular immune deficiency in patients with recurrent genital herpes.

穿孔素在扁平苔癣患者外周血淋巴细胞及皮肤浸润细胞中的表达

Background: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. Objectives: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes(PBL) in exacerbation and remission phases of the disease as well as in skin lesions. Methods: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. Results: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+perforin+cells) in the exacerbation phase of disease(P < 0.05), which was mostly located in the CD8+subpopulation (CD8+perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+and CD8+phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). Conclusions: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.

Signaling Pathways Associated with Cancer Stem Cells Play a Significant Role in Immunotherapy Resistance

Cancer stem cells(CSCs)are a subpopulation of tumor cells with properties of self-renewal,pluripotency,plasticity,and differentiation,and are associated with various aberrantly stimulated signaling pathways.They are responsible for tumor recurrence,distant metastasis,and drug resistance,thus inducing poor prognosis.Immunotherapy has achieved encouraging results.However,the resistance associated with its clinical application is a persistent problem in clinical and scientific researches.Increasing evidence shows that signaling pathways associated with CSCs mediate immunotherapy resistance.This review highlights the link between them,and focuses on the underlying mechanism so as to provide potential strategies and approaches for the development of new targets against the immune resistance challenge.

Malignant Cutaneous Adnexal Tumor in Posterior Occipital Region of a Child:A Case Report

Introduction:The most common cutaneous adnexal tumors in children were follicular,especially pilomatricoma,and a few were predominant glandular/ductal differentiation,malignant forms are occasionally encountered.Case presentation:A 10-year-old male child was presented with a nodular in posterior occipital for half a year with no symptoms.Histopathology showed there was acanthosis in epidermis,partially with local ulceration and crusting;and in the dermis,there was irregular scattered or agglomerated infiltration of diffused epithelial cells,partly presenting as basaloid,but no obvious peripheral palisading arrangement;and in the center there was extensive necrosis;cellular pleomorphism,scattered mitotic figures,focal clear cell areas,and adenoid differentiation can also be seen,there was scattered infiltration of mixed inflammatory cells in the stroma.Immunohistochemistry showed cytokeratin(CK)5/6^(+),CK 8/18^(+),epithelial membrane antigen^(+),gata3 transcription factor 3^(+),cell adhesion15(focal^(+)),Ki67(^(+),30%),carcinoembryonic antigen(focal^(+)),CK 7(focal^(+)),gross cystic disease fluid protein-15-,P63^(+),S-100-.Final diagnosis was the malignant cutaneous adnexal tumor with eccrine differentiation,most likely the nodular clear cell hidradenocarcinoma.The patient has no special discomfort follow-up observation after extended resection and lymph node examination.Discussion:The histopathology showed infiltrative growth pattern,deep extension,necrosis,nuclear pleomorphism,mitoses,desmoplastic stromal reaction and the clear cell area and adenoid differentiation.Immunohistochemistry was positive for CK8/18,EMA,CK5/6,P63,gata3 transcription factor 3 and negative for S-100 and GCDFP-15,some gland-derived markers such as CK7,CEA were focal positive,and we have not found the preexisting benign poroma and porocarcinoma in situ,so we preferred the diagnosis of hidradenocarcinoma.The differential diagnosis such as porocarcinoma,clear cell squamous cell carcinoma,and basal cell carcinoma were taken into account.Conclusion:The diagnosis was challenging by clinical manifestations.Histopathology and immunohistochemistry should be combined with clinical presentation,history to reach the final diagnose.

日晒诱发文身斑处迟发性疣

Multiple warts in a 32- year- old- man are reported thatd eveloped after tattooing and remaining exclusively confined to that area. The tattooing was done 2.5 years earlier by a professional tattoo artist. It was previously a lesion- free tattoo, but when damaged by sunburn developed multiple skin warts. The ability of a latent virus to induce warts after cutaneous ultraviolet exposure was discussed.

Antifungal activity of ibuprofen against aspergillus species and its interaction with common antifungal drugs

Background The incidence of invasive aspergillosis （IA） has increased in frequency in immunocompromised patients with a variety of diseases. The poor prognosis might be due to limited treatment option. This study aimed to evaluate antifungal activity of ibuprofen against clinical isolates of aspergillus species, as well as its interaction with azoles or with amphotericin B or with micafungin. Methods Antifungal activity of ibuprofen against 10 strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus were tested with both disk diffusion assay and standard broth microdilution method. To determine whether ibuprofen combined with itraconazole, voriconazole, amphotericin B, or micafungin had interactive effects on aspergillus spp., we used both disk diffusion assay and Chequerboard method. Results As for disk diffusion method, ibuprofen produced a zone of growth inhibition with diameters of （20.1±3.9） mm at 48 hours of incubation. As for broth microdilution method, the minimal inhibitory concentration （MIC） ranges of ibuprofen against aspergillus spp. were 1000-2000 μg/ml, and the minimal fungicidal concentration （MFC） ranges of that was 2000-8000 μg/ml. For 2 of 5 isolates, when ibuprofen combined with itraconazole or voriconazole, the zones of growth inhibition were larger than those of the individual drug. The results of Chequerboard method showed that fractional inhibitory concentration index （FICI） ranges were 1.125-2.500. Conclusions Ibuprofen is active against aspergillus spp.. And ibuprofen does not affect the in vitro activity of itraconazole, voriconazole, amphotericin B or micafungin against aspergillus spp.

Consensus by Chinese Expert Panel on Chlamydia trachomatis-Resistant and Chlamydia trachomatis-Persistent Infection

Chlamydia trachomatis （Ct） genital infection is the most common sexually transmitted disease （STD） in China and the US. The morbidity of Ct genital infection in China has increased from 32.48/100,000 in 2008 to 37.18/100,000 in 2015.[1] The major areas of Ct infections are concentrated in the Zhujiang Delta, Changjiang Delta, Minjiang Area, and West China. In these areas, the highest incidence of Ct infection reaches 615.99/100,000 citizens. In the US, there are 1,441,789 reported Ct, which include 627.2 females and 278.4 males per 100,000 population. It is now the most prevalent STD, with its rate increasing to 22% in males and 6% in females.[2] Ct genital infection can cause epididymitis, prostatitis, cervicitis, annexitis, infertility, and atopic pregnancy, which have been identified as the major public health problems.

Therapeutic targets and interventional strategies in COVID-19:mechanisms and clinical studies

Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the lack of the understanding of the biological regulation mechanisms underlying COVID-19,alternative or novel therapeutic targets for COVID-19 treatment are still urgently required.SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19.Both the virus and host factors are potential targets for antiviral therapy.Hence,in this study,the current therapeutic strategies of COVID-19 have been classified into"target virus"and"target host" categories.Repurposing drugs,emerging approaches,and promising potential targets are the implementations of the above two strategies.First,a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians.Additionally,their unavailability in the fight against COVID-19 was analyzed.Next,a profound analysis of the emerging approaches was conducted,particularly all licensed vaccines and monoclonal antibodies(mAbs)enrolled in clinical trials against primary SARS-CoV-2 and mutant strains.Furthermore,the pros and cons of the present licensed vaccines were compared from different perspectives.Finally,the most promising potential targets were reviewed,and the update of the progress of treatments has been summarized based on these reviews.

Subcutaneous panniculitis-like T-cell lymphoma accompanied with discoid lupus erythematosus

To the editor： Subcutaneous panniculitis-like T-cell lymphoma （SPTL） is an uncommon type of cutaneous lymphoma, especiallySPTL accompanied with autoimmune disease has been rarely reported. Here we report a case of SPTL accompanied with discoid lupus erythematosus （DLE） and clinical features of dermatomyositis. A 34-year-old woman presented with facial plaque for 6 years and eyelid erythema, papules of the metacarpophalangeal joints and two masses in her breast and back for 4 months. Physical examination revealed symmetrical, violaceous erythema on her cheeks, forehead, eyelids and jaw, and papules over the metacarpophalangeal joints.