Institute of Dermatology & Venereology of the Yunnan Province

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

BACKGROUND: Oral Candida colonization and its relation with predisposing factors in HIV-infected patients have received wide concerns during recent decades. In this study, we investigated asymptomatic oral Candida carriage rate, species distribution and antifungal susceptibility of 604 HIV-infected patients and 851 healthy individuals in Kunming, Yunnan Province of China. METHODS: Mucosal swab sampling was taken from each subject and CHROMagar Candida agar medium and API 20C AUX system were used to identify yeast isolates. In vitro antifungal susceptibility was tested by the broth microdilution method according to the M27-A2 document of the Clinical and Laboratory Standard Institute (CLSI). RESULTS: The oral yeast colonization rate in HIV-infected patients (49.5%) was higher than that of healthy subjects (20.7%). Candida albicans constituted the most frequent species, accounting for 82.2% of yeast isolates. The remaining species were composed of C. glabrata, C. parapsilosis, C. krusei, C. tropicalis, C. rugosa, C. norvegensis, Pichia ohmeri and Saccharomyces cerevisiae. In HIV-infected patients, asymptomatic oral yeast colonization was associated with low CD4 cell count (<200 cells/mm3) and lack of highly active antiretroviral therapy (HAART). Different Candida species isolated from our samples presented different susceptibility to voriconazole, fluconazole and itraconazole. Amphotericin B had the best inhibiting effect for all isolates. CONCLUSION: Oral yeast colonization in Han Chinese patients with HIV from Kunming had common and unique features and was associated with CD4 cell number and HARRT. Amphotericin B should be used with first priority in controlling Candida infection in Han Chinese patients from Kunming. Our results provide first hand information on monitoring oral yeasts colonization in HIV-infected patients from Kunming, China.

Melasma is a specific type of facial hyperpigmentation seen in women taking oral contraceptives, in non-pregnant women who have not used oral contraceptives, and in some pregnant women during the progression of gestation, but rarely in men. Circulating LH, FSH, PRL, and E2-17 beta on day 5, 7, 9, and 11 of the menstrual cycle and progesterone (P) on day 17, 19, and 21 were measured in thirty-six ovulating women with melasma (study group) age 25-35 years and twelve healthy controls (control group). Twenty-seven subjects in the study group had normal pregnancies; 9 others were married or single and had no history of contraceptive pill use. Higher levels of FSH on day 7 (p < 0.05); E2-17 beta on 5, 7, 9 (p < 0.05) and LH on day 9 (p < 0.002) were observed in the study group than in the control group. There were no significant differences between the LH/FSH ratio in the two groups. Serum PRL was lower on day 9 in the study group (p < 0.05) than in the control group. Serum P was similar in the patients and the controls. These findings indicate a possible role of high E2-17 beta in the maintenance of melasma.

significantly decreased with year. Notably, a dramatic decline in sperm density was recorded over the first 5 years of study. This research reported a decline in sperm concentration among young adults in Wuhan, Central China, in 2010-2015.

BACKGROUND: An increasing number of studies have reported that exosomes from adipose-derived stem cells (ADSCs) have antioxidant and anti-inflammatory properties. In the present study, we aimed at elucidating the potential therapeutic mechanism underlying ADSC exosomes in ultraviolet B-light (UVB)-induced skin injury. METHODS: We isolated the exosomes from ADSCs and hypoxia-pretreated ADSCs. High-throughput sequencing was applied to identify differential circRNA expression. Then, a UV-induced murine skin injury model was constructed and the therapeutic effect of exosomes was determined using immunofluorescence and ELISA. The regulatory mechanism was demonstrated using luciferase reporter analysis and an in vitro experiment. RESULTS: Exosomes from hypoxia-pretreated ADSCs inhibited UVB light-induced vascular injury by reversing ROS and inflammatory factor expression. High-throughput sequencing showed that exosomes from hypoxia-pretreated ADSCs (HExo) improved UV-induced skin damage via delivery of circ-Ash1l. Downregulation of circ-Ash1l inhibited the therapeutic effect of HExo on UV-induced skin damage. It was further shown that GPX4 and miR-700-5p were circ-Ash1l downstream targets. MiR-700-5p overexpression or GPX4 downregulation inhibited the circ-Ash1l protective effects of UV-induced endothelial progenitor cell (EPC) damage. CONCLUSION: Thus, exosomes from hypoxia-pretreated ADSCs attenuated UV light-induced skin injury via circ-Ash1l delivery and ferroptosis inhibition.

BACKGROUND: Elastic light single-scattering spectroscopy (ELSSS) is a noninvasive and real-time technique that has been used to differentiate tumors from surrounding nontumor tissue in animal models and humans. OBJECTIVE: To investigate potential application of ELSSS as an adjunctive tool for noninvasive, in vivo, real-time differentiation of malignant and benign skin lesions and to detect positive surgical margins of excised biopsy samples. METHODS: In vivo spectroscopic measurements were performed on 28 lesions in 23 patients. The distribution of the lesions was as follows: nine basal cell carcinoma (BCC), four melanoma, two squamous cell carcinoma (SCC), and 13 benign lesions. Intraoperative margin assessments were performed on the 28 biopsy samples using ELSSS. RESULTS: The sign of the spectral slopes was positive for benign and negative for malignant tissues. It was used as a discrimination parameter between malignant and benign lesions with a sensitivity and specificity of 87% and 85%, respectively. Sensitivity and specificity of the system in detecting positive surgical margins on 14 excised biopsy samples were 80% and 90%, respectively. CONCLUSION: ELSSS has the potential for use as an adjunctive tool to reduce the number of negative biopsies and to detect positive surgical margins in real time.

Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound.

Background/aim: Vitiligo is a depigmentation disorder that leads to serious psychological burden in patients, who are frequently reported to have depression and anxiety. The aim of this study was to investigate the association between stress-related hormone levels and psychological stress in vitiligo. Materials and methods: In this study46 vitiligo patients and 46 controls were enrolled; their cortisol, dehydroepiandrosterone sulfate (DHEAS),and cortisol/DHEAS levels were measured. Psychological burden was assessed by the Beck Depression Inventory and Perceived Stress Scale. Results: Patients and controls did not differ in terms of cortisol, DHEAS, or cortisol/DHEAS. Patients had higher perceived stress than controls but did not differ in terms of depression scores. Correlation analyses revealed that cortisol/DHEAS correlated positively with perceived stress (P = 0.009, r = 0.272). The correlation between cortisol/DHEAS and perceived stress was stronger in the patient group (P = 0.013, r = 0.363) and close to zero among controls. In regression analyses, lower depression and higher perceived stress were shown to predict cortisol/DHEAS values. Conclusion: Vitiligo patients significantly differed from the healthy population in terms of hormones and psychological distress. There was also an association between perceived stress and cortisol/DHEAS ratio in vitiligo. Abnormality of hormonal response to distress lowers DHEAS, which is known for its antioxidant properties, a possible mechanism for vitiligo development. Another important finding is the significance of using the composite variable cortisol/DHEAS, which seems to be more sensitive to distress than each of its components. We suggest its use in future studies on psychological distress–hormone relationships.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common and fastest increasing forms of cancer worldwide with metastatic potential. Long noncoding RNAs (lncRNAs) are a group of RNA molecules with essential regulatory functions in both physiological and pathological processes. OBJECTIVES: To investigate the function and mode of action of lncRNA plasmacytoma variant translocation 1 (PVT1) in cSCC. METHODS: Quantitative reverse transcriptase polymerase chain reaction and single-molecule in situ hybridization were used to quantify the expression level of PVT1 in normal skin, premalignant skin lesions, actinic keratosis (AK) and primary and metastatic cSCCs. The function of PVT1 in cSCC was investigated both in vivo (tumour xenografts) and in vitro (competitive cell growth assay, 5-ethynyl-2'-deoxyuridine incorporation assay, colony formation assay and tumour spheroid formation assay) upon CRISPR-Cas9-mediated knockout of the entire PVT1 locus, the knockout of exon 2 of PVT1, and locked nucleic acid (LNA) gapmer-mediated PVT1 knockdown. RNA sequencing analysis was conducted to identify genes and processes regulated by PVT1. RESULTS: We identified PVT1 as a lncRNA upregulated in cSCC in situ and cSCC, associated with the malignant phenotype of cSCC. We showed that the expression of PVT1 in cSCC was regulated by MYC. Both CRISPR-Cas9 deletion of the entire PVT1 locus and LNA gapmer-mediated knockdown of PVT1 transcript impaired the malignant behaviour of cSCC cells, suggesting that PVT1 is an oncogenic transcript in cSCC. Furthermore, knockout of PVT1 exon 2 inhibited cSCC tumour growth both in vivo and in vitro, demonstrating that exon 2 is a critical element for the oncogenic role of PVT1. Mechanistically, we showed that PVT1 was localized in the cell nucleus and its deletion resulted in cellular senescence, increased cyclin-dependent kinase inhibitor 1 (p21/CDKN1A) expression and cell cycle arrest. CONCLUSIONS: Our study revealed a previously unrecognized role for exon 2 of PVT1 in its oncogenic role and that PVT1 suppresses cellular senescence in cSCC. PVT1 may be a potential biomarker and therapeutic target in cSCC.

BACKGROUND: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. OBJECTIVES: To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. METHODS: Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. RESULTS: On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05). STUDY LIMITATIONS: The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. CONCLUSION: The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

Endocrine therapy has played an essential role in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2- advanced breast cancer has been greatly improved. Their adverse reactions also need more attention in response to the climbing number of CDK4/6 inhibitors. The common side effects of CDK4/6 inhibitors were hematological toxicity, diarrhea, and liver function damage. Skin toxicity related to CDK4/6 inhibitors was rare. We describe herein our preliminary observation of one HR+HER2- advanced metastatic breast cancer patient diagnosed with vitiligo-like lesions after 10 months of taking Palbociclib. Hoping to share our experience to increase the clinician awareness of this unusual adverse and contribute to the information in the literature.

Background: Photoreceptive proteins play critical physiological roles in human skin cells. The retinal G protein-coupled receptor (RGR) is a photoisomerase in the human retina, but its expression and cellular functions in human skin cells have not been reported. Objectives: We aimed to detect RGR expression in various skin cells and evaluate its regulation of the cellular functions of keratinocytes. Methods: The expression, distribution, and subcellular location of the RGR in normal human epidermal keratinocytes and cells with pathological conditions including psoriasis, seborrheic keratosis, and squamous cell carcinoma were determined using microscopic tools (immunohistochemical staining, immunofluorescence staining, and immunoelectron microscopy) and Western blotting (WB). The protein levels of the RGR in primary human melanocytes, keratinocytes, and fibroblasts isolated from the neonatal foreskin were measured by WB. The expression and subcellular localization of the RGR in these cells were detected by immunofluorescence staining under a fluorescence microscope and laser scanning confocal microscope. Additionally, the levels of RGR expression in normal keratinocytes exposed to ultraviolet (UV)-A or total ultraviolet radiation (UVR) in the presence or absence of all-trans-retinal were measured by WB. Furthermore, the effects of the RGR on human keratinocyte functions including proliferation, migration, and apoptosis were evaluated using the Cell Counting Kit 8, wound healing, and Transwell assays after reducing the RGR mRNA level in keratinocytes using small interfering RNA technology. Results: The RGR was primarily located in the epidermal basal and spinous layers and skin appendages. Its expression increased in psoriatic lesions, seborrheic keratosis, and squamous cell carcinoma. Confocal microscopy showed that the RGR was located in the cell membrane and nucleus of keratinocytes, melanocytes, and fibroblasts. Keratinocytes had a higher expression of the RGR than melanocytes and fibroblasts, as well as nuclear expression, according to nuclear/cytoplasmic fractionation. Colloidal gold immunoelectron microscopy technology further confirmed that the RGR is mainly located in the nucleoplasm and mitochondria and is scattered in the cytoplasm and other organelles in the epidermal keratinocytes. Notably, RGR knockdown in keratinocytes led to the inhibition of cell proliferation and migration, augmenting cell apoptosis. Conclusions: This study is the first to demonstrate the presence of RGR in the human skin. Our findings indicate that the RGR may play a critical role in the physiological function of epidermal keratinocytes.

Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated. Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7-overexpressed normal human epidermal keratinocytes (NHEKs). Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3 , were associated with epigenetic modifications, immune regulation, and metabolic pathways. Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.

Leukotrichia frequently accompanies vitiligo on hairy areas such as the scalp. Treatment with conventional medical therapy is usually unsuccessful because of deficiencies in the melanocyte reservoir. We describe transplantation of autologous cultured pure melanocytes for scalp vitiligo with leukotrichia in a 9-year-old girl, resulting in almost complete and stable repigmentation of skin and hair.

Topomyia (Suaymyia)nemorosa sp. nov.(Figs. 1-7)The new species is distinguished from the other members of the subgenus,with the exception of To. yanbarensis,To. (Sua.)dulongensis Gong et Lu, 1995 and To. (Sua.) bannaensis Gong et Lu, 1995, by the presence of a row of large broad pale scales on lateral margin from scuteal angle to wing root or supraalars on mesonotum. To. yanbarensis differs from the former in the color of flat broad scales of middorsal line on mesomotum which are translucent,and the strongly bifurcate; distitnere; the broad scales of lateral margin of mesonotum of To. dulongensis are silvery and with strongly dorsocentrals; To. bannaensis differs from the new species in the absence of ventral yellow lines on tibiae and tarsi, a light patche on the ventral of base of costa.The larva of the new species differs from To. yanbarensis and To. dulongensis by thepresence of a digit process of the well developed maxilla. It also differs from To. hoztghtoniand other members of the subgenus in the absence of pecten,but with minute spicules frombase to apex of siphon.Holotype /, paratypes 10 / /, 25 1 l; 33 larvae or larval skins,collected from bam-boo stumps in Ruth City (24. 34N, 98E, fat. 1400m) (Gong, 1992),Yunnan Province. Alltypes are depisted in the institute of Epidemiology of Yunnan Province.

Eye movement (EM), as a mature observation technology, has been widely used in the research of psychology, and it is also one of the important methods of multi-quality psychological testing technology. However, there are relatively few researches on psychological testing based on EM technology at present. By introducing convolution neural network (CNN) network into deep long short memory network (DLSTM), this paper develops a new network structure, designs a fusion strategy, and proposes an EM tracking data fusion algorithm based on deep learning (EYE-CNN-DLSTM). By comparing the fusion effect and index values of EYE-CNN-DLSTM algorithm with two deep learning algorithms MLP and DLSTM on 10 sets of real EM data sets and 10 sets of real tracking data sets, the experimental results show that EYE-CNN-DLSTM algorithm performs well in fusion quality. It provides a theoretical basis for the new objective evaluation index of patients with mental disorders.

Generalized pustular psoriasis, the most severe form of psoriasis, is a rare variant characterized by widespread sterile pustule associated with systemic inflammation. The disease lacks of specific treatment, drugs approved for plaque psoriasis are used in the clinical practice, with variable results.

Dermatology has benefited considerably from the use of artificial intelligence (AI), which has emerged as a crucial tool in healthcare. Algorithms for machine learning (ML) and deep learning (DL), in particular convolutional neural networks (CNNs), have demonstrated significant promise in the diagnosis of skin disorders, classification of lesions, and telemedicine support. The use of AI in dermatology is examined in this paper, with particular attention paid to how it might improve patient care, increase access to dermatological treatments, and improve diagnostic accuracy. It also discusses the difficulties, moral dilemmas, and potential applications of AI in dermatology. It highlights the necessity of cooperation between researchers, practitioners, and regulatory agencies to guarantee a secure and efficient transition into clinical practice.

OBJECTIVE: To explore the factors influencing the steady transmission of leprosy as indicated by new case detection rate in Qiubei county, Yunnan province, China despite the implementation of MDT for the last 25 years. METHODS: Information related to case-finding was collected. ELISA and PCR were applied to detect anti-PGL-1 antibody in sera and Mycobacterium leprae in nasal secretions respectively, in leprosy patients, their household contacts and the general population. M. leprae by PCR was also detected from water in the highly endemic villages. VNTR typing was performed to explore the mode and chain of transmission of M. leprae. RESULTS: Prior to 2001, the proportion of new cases detected from the examination of household contacts of leprosy patients was low (number, compared to), while the proportion of patients whose identification was delayed by more than 2 years, was high (number, compared to). Qualities of these two indicators has been improved, along with the improvement of leprosy control program since 2001, but the detection rates has been steady at 4-5/100 000 during 1986 - 2010. The PGL-1 seropositivity rate was 20% - 30% in general population, with the peak rate (30%) detected in the teenage population in the endemic villages. In addition to the fact that M. leprae was detected in nasal secretion from patients, their contacts and from water, the M. leprae VNTR genotypes were found to be highly similar between skin biopsy and nasal secretion in untreated cases. Families with multi-cases were clustered and located in the Northern part of the County, and the genotypes of M. leprae were identical within those families. The percentage of clusters was considerably higher in Northern rather than Southern parts of the County. CONCLUSION: Results from this molecular study demonstrated evidence that transmission of leprosy within the families and in the endemic-villages was severe. M. leprae were detected in waters from the endemic villages and others areas which might have a relation to the continued transmission of leprosy.

Background: Melasma is a common hyperpigmentation disorder that presents a significant therapeutic challenge. This study aims to evaluate the efficacy and safety of a novel combination approach using a picosecond laser followed by microinjections of a sodium hyaluronate composite solution for the treatment of mixed-type melasma. Methods: In this retrospective study, 30 female patients with mixed-type melasma received 3 treatment sessions. Each session consisted of a fractional picosecond laser treatment followed by the administration of a non-cross-linked sodium hyaluronate composite solution. Efficacy was primarily assessed by the change in the Melasma Area and Severity Index score from baseline to 4 weeks posttreatment, as evaluated by an independent blinded investigator. Secondary endpoints included Physician's Global Assessment and patient satisfaction. Results: < 0.05). Physician assessments showed marked or moderate improvement in 70% of patients, and the overall patient satisfaction rate was high (86.7%). The treatment was well tolerated with only mild, transient side effects and no serious adverse events reported. Conclusions: The combination of a picosecond laser with a sodium hyaluronate composite solution demonstrated significant short-term efficacy at 4 weeks posttreatment with an acceptable safety profile, offering a promising approach for its clinical management.