Livin is protective in UVB-induced skin photodamage by regulating keratinocyte activation and inflammatory responses.

UVB radiation can lead to skin photodamage, which might arise from keratinocyte (KC) activation. Nuclear factor kappa B (NF-κB) assumes an essential function in the context of UVB-triggered skin photodamage. Initiating the NF-κB cascade leads to the release of inflammatory factors from KCs. Livin can modulate both KC activation and function, yet it remains uncertain whether and how Livin regulates KC activation induced by UVB. To explore the involvement of Livin in UVB-triggered skin photodamage and its impact on skin damage through NF-κB activation. Immunofluorescence staining was used to analyse the expression of Livin in individuals with skin photodamage and in mice treated with UVB radiation. KC-specific Livin knockout (LivinΔKC ) mice and HaCaT cells with Livin knockdown were employed to examine the function of Livin in regulating KC activation induced by UVB radiation. Additionally, the impact of Livin on the NF-κB cascade during KC activation was confirmed via western blot analysis. In patients with skin photodamage, UVB-treated mice and HaCaT cells, Livin expression was reduced in KCs. LivinΔKC mice displayed heightened sensitivity to UVB radiation, resulting in more pronounced skin damage and inflammatory responses compared to the control Livinfl/fl mice. Following UVB exposure, both LivinΔKC mice and Livin-knockdown HaCaT cells released elevated levels of cytokines compared to their respective controls. Moreover, the UVB-induced activation of NF-κB in HaCaT cells was significantly enhanced following Livin knockdown. Our findings propose that Livin within KCs could contribute to reducing UVB-induced skin photodamage by regulating the NF-κB pathway.

Analysis of circRNA profiles and clinical value in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are challenging to be early diagnosed and evaluate their prognoses. This investigation aimed to analyse the expression profiles of SJS/TEN in peripheral blood mononuclear cells (PBMC) and assess the correlation between circular RNA (circRNA) and disease severity. Sixteen SJS/TEN patients and sixteen controls were enrolled and serum samples of both groups were obtained. CircRNA expression profiles in three SJS/TEN patients and three controls were detected by RNA sequencing and bioinformatic analyses were then performed. The differentially expressed circRNAs were verified by quantitative polymerase chain reaction (qPCR). Then, analysing the correlation of circRNAs with the toxic epidermal necrolysis-specific severity of illness score (SCORTEN) and the epidermal detachment area. A total of 134 circRNAs were differentially expressed in the PBMCs of SJS/TEN individuals, according to our results. The qPCR showed that three circRNAs (hsa_circ_0000711, hsa_circ_0083619 and hsa_circ_0005615) were down-regulated, and one circRNA (hsa_circ_0003028) was up-regulated, which were compatible with the sequencing findings. The concentration of hsa_circ_0083619 was closely associated with the SCORTEN scale (r = -0.581, p = 0.037) and the epidermal detachment area (r = -0.576, p = 0.039). The circRNA-miRNA-mRNA prediction network was used to construct the hsa_circ_0083619/miR-18a-5p/BCL2L10 axis. The hsa_circ_0083619 could serve as a disease severity indicator for SJS/TEN. Through bioinformatics analysis, we speculated that hsa_circ_0083619/miR-18a-5p/BCL2L10 axis might play a role in SJS/TEN pathogenesis.

Functional Involvement of ADRA1D in Cutaneous Melanoma Progression and Angiogenesis.

Cutaneous melanoma is a highly aggressive and malignant skin cancer, and its high recurrence rate and drug resistance increase the difficulty of treating advanced-stage patients. Studies have revealed that treatment via stimulation of alpha-1 adrenergic receptor (ADRA1) subtypes inhibits melanoma growth in mice. However, the associations between alpha-1D adrenergic receptor (ADRA1D) and cutaneous melanoma are poorly understood. Tissue specimens from 16 pairs of patients with a pigmented nevus and cutaneous melanoma were analyzed for ADRA1D expression using immunohistochemical staining. Western blotting and RT-qPCR were carried out in order to detect ADRA1D expression levels in melanoma cells and human epidermal melanocytes (HEMs), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) levels in HUVECS. A375 cells were transfected with a lentivirus overexpressing ADRA1D. Wound-healing, Transwell, and cell proliferation assays were utilized to identify the ADRA1D effect on the migration, invasion, and proliferation of the two groups of A375 cells in vitro. In order to evaluate the function of ADRA1D in vivo, a melanoma xenograft model was developed in immunodeficient mice. ADRA1D was low expressed in cutaneous melanoma tissues. Overexpression of ADRA1D inhibited the tubulation and migration of HUVECs in vitro. Overexpression of ADRA1D significantly decreased the HIF-1α and VEGF expression. Overexpression of ADRA1D inhibited the invasion and proliferation of A375 melanoma cells in vitro and reduced its angiogenesis in vivo. ADRA1D inhibits cutaneous melanoma growth and angiogenesis. It attenuates melanoma cell proliferation and invasion. Meanwhile, its anti-angiogenic effect is achieved by negatively regulating the HIF-1α/VEGF axis in melanoma tissue, thereby attenuating the growth of cutaneous melanoma and reducing the potential of metastasis.

Clinical efficacy of LED golden light combined with acyclovir in the treatment of herpes zoster: a single-center prospective study.

This study aimed to explore the safety and clinical efficacy of light emitting diode (LED) golden light combined with acyclovir in treating herpes zoster (HZ). According to the random number table, 54 inpatients with HZ were divided into control group, golden-light group, and red-light group, with 18 cases in each group. The control group received acyclovir intravenous drip, while the patients in the red-light group received acyclovir intravenous drip and red-light LED phototherapy, and the golden-light group received acyclovir intravenous drip and golden-light LED phototherapy. Primary assessments included herpes stopping time, incrustation time, decrustation time, pain visual analog scale scores (VAS), and incidence of postherpetic neuralgia (PHN) on the 30th and 90th days. Golden-light group and red-light group showed a shorter herpes stopping time, incrustation time, and decrustation time (P < 0.05) compared to the control group (P < 0.05), while the golden-light group showed a shorter incrustation time and decrustation time than the red light group (all P < 0.05). After treatment VAS scores, the golden-light group showed a significant improvement compared to the control group. The golden-light group showed a better PHN incidence than the control group at 30 days follow-up. Compared with the comprehensive curative effect, the total effective rates of the golden-light group, red-light group, and control group were 88.89%, 77.78%, and 72.22%, respectively, and the efficacy of the golden-light group was better than that of the control group and red-light group. Golden light combined with acyclovir can shorten the course of HZ, relieve pain, and reduce the occurrence of PHN, and the effect is better than that of the red-light group and the control group.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

Differentially expressed microRNAs in peripheral blood mononuclear cells of non-segmental vitiligo and their clinical significance.

BACKGROUND: Vitiligo is a frequent acquired depigmentation skin disease due to a loss of melanocytes. This study sought to characterize the expression pattern of microRNA (miRNA) in the peripheral blood mononuclear cells (PBMCs) of non-segmental vitiligo (NSV) patients. We also screened for molecular markers that can be used to evaluate the clinical stages of NSV. METHODS: The miRNA expression profile in the PBMCs of four patients with progressive NSV and four healthy controls was determined using high-throughput RNA sequencing. The divergently expressed miRNA was verified via qRT-PCR in 26 progression, 26 stable NSV, and 26 healthy controls. RESULTS: Our findings posited that 323 miRNAs were differentially expressed in the PBMCs of NSV patients. The top 10 up-regulated miRNAs in patients were hsa-miR-335-5p, hsa-miR-20a-5p, hsa-miR-514a-3p, hsa-miR-144-5p, hsa-miR-450b-5p, hsa-miR-369-3p, hsa-miR-101-3p, hsa-miR-142-5p, hsa-miR-19b-3p, and hsa-miR-340-5p. The top 10 down-regulated miRNAs in patients were hsa-miR-4443, hsa-miR-1248, hsa-miR-6859-3p, hsa-miR-668-3p, hsa-miR-7704, hsa-miR-323a-5p, hsa-miR-1237-3p, hsa-miR-3127-3p, hsa-miR-6735-3p, and hsa-miR-127-3p. The expressions of hsa-miR-20a-5p in PBMCs of progressive and stable NSV were remarkably elevated relative to the healthy controls. In the characteristics curve analysis of hsa-miR-20a-5p for differentiating progressive and stable NSV from normal subjects in PBMCs, the area under curve (AUC) was 0.92 and 0.81. Compared with patients in stable NSV, the hsa-miR-20a-5p was markedly increased in PBMCs of progressive NSV patients, and the AUC was 0.81. CONCLUSION: Our results showed that divergently expressed miRNAs contribute to the pathogenesis of NSV and that hsa-miR-20a-5p can be applied as a biosignature for stage assessment in PBMCs of patients with NSV.

Whole genome assembly and functional portrait of hypervirulent extensively drug-resistant NDM-1 and KPC-2 co-producing Klebsiella pneumoniae of capsular serotype K2 and ST86.

OBJECTIVES: To characterize an emergent carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strain, NUHL30457, which co-produces NDM-1 and KPC-2 carbapenemases. METHODS: We performed WGS analysis on a clinical carbapenemase-producing hypervirulent K. pneumoniae (CP-hvKP) strain NUHL30457. Sequence data were analysed using comparative genomics and phylogenetics. WGS was used to perform MLST, capsular genotyping and identification of virulence and antimicrobial resistance genes. The virulence of NUHL30457 was analysed by serum killing assay, neutrophil phagocytosis and mouse lethality assay. RESULTS: The NUHL30457 strain was carbapenem resistant and belonged to ST86 and serotype K2. A significant increase in resistance to serum killing and antiphagocytosis was found in the NUHL30457 strain compared with the reference strain. The murine lethality assay showed an LD50 of 2.5 × 102 cfu for the NUHL30457 strain, indicating hypervirulence. WGS revealed that NUHL30457 has a single 5.3 Mb chromosome (57.53% G + C content) and four plasmids in the range 49.2-215.7 kb. The incompatibility group (Inc)N plasmid p30457-4 carried the blaNDM-1 and qnrS1 genes. The IncFII(K) plasmid p30457-3 also carried an array of resistance elements, including blaCTX-M-65, blaTEM-1 and blaKPC-2. The IncHI1/IncFIB plasmid p30457-1, which carried virulence genes, was identical to a pLVPK plasmid reported previously. CONCLUSIONS: To the best of our knowledge, this is the first report to isolate an ST86 hvKP strain that co-produces NDM-1 and KPC-2 carbapenemase. Further investigation is required to reinforce our understanding of the epidemiology and virulence mechanisms of this clinically significant CP-hvKP.

Global burden and future trends in psoriasis epidemiology: insights from the global burden of disease study 2019 and predictions to 2030.

BACKGROUND: Millions of people worldwide are affected by psoriasis, one of the most prevalent skin conditions. Currently, there is a lack of high-quality epidemiological reports on psoriasis. OBJECTIVE: This study aimed to reveal trends in psoriasis epidemiology in 1990-2019. METHODS: Using data from the GBD study 2019, we examined psoriasis epidemiology globally and across regions defined by the social-demographic index (SDI). Trends in incidence, prevalence, and disability-adjusted life year (DALY) rates were assessed using estimated annual percentage changes (EAPC)s. Age-period-cohort analysis examined risk variations, and decomposition analysis identified factors impacting the psoriasis burden. A Bayesian Age-Period-Cohort model predicted future incidence. Frontier analysis associated psoriasis outcomes with socio-demographic development. RESULTS: In 2019, the global psoriasis burden included 4,622,594 incidence, 40,805,386 prevalence, and 3,505,736 DALY cases. Despite variations in SDI regions, the overall trend showed a decline in psoriasis rates from 1990 to 2019 (EAPC = - 0.76). The age-specific analysis indicated that the highest incidence of psoriasis was observed among individuals aged 40-64 years (global, 1,606,429). Epidemiological shifts contributed negatively to global incidence and DALYs by - 80.52% and - 103.06%, respectively. Countries like San Marino and Spain displayed the highest effective differences in the decomposition analysis. By 2030, while incidence cases per 10,000 might rise (487.36, 423.62 to 551.10), age-standardized incidence rates per 100,000 were predicted to decline (53.67, 0.00 to 259.99). CONCLUSION: This research revealed a global decline in psoriasis incidence rate from 1990 to 2019, with predictions suggesting this trend continues through 2030. Geographic disparities underscore the importance of tailored healthcare policies.

Talaromyces marneffei infection with IFNGR1 gene mutation in a patient with negative Anti-Interferon-γ autoantibodies.

BACKGROUND: Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. OBJECTIVE: To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. METHODS: Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. RESULTS: The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). STUDY LIMITATIONS: The mechanism of the IFNGR1 gene has not been further investigated in this study. CONCLUSIONS: The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.

Analysis of clinical features and inflammatory-related molecules with the disease in acute infectious urticaria.

Acute infectious urticaria, a subset of acute urticaria, with severe persistence wheals and systemic symptoms, response well to corticosteroids treatment in combination with antibiotics. The exact pathogenic mechanisms are not fully understood. In this study, we aim to analyze the different clinical features, compare the level of neutrophil activation, and investigate the expression of inflammatory related cytokine in patients with acute urticaria and acute infectious urticaria. Eighteen patients with acute infectious urticaria and eighteen patients with acute urticaria were included in this study. We analyzed the difference between the clinical features and the serum expressions of pro-inflammatory factors in the two groups, then examined the levels of inflammation-associated cytokines before and after treatment of acute infectious urticaria. Hematoxylin & eosin (HE) staining and immunohistochemistry (IHC) were used to further study the relationship between neutrophil and neutrophil-derived Myeloperoxidase (MPO) of lesions in the two groups. The expression levels of C-reactive protein (CRP), D-dimer, interleukin 6 (IL-6), IL-8 and chemokine ligand 8 (CCL8) in serum were significantly higher in acute infectious urticaria than acute urticaria. In acute infectious urticaria, the serum expression levels of CCL8 were significantly decreased after the treatment, a significant correlation observed between CRP levels and IL-6, both CCL8 and CRP were positively correlated with neutrophil granulocytes. Neutrophils infiltration were not observed by HE stains in two groups, but in IHC stains we found a positive expression of MPO in acute infectious urticaria lesions. Elevated neutrophil in the serum, which is associated with the levels of IL-8 & CCL8, and positively expressed MPO in lesions, may be involved in the pathogenic mechanism of acute infectious urticaria.

Classic Eosinophilic Pustular Folliculitis in an Immunocompetent Patient with Syphilis: Are They Related?

Eosinophilic pustular folliculitis (EPF) is a rare, chronic, non-infectious inflammatory skin disease. Although the pathogenesis of EPF is unknown, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection, malignancies or syphilis. Here, we report the first case of EPF associated with syphilis, indicating that syphilis and EPF are correlated with T-helper type 2 immune responses. A 48-year-old man gradually developed erythema and pustules on the face, neck. Physical examination revealed multiple infiltrative red patches and plaques on the face, neck with tiny pustules. Skin biopsy results revealed that the dermal follicular sebaceous gland unit was infiltrated by a large number of neutrophils and eosinophils, forming eosinophilic microabscesses. Therefore, the patient was diagnosed with EPF associated with syphilis and received drug treatment. After the treatment, the pustules markedly decreased, leaving behind pigmentation. Furthermore, the patient is still being followed up.

Clinical value of the prognostic nutritional index and red blood cell distribution width-to-albumin ratio for the prediction of severity of and mortality associated with Stevens-Johnson syndrome/toxic epidermal necrolysis.

The prognostic nutritional index (PNI) and red blood cell distribution width-to-albumin ratio (RAR) are considered to be related to the prognosis of disease severity. However, the role of these biomarkers in predicting Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) severity and mortality is unclear. The aim of the current study was to investigate the association of PNI and RAR with severity and mortality in individuals with SJS/TEN. Clinical data were retrospectively collected from 74 individuals with SJS/TEN and 74 healthy individuals, who were matched for age and sex during the same period. PNI, RAR, and other indicators were compared between individuals with SJS/TEN and healthy controls. The association of PNI and RAR with SJS/TEN severity was assessed using Spearman or Pearson correlation analyses. Individuals with SJS/TEN were categorized into two groups, either survivors or nonsurvivors. The correlation between PNI, RAR, and SJS/TEN mortality was analyzed using univariate and multivariate logistic regression. The predictive value of the previously mentioned indicators on the mortality of patients with SJS/TEN was assessed using receiver operating characteristic curve analysis. The RAR level of patients with SJS/TEN was greater than that of the control group (p < 0.05), whereas PNI was lower. In compliance with correlation analysis, RAR was positively correlated with SCORTEN (Score of Toxic Epidermal Necrolysis) and ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area) (p < 0.05), and PNI was negatively correlated (p < 0.05). RAR is a risk factor for death in patients with SJS/TEN, but an elevated PNI level is a protective factor for mortality. The best cutoff values of PNI and RAR for predicting death in patients with SJS/TEN were 31.375 (sensitivity, 84.7%; specificity, 80%) and 0.486 (sensitivity, 73.3%; specificity, 84.7%). These results underscore the potential clinical value of PNI and RAR as appropriate and meaningful biomarkers to assess the severity of SJS/TEN and the mortality associated with it.

Comparative Efficacy Between Intense Pulsed Light Narrow Spectrum and Broad Spectrum in the Treatment of Post-Acne Erythema (PAE).

Purpose: Post-acne erythema (PAE) is one of the most common physical sequelae of acne regression, PAE can resolve spontaneously, but in some patients it may last for years. This study aimed to evaluate the efficacy and safety of narrow and broad spectrum filters of intense pulsed light (IPL) for the treatment of PAE. Patients and Methods: This prospective study evaluated 60 patients with PAE for at least 6 months, assigned equally to three groups: 1st group received narrow-spectrum with vascular filter (530-650 nm and 900-1200 nm), 2nd group received broad-spectrum with (560/590-1200 nm) filters, the appropriate adjustments were made according to patient's skin colour. Every patient received four sessions one month apart. 3rd group is blank control group did not receive any treatment. CAT (CEA (Clinical Erythema Assessment), Area, and Telangiectasia) used to grade clearance of PAE before and after treatment, Investigators Global Assessment (IGA) used to assess the improvement score after the treatment, and Cardiff Acne Disability Index (CADI) used to evaluate the impact of PAE on patients' Quality of Life (QoL). Self-satisfaction scale completed at the follow-up. Adverse events and acne relapse were recorded. Results: A significant decrease of CAT score in vascular group (P<0.05). IGA scale showed significant improvement after vascular treatment. A significant decrease in CADI (P<0.05) after vascular treatment. Patient satisfaction was higher in vascular group than control and blank control groups. Acne relapse observed in control and blank control groups (40% and 15%, respectively).10% of patients showed pigmentation, 15% had blisters after 590 nm treatment. Conclusion: IPL vascular filter (530-650 nm and 900-1200 nm) have efficacy in the treatment of PAE. CADI score, patient satisfaction, and acne relapse were significantly better after vascular narrow spectrum treatment than broad-spectrum treatment.

Considering Computational Mathematics IGHG3 as Malignant Melanoma Is Associated with Immune Infiltration of Malignant Melanoma.

Malignant melanoma is one of the most threatening cancers to human health. Only 14% of patients with malignant melanoma have a remaining life span of 5 years. At present, there have been some studies looking for potential prognostic indicators of esophageal cancer from the level of genes and infiltrating immune cells, but there are still some problems that need to be resolved urgently. This paper proposes IGHG3 as the immune infiltration of malignant melanoma, which takes into account the computational mathematics. It aims to deduce the characteristics of immune cell infiltration in malignant melanoma and study the relationship between different immune cell infiltration characteristics and prognosis. The method in this article is to establish a computational mathematical model for the immunotherapy of melanoma, then study the method of identification of the affinity of the IGHG3 reagent, and finally obtain the gene expression of immune infiltration. The functions of these methods are, respectively, to predict the dynamic behavior of T cells with two different specificities through mathematical models and to test the matching degree of different concentrations of IGHG3 reagent with the human body. Then use the ssGSEA algorithm to obtain immune infiltration related data and calculate the difference between the weighted empirical cumulative distribution function of all genes in the effect of IGHG3 on melanoma that was carried out. The experimental results showed the computational mathematical method genome and all the remaining genes. In this study, a computational mathematical method to detect the IGHG3 gene expression had a significant inhibitory effect on A375 cells in the experimental group, and the knockdown efficiency reached 85.6%.

Successful treatment of tuberculosis verrucosa cutis with fester as primary manifestation with photodynamic therapy and anti-tubercular drugs.

Tuberculosis verrucosa cutis (TBVC) is a rare type of cutaneous tuberculosis, which often occurs in the body with good immunity to tuberculosis bacilli. It usually presents as a hyperkeratotic verrucous plaque with polygonal boarders but can mimic or evolved into other dermatosis such as verruca vulgaris, chromoblastomycosis, hyperkeratotic lupus vulgaris, hypertrophic lichen planus, or squamous cell carcinoma, leading to delayed diagnosis. Here, we reported that a 62-year-old patient diagnosed by TBVC with fester as primary manifestation. Photodynamic therapy combined with anti-tuberculosis drugs is an effective method to treat TBVC lesions with fester, and it may shorten the treatment cycle of anti-tuberculosis drugs.

Prediction of Diagnostic Gene Biomarkers Associated with Immune Infiltration for Basal Cell Carcinoma.

Purpose: Basal cell carcinoma (BCC) is a frequent tumor of the surface layer of skin or its accessories, and ranks first among the prevalence of skin cancer cases. However, its pathogenesis remains unclear. The purpose of this analysis was to scientifically evaluate the role of mRNAs in the occurrence and progression of BCC and further elucidate their underlying potential molecular mechanisms of action. Methods: Differentially expression genes (DEGs) between nineteen BCC cases and five controls which initiate from the GSE103439 and GSE7553 datasets were identified and the transcriptome sequencing information was obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Ontology (GO) annotation were performed. Logistic regression (LASSO) and support vector machine (SVM) analyses were performed to identify candidate biomarkers obtained from protein-protein interaction (PPI) analysis. The tumor microenvironment comprising hub genes in BCC was investigated by immune infiltration analysis. The expression of two representative hub genes (KIF23 and NCAPG) was measured by qRT-PCR. Finally, the potential miRNAs and lncRNAs related to the hub genes were analyzed on relevant websites to obtain a ceRNA interaction network. Results: Twenty-seven DEGs were identified. Fifteen hub genes were screened in the protein-protein interaction network. These showed marked enrichment in the cell cycle and p53 signaling pathway. FGF20, KIF23, and NCAPG were identified as the diagnostic markers of BCC. Immune cell infiltration analysis suggested their significant association with T cells CD4 memory activated, macrophages M1, and natural killer (NK) resting cells. Two miRNAs and twelve lncRNAs were used to construct the lncRNA-miRNA-mRNA ceRNA network. Conclusion: FGF20, KIF23, and NCAPG are potential diagnostic markers of BCC. Our findings may shed new light on the molecular mechanisms underlying BCC occurrence.

Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation.

Inherited erythromelalgia (IEM), an autosomal dominant disorder characterized by severe burning pain in response to mild warmth, has been shown to be caused by gain-of-function mutations of sodium channel Na(v)1.7 which is preferentially expressed within dorsal root ganglion (DRG) and sympathetic ganglion neurons. Almost all physiologically characterized cases of IEM have been associated with onset in early childhood. Here, we report the voltage-clamp and current-clamp analysis of a new Na(v)1.7 mutation, Q10R, in a patient with clinical onset of erythromelalgia in the second decade. We show that the mutation in this patient hyperpolarizes activation by only -5.3 mV, a smaller shift than seen with early-onset erythromelalgia mutations, but similar to that of I136V, another mutation that is linked to delayed-onset IEM. Using current-clamp, we show that the expression of Q10R induces hyperexcitability in DRG neurons, but produces an increase in excitability that is smaller than the change produced by I848T, an early-onset erythromelalgia mutation. Our analysis suggests a genotype-phenotype relationship at three levels (clinical, cellular and molecular/ion channel), with mutations that produce smaller effects on sodium channel activation being associated with a smaller degree of DRG neuron excitability and later onset of clinical signs.

Development and validation of prognostic nomogram in patients with nonmetastatic malignant melanoma: a SEER population-based study.

BACKGROUND: The condition of tumor recurrence and overall death can be worried in the progress of nonmetastatic malignant melanoma (NMMM). Our goal was to construct and validate a prognostic nomogram from a large population database, which is vital for physicians to predict the 3- and 5-year overall survival (OS) rates of patients with NMMM. METHODS: According to the Surveillance, Epidemiology, and End Results (SEER) program, patients were collected and randomly assigned into the training and validation cohorts. Several independent risk factors were identified based on the methods of univariable and multivariable cox hazards regression and were incorporated to develop a nomogram. The concordance index (C-index), the area under the receiver operating characteristics (AUC) curve and calibration plot were confirmed to assess predictive power of the nomogram. Decision curve analysis (DCA) was performed to measure nomogram for the clinical practice. RESULTS: A total of 66192 eligible patients, randomly assigned into 70% of training (n = 46 336) and 30% of validation cohorts (n = 19 856), were selected in this study. The selected independent factors were applied to develop a nomogram, and validated indexes indicated nomogram had a good discrimination ability. The C-index for OS rates was 0.817 (95% CI: 0.811-0.823) in training cohort and 0.817 (95% CI: 0.809-0.825) in validation cohort, respectively. The AUCs of 3- and 5-year OS rates were more than 0.79, and the calibration plots also showed a good power for the nomogram. DCA demonstrated that constructed nomogram can provide clinical net benefit. CONCLUSION: We constructed a novel nomogram that more accurately and comprehensively predict OS with nonmetastatic malignant melanoma patients, which is vital for clinician to improve individual treatment, make reasonable clinical decisions, and set appropriate follow-up strategies.

Prevalence of Carbapenem-Resistant Klebsiella pneumoniae Infection in Southern China: Clinical Characteristics, Antimicrobial Resistance, Virulence, and Geographic Distribution.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains pose a significant threat to public health. In this study, a survey was conducted in the Jiangxi Province of China, covering a total of 140 CRKP strains collected from 11 hospital laboratories from June 2016 to January 2018. All CRKP isolates were subjected to antimicrobial susceptibility testing, capsular serotypes, virulence gene profiles, multilocus sequence typing, and pulsed-field gel electrophoresis. The differences in the patient characteristics and distributions among the various regions were statistically significant (p ≤ 0.001). Most patients were hospitalized in intensive care units (30.0%) and burn departments (13.6%), with lower respiratory (52.1%) and urinary tract (15.7%) infections being most prevalent. A higher ratio of CRKP isolates were identified in the southern and central regions of Jiangxi than in the other regions. Only two carbapenemase genes, blaKPC and blaNDM, were responsible for phenotypic resistance in the tested CRKP strains (46.5% and 22.1%, respectively), among which several major sequence types (STs), such as ST11 (27.8%) and ST23 (14.8%), were identified. A total of 39 virulent strains were detected, of which 22 strains were classified by capsule serotyping. Hypervirulent genes were most common in the eastern and central regions of Jiangxi. In conclusion, CRKP strains in the Jiangxi Province have varied geographic distributions; the resistance rates of isolates harboring blaKPC decreased from southern to northern regions, whereas the drug resistance gene blaNDM showed a tendency to spread from a central point to the surrounding areas. ST23 carbapenem-resistant hypervirulent K. pneumoniae is emerging, resulting in an urgent need to enhance clinical awareness.

Talaromyces marneffei infection with IFNGR1 gene mutation in a patient with negative Anti-Interferon-γ autoantibodies

Abstract Background Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. Objective To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. Methods Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. Results The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). Study limitations The mechanism of the IFNGR1 gene has not been further investigated in this study. Conclusions The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.