Merkel cell carcinoma overlapping Bowen's disease: two cases report and literature review.

PURPOSE: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, which mainly occurs in the sun exposed sites of white patients over 65 years, with a higher recurrence and metastasis rate. Clinically, MCC overlapping Bowen's disease (BD) is a very rare subtype of MCC. Few cases in the literature have been described and the management is not well defined. We summarize and update the epidemiology, clinical and histopathological features, metastasis characteristics, local recurrence rate and management of it by presenting two cases of MCC overlapping BD and reviewing the literature over the last 11 years. DESIGN: We consulted databases from PubMed, ResearchGate and Google Scholar by MeSh "Merkel cell carcinoma" and "Bowen's disease", "Bowen disease" or "squamous cell carcinoma in situ", from January 2013 to December 2023 and reviewed the literatures. We reported two additional cases. RESULTS: Total 13 cases of MCC overlapping BD were retrospectively analyzed, in whom mainly in elderly women over 70 years, the skin lesions were primarily located on the faces, followed by the extremities and trunk. Most of them were asymptomatic, firm, dark red nodules arising on rapidly growing red or dark brown patches, or presenting as isolated nodules. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. All cases were confirmed by histopathology and immunohistochemistry. The most definitive treatment was extended local excision, but local recurrences were common. Of the 13 cases, 4 cases experienced local or distant metastasis. One suffered from an in-transit recurrence of MCC on the ipsilateral leg after local excision and lymph node dissection, whose metastasis completely subsided after avelumab treatment and without recurrence or metastasis during 6 months of follow-up. CONCLUSIONS: MCC overlapping BD is a very rare skin tumor mainly predisposed on the faces, with high misdiagnosis rate and recurrence rate. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. The acronym, AEIOUN, has been proposed to aid in clinical identification. Our reports and the literature review can provide a better awareness and management of it.

Identification of m6A-Related Biomarkers in Systemic Lupus Erythematosus: A Bioinformation-Based Analysis.

Background: Systemic Lupus Erythematosus (SLE), a prototypical autoimmune disorder, presents a challenge due to the absence of reliable biomarkers for discerning organ-specific damage within SLE. A growing body of evidence underscores the pivotal involvement of N6-methyladenosine (m6A) in the etiology of autoimmune conditions. Methods: The datasets, which primarily encompassed the expression profiles of m6A regulatory genes, were retrieved from the Gene Expression Omnibus (GEO) repository. The optimal model, selected from either Random Forest (RF) or Support Vector Machine (SVM), was employed for the development of a predictive nomogram model. To identify pivotal genes associated with SLE, a comprehensive screening process was conducted utilizing LASSO, SVM-RFE, and RF techniques. Within the realm of SLE susceptibility, Weighted Gene Co-expression Network Analysis (WGCNA) was harnessed to delineate relevant modules and hub genes. Additionally, MeRIP-qPCR assays were performed to elucidate key genes correlated with m6A targets. Furthermore, a Mendelian randomization study was conducted based on genome-wide association studies to assess the causative influence of MMP9 on ischemic stroke (IS), which is not only a severe cerebrovascular event but also a common complication of SLE. Results: Twelve m6A regulatory genes was identified, demonstrating statistical significance (p < 0.05) and utilized for constructing a nomogram model using the RF algorithm. EPSTI1, USP18, HP, and MMP9, as the hub genes, were identified. MMP9 uniquely correlates with m6A modification and was causally linked to an increased risk of IS, as indicated by our inverse variance weighting analysis showing an odds ratio of 1.0134 (95% CI=1.0004-1.0266, p = 0.0440). Conclusion: Our study identified twelve m6A regulators, shedding light on the molecular mechanisms underlying SLE risk genes. Importantly, our analysis established a causal relationship between MMP9, a key m6A-related gene, and ischemic stroke, a common complication of SLE, thereby providing critical insights for presymptomatic diagnostic approaches.

Ferroptosis in peripheral blood mononuclear cells of systemic lupus erythematosus.

OBJECTIVES: To investigate the evidence of ferroptosis in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: PBMCs were collected from 30 patients diagnosed as SLE and without any standardised treatment previously and 10 healthy controls. Meanwhile the clinical and laboratory data were collected. The intracellular Fe2+, reactive oxygen species (ROS) and lipid peroxidation (LPO) were detected by fluorescence probe and flow cytometry. The morphology of cells and intracellular organelles were observed by transmission electron microscopy. RT-qPCR and Western blot were applied to compare the expression of GPX4 in PBMCs. RESULTS: The concentration of Fe2+, levels of ROS and LPO in PBMCs from SLE patients were significantly higher than those in healthy controls (p<0.05), and significant differences between the two groups were observed in CD14+ monocytes, CD19+B cells, and CD56+ NK cells respectively. The more prominent differences were observed in SLE patients with renal involvement, liver injury and higher disease activity score. There was no significant difference in GPX4 mRNA expression between SLE patients and healthy controls, however GPX4 protein expression was significantly lower in SLE patients compared to healthy controls, with a negative correlation with the SLE disease activity index. Transmission electron microscopy revealed typical morphological features of ferroptosis such as decreased mitochondrial volume, increased mitochondrial membrane density, and disappearance of mitochondrial cristas. CONCLUSIONS: Ferroptosis occurred more frequently in PBMCs of SLE patients than healthy controls, including CD14+ monocytes, CD19+B cells, CD56+ NK cells, and so on, with negative association with SLE disease activity, which indicated the correlation between ferroptosis with the pathogenesis of SLE.

Photodynamic therapy for male genital lichen sclerosus with urethral stricture-Case report.

Male genital lichen sclerosus (MGLSc) typically impacts the external genitalia, resulting in balanitis, erectile pain, urination symptoms, and/or urinary retention. Urethral stricture develops in up to 20 % of these patients, which is usually found in the distal part of the urethra but can, in severe instances, impact the entire urethra and cause structural changes. Patients with skin lesions limited to the foreskin and partially extending to the glans can typically be cured by circumcision, but the recurrence rate of stricture is high when the glans or urethra is extensively involved. In the following case report, we describe a 45-year-old man with a history of MGLSc for 3 years and urethral stricture for 2 years, and these conditions remained untreated after circumcision. We emphasize that treatment with 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) may further improve outcomes in such severe cases.

A New Assessment Method of Vitiligo by Combination of Dermoscopy and Reflectance Confocal Microscopy.

Purpose: The aim is to investigate the application value of dermoscopy combined with reflectance confocal microscopy (RCM) in assessing vitiligo disease activity and treatment response. Patients and Methods: We enrolled 279 patients with vitiligo and evaluated the disease activity by Vitiligo Disease Activity (VIDA) score, dermoscopy, RCM and dermoscopy combined with RCM respectively. The sensitivity and specificity of different assessment techniques were compared with VIDA score by the differences and consistency. The different characteristics of dermoscopy and RCM with different treatment responses were also analyzed. Results: The results showed that the sensitivity and specificity of dermoscopy combined RCM were higher than RCM or dermoscopy alone (P values less than 0.05). In the repigmentation process, leukotrichia, pigment network absent and perilesional hyperpigmentation under dermoscopy at the baseline suggested a poor treatment response, while the incompletely disappearing pigment rings under RCM and perifollicular hyperpigmentation under dermoscopy indicated a good treatment response. We also found the proportion of patients with telangiectasia, increased pigment at the lesions and around the hair follicles was significantly higher in the good treatment response group than that in the poor one by dermoscopy (χ2 = 4.423, 32.471, 4.348, P = 0.035 0.000, 0.037) and by RCM the proportion of patients with both increased pigment granules and dendritic melanocytes in the good treatment response group was higher than that in the poor one (χ2 = 38.215, 5.283, P = 0.000, 0.022, respectively). Conclusion: With the higher sensitivity and specificity than dermoscopy or RCM alone, a combination of dermoscopy and RCM may be a new more accurate measure to assess the vitiligo disease activity and the treatment response.

CircPTPN22 modulates T-cell activation by sponging miR-4689 to regulate S1PR1 expression in patients with systemic lupus erythematosus.

BACKGROUND: Circular RNAs are involved in autoimmune disease pathogenesis. Our previous study indicated that circPTPN22 is involved in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, but the underlying mechanisms remain unclear. METHODS: First, the expression of circPTPN22 was detected by real-time PCR and western blotting. After overexpression or knockdown of circPTPN22, the proliferation of Jurkat cells was detected by the CCK-8 assay, and the apoptosis of Jurkat cells was detected by flow cytometry. In addition, the relationship between circPTPN22-miR-4689-S1PR1 was confirmed by bioinformatic analyses, fluorescence in situ hybridization assays, RNA-binding protein immunoprecipitation, and dual luciferase reporter assays. RESULTS: We found that circPTPN22 expression was downregulated in the PBMCs of SLE patients compared to those of healthy controls. Overexpression of circPTPN22 increased proliferation and inhibited apoptosis of Jurkat T cells, whereas knockdown of circPTPN22 exerted the opposite effects. CircPTPN22 acts as a miR-4689 sponge, and S1PR1 is a direct target of miR-4689. Importantly, the circPTPN22/miR-4689/S1PR1 axis inhibited the secretion of TNF-α and IL-6 in Jurkat T cells. CONCLUSIONS: CircPTPN22 acts as a miR-4689 sponge to regulate T-cell activation by targeting S1PR1, providing a novel mechanism for the pathogenesis of SLE.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Recurrent Skin and Soft Tissue Infections Caused by Ureaplasma urealyticum in an Immunocompromised Adult Patient: A Case Report.

Ureaplasma urealyticum (U. urealyticum) is a normal commensal that colonizes the human genital tract and usually of low virulence; however, it can trigger serious extragenital infections in immunocompromised patient. In this case, a 48-year-old female immunocompromised patient with a four-year history of recurrent ulcer on extremities was presented to our hospital due to aggravation of lesions 10 months before. She was initially diagnosed as Pseudomonas aeruginosa infection secondary to lupus panniculitis and slightly responded to ceftazidime treatment; however, a new rash appeared on her left hip 16 days after admission, which was aggravated even under antibiotic treatment. After multiple negative cultures, U. urealyticum was identified in her left hip tissue using metagenomic next-generation sequencing (mNGS). U. urealyticum was also confirmed in her secretion samples from left hip, left thigh, right calf and uterine neck using mycoplasma culture and quantitative real-time polymerase chain reaction. Her lesions, especially the new rash, were positively responded to sensitive antibiotic treatment. To the best of our knowledge, this is the first case of U. urealyticum induced recurrent skin and soft-tissue infections (SSTIs) in an immunocompromised adult patient. This case suggests that the prevalence of this kind of infections may be underestimated because of the limitation of routine culture. mNGS may be considered to look for atypical pathogens to improve the antimicrobial treatment of complicated infections.

miR-31-5p Regulates Type I Interferon by Targeting SLC15A4 in Plasmacytoid Dendritic Cells of Systemic Lupus Erythematosus.

Background: Plasmacytoid dendritic cells (pDCs) are the main producers of type I interferon (IFN-I), and the excessive production of IFN-I is a hallmark of systemic lupus erythematosus (SLE). Both SLC15A4 and miR-31-5p are SLE susceptibility-related genes, and SLC15A4 has been implicated an important role in endolysosomal toll-like receptor (TLR) activation in pDCs. However, whether miR-31-5p exerts a regulating effect on SLC15A4 expression in pDCs is unclear. Methods: The expression of SLC15A4 and miR-31-5p in peripheral blood mononuclear cells (PBMCs) of SLE patients was measured by RT-qPCR analyses. The quantitative analysis of IFN-α secretion in the patients' serum was performed by ELISA assay. Luciferase-reporter assay was applied to confirm the interaction between miR-31-5p and SLC15A4. The expression of miR-31-5p, SLC15A4 and IFN-stimulated genes (ISGs, such as MX1, OAS1 and IFIT3) was detected by Western blot and RT-qPCR assays and further IRF5 phosphorylation was evaluated by immunofluorescence after transfected with miR-31-5p mimics or inhibitor in THP-1 and CAL-1 cells. Results: The expression of miR-31-5p was downregulated and negatively correlated with the overexpression of SLC15A4 in PBMCs of SLE patients. In addition to this, the secretion of IFN-α was overexpressed in sera of SLE and positively correlated with SLC15A4 level. We found that miR-31-5p directly targeted SLC15A4 and negatively regulated the expression of SLC15A4 in THP-1 and CAL-1 cells. In vitro inhibition of miR-31-5p increased the phosphorylation of IRF5 and the induction of ISGs stimulated by R848, overexpression of miR-31-5p get the reverse results. Conclusion: miR-31-5p might involve in SLE pathogenesis through regulating IFN-I expression by negatively regulating SLC15A4 to increase the levels of IFN-α and ISGs in pDCs.

Fatal Balamuthia mandrillaris infection with red plaques on the nasal dorsum as the first presentation

Abstract Balamuthia mandrillaris infection is a rare infectious disease around the world, with high rates of morbidity and mortality. Its early and correct diagnosis is a big challenge for us, and without it the delay in starting effective treatment can lead to the development of encephalitis. This is a report of a case of Balamuthia mandrillaris infection in a Chinese boy, with red plaques on the nasal dorsum as the first presentation, who finally developed into fatal encephalitis. The authors have reviewed the related literature and share the special skin features in order to favor the early diagnosis of the disease and increase the chances of survival.

Fatal Balamuthia mandrillaris infection with red plaques on the nasal dorsum as the first presentation.

Balamuthia mandrillaris infection is a rare infectious disease around the world, with high rates of morbidity and mortality. Its early and correct diagnosis is a big challenge for us, and without it the delay in starting effective treatment can lead to the development of encephalitis. This is a report of a case of Balamuthia mandrillaris infection in a Chinese boy, with red plaques on the nasal dorsum as the first presentation, who finally developed into fatal encephalitis. The authors have reviewed the related literature and share the special skin features in order to favor the early diagnosis of the disease and increase the chances of survival.

Metformin Increases Sensitivity of Melanoma Cells to Cisplatin by Blocking Exosomal-Mediated miR-34a Secretion.

Melanoma, also known as malignant melanoma, is a type of cancer derived from the pigment-containing cells known as melanocytes. Cisplatin (CDDP) is widely used in the treatment of different types of tumors with high response rates, but it generally has low efficiency in melanoma. This study aimed to investigate whether metformin could sensitize the melanoma cell line A375 to cisplatin. Our results for the first time indicated that CDDP increased the miR-34a secretion by exosomes in melanoma A375 cells, which was, at least partially, related to the cisplatin resistance of melanoma cells. Moreover, metformin significantly sensitized A375 cells to cisplatin. Mechanistically, metformin significantly blocked the exosome-mediated miR-34a secretion induced by cisplatin. Our study not only reveals a novel mechanism that exosomal secretion of miR-34a is involved in the cisplatin resistance of melanoma cells but also provides a promising therapeutic strategy by synergistic addition of metformin.

Secondary Syphilis in a 12-Year-Old Girl Misdiagnosed as Pityriasis lichenoides et varioliformis acuta: A Case Report.

Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Herein, we report a rare case of secondary syphilis with probable neurosyphilis that was misdiagnosed as pityriasis lichenoides et varioliformis acuta (PLEVA) in a 12-year-old human immunodeficiency virus (HIV) negative patient. A female patient presented to our hospital with a four-month history of relapsed systemic rash, accompanied by hair loss, arthralgia and fatigue. Based on physical examination and skin biopsy, she was initially diagnosed as PLEVA and treated both locally and systemically but failed to present a dermatologic improvement. The diagnosis of secondary syphilis with probable neurosyphilis was made based on serologic and cerebrospinal fluid tests. After neurosyphilis therapy, the clinical manifestations of the patient were significantly improved. Physicians should be alert for the possibility of syphilis when encountering cases with unusual clinical manifestations.

Tumor with slow-developing and recurring lumps of the external ear with skull base and lung metastasis: A case report.

The present case report describes a rare case of recurring lumps on the external ear in a 46-year-old Chinese male with a history of >10 years, who presented with large irregular red lumps on the right temple and with lung and skull base metastasis. The patient had a lesion in the right auricle and experienced recurrence following surgical resection. A thorough systemic evaluation revealed no other obvious abnormalities. The patient was diagnosed with adenoid cystic carcinoma (ACC), a slow-growing form of high-grade adenocarcinoma, and refused any further treatment at the present hospital (The First Affiliated Hospital of Army Medical University). At 2 years post-follow-up, the patient had become more frail but was in good spirits. The present study indicated that ACC is a low-grade and commonly slow-developing malignancy that primarily arises from a salivary gland, with recurring and metastatic characteristics.

Bacteremia in female Chinese patients with systemic lupus erythematosus: a case-control study.

INTRODUCTION: Bacteremia is a common complication in systemic lupus erythematosus (SLE) patients, causing high morbidity and mortality. We investigated characteristics, pathogens, and sites of infection using a cohort of 64 female adults from a single university hospital in China. METHODOLOGY: SLE patients who had at least one episode of bacteremia (n = 16) were compared with non-bacteremia SLE patients (n = 48) in a case-control fashion, matching for age at SLE diagnosis and time of admission. Demographic characteristics, clinical and laboratory data, and bacteriologic examinations were collected and reviewed. RESULTS: A series of parameters were found to be significantly different between controls and cases at bacteremia diagnosis, including an SLE disease activity index, multiple major organ involvement (> 2), active renal disease, leukocytes, neutrophils, 24-hour urine protein, erythrocyte sedimentation rate (ESR), aspartate aminotransferase (AST), creatinine, hemoglobin, lymphocyte, platelets, and albumin. Eighteen episodes of bacteremia were analyzed, with Escherichia coli and Staphylococcus aureus being the most frequent isolates. Additionally, Listeria monocytogenes, Rhodotorula mucilaginosa, and Salmonella choleraesuis, which were very rare in the general population, were isolated from the bloodstreams of the cases. Apart from bacteremia without focus, respiratory tract, gastrointestinal tract, urinary tract, skin, and soft tissue were the major origins of infection. CONCLUSIONS: The present study depicts the nature of a cohort of female Chinese SLE patients with bacteremia, revealing that bacteremia is a critical factor contributing to the aggravation of SLE. Our findings provide useful information regarding the control and prevention of bacteremia in female SLE patients in China.

Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases.

PURPOSE: The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. MATERIALS AND METHODS: The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan-Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software. RESULTS: In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. CONCLUSIONS: The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant.

Association Study Between SLC15A4 Polymorphisms and Haplotypes and Systemic Lupus Erythematosus in a Han Chinese Population.

OBJECTIVE: The gene SLC15A4 (solute carrier family 15 [oligopeptide transporter], member 4) has been reported as contributing to the pathogenesis of systemic lupus erythematosus (SLE). We performed a case-control replication study to investigate further the association between single-nucleotide polymorphisms (SNPs) in the SLC15A4 gene and systemic SLE in a Han Chinese population. METHODS: In Han Chinese SLE patients and healthy individuals (n = 355, 375, respectively), 18 SNPs in the SLC15A4 gene were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and TaqMan SNP genotyping assays. Analyses of allele frequencies and genotypes using codominant, dominant, and recessive models were conducted, as well as a linkage disequilibrium analysis. P values < 0.05 were considered significant. RESULTS: Allele frequencies of five of the analyzed SNPs were significantly associated with SLE. Under a codominant model the genotype frequencies of rs3765108 AG and rs7308691 AT were significantly higher in the SLE group than the control group (p = 0.019, 0.049, respectively). Under a dominant model the rs1385374 (TT+CT) SNP carried a higher risk of SLE than (CC) (p = 0.042). One SLC15A4 haplotype (TA), which consists of 2 SNPs (rs959989 and rs983492), was associated with SLE (p = 0.024). CONCLUSION: Our study determined that five SNPs (rs959989, rs1385374, rs983492, rs12298615, and rs10847697) are associated with SLE. Thus, SLC15A4 may be important in the pathogenesis of SLE in Han Chinese patients.