Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ul...Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.展开更多
Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2...Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2024).BCC and cSCC have been identified as two major components of NMSC,comprising one-third of all malignancies(Burton et al.,2016).Generally speaking,patients with NMSC tend to have relatively favorable survival outcomes,while different histopathological subtypes of NMSC exhibit distinct biological behaviors(Stătescu et al.,2023).展开更多
Background:Terpinen-4-ol(T4O),a key constituent of tea tree essential oil and various aromatic plants,has shown promising antiproliferative and pro-apoptotic effects in melanoma and other cancer types.However,its effi...Background:Terpinen-4-ol(T4O),a key constituent of tea tree essential oil and various aromatic plants,has shown promising antiproliferative and pro-apoptotic effects in melanoma and other cancer types.However,its efficacy against cutaneous squamous cell carcinoma(cSCC)remains unclear.Thus,in this study,we investigated the in vivo and in vitro effects of T4O on cSCC cell lines and preliminarily explored its impacting pathways.Methods:Using CCK8 and assay colony formation,we assessed the viability of cSCC A431,SCL-1,and COLO-16 cells treated with T40 at varying concentrations(0,1,2,and 4μM).Flow cytometry was employed to evaluate T4O’s effect on cSCC cell’s cycle progression and apoptosis induction.Additionally,western blotting was utilized to examine the expression intensities of N-cadherin and E-cadherin,two indicative markers of the epithelial-mesenchymal transition(EMT)pathway.T4O’s in vivo effect on inhibiting tumor progression was evaluated on an established xenograft tumor model.Then,the molecular mechanisms of T4O’s antitumor effect were explored by an integrated genome-wide transcriptomics and proteomics study on cSCC A431c cells.Finally,calpain-2’s potential mediator role in T4O’s anti-tumor mechanism was investigated in calpain-2 knockdown cell lines prepared via siRNA transfection.Result:It’s demonstrated that T4O treatment inhibited cSCC proliferation,clonogenicity,migration,and invasion while inducing apoptosis and suppressing the EMT pathway.T4O administration also inhibited cSCC tumorigenesis in the xenograft tumor model.RNA-sequencing and iTRAQ analysis detected significant upregulation of calpain-2 expression in T4O-treated cSCC cells.Western blotting confirmed that T4O significantly increased calpain-2 expression and promoted proteolytic cleavage ofβ-catenin and caspase-12,two calpain-2 target proteins.Importantly,siRNA-mediated calpain-2 knockdown relieved T4O’s suppressive effect on cSCC cell proliferation and motility.Mechanistically,T4O upregulates calpain-2 expression and promotes the cleavage ofβ-catenin and caspase-12,with siRNA-mediated calpain-2 knockdown mitigating T4O’s suppressive effects.Conclusion:These findings suggest that T4O’s antitumor activity in cSCC is mediated through the upregulation of calpain-2 expression and subsequent modulation ofβ-catenin and caspase-12.展开更多
Rationale:Central nervous system(CNS)actinomycosis is rare,spreading hematogenously from distant infections.Cutaneous actinomycosis with skull/meninges spread is especially unusual.Patient concerns:A 57-year-old man p...Rationale:Central nervous system(CNS)actinomycosis is rare,spreading hematogenously from distant infections.Cutaneous actinomycosis with skull/meninges spread is especially unusual.Patient concerns:A 57-year-old man presented with complaints of discharge from the back of his scalp for six months,an ataxic gait,and bilateral upper and lower limb weakness and numbness over the past 4-5 months.Diagnosis:CNS actinomycosis.Interventions:Intravenous injection of ceftriaxone followed by oral amoxicillin-clavulanic acid therapy.Outcomes:The patient was able to walk without support,with complete resolution of sinus discharge.Lessons:In patients presenting with discharging sinuses especially when accompanied by CNS symptoms,actinomycosis should be considered as a differential,along with tuberculosis,non-tubercular mycobacterial infection,and aspergillosis.Microbiological confirmation should be attempted wherever possible,for accurate diagnosis and treatment,as clinic-radiological picture alone may not differentiate these infections,as treatment of each is diametrically opposite and patients can be cured with timely and appropriate treatment.展开更多
Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was de...Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was designed,in which data related to sociodemographic information,history of leishmaniasis,clinical characteristics,treatment,therapeutic response and adverse events were collected from the review of the clinical records.Results:The analysis was conducted in 156 pediatric patients with median age of 10.5(6-14)years.Regarding clinical and therapeutic characteristics,the lesions in these patients were mostly single ulcers,primarily located on the upper and lower extremities.A total of 114 patients were managed at Programa de Estudio y Control de Enfermedades Tropicales(PECET),and 26 of them received more than one treatment.Upon administration of the first therapeutic option,intralesional meglumine antimoniate had a cure rate of 43.18%(19/44 patients),followed by systemic meglumine antimoniate with a cure rate of 40%(8/20)and topical investigational medication with a cure rate of 25%(5/20).The most frequent adverse events were:arthralgia and myalgia for systemic meglumine antimoniate;nausea and vomiting for miltefosine;and local pain,edema,erythema and rash for topical treatment.Conclusions:Although more prospective studies are needed to generate evidence-based recommendations and management protocols,miltefosine appears to be a favorable,safe and well-tolerated therapeutic option for the pediatric population.Despite the high percentage of loss to follow-up,the success achieved in pediatric patients with local treatments suggests that local therapies could also be considered for managing this condition in this population.展开更多
Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous ma...Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.展开更多
Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis...Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.展开更多
Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective to...Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective tool with high sensitivity for tumor diagnosis;however,existing probes for cSCC are limited in achieving rapid and specific imaging.In this study,we introduce FC-1,a dualtandem activatable fluorescent probe designed for precise cSCC diagnosis by simultaneously targeting fibroblast activation proteinαand cathepsin C(CTSC).This dual-locked activation strategy effectively reduces nonspecific signals in normal tissues while enhancing diagnostic specificity.In vivo studies in SCC-7 xenografted mice demonstrated FC-1's ability to visualize subcutaneous tumors with high sensitivity and specificity.Moreover,FC-1 enabled clear differentiation between cSCC and keloids.The probe's dual-activation mechanism and robust performance underscore its potential as a clinically translatable tool for early cSCC detection and differential diagnosis.展开更多
Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Noc...Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Nocardia brasiliensis skin infection in a 93-year-old patient with chronic renal insufficiency.This editorial explores the importance of timely diagnosis,microbiological confirmation,and tailored antibiotic therapy.Emphasis is placed on the role of immune status evaluation,drug concentration monitoring,and the necessity of long-term antimicrobial therapy.Improved clinician awareness and adherence to evidencebased management protocols are essential to achieving better outcomes in nocardiosis cases.展开更多
BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI...BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI),particularly when combined with diffusion-weighted imaging(DWI),has emerged as promising tool for comprehensive,radiation-free assessment of metastatic spread.AIM To systematically review the diagnostic performance and clinical utility of WBMRI in the staging and restaging of cutaneous melanoma,with comparison to conventional imaging modalities such as computed tomography(CT)and positron emission tomography/CT(PET/CT).METHODS A systematic literature review was conducted using PubMed,Embase,Scopus and Web of Science databases for studies published in the last 10 years.Inclusion criteria focused on comparative diagnostic accuracy studies of WB-MRI vs CT and PET/CT for melanoma staging.The methodological quality of the studies was appraised using the QUADAS-2 tool.RESULTS Sixteen studies involving over 700 patients met the inclusion criteria.WB-MRI showed high sensitivity(73%-90%)and specificity(up to 98%)in detecting metastases,particularly in bone,liver and soft tissue.DWI enhanced lesion detection,and WB-MRI often influenced clinical management decisions.However,CT outperformed WB-MRI in identifying small pulmonary nodules.AI-assisted analysis and contrastenhanced sequences further improved diagnostic confidence.CONCLUSION WB-MRI represents a robust imaging modality for staging cutaneous melanoma,offering superior soft-tissue contrast and functional imaging without ionizing radiation.Its strengths lie in detecting bone,liver and brain metastases.Challenges include limited lung lesion detection,cost,and availability.Advances in artificial intelligence,Hybrid PET/MRY systems,and radiomics are poised to expand WB-MRI’s role in personalized melanoma management.展开更多
Objective To observe the clinical effects of centro-square needling combined with ginger moxibustion on neuritis of lateral cutaneous nerve of thigh. Methods Centro-square needling combined with ginger moxibustion was...Objective To observe the clinical effects of centro-square needling combined with ginger moxibustion on neuritis of lateral cutaneous nerve of thigh. Methods Centro-square needling combined with ginger moxibustion was used in all the thirty-five cases. Ashi points, Xuèhǎi （血海 SP 10）, Zúsānlǐ （足三里 ST 36）, Yīnlíngquán （阴陵泉 SP 9） and Sānyīnjīao （三阴交 SP 6） on affected side were chosen. The treatment frequency was once a day, and a course was 2 weeks. The clinical effects were observed after 2 courses. Results 23 cases got cure, 7 cases were marked effective, 3 cases were effective and 2 were failed in all the 35 cases. The total effective rate was 94.3% （33/35）. Conclusion The centro-square needling combined with ginger moxibustion has obvious effect on neuritis of lateral cutaneous nerve of thigh.展开更多
Over-the-scope-clips (OTSC<sup>®</sup>) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for...Over-the-scope-clips (OTSC<sup>®</sup>) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC<sup>®</sup> treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC<sup>®</sup> closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC<sup>®</sup> closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC<sup>®</sup> closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC<sup>®</sup> was achieved in all patients with no immediate or long-term complications. OTSC<sup>®</sup> is a promising endoscopic treatment option for this condition with a potentially high immediate and long term success rate in patients with multiple comorbidities.展开更多
OBJECTIVE To report results of radiation therapy treatment of 30 B-cell lymphoma patients with an initial cutaneous presentation according to the new classification by the WHO/EORTC. METHODS Thirty patients with cutan...OBJECTIVE To report results of radiation therapy treatment of 30 B-cell lymphoma patients with an initial cutaneous presentation according to the new classification by the WHO/EORTC. METHODS Thirty patients with cutaneous B-cell lymphoma （CBCL） were treated by cutaneous irradiation based on the number and location of the lesions and the stage of their tumor. Treatment was conducted using a Satume Clinac. RESULTS A complete response （CR） from the treatment for our series was 86%. The length of complete remission ranged from 4 to 301 months. Three patients （11%） developed a partial response （PR）. One patient was progressive. Disease-free survival（DFS） at 10 years was 87%. Three patiens died [One PCMZL two PCLBCL leg type （29%）]. Radiotherapy was generally well tolerated. CONCLUSION According to the WHO/EORTC classification, the survivor results were good for PCMZL and PCFCL. The PCLBCL leg type had a poor prognosis. Localized field irradiation is an effective treatment for some localized forms of primary cutaneous B-cell lymphoma, and this mode of therapy can produce prolonged remissions.The patients with wide-spread skin involvement are usually candidates for extended field irradiation and/or chemotherapy. For advanced stages of cutaneous B-cell lymphoma, where chemotherapy is the treatment of choice, a degree of palliation can be achieved using local field irradation.展开更多
Leakage currents, tiny currents flowing from an everyday-life appliance through the body to the ground, can cause a non-adequate perception （called electrocutaneous sensation, ECS） or even pain and should be avoided...Leakage currents, tiny currents flowing from an everyday-life appliance through the body to the ground, can cause a non-adequate perception （called electrocutaneous sensation, ECS） or even pain and should be avoided. Safety standards for low-frequency range are based on experimental results of current thresholds of electrocutaneous sensations, which however show a wide range between about 50 pA （rms） and 1000 μA （rms）. In order to be able to explain these differences, the perception threshold was measured repeatedly in experiments with test persons under identical experimental setup, but by means of different methods （measuring strategies）, namely： direct adjustment, classical threshold as amperage of 50% perception probability, and confidence rating procedure of signal detection theory. The current is injected using a I cm2 electrode at the highly touch sensitive part of the index fingertip. These investigations show for the first time that the threshold of electrocutaneous sensations is influenced both by adaptation to the non-adequate stimulus and individual, emotional factors. Theretbre, classical methods, on which the majority of the safety investigations are based, cannot be used to determine a leakage current threshold. The confidence rating procedure of the modem signal detection theory yields a value of 179.5 μA （rms） at 50 Hz power supply net frequency as the lower end of the 95% confidence range considering the variance in the investigated group. This value is expected to be free of adaptation influences, and is distinctly lower than the European limits and supports the stricter regulations of Canada and USA.展开更多
Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cut...Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor(GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB(NF-κB), p38 mitogen-activated protein kinase(P38 MAPK) and activator protein-1(AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.展开更多
Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary...Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion(DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation(colitis, urocystitis, and acute gastritis) rat models.In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from doublelabeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.展开更多
Objective: To predict the trend of cutaneous leishmaniasis and assess the relationship between the disease trend and weather variables in south of Fars province using Seasonal Autoregressive Integrated Moving Average(...Objective: To predict the trend of cutaneous leishmaniasis and assess the relationship between the disease trend and weather variables in south of Fars province using Seasonal Autoregressive Integrated Moving Average(SARIMA) model,Methods: The trend of cutaneous leishmaniasis was predicted using Mini tab software and SARIMA model,Besides,information about the disease and weather conditions was collected monthly based on time series design during January 2010 to March 2016,Moreover,various SARIMA models were assessed and the best one was selected,Then,the model's fitness was evaluated based on normality of the residuals' distribution,correspondence between the fitted and real amounts,and calculation of Akaike Information Criteria(AIC) and Bayesian Information Criteria(BIC),Results: The study results indicated that SARIMA model(4,1,4)(0,1,0)(12) in general and SARIMA model(4,1,4)(0,1,1)(12) in below and above 15 years age groups could appropriately predict the disease trend in the study area,Moreover,temperature with a three-month delay(lag3) increased the disease trend,rainfall with a four-month delay(lag4) decreased the disease trend,and rainfall with a nine-month delay(lag9) increased the disease trend,Conclusions: Based on the results,leishmaniasis follows a descending trend in the study area in case drought condition continues,SARIMA models can suitably measure the disease trend,and the disease follows a seasonal trend.展开更多
Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by ...Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.展开更多
Objective: To examine the prevalence and clinical manifestations of cutaneous leishmaniasis(CL) in Iran.Methods: This study was conducted in Iran between 2011 and 2013. Sampling, preparing, developing, and fixing of s...Objective: To examine the prevalence and clinical manifestations of cutaneous leishmaniasis(CL) in Iran.Methods: This study was conducted in Iran between 2011 and 2013. Sampling, preparing, developing, and fixing of suspicious skin lesions were completed in healthcare centers in 31 Iranian provinces as well as in the Academic Reference Laboratory and the National Reference Laboratory. The information was then analyzed at the Ministry of Health's Information Management Center of Contagious Diseases.Results: Over a three-year period, the number of people identified with CL was 56 546.The highest incidence was reported in 2011(27.5 per 100 000). Wet CL accounted for 43.7% of cases while 43.3% resulted from sporotrichoid leishmaniasis. The results showed that there was a higher incidence of CL due to Leishmania major(50.2%) than to Leishmania tropica. The results of this study found that the highest incidence of CL had happened respectively in Ilam, Fars and, Khorasan Razavi Provinces between 2011 and 2013.Conclusions: Although the incidence of the disease is declining, CL is still a public health concern and disease control protocols need to be established. Therefore, further studies are needed to identify the vectors, reservoirs, and disease species as well as to develop appropriate disease control strategies.展开更多
Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated ...Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.展开更多
基金supported by the Natural Science Foundation of Hebei Province(Grant number:C2025405060).
文摘Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.
基金supported by the National Natural Science Foundation of China(No.82003372)the Medical and Health Technology Project of Zhejiang Province(No.2024KY984),China.
文摘Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2024).BCC and cSCC have been identified as two major components of NMSC,comprising one-third of all malignancies(Burton et al.,2016).Generally speaking,patients with NMSC tend to have relatively favorable survival outcomes,while different histopathological subtypes of NMSC exhibit distinct biological behaviors(Stătescu et al.,2023).
基金supported by the Basic Research Program of the Guizhou Science Cooperation Foundation Project(Grant Number:ZK[2021]466)Guizhou Provincial Health Commission(Grant Number:gzwkj2022-062).
文摘Background:Terpinen-4-ol(T4O),a key constituent of tea tree essential oil and various aromatic plants,has shown promising antiproliferative and pro-apoptotic effects in melanoma and other cancer types.However,its efficacy against cutaneous squamous cell carcinoma(cSCC)remains unclear.Thus,in this study,we investigated the in vivo and in vitro effects of T4O on cSCC cell lines and preliminarily explored its impacting pathways.Methods:Using CCK8 and assay colony formation,we assessed the viability of cSCC A431,SCL-1,and COLO-16 cells treated with T40 at varying concentrations(0,1,2,and 4μM).Flow cytometry was employed to evaluate T4O’s effect on cSCC cell’s cycle progression and apoptosis induction.Additionally,western blotting was utilized to examine the expression intensities of N-cadherin and E-cadherin,two indicative markers of the epithelial-mesenchymal transition(EMT)pathway.T4O’s in vivo effect on inhibiting tumor progression was evaluated on an established xenograft tumor model.Then,the molecular mechanisms of T4O’s antitumor effect were explored by an integrated genome-wide transcriptomics and proteomics study on cSCC A431c cells.Finally,calpain-2’s potential mediator role in T4O’s anti-tumor mechanism was investigated in calpain-2 knockdown cell lines prepared via siRNA transfection.Result:It’s demonstrated that T4O treatment inhibited cSCC proliferation,clonogenicity,migration,and invasion while inducing apoptosis and suppressing the EMT pathway.T4O administration also inhibited cSCC tumorigenesis in the xenograft tumor model.RNA-sequencing and iTRAQ analysis detected significant upregulation of calpain-2 expression in T4O-treated cSCC cells.Western blotting confirmed that T4O significantly increased calpain-2 expression and promoted proteolytic cleavage ofβ-catenin and caspase-12,two calpain-2 target proteins.Importantly,siRNA-mediated calpain-2 knockdown relieved T4O’s suppressive effect on cSCC cell proliferation and motility.Mechanistically,T4O upregulates calpain-2 expression and promotes the cleavage ofβ-catenin and caspase-12,with siRNA-mediated calpain-2 knockdown mitigating T4O’s suppressive effects.Conclusion:These findings suggest that T4O’s antitumor activity in cSCC is mediated through the upregulation of calpain-2 expression and subsequent modulation ofβ-catenin and caspase-12.
文摘Rationale:Central nervous system(CNS)actinomycosis is rare,spreading hematogenously from distant infections.Cutaneous actinomycosis with skull/meninges spread is especially unusual.Patient concerns:A 57-year-old man presented with complaints of discharge from the back of his scalp for six months,an ataxic gait,and bilateral upper and lower limb weakness and numbness over the past 4-5 months.Diagnosis:CNS actinomycosis.Interventions:Intravenous injection of ceftriaxone followed by oral amoxicillin-clavulanic acid therapy.Outcomes:The patient was able to walk without support,with complete resolution of sinus discharge.Lessons:In patients presenting with discharging sinuses especially when accompanied by CNS symptoms,actinomycosis should be considered as a differential,along with tuberculosis,non-tubercular mycobacterial infection,and aspergillosis.Microbiological confirmation should be attempted wherever possible,for accurate diagnosis and treatment,as clinic-radiological picture alone may not differentiate these infections,as treatment of each is diametrically opposite and patients can be cured with timely and appropriate treatment.
文摘Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was designed,in which data related to sociodemographic information,history of leishmaniasis,clinical characteristics,treatment,therapeutic response and adverse events were collected from the review of the clinical records.Results:The analysis was conducted in 156 pediatric patients with median age of 10.5(6-14)years.Regarding clinical and therapeutic characteristics,the lesions in these patients were mostly single ulcers,primarily located on the upper and lower extremities.A total of 114 patients were managed at Programa de Estudio y Control de Enfermedades Tropicales(PECET),and 26 of them received more than one treatment.Upon administration of the first therapeutic option,intralesional meglumine antimoniate had a cure rate of 43.18%(19/44 patients),followed by systemic meglumine antimoniate with a cure rate of 40%(8/20)and topical investigational medication with a cure rate of 25%(5/20).The most frequent adverse events were:arthralgia and myalgia for systemic meglumine antimoniate;nausea and vomiting for miltefosine;and local pain,edema,erythema and rash for topical treatment.Conclusions:Although more prospective studies are needed to generate evidence-based recommendations and management protocols,miltefosine appears to be a favorable,safe and well-tolerated therapeutic option for the pediatric population.Despite the high percentage of loss to follow-up,the success achieved in pediatric patients with local treatments suggests that local therapies could also be considered for managing this condition in this population.
文摘Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.
基金supported by the National Key Research and Development Project(No.2023YFC3404400)。
文摘Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.
基金supported by the National Natural Science Foundation of China(No.22325401,22404049)Special Funds for the Construction of Innovative Provinces in Hunan Province(No.2021RC4021)the China Postdoctoral Science Foundation(No.2024 M750866).
文摘Cutaneous squamous cell carcinoma(cSCC),the second most common skin cancer,requires early and accurate detection to optimize clinical management.Fluorescence imaging has emerged as a non-invasive and cost-effective tool with high sensitivity for tumor diagnosis;however,existing probes for cSCC are limited in achieving rapid and specific imaging.In this study,we introduce FC-1,a dualtandem activatable fluorescent probe designed for precise cSCC diagnosis by simultaneously targeting fibroblast activation proteinαand cathepsin C(CTSC).This dual-locked activation strategy effectively reduces nonspecific signals in normal tissues while enhancing diagnostic specificity.In vivo studies in SCC-7 xenografted mice demonstrated FC-1's ability to visualize subcutaneous tumors with high sensitivity and specificity.Moreover,FC-1 enabled clear differentiation between cSCC and keloids.The probe's dual-activation mechanism and robust performance underscore its potential as a clinically translatable tool for early cSCC detection and differential diagnosis.
文摘Nocardiosis remains a rare and often underdiagnosed bacterial infection,particularly in immunocompromised individuals.The case report by Zhang et al highlights the diagnostic and therapeutic challenges in managing Nocardia brasiliensis skin infection in a 93-year-old patient with chronic renal insufficiency.This editorial explores the importance of timely diagnosis,microbiological confirmation,and tailored antibiotic therapy.Emphasis is placed on the role of immune status evaluation,drug concentration monitoring,and the necessity of long-term antimicrobial therapy.Improved clinician awareness and adherence to evidencebased management protocols are essential to achieving better outcomes in nocardiosis cases.
文摘BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI),particularly when combined with diffusion-weighted imaging(DWI),has emerged as promising tool for comprehensive,radiation-free assessment of metastatic spread.AIM To systematically review the diagnostic performance and clinical utility of WBMRI in the staging and restaging of cutaneous melanoma,with comparison to conventional imaging modalities such as computed tomography(CT)and positron emission tomography/CT(PET/CT).METHODS A systematic literature review was conducted using PubMed,Embase,Scopus and Web of Science databases for studies published in the last 10 years.Inclusion criteria focused on comparative diagnostic accuracy studies of WB-MRI vs CT and PET/CT for melanoma staging.The methodological quality of the studies was appraised using the QUADAS-2 tool.RESULTS Sixteen studies involving over 700 patients met the inclusion criteria.WB-MRI showed high sensitivity(73%-90%)and specificity(up to 98%)in detecting metastases,particularly in bone,liver and soft tissue.DWI enhanced lesion detection,and WB-MRI often influenced clinical management decisions.However,CT outperformed WB-MRI in identifying small pulmonary nodules.AI-assisted analysis and contrastenhanced sequences further improved diagnostic confidence.CONCLUSION WB-MRI represents a robust imaging modality for staging cutaneous melanoma,offering superior soft-tissue contrast and functional imaging without ionizing radiation.Its strengths lie in detecting bone,liver and brain metastases.Challenges include limited lung lesion detection,cost,and availability.Advances in artificial intelligence,Hybrid PET/MRY systems,and radiomics are poised to expand WB-MRI’s role in personalized melanoma management.
文摘Objective To observe the clinical effects of centro-square needling combined with ginger moxibustion on neuritis of lateral cutaneous nerve of thigh. Methods Centro-square needling combined with ginger moxibustion was used in all the thirty-five cases. Ashi points, Xuèhǎi （血海 SP 10）, Zúsānlǐ （足三里 ST 36）, Yīnlíngquán （阴陵泉 SP 9） and Sānyīnjīao （三阴交 SP 6） on affected side were chosen. The treatment frequency was once a day, and a course was 2 weeks. The clinical effects were observed after 2 courses. Results 23 cases got cure, 7 cases were marked effective, 3 cases were effective and 2 were failed in all the 35 cases. The total effective rate was 94.3% （33/35）. Conclusion The centro-square needling combined with ginger moxibustion has obvious effect on neuritis of lateral cutaneous nerve of thigh.
文摘Over-the-scope-clips (OTSC<sup>®</sup>) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC<sup>®</sup> treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC<sup>®</sup> closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC<sup>®</sup> closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC<sup>®</sup> closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC<sup>®</sup> was achieved in all patients with no immediate or long-term complications. OTSC<sup>®</sup> is a promising endoscopic treatment option for this condition with a potentially high immediate and long term success rate in patients with multiple comorbidities.
文摘OBJECTIVE To report results of radiation therapy treatment of 30 B-cell lymphoma patients with an initial cutaneous presentation according to the new classification by the WHO/EORTC. METHODS Thirty patients with cutaneous B-cell lymphoma （CBCL） were treated by cutaneous irradiation based on the number and location of the lesions and the stage of their tumor. Treatment was conducted using a Satume Clinac. RESULTS A complete response （CR） from the treatment for our series was 86%. The length of complete remission ranged from 4 to 301 months. Three patients （11%） developed a partial response （PR）. One patient was progressive. Disease-free survival（DFS） at 10 years was 87%. Three patiens died [One PCMZL two PCLBCL leg type （29%）]. Radiotherapy was generally well tolerated. CONCLUSION According to the WHO/EORTC classification, the survivor results were good for PCMZL and PCFCL. The PCLBCL leg type had a poor prognosis. Localized field irradiation is an effective treatment for some localized forms of primary cutaneous B-cell lymphoma, and this mode of therapy can produce prolonged remissions.The patients with wide-spread skin involvement are usually candidates for extended field irradiation and/or chemotherapy. For advanced stages of cutaneous B-cell lymphoma, where chemotherapy is the treatment of choice, a degree of palliation can be achieved using local field irradation.
文摘Leakage currents, tiny currents flowing from an everyday-life appliance through the body to the ground, can cause a non-adequate perception （called electrocutaneous sensation, ECS） or even pain and should be avoided. Safety standards for low-frequency range are based on experimental results of current thresholds of electrocutaneous sensations, which however show a wide range between about 50 pA （rms） and 1000 μA （rms）. In order to be able to explain these differences, the perception threshold was measured repeatedly in experiments with test persons under identical experimental setup, but by means of different methods （measuring strategies）, namely： direct adjustment, classical threshold as amperage of 50% perception probability, and confidence rating procedure of signal detection theory. The current is injected using a I cm2 electrode at the highly touch sensitive part of the index fingertip. These investigations show for the first time that the threshold of electrocutaneous sensations is influenced both by adaptation to the non-adequate stimulus and individual, emotional factors. Theretbre, classical methods, on which the majority of the safety investigations are based, cannot be used to determine a leakage current threshold. The confidence rating procedure of the modem signal detection theory yields a value of 179.5 μA （rms） at 50 Hz power supply net frequency as the lower end of the 95% confidence range considering the variance in the investigated group. This value is expected to be free of adaptation influences, and is distinctly lower than the European limits and supports the stricter regulations of Canada and USA.
基金supported by the National Natural Science Foundation of China(No.81602108)
文摘Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor(GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB(NF-κB), p38 mitogen-activated protein kinase(P38 MAPK) and activator protein-1(AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.
基金supported by Grants from the National Science Foundation of China(81771205,91632113,81973963,81674085,and 81674075)the National Key Research and Development Program of China(2018YFC1704600)+1 种基金the Natural Science Foundation and Major Basic Research Program of Shanghai(16JC1420500 and 16JC1420502)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-3-008)。
文摘Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion(DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation(colitis, urocystitis, and acute gastritis) rat models.In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from doublelabeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.
基金financially supported by Shiraz University of Medical Sciences(grant No.94-01-04-10456)
文摘Objective: To predict the trend of cutaneous leishmaniasis and assess the relationship between the disease trend and weather variables in south of Fars province using Seasonal Autoregressive Integrated Moving Average(SARIMA) model,Methods: The trend of cutaneous leishmaniasis was predicted using Mini tab software and SARIMA model,Besides,information about the disease and weather conditions was collected monthly based on time series design during January 2010 to March 2016,Moreover,various SARIMA models were assessed and the best one was selected,Then,the model's fitness was evaluated based on normality of the residuals' distribution,correspondence between the fitted and real amounts,and calculation of Akaike Information Criteria(AIC) and Bayesian Information Criteria(BIC),Results: The study results indicated that SARIMA model(4,1,4)(0,1,0)(12) in general and SARIMA model(4,1,4)(0,1,1)(12) in below and above 15 years age groups could appropriately predict the disease trend in the study area,Moreover,temperature with a three-month delay(lag3) increased the disease trend,rainfall with a four-month delay(lag4) decreased the disease trend,and rainfall with a nine-month delay(lag9) increased the disease trend,Conclusions: Based on the results,leishmaniasis follows a descending trend in the study area in case drought condition continues,SARIMA models can suitably measure the disease trend,and the disease follows a seasonal trend.
文摘Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.
文摘Objective: To examine the prevalence and clinical manifestations of cutaneous leishmaniasis(CL) in Iran.Methods: This study was conducted in Iran between 2011 and 2013. Sampling, preparing, developing, and fixing of suspicious skin lesions were completed in healthcare centers in 31 Iranian provinces as well as in the Academic Reference Laboratory and the National Reference Laboratory. The information was then analyzed at the Ministry of Health's Information Management Center of Contagious Diseases.Results: Over a three-year period, the number of people identified with CL was 56 546.The highest incidence was reported in 2011(27.5 per 100 000). Wet CL accounted for 43.7% of cases while 43.3% resulted from sporotrichoid leishmaniasis. The results showed that there was a higher incidence of CL due to Leishmania major(50.2%) than to Leishmania tropica. The results of this study found that the highest incidence of CL had happened respectively in Ilam, Fars and, Khorasan Razavi Provinces between 2011 and 2013.Conclusions: Although the incidence of the disease is declining, CL is still a public health concern and disease control protocols need to be established. Therefore, further studies are needed to identify the vectors, reservoirs, and disease species as well as to develop appropriate disease control strategies.
基金The study was financially supported by INSF(grant number 96006039).
文摘Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.
