Vitamin D regulates immune function, cell proliferation, and differentiation, and may inhibit carcinogenesis. Both serum vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene have been linked to melanoma, but findings are inconsistent. This umbrella meta-analysis critically appraised existing evidence on vitamin D intake, serum concentration, and six VDR polymorphisms (FokI, BsmI, TaqI, ApaI, EcoRV, Cdx2) in relation to melanoma risk. PubMed, Scopus, and Web of Science were searched to November 2025 for meta-analyses examining vitamin D intake, serum concentration, or VDR polymorphisms and melanoma risk in adults. Eligible studies reported relative risks (RR) or odds ratios (OR) with 95
BackgroundThe immune microenvironment and oxidative stress of melanoma show significant heterogeneity, which affects tumor growth, invasion and treatment response. Single-cell and bulk RNA-seq data were used to explore the heterogeneity of the immune microenvironment and oxidative stress of melanoma.MethodsThe R package Seurat facilitated the analysis of the single-cell dataset, while Harmony, another R package, was employed for batch effect correction. Cell types were classified using Uniform Manifold Approximation and Projection (UMAP). The Secreted Signaling algorithm from CellChatDB.human was applied to elucidate cell-to-cell communication patterns within the single-cell data. Consensus clustering analysis for the skin cutaneous melanoma (SKCM) samples was executed with the R package ConsensusClusterPlus. To quantify immune infiltrating cells, we utilized CIBERSORT, ESTIMATE, and TIMERxCell algorithms provided by the R package Immuno-Oncology Biological Research (IOBR). Single nucleotide variant (SNV) analysis was conducted using Maftools, an R package specifically designed for this purpose. Subsequently, the expression levels of PXDN and PAPSS2 genes were assessed in melanoma tissues compared to adjacent normal tissues. Furthermore, in vitro experiments were conducted to evaluate the proliferation and reactive oxygen species expression in melanoma cells following transfection with siRNA targeting PXDN and PAPSS2.ResultsMalignant tumor cell populations were reclassified based on a comprehensive single-cell dataset analysis, which yielded six distinct tumor subsets. The specific marker genes identified for these subgroups were then used to interrogate the Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) cohort, derived from bulk RNA sequencing data, resulting in the delineation of two immune molecular subtypes. Notably, patients within the cluster2 (C2) subtype exhibited a significantly more favorable prognosis compared to those in the cluster1 (C1) subtype. An alignment of immune characteristics was observed between the C2 subtype and unique immune functional tumor cell subsets. Genes differentially expressed across these subtypes were subsequently leveraged to construct a predictive risk model. In vitro investigations further revealed elevated expression levels of PXDN and PAPSS2 in melanoma tissue samples. Functional assays indicated that modulation of PXDN and PAPSS2 expression could influence the production of reactive oxygen species (ROS) and the proliferative capacity of melanoma cells.ConclusionThe constructed six-gene signature can be used as an immune response and an oxidative stress marker to guide the clinical diagnosis and treatment of melanoma.
Purpose: To assess diagnostic performance and reproducibility of reduced bowel wall enhancement evaluated by quantitative methods using CT to identify bowel necrosis among closed -loop small bowel obstruction (CL-SBO) patients. Methods: This retrospective single -center study included patients who diagnosed with CL-SBO caused by adhesion or internal hernia during January 2016 and May 2022. Patients were divided into necrotic group (n = 41) and non -necrotic group (n = 67) according to surgical exploration and postoperative pathology. Two doctors independently measured the attenuation of bowel wall and consensus was reached through panel discussion with a third gastrointestinal radiologist. Reduced bowel wall enhancement was assessed by four quantitative methods. Univariate analyses were used to evaluate the association between each method and bowel necrosis, and kappa/ intraclass correlation coefficient values were used to assess interobserver agreement. Diagnostic performance parameters were calculated for each method. Results: Reduced bowel wall enhancement in arterial phase (OR 8.98, P < 0.0001), reduced bowel wall enhancement in portal phase (OR 16.84, P < 0.001), adjusted reduced bowel wall enhancement in arterial phase (OR 29.48, P < 0.001), adjusted reduced bowel wall enhancement in portal phase (OR 145.69, P < 0.001) were significantly associated with bowel necrosis. Adjusted reduced bowel wall enhancement in portal phase had the best diagnostic performance (AUC: 0.92; Youden index: 0.84; specificity: 94.03 %) and interobserver agreement (kappa value of 0.59-0.73) to predict bowel necrosis. Conclusion: When assessing reduced bowel enhancement to predict bowel necrosis among CL-SBO patients, using unenhanced CT images and proximal dilated loop as standard references in portal phase is the most accurate quantitative method among those tested.
Background: Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose: To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed -loop small bowel obstruction (CL-SBO). Materials and Methods: This retrospective single -center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen kappa was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results: This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (kappa = 0.84 and 0.59, respectively). Conclusion: Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. (c) RSNA, 2024
Cutaneous endometriosis, characterized by the presence of endometrium or endometrial-like tissue outside of the uterine cavity, is an uncommon and chronic disease. Depending on a patient's history, cutaneous endometriosis is classified as either primary cutaneous endometriosis (PCE) or secondary cutaneous endometriosis (SCE). We report a case of SCE presenting with the classic triad of previous caesarean section, subcutaneous nodules at the site of the scar, and pain associated with menstruation. Considering histopathology as the standard, we confirmed a diagnosis of cutaneous endometriosis by ultrasound and histopathology. Furthermore, we compared and analyzed the clinical characteristics of PCE and SCE, the study included 20 and 14 patients with cutaneous endometriosis diagnosed with PCE and SCE respectively. In the PCE group, the mean age of patients at the onset was 33.7 years, while it was 40.6 years in the SCE group. The mean disease-duration time of PCE was shorter than that of SCE (1.3 vs. 2.8 years, P > 0.05). The most common clinical presentation of PCE and SCE was a nodule (90% vs. 86%). The PCE was mainly bleeding with pain (45%), whereas the SCE of only pain and bleeding with pain accounted for the same proportion (45%). The most common sites of PCE and SCE were in the umbilical region (90% vs. 57%, P < 0.05). In our study, some statistically significant difference was found between different types of CE and it may contribute to improve clinicians' understanding of the disease, and perform early diagnosis and treatment.
AbstractOptogenetic systems and tetracycline‐induced expression systems have been used in biological research. In gene circuits, light and tetracycline are often used to control the activation or inhibition of gene expression. In our study, we used a blue light induction system and tetracycline induction system to construct an “OR” logic gate, which can specifically induce the expression of p53 protein or E‐cadherin in the case of blue light or tetracycline, thus inhibiting the growth of cutaneous squamous cell carcinoma cells. Cutaneous squamous cell carcinoma is a kind of skin surface tumour. The activation of two tumour suppressor genes has a synergistic inhibitory effect on cutaneous squamous cell carcinoma, and blue light and tetracycline also provide a flexible means for gene regulation.
Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database. We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed. A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (chi(2)) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all). The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.
The aim of this study was to investigate the role of tumor-associated neutrophils (TANs) in the metastasis of pancreatic ductal adenocarcinoma (PDAC), to explore the regulation of TANs, and to determine the mechanisms governing the metastasis of PDAC. The correlation between neutrophils and the patient's clinical pathological data was first evaluated. Then, the effects of neutrophils on the invasion of PDAC were analyzed using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and PDAC cell lines (Panc-1, MiaPaCa-2 and AsPC-1). The cytokines secreted by neutrophils were detected through ELISA. TAN density was significantly correlated with poor metastasis-free survival (P< .05). Through coculture, it was found that the effect of neutrophils on pancreatic cancer cells was dependent on concentration, and a high concentration of neutrophils showed a lethal effect, while a low concentration of neutrophils primarily promoted the migration ability of cancer cells. The results of the wound-healing assay, the Transwell invasion assay, and laser confocal microscopy confirmed the promoting effect and indicated that the effect of neutrophils toward cancer cells may function indirectly by releasing a series of cytokines. The results of ELISA show that this effect may be achieved through the secretion of a large amount of TNF-alpha and TGF-beta 1 by neutrophils. Our study indicated that neutrophils may increase the metastasis of PDAC by releasing a series of cell cytokines, such as TNF-alpha and TGF-beta 1.
Background: To summarize the characteristics of cystic pancreatic adenocarcinoma, and to improve the general understanding of the imaging and pathologic features, and other pancreatic cystic diseases are compared for differential diagnosis.
AbstractDuring our research on circulating tumor cells (CTCs) derived from tumor-adjacent vessels in pancreatic ductal adenocarcinoma (PDAC), we found that CTCs are sometimes surrounded by white blood cells (WBCs) in blood. We hypothesize that such interaction between WBCs and CTCs in blood is a mechanism by which WBCs assist in the metastasis of CTCs. We present our laboratory finding, with our evaluation of the association between the neutrophil-to-lymphocyte ratio (NLR, the most investigated clinical parameter of WBCs) and distant metastasis after curative surgery in PDAC. The laboratory finding was presented through immunofluorescence. In the clinical segment, we performed a retrospective study on PDAC patients with distant metastasis after curative surgery who were referred to Peking University Third Hospital between 2005 and 2014. The data on the possible clinical factors were collected by a retrospective review of the patients’ records. Immunofluorescence results showed that CTCs are surrounded by WBCs in tumor-adjacent vessels of PDAC patients. In the clinical segment, 112 (70%) of a total of 160 PDAC patients were found to have developed distant metastases after surgery; among the 112 patients, only 89 had entire data and were enrolled for further analysis (84.3% patients had liver metastasis). No significant association was found between the NLR and overall survival (hazard ratio [HR] = 1.027, 95% confidence interval [CI] 0.723–1.459, P = 0.88); however, a significant relationship between the NLR and distant metastasis after curative surgery was found on the univariate (HR = 1.641, 95% CI 1.058–2.545, P = 0.027) and multivariate analyses (HR = 2.15, 95% CI 1.279–3.615, P = 0.004). Neutrophils might assist in distant metastasis through interaction with CTCs in blood. Moreover, NLR is an effective predictor for distant metastasis after curative surgery for PDAC.
BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation.METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group). The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared.RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P<0.05). There was no significant difference in the time of HBV recurrence, patient survival rate and survival time between lamivudine-treated and combination therapy groups (P>0.05).CONCLUSION: Compared with lamivudine monotherapy, combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation. (Hepatobiliary Pancreat Dis Int 2013;12:149-153)
OBJECTIVE:To investigate the value of liver transplantation for late hepatocellular carcinoma.METHODS:Thirty-six patients were treated by liver transplantation from August 2000 to February 2002, of which 15 patients had had advanced hepatocellular carcinoma and thirteen of these 15 patients were evaluated for results.RESULTS:The 1-year survival rate was 86% (6/7). Only one patient died of recurrence within 6 months. The tumor-free survival was 5 to 19 months. Till February 2002, two patients have survived for 10 months and 19 months with recurrence.CONCLUSION:In our country, if the patients can afford liver transplantation, advanced hepatocellular carcinoma without extrahepatic metastasis is still indicated for liver transplantation, since some patients may survive relatively long.