BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients. METHODS:In this population-based cohort study, we investigated the clinical features of 5,023 patients newly diagnosed with DLBCL. Their clinical conditions, eligibility criteria, and sociodemographic details were recorded and analyzed. Gene panel sequencing was performed on 1,050 patients to discern molecular patterns according to ENI. RESULTS:The 2-year overall survival (OS) rate was 76.2% [95% confidence interval (CI), 74.0%-78.2%], and the 5-year OS rate was 67.9% (95% CI, 65.2%-70.4%). The primary treatment was immunochemotherapy with rituximab. Specific lymphoma involvement sites, especially the bones, bone marrow, and central nervous system, were identified as independent adverse prognostic factors. A high prevalence of non-germinal center B-cell (non-GCB) phenotype and myeloid differentiation primary response 88 (MYD88)/CD79B mutations were noted in lymphomas affecting the breasts, skin, uterus, and immune-privileged sites. Conversely, the thyroid and gastrointestinal tract showed a low occurrence of non-GCB phenotype. Remarkably, patients with multiple ENIs exhibited a high frequency of MYD88, tet methylcytosine dioxygenase 2 (TET2), CREB binding protein (CREBBP) mutations, increased MYD88L265P and CD79B mutation (MCD)-like subtypes, and poor prognosis. Genetic subtype-guided immunochemotherapy showed good efficacy in subgroup analyses after propensity score matching with 5-year OS and progression-free survival rates of 85.0% (95% CI, 80.6%-89.5%) and 72.1% (95% CI, 67.3%-76.7%). CONCLUSIONS:In the rituximab era, this large-scale retrospective analysis from Asia confirmed the poor prognosis of DLBCL with multiple ENIs and underscored the efficacy of genetic subtype-guided immunochemotherapy in treating extranodal DLBCL.

Objective Investigate miR-486-3p’s role in alleviating age-related angiogenic decline in Moyamoya disease (MMD) by regulating senescent endothelial cells. Methods Clinical analysis of 151 MMD patients correlated age with postoperative angiogenesis (DSA grading). Senescent HUVECs (SA-β-gal>80%) exhibited elevated SASP factors (IL-6/IL-8/MCP-1). Functional assays (EdU/Transwell/Matrigel) and bioinformatics identified miR-486-3p targets, validated via luciferase/Western blot. Results Patients ≥35 years had 3.67-fold higher risk of poor angiogenesis (OR=3.67). Senescent HUVECs showed 10-16-fold higher SASP secretion (p<0.01). miR-486-3p overexpression increased proliferation (EdU+25%), migration (1.7-fold), and tube formation (+40% branches) in senescent cells (p<0.01) and enhanced angiogenesis in vivo (p<0.001). miR-486-3p directly targeted FOXO4, reducing its luciferase activity (−35%) and protein levels (−37%) (p<0.01), suppressing SASP. Conclusion miR-486-3p enhances post-revascularization angiogenesis in MMD by inhibiting FOXO4-mediated SASP, offering a therapeutic target and predictive biomarker. ### Competing Interest Statement The authors have declared no competing interest.

Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer, causing a considerable number of deaths globally. Mitochondrial dysfunction was found to promote malignant progression. However, the underlying mechanism remains unclear. Acyl-CoA synthetase short chain family member 3 (ACSS3) is mainly located in mitochondria, which abnormal regulation is usually accompanied by the occurrence and development of tumors. In this study, we found that the expression level of ACSS3 was correlated with poor prognosis in patients with NSCLC. Moreover, we demonstrated that ACSS3 knockdown led to mitochondrial contraction, increased reactive oxygen species levels, decreased mitochondrial membrane potential, and subsequently inhibited tumor growth of NSCLC cells in vitro and in vivo, whereas its overexpression promoted these processes. Mechanistically, ACSS3 knockdown promoted ferroptosis through transcriptional control of SLC7A11 and GPX4. Further investigations indicated that ACSS3 loss inhibited the SLC7A11/GPX4 axis by enhancing p53 stability. Taken together, our data confirmed that ACSS3 promotes NSCLC tumorigenesis through inhibiting the p53-mediated ferroptosis. Hence, ACSS3 emerges as a promising therapeutic target for NSCLC treatment.

Objective The aim of this research was to investigate the specific regulatory role of miR-6760-5p in angiogenesis in moyamoya disease. Methods HUVECs were transfected with miR-6760-5p inhibitor and mimics fragments, then subjected to assays for cell proliferation, migration, and tube formation. Subsequently, downstream target genes of miR-6760-5p were predicted and the protein expression levels of these genes were evaluated. The presence of miR-6760-5p and YAP1 was verified by a dual luciferase reporter gene test, followed by an assessment of the effects of YAP1 and miR-6760-5p on the HUVECs. Results Comparatively to the control group, increased expression of miR-6760-5p decreased cell growth, movement, and tube formation. YAP1 gene was discovered as a target controlled by miR-6760-5p, with subsequent investigation confirming YAP1 as a gene regulated by miR-6760-5p. Additionally, miR-6760-5p was found to counteract the angiogenesis-promoting effect of YAP1. Conclusion The results of this research suggest a possible link between the miR-6760-5p gene found in the cerebrospinal fluid of individuals with moyamoya disease and the process of vascularization in this particular condition. The findings indicate that miR-6760-5p may be a new molecular indicator and potential target for the diagnosis of moyamoya disease.

患者女,16岁. 主诉:右侧小腿斑丘疹伴轻度瘙痒7年. 现病史:患者于7年前发现右侧股外侧、膝关节伸侧至小腿伸侧棕黄色丘疹,伴轻度瘙痒,丘疹逐渐呈环状扩大形成边缘轻度堤状环形角化斑块,并逐渐增多呈线状分布,为明确诊断,于2020年8月17日来武汉协和医院皮肤科门诊就诊. 既往史及家族史:既往体健.家族成员中无类似疾病患者,家族中无遗传病史.

As a kind of tumor commonly seen, no effective treatment is available for esophageal squamous cell carcinoma (ESCC). Therefore, seeking a new treatment is urgent. Demethylzeylasteral (T-96) isolated from Tripterygium wilfordii root bark embraces outstanding good antitumor activity. However, as for the mechanism of T-96 work on ESCC cells, it is rarely reported. In this study, we found that T-96 has inhibition when ESCC cells are proliferating, migrating and cloning. Moreover, relevant effects are influenced by dose and time. And T-96 can result in the stop of G2/M phase and induce apoptosis of ESCC cells. In addition, the expressions of Cyclin B1, Cyclin D1, Bcl-2, PARP1 and Survivin were decreased after starch demethylation. Despite of this, Bax and PARP1's expressions went up. To add up, there was an obvious increase in the expression of E-cadherin, while that of N-cadherin, Vimentin and MMP9 decreased after T-96 treatment. Moreover, the expression of Wnt/β-Catenin pathway, which concerns proteins β-Catenin, c-Myc and Wnt3a decreased. Our study shows that T-96 inhibits the proliferation and migration of esophageal cancer cells through Wnt/β-catenin pathway. Moreover, it gives rise to cell cycle arrest and apoptosis. According to the research results, T-96 tends to be put into use when treating ESCC patients, thus laying the experimental foundation for clinical research.

临床资料 患者,男,46 岁. 因"面颊、腰背部及四肢伸侧多发暗红丘疹结节1年余,伴瘙痒"来我科就诊.患者1年前发现面颊、腰背部及四肢伸侧暗红丘疹,伴痒感,外院曾以"湿疹、虫咬皮炎及结节性痒疹"等治疗,疗效欠佳,后皮损缓慢增多,搔抓后结痂,来我科就诊.患者长期居住于湖北省恩施市,无明确麻风接触史.否认肝炎、结核及麻风等传染病史.否认家族中有类似疾病史.

In the original publication of this manuscript [1], Fig. 6 contains a repeated image in error (the left image of 'Migration' and the left image of 'Invasion').

家族性慢性良性天疱疮(familial chronic benign pemphigus,FCBP),又称Hailey-Hailey病,是一种少见的常染色体显性遗传性疾病.其临床特征表现为边界清楚的红斑、结痂,伴烧灼感或瘙痒感.皱褶及易摩擦处是最常见的受累部位,颈部也经常累及.家族性慢性良性天疱疮临床上治疗困难、易误诊,本文就近年来该病的发病机制、临床表现及组织病理特点、诊断及鉴别诊断、治疗等方面做一综述.

Background Cutis laxa is a connective tissue disease characterized by loose, wrinkled, and redundant skin. It is either inherited or acquired. In most cases, acquired cutis laxa is associated with neoplasms, drugs, and autoimmune diseases. We present a rare case of acquired cutis laxa following a recurrent urticaria-like eruption in the absence of an autoimmune disease, neoplasm, drugs and or syndrome. Case presentation We report a case of a 45-year-old Chinese lady with a 1-year history of widespread pruritic urticarial eruption and a 6-month history of progressive skin wrinkling. On examination, the patient appeared older than her actual age, with apparent wrinkling on the mid-torso with generalized smooth, erythematous macules and wheals. A family history of similar conditions was absent. Biopsy revealed hypersensitivity and atrophy. Following the Food and Drug Administration (FDA) guidelines, we administered antihistamines, which relieved the itching, but her hyperpigmentation and cutis laxa never improved. Conclusion Our case shows that the decrease of elastic fibers may be associated with the infiltration of inflammatory cells in the dermis. This supports the hypothesis that chemical mediators may play a major role in the destruction of elastic fibers, thus causing cutis laxa. In addition, we advise practitioners to take a complete clinical and family history to determine if the condition is inherited or acquired.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in China. Nowadays, no quite effective treatment is available. Therefore, seeking a new treatment is urgent. Demethylzeylasteral(T-96) isolated from Tripterygium wilfordii root bark embraces outstanding good antitumor activity. However, as for the mechanism of Demethylzeylasteril’s work on ESCC cells, it is rarely reported. In this study, it is found out that Demethylzeylasterial can inhibit the proliferation, migration and clonogenesis of ESCC cells in a dose and time dependent manner. And Demethylzeylasteril can result in the stop of G2 / M phase and induce apoptosis of ESCC cells. Besides, when observing cells processed by Demethylzeylasteral, the expression of Cyclin B1, Cyclin D1, Bcl-2, PARP1 and Survivin decreased, while the expression of BAX,Cleaved PARP1 increased. In addition, the expression of E-cadherin increased obviously, while that of N-cadherin, Vimentin and MMP9 decreased after Demethylzeylasteril treatment. Moreover, the expression of Wnt / β-Catenin pathway related proteins β-Catenin, cMyc and Wnt3a decreased. Based on our research, it is demonstrated that Demethylzeylasteral inhibits the proliferation and migration of esophageal cancer cells through the Wnt / β-catenin pathway and induces its cell cycle arrest and apoptosis.And the result indicates that Demethylzeylasteril is likely to be applied when treating ESCC patients, which lays the experimental foundation for clinical research.

目的 探讨皮肤混合瘤临床、组织病理特点及鉴别诊断.方法 回顾性归纳分析华中科技大学同济医学院附属协和医院皮肤科1999—2017年17例皮肤混合瘤患者的临床病理资料.结果 17例患者中14例向顶泌汗腺分化,其中10例有明显的管泡状结构,9例有导管结构,4例见角质囊肿及毛乳头结构;17例患者均见黏液样、纤维化间质,间质中均见浆细胞样细胞、多角形细胞、梭形细胞,1例出现软骨样间质;初诊误诊15例,误诊率为88.24％.结论 皮肤混合瘤虽然组织病理学上具有特征性,但临床误诊率极高,应引起临床医生的重视.

Exosomal microRNAs (miRNAs) have been recently shown to play vital regulatory and communication roles in cancers. In this study, we showed that the expression levels of miR-652-5p in tumour tissues and serum samples of oesophageal squamous cell carcinoma (OSCC) patients were lower compared to non-tumorous tissues and serum samples from healthy subjects, respectively. Decreased expression of miR-652-5p was correlated with TNM stages, lymph node metastasis, and short overall survival (OS). More frequent CpG sites hypermethylation in the upstream of miR-652-5p was found in OSCC tissues compared to adjacent normal tissues. Subsequently, miR-652-5p downregulation promoted the proliferation and metastasis of OSCC, and regulated cell cycle both in cells and in vivo. The dual-luciferase reporter assay confirmed that poly (ADP-ribose) glycohydrolase (PARG) and vascular endothelial growth factor A (VEGFA) were the direct targets of miR-652-5p. Moreover, the delivery of miR-652-5p agomir suppressed tumour growth and metastasis, and inhibited the protein expressions of PARG and VEGFA in nude mice. Taken together, our findings provide novel insight into the molecular mechanism underlying OSCC pathogenesis.

报告1例席纹状胶原瘤.患者男,46岁.背部肿物40年余,缓慢增长,无自觉症状.无系统性疾病病史.皮损组织病理检查示表皮轻度萎缩,真皮内可见一边界清楚的结节,无包膜,病变均匀、局限,由大量透明样变的胶原束组成,胶原束之间见许多裂隙,排列成席纹状.诊断:席纹状胶原瘤.

Background: Lung adenocarcinoma (LUAD) is the most aggressive and most frequently seen histological variant of lung cancers, comprising nearly 45% of the overall cases of lung carcinoma and its incidence has been increased significantly worldwide in the last several decades. However, there was limited available evidence with respect to the signalling pathways and miRNAs related to the LUAD.Methods: To identify the differentially-expressed miRNAs (DE-miRNAs) in different stages of LUAD, we performed a microarray on 514 LUAD and 54 normal tissues. At the mean time, the potentially targeted genes as well as the highly-enriched signaling pathways and the relevant protein–protein interaction (PPI) network were analyzed and constructed by using a series of bioinformatic methods. Moreover, the identified DE-miRNAs in different stages of the LUAD were verified by using the TCGA dataset.Results : Overall 41 down-regulated -and 82 up-regulated DE-miRNAs were identified, of which 1,716 potential targeted genes were selected. Moreover, the enriched pathways of the above genes were screened by using the GO term and KEGG pathway analyses, including the AMPK signalling pathway, FoxO signalling pathway, MAPK signalling pathway, PI3K-Akt signalling pathway and hippo signalling pathway.Conclusions: Our study could provide additional understanding of the underlying molecular events and increase the precision of prognostic prediction.

Novel therapies tailored to the molecular composition mechanism of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. miR-20b-5p expression was significantly upregulated in cancerous tissues and associated with lymph node metastasis, clinical stage, and overall survival (OS). An analysis of the methylation status of the miR-20b-5p gene indicated that the hypomethylation of the CpG sites located upstream of the miR-20b-5p gene in the ESCC tissues was more frequent than in the adjacent normal tissues, and the methylation status of miR-20b-5p correlated inversely with its expression levels. Notably, a series of gain- and loss-of-function assays elucidated that miR-20b-5p promoted ESCC cell proliferation, migration, and invasion both in vitro and in vivo. Luciferase reporter assays, western blot, and qRT-PCR revealed that RB1 and TP53INP1 were the direct targets of miR-20b-5p. Moreover, the effects of ectopic miR-20b-5p expression were abrogated by RB1 and TP53INP1 overexpression. In contrast, the effects of miR-20b-5p depletion were impaired by RB1 and TP53INP1 knockdown. Treatment with a miR-20b-5p antagomir dramatically increased tumor growth and inhibited RB1 and TP53INP1 protein expression in nude mice. This work provided novel insights on the molecular mechanism of ESCC and further provided suggestions for therapy development.

Esophageal squamous cell carcinoma (ESCC) is an invasive gastrointestinal malignancy and in urgent need of new effective therapies. Gambogic acid (GA) exhibits anti-cancer effects in many cancer cells, but it remains to be determined whether GA has the same effect on ESCC. Here, we reported that GA treatment caused an inhibition in ESCC cell proliferation, migration and invasion. Meanwhile, GA induced dose-dependent apoptosis of ESCC cells, repressed the expression of Bcl2 and up-regulated the levels of Bax protein, cleaved-PARP1 and cleaved-caspase 3/9. Further investigation showed that GA down-regulated the levels of PI3K, p-AKT and p-mTOR, while promoted PTEN expression in ESCC cells. Taken together, we provided the first demonstration that GA exerts anti-tumor effects on ESCC cells presumably through regulating PTEN-PI3K-AKT-mTORpathway, suggestive of a therapeutic potential for ESCC.

临床资料 患者,女,83岁. 左手小指外侧缘浸润性红色斑块3年余. 患者于3年前出现左手小指外侧缘浸润性斑块,无任何自觉症状,未予诊治,皮疹范围较前增大,自行购药外涂,皮疹未见消退,遂于2016年3月来我科就诊. 发病以来,患者精神状态、饮食、睡眠及大小便正常. 既往无外伤史,家族未见类似疾病患者. 体格检查:系统检查无明显异常. 皮肤科检查:左手小指外侧缘可见一境界清楚的红色浸润性斑块,表面轻度糜烂,其周可见脱屑(图1). 其他部位未见类似皮损.

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various tumorigenesis processes. In this study, our results revealed that miR-602 expression levels in tumor tissues and preoperative serum from esophageal squamous cell carcinoma (ESCC) patients were higher than those in non-tumorous tissues and healthy volunteers. miR-602 overexpression was closely related to lymph node metastasis and TNM stages and correlated short overall, and it acted as an independent prognostic marker of ESCC. The methylation status of the miR-602 gene indicated more frequent hypomethylation of the CpG sites located upstream of the miR-602 gene in the ESCC tissues than in the adjacent normal tissues, and the methylation status of miR-602 correlated inversely with its expression levels. Subsequently, miR-602 overexpression promoted ESCC proliferation and metastasis and regulated cell cycles in vitro and in vivo. Mechanistically, a dual-luciferase experiment validated that Fork head box (FOX)K2 (FOXK2) was a direct target of miR-602. More importantly, systemic delivery of formulated miR-602 antagomir could reduce tumor growth and increased FOXK2 protein expression in nude mice. This work provides novel insight into the molecular pathogenesis of ESCC.