Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma: A Case Report and Literature Review.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive B-cell lymphoma. The heterogeneity of its clinical symptoms makes it hard to be diagnosed. The diagnosis is followed by pathological examination of affected tissues and organs including skin, central nervous system, and bone marrow. Random skin biopsy (RSB) with high sensitivity and less invasiveness becomes a common method for diagnosis in suspected patients without skin lesions. CASE REPORT: We reported the case of a 67-year-old man who complained of fever, dizziness, unsteady gait, numbness in both lower extremities, and incontinence. Blood routine examination suggested elevated levels of lactate dehydrogenase. Enhanced magnetic resonance imaging of the head and thoracolumbosacral spine, next-generation sequencing in blood, cerebrospinal fluid collection, bone marrow aspiration, and positron emission tomography-computed tomography presented no evidence of solid tumors. However, there were intravascular tumor cell growth and morphosis as determined by RSB. CD20, CD79a, CD5, BCL-6, and BCL-2 were positive as tested by immunohistochemistry, and Ki-67 showed high proliferative activity. Taking the medical history as an element, the patient received a diagnosis of IVLBCL. After he completed 3 cycles of RCDOP + orelabrutinib, his general condition improved. CONCLUSION: IVLBCL is an aggressive, lethal cancer that is difficult to diagnose; therefore, it is recommended for the suspected patients to receive RSB promptly and early treatment at the earliest opportunity to achieve amelioration in prognosis.

The risk factors for deep venous thrombosis in critically ill older adult patients: a subgroup analysis of a prospective, multicenter, observational study.

BACKGROUND: Older adult patients mainly suffer from multiple comorbidities and are at a higher risk of deep venous thrombosis (DVT) during their stay in the intensive care unit (ICU) than younger adult patients. This study aimed to analyze the risk factors for DVT in critically ill older adult patients. METHODS: This was a subgroup analysis of a prospective, multicenter, observational study of patients who were admitted to the ICU of 54 hospitals in Zhejiang Province from September 2019 to January 2020 (ChiCTR1900024956). Patients aged > 60 years old on ICU admission were included. The primary outcome was DVT during the ICU stay. The secondary outcomes were the 28- and 60-day survival rates, duration of stay in ICU, length of hospitalization, pulmonary embolism, incidence of bleeding events, and 60-day coagulopathy. RESULTS: A total of 650 patients were finally included. DVT occurred in 44 (2.3%) patients. The multivariable logistic regression analysis showed that age (≥75 vs 60-74 years old, odds ratio (OR) = 2.091, 95% confidence interval (CI): 1.308-2.846, P = 0.001), the use of analgesic/sedative/muscarinic drugs (OR = 2.451, 95%CI: 1.814-7.385, P = 0.011), D-dimer level (OR = 1.937, 95%CI: 1.511-3.063, P = 0.006), high Caprini risk score (OR = 2.862, 95%CI: 1.321-2.318, P = 0.039), basic prophylaxis (OR = 0.111, 95%CI: 0.029-0.430, P = 0.001), and physical prophylaxis (OR = 0.322, 95%CI: 0.109-0.954, P = 0.041) were independently associated with DVT. There were no significant differences in 28- and 60-day survival rates, duration of stay in ICU, total length of hospitalization, 60-day pulmonary embolism, and coagulation dysfunction between the two groups, while the DVT group had a higher incidence of bleeding events (2.6% vs. 8.9%, P < 0.001). CONCLUSION: In critically ill older adult patients, basic prophylaxis and physical prophylaxis were found as independent protective factors for DVT. Age (≥75 years old), the use of analgesic/sedative/muscarinic drugs, D-dimer level, and high Caprini risk score were noted as independent risk factors for DVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024956).URL: http://www.chictr.org.cn/listbycreater.aspx .

Knockdown of long non-coding RNA XIST suppresses nasopharyngeal carcinoma progression by activating miR-491-5p.

Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development and progression of human cancers. X-inactive specific transcript (XIST), an lncRNA, is known as an oncogene in multiple tumors. However, the roles of XIST and its related miRNAs in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we found that XIST expression was significantly upregulated in NPC tissues and cell lines. Knockdown of XIST inhibited NPC cell proliferation and invasion and induced apoptosis in vitro, as well as suppressed NPC tumor growth in vivo. Further analysis revealed that XIST and miR-491-5p interact with and repress each other. XIST may function as an endogenous miR-491-5p sponge to regulate the target gene of miR-491-5p. Taken together, these results provide a comprehensive view of the XIST/miR-491-5p axis in human NPC cells and may provide a new therapeutic target for treating NPC.

The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro.

The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.

Exosomal microRNA-301a-3p promotes the proliferation and invasion of nasopharyngeal carcinoma cells by targeting BTG1 mRNA.

Aberrant microRNA (miRNA/miR) expression plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the present study, the role and underlying molecular mechanism of miR­301a­3p in NPC cells were determined. It was observed that miR­301a­3p upregulation promoted NPC cell proliferation, migration, invasion and epithelial­mesenchymal transition in vitro, whereas its downregulation resulted in the opposite effect. B­cell translocation gene 1 (BTG1) mRNA was identified as the novel target of miR­301a­3p. BTG1 overexpression partially attenuated miR­301a­3p­induced increase in cell proliferation and invasion. miR­301a­3p can be transferred by exosomes and positively regulate the proliferation and invasion of NPC cells. Altogether, the present study highlights that exosomal miR­301a­3p can promote NPC cell proliferation and invasion by repressing BTG1, thereby resulting in the development of NPC.

Prevention, treatment, and risk factors of deep vein thrombosis in critically ill patients in Zhejiang province, China: a multicenter, prospective, observational study.

PURPOSE: The aim of this study is to investigate the prevention and treatment patterns of deep vein thrombosis (DVT) in critically ill patients and to explore the risk factors for DVT in people from Zhejiang Province, China. MATERIALS AND METHODS: This study prospectively enrolled patients admitted in intensive care units (ICUs) of 54 hospitals from 09/16/2019 to 01/16/2020. The risk of developing DVT and subsequent prophylaxis was evaluated. The primary outcome was DVT occurrence during ICU hospitalisation. Univariate and multivariate logistic regression were performed to determine the risk factors for DVT. RESULTS: A total of 940 patients were included in the study. Among 847 patients who received prophylaxis, 635 (75.0%) patients received physical prophylaxis and 199 (23.5%) patients received drug prophylaxis. Fifty-eight (6.2%) patients were diagnosed with DVT after admission to the ICU, and 36 patients were treated with anticoagulants (all patients received low molecular weight heparin [LMWH]). D-dimer levels (OR = 1.256, 95% CI: 1.132-1.990), basic prophylaxis (OR = 0.092, 95% CI: 0.016-0.536), and physical prophylaxis (OR = 0.159, 95% CI: 0.038-0.674) were independently associated with DVT in ICU patients. The short-term survival was similar between DVT and non-DVT patients. CONCLUSIONS: DVT prophylaxis is widely performed in ICU patients. Prophylaxis is an independent protective factor for DVT occurrence. The most common treatment of DVT patients is LMWH, although it might increase the rate of bleeding.Key messagesThis is the only multicenter and prospective study of DVT in ICUs in China.d-dimer levels were independently associated with DVT in ICU patients.Prophylaxis was an independent protective factor for DVT occurrence in ICU.

miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR­491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.