Primary adenomatoid tumor of the adrenal gland: A case report and literature review.

RATIONALE: Adenomatoid tumors are rare benign tumors, mainly involving the reproductive tract, such as the epididymis in men and the uterus and fallopian tubes in women. However, a few cases can occur outside the reproductive tract. Herein, we report a rare case of a primary adenomatoid tumor of the adrenal gland. PATIENT CONCERNS: A 50-year-old man underwent ultrasound examination and was found to have a right adrenal mass without elevated blood pressure, weakness after fatigue, frequent nocturnal urination urgency, pain, or a history of hematuria. The patient's general health was normal. Computed tomography revealed a polycystic mixed-density lesion in the right adrenal region, approximately 7.3 × 4.5 cm in size. DIAGNOSES: Based on the clinical information, morphological features, and immunohistochemistry results, a pathological diagnosis of primary adenomatoid tumor of the adrenal gland was made. INTERVENTION: Excision of the right adrenal gland and tumor through the 11 ribs. OUTCOMES: The patient's postoperative course was uneventful. LESSONS: Preventing misdiagnosis adenomatoid tumors with other types of adrenal gland tumors or metastatic tumors is imperative. Morphological and immunohistochemical features can help diagnose primary adenomatoid tumors of the adrenal gland.

Research trends and prospects on brain metastasis from breast cancer: A bibliometric analysis.

Introduction: Brain metastasis is the terminal event of breast cancer with poor prognoses. Therefore, this article aimed to provide an updated summary on the development, hotspots, and research trends of brain metastasis from breast cancer based on bibliometric analysis. Method: Publications on breast cancer with brain metastasis retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and other online bibliometric analysis platforms were used to analyze and visualize the result. Result: In totality, 693 researchers from 3,623 institutions across 74 counties and regions published a total of 2,790 papers in 607 journals. There was a noticeable increase in publications in 2006. The United States was the dominant country with the most publications followed by China. University Texas MD Anderson Cancer Center was the most productive institution, while Dana Farber Cancer Institution was the most cited. Journal of Neuro-Oncology published the most papers, while Journal of Clinical Oncology ranked first based on cocited analysis. Nancy U. Lin was the most productive and cited author with high influence. There was a focus on basic research, clinical trials, local therapy, treatment optimization, and epidemiological studies regarding brain metastases from breast cancer. References focused on pathogenesis, prevention, treatment, and prognosis were cited most frequently, among which the clinical trial of novel treatment attracted most attention from researchers. Reference citation burst detection suggested that new therapies such as the novel tyrosine kinase inhibitor and antibody-drug conjugate may lead the research trends in the future. Conclusion: High-income countries contributed more to the field of breast cancer with brain metastasis, while developing countries like China developed quickly. Furthermore, the success of novel therapies in recent years may lead to the new era of treatment of breast cancer with brain metastasis in the future.

Primary acinic cell carcinoma of the trachea: A case report and literature review.

RATIONALE: Salivary gland-type acinic cell carcinoma (ACC) is a low-grade malignancy. Primary ACC of the trachea and lungs is rare; here, we describe 1 such case. The histological morphology of tracheal ACC was similar to that of its salivary gland-associated equivalent. Because of its rarity, it is easily misdiagnosed as another type of tracheal or lung tumor. Microscopic analysis of pathological features and immunohistochemistry help diagnose primary ACC of the trachea and lungs. PATIENT CONCERNS: A 33-year-old female complained of shortness of breath and hemoptysis for 2 years, and reported the symptoms to have aggravated over the last 4 months. The patient was admitted to our hospital for further treatment. Enhanced computed tomography revealed a soft tissue density nodule shadow in the trachea, which was approximately 1.3 × 1.2 cm in size. DIAGNOSES: Based on the clinical information, morphological features, and immunohistochemistry, the pathological diagnosis was primary ACC of the trachea. INTERVENTION: The tracheal lesion was resected with an electric snare, electrotomy, freezing, and an argon knife using a rigid bronchoscope. OUTCOMES: The patient's postoperative course was uneventful. LESSONS: It is important to prevent misdiagnosis of this type of tumor as another type of lung tumor. Morphological and immunohistochemical features can be useful in diagnosing primary ACC of the trachea and lungs.

Thymic lipofibroadenomas: Three case reports.

BACKGROUND: Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas. CASE SUMMARY: This study included three patients with thymic lipofibroadenomas. We retrospectively analyzed the patient data to determine the clinicopathological characteristics of thymic lipofibroadenomas. The study included one man and two women [mean age, 43 (33-59) years]. All patients were non-smokers and presented with well-defined anterior mediastinal tumors. The cut surfaces of the tumors were solid, with a mixture of yellow and white areas. Microscopic evaluation of resected specimens showed scattered cord-like structures of epithelial cells embedded within abundant fibrotic and hyaline stroma admixed with variable quantities of adipose tissue. One patient showed hyperplastic thymic tissue in a part of the tumor. CONCLUSION: Thymic lipofibroadenomas are an extremely rare type of benign thymic tumor. Surgical removal of lipofibroadenomas is usually curative.

Resection of Thymic Neuroendocrine Carcinoma Guided by Three-Dimensional Reconstruction: A Case Report.

Primary thymic small cell neuroendocrine carcinoma (SCNEC), which possesses a more aggressive biological behaviour, including invasion of proximal structures, local recurrence, and distant metastasis, is extremely rare. According to a previous literature report, only a few patients with this disease have been reported, compared to patients with distant metastasis of bones, lungs, spleen, liver, and adrenal glands (1, 2). The report data suggest that SCNEC is a highly malignant tumour compared to most other tumours of the human body. In this study, we presented the case of a patient who underwent surgery guided by three-dimensional reconstruction modelling before the operation. We were fully prepared for the resection of this tumour using three-dimensional reconstruction modelling, even after reading the computed tomography (CT) images that showed a closed relationship with the pericardium, the vein of the right middle lung lobe, and the phrenic nerve. All these features demonstrate that SCNEC is highly malignant. To date, there are no procedural reports for three-dimensional reconstruction modelling in malignant thymus tumours.

Overexpression of miR-328-5p influences cell growth and migration to promote NSCLC progression by targeting LOXL4.

Background: Lung cancer is the leading cause of cancer-associated mortality worldwide, and most lung cancers are classified as non-small cell lung cancer (NSCLC). MiR-328 influence the progression of multiple tumors, but the role of miR-328-5p in NSCLC has not been elucidated. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the miR-328-5p and lysyl oxidase like 4 (LOXL4) in NSCLC. Methods: Expression of miR-328-5p was detected by real-time quantitative polymerase chain reaction (qRT-PCR) in tumor and non-tumor adjacent tissues. After Lentivirus-miR-328-5p was employed to intervene this miRNA in NSCLC cell lines, RT-qPCR was used to detect the expression levels of miR-328-5p. Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, wound healing, Transwell assays were used to determine the malignant phenotypes of NSCLC cells. Nude mice models of subcutaneous tumors were established to observe the effect of miR-328-5p on tumorigenesis. Targeting the 3'UTR of LOXL4 by miR-328-5p was verified by integrated analysis including transcriptome sequencing, dual-luciferase and western-blot assays. Results: High miR-328-5p level was observed in NSCLC cells from The Cancer Genome Atlas (TCGA) database and tumor tissues collected from NSCLC patients. Overexpressed miR-328-5p promoted NSCLC cell proliferation, survival, and migration, and promoted tumor growth in vivo. Knockdown of miR-328-5p suppressed tumorigenic activities. Transcriptome sequencing analysis revealed that LOXL4 was downregulated by miR-328-5p, which was confirmed by dual-luciferase reporter and western-blot assays. Conclusions: miR-328-5p showed targeted regulation of LOXL4 to promote cell proliferation and migration in NSCLC.

Mapping single-nucleotide m6A by m6A-REF-seq.

The past few years have witnessed rapid progress in the field of RNA modifications. As the most prevailing modification on eukaryotic mRNA, m6A is characterized to play a vital role in various cellular activities. However, limitations of the detection method impede functional studies of m6A. Here we introduce m6A-REF-seq, a powerful and straightforward method to identify m6A at single-nucleotide resolution. m6A-REF-seq relies on the recognition of RNA endonuclease MazF towards m6A at the ACA motif, providing an orthogonal method independent of the m6A antibody being adopted by most of current methods. We describe a detailed protocol to perform m6A-REF-seq, including NGS library construction and sequencing data analysis. In particular, we describe an optimized assay to validate individual m6A sites identified by m6A-REF-seq, which can also be applied to detect any candidate m6A sites.

Silibinin Promotes Cell Proliferation Through Facilitating G1/S Transitions by Activating Drp1-Mediated Mitochondrial Fission in Cells.

Heart, liver, and kidney, which are known as the essential organs for metabolism, possess the unique ability to regulate the proliferation function of the body against injury. Silibinin (SB), a natural polyphenolic flavonoid extracted from traditional herb Silybum marianum L., has been used to protect hepatocytes. Whether SB can regulate mitochondrial fission in normal cells and the underlying mechanisms remain unclear. Here, we showed that SB markedly promoted cell proliferation by facilitating G1/S transition via activating dynamin-related protein 1 (Drp1), which in turn mediated mitochondrial fission in these normal cells. SB dose-dependently increased the mitochondrial mass, mtDNA copy number, cellular adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species in normal cells. Furthermore, SB dose-dependently increased the expression of Drp1. Blocking Drp1 abolished SB-induced mitochondrial fission. In conclusion, we demonstrate that SB promotes cell proliferation through facilitating G1/S transition by activating Drp1-mediated mitochondrial fission. This study suggests that SB is a potentially useful herbal derivative for the daily prevention of various diseases caused by impaired mitochondrial fission.

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer.

Cervical cancer is the fourth leading cancer type and the second most common gynecological malignancy among women worldwide. Silibinin (SB), a chief bioactive natural polyphenolic flavonoid of Silybum marianum L., has been used clinically for its hepatocyte protective effects. It also has anticancer effects via the induction of apoptosis and cell cycle arrest. However, the effects of SB on cervical cancer cells through mitochondrial fission have not been studied. Here, we showed that SB markedly suppressed cervical cell proliferation by inducing G2/M cell cycle arrest via the activation of dynamin-related protein 1 (Drp1), which in turn mediated the mitochondrial fission dysfunction both in vitro and in vivo. SB decreased the ATP content, mitochondrial membrane potential, and mtDNA copy number, as well as reduced the reactive oxygen species levels in cervical cells. Furthermore, SB induced excessive mitochondrial fragmentation and reduced tubule formation. Further study showed that knockdown of Drp1 abolished the SB-induced G2/M cell cycle arrest in cervical cancer cells by inhibiting the mitochondrial fission pathway. More importantly, SB inhibited Hela cell growth in vivo model. In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment.

Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1.

The battle between hepatitis B virus (HBV) infection and the host immune defense determines the outcome of the disease. Scavenger receptor A (SRA) is a phagocytic pattern recognition receptor involved in various cellular processes, including lipid metabolism, recognition, and clearance of pathogens or modified self-molecules. Emerging evidence pointed out that SRA might act as an immunomodulator that contributes to innate immune defense against invading pathogens. Herein, we examined the role of SRA in the initiation of type I interferon (IFN) response to HBV infection and the virus clearance. Our results showed that SRA-deficient (SRA-/- ) mice were resistant to HBV infection developed by hydrodynamic injection of HBV replicon plasmid. We found lower levels of HBV DNA and viral protein expression in SRA-/- mice, which was associated with enhanced type I IFN production, compared with wild-type controls. Besides, we performed gain and loss of function experiments and determined that SRA inhibits innate antiviral immune responses to HBV. SRA could interact directly with tumor necrosis factor receptor-associated factor 3 (TRAF3) and inhibit its K63-linked ubiquitination. Moreover, we provided evidence that SRA negatively regulates the stability of TRAF3 protein by promoting the recruitment of OTUB1 to TRAF3. Our findings indicate that SRA plays a crucial role in innate immune signaling by targeting TRAF3 for degradation and balancing the innate antiviral immunity.

Single-base mapping of m6A by an antibody-independent method.

N 6-methyladenosine (m6A) is one of the most abundant messenger RNA modifications in eukaryotes involved in various pivotal processes of RNA metabolism. The most popular high-throughput m6A identification method depends on the anti-m6A antibody but suffers from poor reproducibility and limited resolution. Exact location information is of great value for understanding the dynamics, machinery, and functions of m6A. Here, we developed a precise and high-throughput antibody-independent m6A identification method based on the m6A-sensitive RNA endoribonuclease recognizing ACA motif (m6A-sensitive RNA-Endoribonuclease-Facilitated sequencing or m6A-REF-seq). Whole-transcriptomic, single-base m6A maps generated by m6A-REF-seq quantitatively displayed an explicit distribution pattern with enrichment near stop codons. We used independent methods to validate methylation status and abundance of individual m6A sites, confirming the high reliability and accuracy of m6A-REF-seq. We applied this method on five tissues from human, mouse, and rat, showing that m6A sites are conserved with single-nucleotide specificity and tend to cluster among species.

Lung protective ventilation in patients undergoing major surgery: a systematic review incorporating a Bayesian approach.

OBJECTIVE: Protective ventilation (PV) has been validated in patients with acute respiratory distress syndrome. However, the effect of PV in patients undergoing major surgery is controversial. The study aimed to explore the beneficial effect of PV on patients undergoing a major operation by systematic review and meta-analysis. SETTING: Various levels of medical centres. PARTICIPANTS: Patients undergoing general anaesthesia. INTERVENTIONS: PV with low tidal volume. PRIMARY AND SECONDARY OUTCOME MEASURES: Study end points included acute lung injury (ALI), pneumonia, atelectasis, mortality, length of stay (LOS) in intensive care unit (ICU) and hospital. METHODS: Databases including PubMed, Scopus, EBSCO and EMBASE were searched from inception to May 2015. Search strategies consisted of terms related to PV and anaesthesia. We reported OR for binary outcomes including ALI, mortality, pneumonia, atelectasis and other adverse outcomes. Weighted mean difference was reported for continuous outcomes such as LOS in the ICU and hospital, pH value, partial pressure of carbon dioxide, oxygenation and duration of mechanical ventilation (MV). MAIN RESULTS: A total of 22 citations were included in the systematic review and meta-analysis. PV had protective effect against the development of ALI as compared with the control group, with an OR of 0.41 (95% CI 0.19 to 0.87). PV tended to be beneficial with regard to the development of pneumonia (OR 0.46, 95% CI 0.16 to 1.28) and atelectasis (OR 0.68, 95% CI 0.46 to 1.01), but statistical significance was not reached. Other adverse outcomes such as new onset arrhythmia were significantly reduced with the use of PV (OR 0.47, 95% CI 0.48 to 0.93). CONCLUSIONS: The study demonstrates that PV can reduce the risk of ALI in patients undergoing major surgery. However, there is insufficient evidence that such a beneficial effect can be translated to more clinically relevant outcomes such as mortality or duration of MV. TRIAL REGISTRATION NUMBER: The study was registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416.

Involvement of soluble scavenger receptor A in suppression of T cell activation in patients with chronic hepatitis B.

BACKGROUND: Scavenger receptor A (SRA) is expressed predominantly in phagocytic cells playing an essential role in the host immune defense against invading microorganisms. Our previous study reported the presence of SRA in a soluble form in patients with infection of hepatitis B viruses (HBV). However, the association of soluble SRA with stages of HBV infection and the immune response induced by HBV is not fully determined. METHODS: In this study, we detected soluble SRA in serum from 29 chronic hepatitis B (CHB) patients, 28 chronic HBV carriers in the immune tolerant (IT) stage, 33 in the HBeAg-negative inactive carrier (IC) stage, and 22 healthy controls (HCs), respectively. We further analyzed the correlation of detected soluble SRA to inflammation and serum viral load. In addition, we investigated the regulatory role of soluble SRA in T cell activation, especially in CD8(+) T cell response to HBV peptide. RESULTS: We demonstrated that Median levels of serum soluble SRA in CHB and IT patients were significantly higher than those of IC patients and HCs. Additionally, the concentrations of soluble SRA were negatively correlated with alanine transaminase levels in CHB patients. We also found that serum concentration of SRA was decreased during telbivudine treatment. Expressed SRA extracellular domain suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in CD8(+) T cells, and it bound to T cells in a higher frequency in CHB patients than in HCs. Furthermore, we observed that naïve human T cells stimulated by anti-CD3 and CD28 antibodies in the presence of the recombinant SRA protein had reduced activation and proliferation. CONCLUSION: In summary, we determined the level of soluble SRA in different stages of CHB patients. SRA might inhibit T cell proliferation and activation as a soluble form. These results not only revealed a previously unknown feature of soluble SRA in CHB patients but also provided broad understanding of SRA in T cell activation.

Lung protective ventilation in patients undergoing major surgery: a systematic review protocol.

INTRODUCTION: There is growing interest in the use of low tidal volume ventilation in patients undergoing general anaesthesia. However, its potential benefit has long been debated and conflicting results have been reported. We describe here the protocol of a systematic review and meta-analysis for investigating the beneficial effects of low tidal volume ventilation in patients undergoing general anaesthesia. METHODS AND ANALYSIS: Data sources include PubMed, Scopus, Embase and EBSCO. Patients undergoing general anaesthesia will be included irrespective of type of surgery. The intervention is low tidal volume ventilation or protective ventilation, and the control is conventional ventilation. The quality of included trials will be assessed by using Delphi consensus. Outcomes include new onset lung injury, atelectasis, arrhythmia, levels of inflammatory biomarkers, arterial oxygenation, partial pressure of carbon dioxide and alveolar-arterial oxygen gradient. Conventional approaches for meta-analysis will be used, and heterogeneity will be investigated by using subgroup analysis and meta-regression if appropriate. The Bayesian method will be used for the synthesis of binary outcome data. ETHICS AND DISSEMINATION: The systematic review was approved by the ethics committee of Jinhua hospital of Zhejiang university and will be published in a peer-reviewed journal and will be disseminated electronically and in print. REGISTRATION DETAILS: The study protocol has been registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416.

[Inhibitory effect of cyclopamine on metastatic ability of EC109 cells and its mechanism].

OBJECTIVE: To investigate the effect of cyclopamine on metastatic ability of human esophageal cancer EC109 cells and explore the possible mechanism. METHODS: Transwell chamber assay and angiogenesis assay were used to examine the metastatic ability, invasiveness and angiogenesis of EC109 cells treated with cyclopamine for 48 h. The expression of Gli-1 mRNA was detected using RT-PCR, and Western blotting was used to examine the protein expressions of Gli-1, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF). RESULTS: Inhibition of the hedgehog signaling pathway by cyclopamine suppressed the migration, invasion, and angiogenesis of EC109 cells. Cyclopamine treatment significantly lowered the expression of Gli-1 mRNA (P<0.05) and the protein expressions of Gli-1, MMP-9 and VEGF (P<0.05). CONCLUSION: Cyclopamine can significantly inhibit the metastatic capacity of EC109 cells possibly by down-regulating MMP-9 and VEGF expression as a result of Gli-1 inhibition.

[The expression of melatonin MT1 receptor in acute necrotizing pancreatitis rats and the protective effects of melatonin].

OBJECTIVE: To investigate the expression of melatonin MT1 receptor in rats with acute necrotizing pancreatitis (ANP) and the protective effects of melatonin (MT) pre-intervention for the pancreas. METHODS: Fifty-four male Sprague-Dawley (SD) rats were randomly divided into three groups: sham-operation group, ANP group and MT-pretreated group. The models of ANP were induced by retrograde injection sodium taurocholate into the bili-pancreatic duct. MT group undergoing intraperitoneal injection 50 mg/kg 30 minutes before the establishment of ANP models. Four, 8 and 12 hours after the onset of operation, the levels of serum amylase and pathological changes of the pancreas were observed. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNFα) in the pancreas were measured. The expression of MT1 protein and MT1 mRNA in pancreas were separately analyzed by immunohistochemistry and real-time PCR. RESULTS: (1) Pancreatic pathological damage in ANP groups was progressive exacerbated. It was obviously ameliorated in MT group as compared with ANP group (P < 0.05); (2) Compared with SO group, the levels of serum amylase, MDA and TNFα in the pancreas were significantly increased in ANP group (P < 0.05 or P < 0.01). They were markedly decreased in MT group as compared with ANP group [12 h, (2348.00 ± 278.90) U/L vs (3194.83 ± 538.10) U/L, (2.255 ± 0.472) µmol/L vs (2.960 ± 0.722) µmol/L, (102.929 ± 29.399) ng/L vs (378.544 ± 183.454) ng/L, P < 0.05]. The level of SOD was decreased in ANP group compared with SO group (P < 0.05) and increased in MT group [12 h, (11.448 ± 1.594) U/L vs (8.427 ± 1.950) U/L, P < 0.05]; (3) Compared with SO group, the expression of MT1 protein and MT1 mRNA in ANP group were down-regulated as the severity of the disease increased (P < 0.05). They were significantly higher in MT group than ANP group. CONCLUSIONS: Melatonin pre-intervention is able to increase SOD level and decrease MDA, TNFα levels, thereby reducing pancreatic injury. The MT1 might play an important role in the pathogenesis of ANP. MT might exert protective effects for the pancreas in ANP rats through increase the expression of MT1.

Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting.

OBJECTIVE: In an effort to minimize transfusions in patients undergoing elective coronary artery bypass grafting operations after recent clopidogrel exposure, we studied laboratory tests predictive of platelet dysfunction and used a strict algorithm-driven treatment of bleeding. METHODS: Forty-five patients receiving clopidogrel within 6 days of the operation and 45 control subjects were studied. Prothrombin time, activated partial thromboplastin time, platelet count, and platelet function test results were measured before heparinization, after protamine administration, and then every 2 hours. No transfusions were administered unless a patient met both laboratory and clinical criteria. RESULTS: Algorithm-driven treatment of bleeding significantly reduced the mean units of all blood components transfused by about one third, as shown by comparison with current control and historical data. Compared with current control subjects, clopidogrel recipients required significantly more transfusions of platelets (9.0 +/- 1.7 vs 1.2 +/- 0.5 U; P <.0001) and packed red blood cells (4.3 +/- 0.6 vs 2.3 +/- 0.5 U; P =.01) and required longer periods of controlled ventilation (12.4 +/- 1.3 vs 8.6 +/- 0.8 hours; P =.02). Preoperative platelet dysfunction before heparin administration for cardiopulmonary bypass, as measured by using adenosine diphosphate aggregometry (response <40%), predicted all but 1 case of severe coagulopathy requiring multiple transfusions (16.6 +/- 2.8 U of platelets and 5.8 +/- 1.0 U of packed red blood cells). CONCLUSIONS: A strict transfusion algorithm can reduce the transfusion requirement for all blood components. Preheparin testing of platelet function with adenosine diphosphate aggregometry can identify patients at highest risk for perioperative bleeding and transfusions and might further reduce the perioperative transfusion requirement.