A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression.

Improving cancer immunotherapy by targeting IL-1.

Interleukin-1 (IL-1) is an inflammatory cytokine associated with tumor invasiveness and metastasis. We recently found that baseline IL-1 in melanomas promoted resistance to immunotherapy by creating an immunosuppressive tumor microenvironment and that IL-1 produced in response to CD40 agonist also induced resistance to therapy. Here, we discuss how naturally occurring and immunotherapy-induced IL-1 in tumors causes immune suppression and resistance to immunotherapy, and we discuss targeting the IL-1 pathway to enhance the efficacy of immunotherapy.

IL-1α Mediates Innate and Acquired Resistance to Immunotherapy in Melanoma.

Inflammation has long been associated with cancer initiation and progression; however, how inflammation causes immune suppression in the tumor microenvironment and resistance to immunotherapy is not well understood. In this study, we show that both innate proinflammatory cytokine IL-1α and immunotherapy-induced IL-1α make melanoma resistant to immunotherapy. In a mouse melanoma model, we found that tumor size was inversely correlated with response to immunotherapy.

Comparative analysis of the down syndrome hippocampal non-coding RNA transcriptomes using a mouse model.

Background: Down syndrome (DS), caused by trisomy 21, is the most common human chromosomal disorder. Hippocampal abnormalities have been believed to be responsible for the DS developmental cognitive deficits. Cumulative evidences indicated that non-coding RNAs (ncRNAs) participated in brain development and function.

Cost-Effectiveness Analysis of Ezetimibe as the Add-on Treatment to Moderate-Dose Rosuvastatin versus High-Dose Rosuvastatin in the Secondary Prevention of Cardiovascular Diseases in China: A Markov Model Analysis.

Background: For patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. The cost-effectiveness of them is unknown in the Chinese context. The aim of this study is to compare the cost and effectiveness of the two regimens, and estimate the incremental cost-effectiveness ratio (ICER).

HOXA9 rs3801776 G>A polymorphism increases congenital talipes equinovarus risk in a Chinese population.

Background: Congenital talipes equinovarus (CTEV) is the most common congenital deformity in children, and muscular dysplasia plays a potential role in the etiology of CTEV. Notably, previous studies have found that HOXA9 rs3801776 and TPM2 rs2025126 genetic polymorphisms play important roles in regulating muscle development in Caucasian children; however, there is a lack of investigations conducted in Chinese children.

Methods: We conducted a hospital-based, case-control study of 189 children with CTEV and 457 CTEV-free children aiming to examine the associations between these two polymorphisms and CTEV susceptibility.

Stromal Modulation Reverses Primary Resistance to Immune Checkpoint Blockade in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat. It is refractory to most existing therapies, including immunotherapies, due to the presence of an excessive desmoplastic stroma, which restricts penetration of drugs and cytotoxic CD8 T cells. Stromal modulation has shown promising results in the enhancement of immune checkpoint blockade treatment in PDAC.

Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8 T Cell Response.

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied l-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells.

Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy.

Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control.

Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy.

Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of experiments in both immune competent and nude mouse models.

Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.

CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8 T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8 T cells that express PD-1 and suppress tumor growth.

Unusual cause of massive hemothorax: spontaneous rupture of nonfunctioning mediastinal paraganglioma.

Mediastinal paraganglioma is a rare neurogenic tumor with a hypervascular feature. The spontaneous rupture of mediastinal paraganglioma is an unusual cause of massive hemothorax. Here we present a case of 39-year-old man with massive hemothorax due to the spontaneous rupture of a mediastinal paraganglioma.

Should tumor with direct adjacent lobe invasion (Tdali) be assigned to T2 or T3 in non-small cell lung cancer: a meta-analysis.

Background: The staging of tumor with direct adjacent lobe invasion (Tdali) or interlobar invasion pleural 3 (ILI PL3) in TNM system of non-small cell lung cancer (NSCLC) is still in controversy. We conducted a meta-analysis to compare the prognosis of Tdali with T2 or T3 disease.

Methods: PubMed and Embase were searched for relevant studies.

Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis.

Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients.

Simultaneous thoracoscopic resection for coexisting pulmonary and thymic lesions.

Background: The management of synchronous thymic and pulmonary lesions remains a challenge due to the lack of case series and surgical guidelines. This study aims to retrospectively review our preliminary experience and results of performing simultaneous thoracoscopic resection of coexisting diseases of the lung and thymus.

Methods: Simultaneous thoracoscopic resection was performed to remove coexisting thymic and pulmonary lesions in nine patients from August 2008 to November 2013.

Surgical treatment of primary mediastinal myelolipoma.

Objectives: Primary mediastinal myelolipoma (PMM) is a rare benign tumour composed of haematopoietic tissue and mature adipose tissue. Here, we report the largest series aiming to investigate the outcomes of surgical treatment for patients with PMM.

Methods: We retrospectively reviewed the data of 12 patients operated in a single institute during the period between April 2008 and December 2014.

Non-grasping en bloc mediastinal lymph node dissection for video-assisted thoracoscopic lung cancer surgery.

Background: This study aims to introduce an optimized method named "non-grasping en bloc mediastinal lymph node dissection (MLND)" through video-assisted thoracoscopic surgery (VATS).

Methods: Between February 2009 and July 2013, 402 patients with clinical stage I non-small cell lung cancer (NSCLC) underwent "non-grasping en bloc MLND" conducted by one surgical team. Target lymph nodes (LNs) were exposed following non-grasping strategy with simple combination of a metal endoscopic suction and an electrocoagulation hook or an ultrasound scalpel.

Prognostic role of circulating tumor cells and disseminated tumor cells in patients with prostate cancer: a systematic review and meta-analysis.

Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) displayed their roles in prognosis prediction in prostate cancer. The objective of the present study was to conduct a systematic review and meta-analysis of published literature while investigating the correlation between survival outcome and CTCs or DTCs counts in patients with prostate cancer. Relevant literature was searched in Pubmed and Embase.

Video-assisted thoracic surgery for pulmonary sequestration compared with posterolateral thoracotomy.

Objectives: Pulmonary sequestration is a rare congenital malformation of the lungs. This study aims to evaluate the effectiveness of video-assisted thoracic surgery for the treatment of pulmonary sequestration in a larger series compared with posterolateral thoracotomy.

Methods: The files of 42 patients with pulmonary sequestration treated via video-assisted thoracic surgery (18 cases) and posterolateral thoracotomy (24 cases) between September 2005 and May 2012 from a single institute were retrospectively reviewed.

Prognostic value of vascular endothelial growth factor expression in resected gastric cancer.

Background And Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature.

Prognostic role of microRNA-21 in non-small cell lung cancer: a meta-analysis.

Introduction: Many studies have reported that microRNA-21 (miR-21) mihght predict the survival outcome in non-small cell lung cancers (NSCLCs) but the opposite opinion has also been expressed. The aim of this study was to summarize the evidence for a prognostic role of miR-21.

Materials And Methods: All the eligible studies was searched by Medline and EMBASE and patients' clinical characteristics and survival outcome were extracted.

Meta-analysis of circulating tumor cells as a prognostic marker in lung cancer.

Introduction: Recent studies have shown that circulating tumor cells (CTCs) play potential roles as diagnostic and prognostic biomarkers with various cancer types. The aim of this study was to comprehensively and quantitatively summarize the evidence for the use of CTCs to predict the survival outcome of lung cancer patients.

Materials And Methods: Relevant literature was identified using Medline and EMBASE.