Surgical resection may provide better survival and lower recurrence rates than RFA for patients with HCC to the Milan criteria.

Objective: Previous meta-analyses concluded that there was insufficient evidence to determine the effect of N95 respirators. We aimed to assess the effectiveness of N95 respirators versus surgical masks for prevention of influenza by collecting randomized controlled trials (RCTs). Methods:We searched PubMed, EMbase and The Cochrane Library from the inception to January 27, 2020 to identify relevant systematic reviews. The RCTs included in systematic reviews were identified. Then we searched the latest published RCTs from the above three databases and searched ClinicalTrials.gov for unpublished RCTs. Two reviewers independently extracted the data and assessed risk of bias. Meta-analyses were conducted to calculate pooled estimates by using RevMan 5.3 software. Results:A total of six RCTs involving 9 171 participants were included. There were no statistically significant differences in preventing laboratory-confirmed influenza (RR = 1.09, 95% CI 0.92-1.28, P > .05), laboratory-confirmed respiratory viral infections (RR = 0.89, 95% CI 0.70-1.11), laboratory-confirmed respiratory infection (RR = 0.74, 95% CI 0.42-1.29) and influenzalike illness (RR = 0.61, 95% CI 0.33-1.14) using N95 respirators and surgical masks. Meta-analysis indicated a protective effect of N95 respirators against laboratory-confirmed bacterial colonization (RR = 0.58, 95% CI 0.43-0.78). Conclusion:The use of N95 respirators compared with surgical masks is not associated with a lower risk of laboratory-confirmed influenza. It suggests that N95 respirators should not be recommended for general public and nonhigh-risk medical staff those are not in close contact with influenza patients or suspected patients.

IntroductionThe vertebrate mesoderm gives rise to a diverse variety of tissues, including the heart, vasculature, and blood. It is formed in the primitive streak (PS) which appears first in the posterior epiblast during gastrulation. The nascent PS then elongates to the anterior part, whereas the epiblast cells ingress through the PS, migrate to appropriate location in the embryo, and become either mesoderm or definitive endoderm. 1 Although the process of mesoderm formation is well understood, the underlying molecular mechanisms remain poorly defined.Previous studies have identified several signaling pathways involved in this process. 2 One is the transforming growth factorbeta (TGF-␤) superfamily member, bone morphogenetic protein-4 (BMP-4). Like other TGF-␤ superfamily members, BMP-4 binds to and brings together the type I and type II receptors on the cell surface, which allows receptor II to phosphorylate the receptor I kinase domain. After this activation, the type I receptor phosphorylates certain members of the Smad proteins (Smad 1, 5, 8; R-Smad). Two phosphorylated R-Smads, in combination with a common mediator Smad (Smad4; Co-Smad), form a heterotrimeric complex, which then translocates into the nucleus and cooperates with other transcription factors to modulate target gene expression. [3][4][5][6] Genetic studies in mice have shown that BMP-4 signaling is required for mesoderm formation. [7][8][9] Mice deficient in the BMP-4 ligand, 7 in the BMP type II receptor, 8 or in a BMP type I receptor Alk3, 9 all fail to develop mesoderm. It has also been demonstrated that BMP-4 plays critical roles in mesoderm induction and mesoderm lineage differentiation from mouse embryonic stem cells (mES cells). [10][11][12][13][14][15][16][17][18][19] The key role of BMP-4 in mouse embryos and mES cells has led us to investigate its function in human embryonic stem cells (hES cells), the differentiation of which can, at least in part, mimic the human embryogenesis. 20,21 Xu et al 22 showed that long-term BMP-4 treatment (up to 7 days) induces hES cell differentiation into trophoblast. Later, Pera et al 23 demonstrated that activation of the same signaling pathway by BMP-2 in hES cells results in the formation of extra-embryonic endoderm. Surprisingly, we found that short-term BMP-4 treatment (24 hours) initiated mesoderm induction at a high efficiency in hES cells. In addition, these mesoderm progenitor cells were able to differentiate into various mesoderm lineages. The differential effects of short-term and long-term BMP-4 treatments on hES cell differentiation suggest that the BMP signaling pathway might play a flexible and time-dependent role in human embryonic development and cell fate determination. Methods Cell culture and differentiationThe H1, H7, and H9 hES cell lines were obtained from WiCell Research Institute (Madison, WI). Cells were cultured and passaged on mitomycin C-treated mouse embryonic fibroblast (MEF) feeders in hES cell culture Submitted February 14, 2007; accepted November 20, 2007. Prepublished...

These findings suggest that all forms of pulmonary hypertension are linked by defects in the signaling pathway involving angiopoietin-1, TIE2, BMPR1A, and BMPR2 and consequently identify specific molecular targets for therapeutic intervention.

Mucinous adenocarcinoma of the lung is a subtype of highly invasive pulmonary tumors and is associated with decreased or absent expression of the transcription factor NK2 homeobox 1 (NKX2-1; also known as TTF-1). Here, we show that haploinsufficiency of Nkx2-1 in combination with oncogenic Kras G12D , but not with oncogenic EGFR L858R , caused pulmonary tumors in transgenic mice that were phenotypically similar to human mucinous adenocarcinomas. Gene expression patterns distinguished tumor goblet (mucous) cells from nontumorigenic airway and intestinal goblet cells. Expression of NKX2-1 inhibited urethane and oncogenic Kras G12D -induced tumorigenesis in vivo. Haploinsufficiency of Nkx2-1 enhanced Kras G12D -mediated tumor progression, but reduced EGFR L858R -mediated progression. Genome-wide analysis of gene expression demonstrated that a set of genes induced in mucinous tumors was shared with genes induced in a nontumorigenic chronic lung disease, while a distinct subset of genes was specific to mucinous tumors. ChIP with massively parallel DNA sequencing identified a direct association of NKX2-1 with the genes induced in mucinous tumors. NKX2-1 associated with the AP-1 binding element as well as the canonical NKX2-1 binding element. NKX2-1 inhibited both AP-1 activity and tumor colony formation in vitro. These data demonstrate that NKX2-1 functions in a context-dependent manner in lung tumorigenesis and inhibits Kras G12D -driven mucinous pulmonary adenocarcinoma. IntroductionMucinous adenocarcinoma of the lung (formerly known as mucinous bronchioalveolar cancer) is pathologically classified as tumor cells with goblet cell morphology containing abundant intracytoplasmic mucin (1). Invasive mucinous adenocarcinoma of the lung has a higher malignant potential than do the more common types of lung adenocarcinoma, such as acinar or papillary adenocarcinoma. Mucinous adenocarcinoma of the lung is associated with decreased or absent expression of the transcription factor NK2 homeobox 1 (NKX2-1; also known as TTF-1) and the expression of mucins, including mucin 5AC, oligomeric mucus/gel-forming (MUC5AC). Genetically, approximately 76% of mucinous adenocarcinomas of the lung have KRAS mutations, a frequent mutation in lung adenocarcinoma associated with tobacco use (2), but mucinous adenocarcinoma of the lung is rarely associated with EGFR mutations. In contrast, nonmucinous lung adenocarcinoma is frequently associated with EGFR mutations (∼45%), but less frequently with KRAS mutations (∼13%; ref. 1).NKX2-1 plays a critical role in lung morphogenesis and respiratory epithelial-specific gene expression, including activation of surfactant proteins and repression of mucins (3, 4). The potential oncogenic role of NKX2-1 in the pathogenesis of adenocarcinoma of the lung was proposed by findings that a region of 14q13.3 containing NKX2-1, NKX2-8, and PAX9 was amplified in approximately 10% of human lung adenocarcinoma (5-7). Loss-offunction and gain-of-function studies in human lung carcinoma and transformed cells supporte...