FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.

BACKGROUND: Marfan syndrome, caused by mutations in the gene for fibrillin-1, leads to thoracic aortic aneurysms (TAAs). Phenotypic modulation of vascular smooth muscle cells (SMCs) and ECM (extracellular matrix) remodeling are characteristic of both nonsyndromic and Marfan aneurysms. The ECM protein FN (fibronectin) is elevated in the tunica media of TAAs and amplifies inflammatory signaling in endothelial and SMCs through its main receptor, integrin α5ß1. We investigated the role of integrin α5-specific signals in Marfan mice in which the cytoplasmic domain of integrin α5 was replaced with that of integrin α2 (denoted α5/2 chimera). METHODS: We crossed α5/2 chimeric mice with Fbn1mgR/mgR mice (mgR model of Marfan syndrome) to evaluate the survival rate and pathogenesis of TAAs among wild-type, α5/2, mgR, and α5/2 mgR mice. Further biochemical and microscopic analysis of porcine and mouse aortic SMCs investigated molecular mechanisms by which FN affects SMCs and subsequent development of TAAs. RESULTS: FN was elevated in the thoracic aortas from Marfan patients, in nonsyndromic aneurysms, and in mgR mice. The α5/2 mutation greatly prolonged survival of Marfan mice, with improved elastic fiber integrity, mechanical properties, SMC density, and SMC contractile gene expression. Furthermore, plating of wild-type SMCs on FN decreased contractile gene expression and activated inflammatory pathways whereas α5/2 SMCs were resistant. These effects correlated with increased NF-kB activation in cultured SMCs and mgR aortas, which was alleviated by the α5/2 mutation or NF-kB inhibition. CONCLUSIONS: FN-integrin α5 signaling is a significant driver of TAA in the mgR mouse model. This pathway thus warrants further investigation as a therapeutic target.

Integrating genomics and transcriptomics to identify candidate genes for high egg production in Wulong geese (Anser cygnoides orientalis).

BACKGROUND: Wulong geese (Anser cygnoides orientalis) are known for their excellent egg-laying performance. However, they show considerable population differences in egg-laying behavior. This study combined genome-wide selection signal analysis with transcriptome analysis (RNA-seq) to identify the genes related to high egg production in Wulong geese. RESULTS: A total of 132 selected genomic regions were screened using genome-wide selection signal analysis, and 130 genes related to high egg production were annotated in these regions. These selected genes were enriched in pathways related to egg production, including oocyte meiosis, the estrogen signaling pathway, the oxytocin signaling pathway, and progesterone-mediated oocyte maturation. Furthermore, a total of 890 differentially expressed genes (DEGs), including 340 up-regulated and 550 down-regulated genes, were identified by RNA-seq. Two genes - GCG and FAP - were common to the list of selected genes and DEGs. A non-synonymous single nucleotide polymorphism was identified in an exon of FAP. CONCLUSIONS: Based on genome-wide selection signal analysis and transcriptome data, GCG and FAP were identified as candidate genes associated with high egg production in Wulong geese. These findings could promote the breeding of Wulong geese with high egg production abilities and provide a theoretical basis for exploring the mechanisms of reproductive regulation in poultry.

Fenofibrate normalizes alkaline phosphatase and improves long-term outcomes in patients with advanced primary biliary cholangitis refractory to ursodeoxycholic acid.

BACKGROUND: Although patients with advanced liver disease have been included in studies evaluating fibrates for the treatment of primary biliary cholangitis (PBC), the frequency of biochemical responses and adverse effects for this group of patients was not reported separately and comprehensively. AIMS: to evaluate the efficacy and safety of additional fenofibrate therapy in patients with advanced and ursodeoxycholic acid (UDCA)-refractory PBC. METHODS: Patients were analyzed retrospectively to determine the clinical therapeutic effects of UDCA with additional fenofibrate therapy versus continued UDCA monotherapy. The liver transplantation (LT)-free survival and the alkaline phosphatase (ALP) normalization rates were estimated using Cox regression analyses and Kaplan-Meier plots with inverse probability of treatment weighting (IPTW). RESULTS: A total of 118 patients were included: 54 received UDCA alone and 64 received UDCA in combination with fenofibrate therapy. In the fenofibrate and UDCA groups, 37% and 11% of patients with advanced and UDCA-refractory PBC, respectively, achieved ALP normalization (P=0.001). Additional fenofibrate therapy improved both LT-free survival and ALP normalization rate after IPTW (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07-0.75, P=0.015; and HR: 11.66, 95% CI: 5.02-27.06, P=0.001, respectively). These effects were supported by parallel changes in the rates of liver decompensation and histologic progression, and the United Kingdom (UK)-PBC and Globe risk scores. During the follow-up period, serum levels of ALP and aminotransferase decreased significantly, while total bilirubin, albumin, platelet, serum creatinine, and estimated glomerular filtration rate remained stable in fenofibrate-treated participants. No fenofibrate-related significant adverse events were observed in our cohort. CONCLUSIONS: Additional fenofibrate therapy significantly improved LT-free survival and ALP normalization in patients with advanced and UDCA-refractory PBC. Furthermore, adding-on fenofibrate therapy appeared to be safe and well tolerated in this population.

Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation.

Hexarelin, a synthetic growth hormone-releasing peptide, is shown to be protective in cardiovascular diseases such as myocardial infraction and atherosclerosis. However, the functional role of hexarelin in abdominal aortic aneurysm (AAA) remains undefined. The present study determined the effect of hexarelin administration (200 µg/kg twice per day) in a mouse model of elastase-induced abdominal aortic aneurysm. Echocardiography and in situ pictures showed hexarelin decreased infrarenal aorta diameter. Histology staining showed elastin degradation was improved in hexarelin-treated group. Hexarelin rescued smooth muscle cell contractile phenotype with increased α-SMA and decreased MMP2. Furthermore, hexarelin inhibited inflammatory cell infiltration, NLRP3 inflammasome activation and IL-18 production. Particularly, hexarelin suppressed NF-κB signaling pathway which is a key initiator of inflammatory response. These results demonstrated that hexarelin attenuated AAA development by inhibiting SMC phenotype switch and NF-κB signaling mediated inflammatory response.

The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study.

Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer. Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8. Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively) Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.

Clinical and molecular characteristics associated with survival among cancer patients receiving first-line anti-PD-1/PD-L1-based therapies.

BACKGROUND: Anti-PD-1/PD-L1-based therapy has emerged recently, and we aimed to figure out the latent value of different clinical and molecular factors to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy compared with non-immunotherapy in the first-line setting. METHODS: We assessed the clinical outcomes of 8711 patients in 13 trials receiving anti-PD-1/PD-L1-based therapy or non-immunotherapy as first-line treatment, and different predictors were investigated. RESULTS: Overall, compared with non-immunotherapy, anti-PD-1/PD-L1-based therapy reduced the risk of death by 31% (HR 0.69, 95%CI: 0.60-0.79) for all cancers. Stratified analysis showed that the progression-free survival (PFS) benefit from anti-PD-1/PD-L1-based therapy existed in all three PD-L1 status subgroups (tumour proportion score, TPS ≥50%: HR 0.54, 95%CI: 0.38-0.78; TPS 1-49%: HR 0.56, 95%CI: 0.46-0.68; TPS <1%: HR 0.82, 95%CI: 0.73-0.91; interaction, p < 0.01). ICI therapy also prolonged PFS in males (HR 0.64, 95%CI: 0.50-0.83) and younger patients (HR 0.70, 95%CI: 0.52-0.93), and they might prolong overall survival (OS) in patients without brain metastasis (HR 0.54, 95%CI: 0.41-0.71). CONCLUSION: PD-L1 expression level alone is imperfect to predict the efficacy of anti-PD-1/PD-L1-based therapies as first-line cancer treatment. Meanwhile, sex, age, and status of brain metastases might also be predictive parameters for the selection of cancer patients.

Human UTP14a promotes angiogenesis through upregulating PDGFA expression in colorectal cancer.

The human UTP14a (hUTP14a) promotes degradation of p53 and RB. Moreover, hUTP14a stabilizes c-Myc and is associated with the metastasis of human colorectal cancer (CRC). Angiogenesis plays a key role in tumor growth and metastasis. However, how hUTP14a regulates angiogenesis is unknown. Here, we show that nucleolar expression of hUTP14a is positively associated with higher microvascular density (MVD) in the CRC tumor tissues. The conditioned medium (CM) from CRC cells HCT116 and LoVo with hUTP14a knockdown impairs tube formation and migration of human umbilical vein endothelial cells (HUVECs). RNA-seq analysis indicates that hUTP14a might regulate expression of angiogenic factors in tumor cells. We further demonstrate that hUTP14a upregulates transcription and secretion of platelet-derived growth factor subunit A (PDGFA) in CRC cells. The CRC-CM derived from hUTP14a-depleted cells inhibits the PDGFA-mediated signaling pathway and induces apoptosis in HUVECs. In contrast, the CRC-CM derived from cells expressing Flag-hUTP14a activates the PDGFA-mediated signaling pathway in HUVECs. Importantly, the CRC-CM derived from Flag-hUTP14a-expressing cells promotes angiogenesis in HUVECs, which is counteracted by PDGFR inhibitor imatinib. We thus demonstrate that hUTP14a promotes angiogenesis by upregulating expression and secretion of PDGFA. The in vivo Matrigel plug assay shows that depletion of hUTP14a dramatically decreased MVD in mice xenografts. Collectively, we demonstrate that hUTP14a promotes angiogenesis in CRC and indicate that targeting hUTP14a might improve the prognosis of the hUTP14a-expressing CRC patients.

First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. METHODS: Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. RESULTS: Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12-1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10-1.28) and sisters only (RR 1.71, 95% CI 1.43-2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74-4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04-1.34) with low-quality evidence. CONCLUSIONS: This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.

Aryl hydrocarbon receptor rs2066853 gene polymorphisms and male infertility risk: a meta-analysis.

To evaluate the relationship between the aryl hydrocarbon receptor (AHR) rs2066853 gene polymorphism and the risk of male infertility. PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant case-control studies up to 31 July 2019. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations. Finally, seven case-control studies involving 1247 cases and 1762 controls were included in this meta-analysis. The pooled results showed that there was no significant association between AHR rs2066853 gene polymorphism and male infertility risk (A vs. G: OR = 1.08, 95% CI = 0.83-1.39; AA vs. GG: OR = 1.16, 95% CI = 0.65-2.04; AA vs. GA + GG: OR = 1.17, 95% CI = 0.66-2.07; AA + GA vs. GG: OR = 0.99, 95% CI = 0.85-1.15). Subgroup analysis by ethnicity showed the same result. However, significant association was found between AHR rs2066853 gene polymorphism and male infertility risk in oligoasthenotspermia (A vs. G: OR = 2.52, 95% CI = 1.72-3.70). In conclusion, our meta-analysis indicated that AHR rs2066853 gene polymorphism might be associated with an increased susceptibility to oligoasthenotspermia.

NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2.

As a genome guardian, p53 maintains genome stability by arresting cells for damage repair or inducing cell apoptosis to eliminate the damaged cells in stress response. Several nucleolar proteins stabilize p53 by interfering Mdm2-p53 interaction upon cellular stress, while other mechanisms by which nucleolar proteins activate p53 remain to be determined. Here, we identify NAT10 as a novel regulator for p53 activation. NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. After DNA damage, NAT10 translocates to nucleoplasm and activates p53-mediated cell cycle control and apoptosis. Finally, NAT10 inhibits cell proliferation and expression of NAT10 decreases in human colorectal carcinomas. Thus, our data demonstrate that NAT10 plays a critical role in p53 activation via acetylating p53 and counteracting Mdm2 action, providing a novel pathway by which nucleolar protein activates p53 as a cellular stress sensor.

Diagnostic Performance of DWI With Multiple Parameters for Assessment and Characterization of Pulmonary Lesions: A Meta-Analysis.

OBJECTIVE: The objective of our study was to evaluate the diagnostic performance of DWI using a 5-point rank scale, lesion-to-spinal cord signal intensity ratio, which we refer to as "LSR," and apparent diffusion coefficient (ADC) for the characterization of pulmonary lesions. MATERIALS AND METHODS: After a literature search in several databases, two investigators independently selected studies, assessed methodologic quality, and extracted data. On a per-lesion basis, we pooled and compared the three parameters for malignant and benign lesions. Also, we determined pooled sensitivity and specificity with individual 95% CIs. RESULTS: In total, 31 articles involving 2368 lesions were included. The mean scores of malignant and benign lesions on the 5-point scale were 3.83 (95% CI, 3.71-3.96) and 2.36 (95% CI, 2.18-2.54), respectively. The mean LSRs of malignant and benign lesions were 1.15 (95% CI, 1.07-1.24) and 0.71 (95% CI, 0.62-0.79). The mean ADC values of malignant and benign lesions were 1.23 (95% CI, 1.21-1.24) and 1.72 (95% CI, 1.68-1.77). All three parameters differed significantly between malignant and benign lesions (p < 0.05). On the basis of these parameters, the pooled sensitivity and specificity were 0.88 (95% CI, 0.84-0.91) and 0.75 (95% CI, 0.68-0.80) for the 5-point scale, 0.80 (95% CI, 0.75-0.85) and 0.85 (95% CI, 0.76-0.92) for LSR, and 0.84 (95% CI, 0.82-0.86) and 0.84 (95% CI, 0.81-0.87) for ADC. CONCLUSION: Three DWI parameters-a visual parameter (score on a 5-point scale), semiquantitative parameter (LSR), and quantitative parameter (ADC)-can help to distinguish malignant from benign pulmonary lesions.

Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis.

Background Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation. Purpose To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer. Material and Methods Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses. Results Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41-0.50) and 0.65 (95% CI, 0.56-0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions. Conclusion Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.

TP53 gene Arg72Pro polymorphism and male infertility risk: A meta-analysis.

To evaluate the association between TP53 codon72 polymorphism and male infertility risk. We conducted a search on Medline, Embase, Web of Science and CNKI up to April 30, 2017. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of the association. Seven studies including 1,818 cases and 2,278 controls met the inclusion criteria. The pooled results indicated that no significant association was observed between TP53 codon72 polymorphism and male infertility risk (G versus C: OR = 1.11, 95%CI = 0.94-1.32; GG versus CC: OR = 1.26, 95%CI = 0.90-1.78; GG versus GC+CC: OR = 1.16, 95%CI = 0.90-1.49; GG+GC versus CC: OR = 1.15, 95%CI = 0.88-1.49). In the subgroup analysis by ethnicity, significant association was observed between TP53 codon72 polymorphism and male infertility risk in non-Chinese (G versus C: OR = 1.47, 95%CI = 1.14-1.89), but not in Chinese population (G versus C: OR = 1.03, 95%CI = 0.87-1.22). In conclusion, this study suggested that TP53 codon72 polymorphism might be associated with an increased susceptibility to male infertility in non-Chinese population, but not in Chinese population. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

[Application of Biological Heart Valves (BHV) and Mechanical Heart Valves (MHV) in the Female Patients of Childbearing Age: a Matched Paired Study].

OBJECTIVE: To observe the efficacy and safety of biological heart valves (BHV) and mechanical heart valves (MHV) in childbearing age women (CAW) during the perinatal and short-moderate term postoperative (SMTP) periods. METHODS: There were 33 patients [(25.2±7.1) yr.] undergoing BHV replacement from September 2009 to December 2014 had completely followed-up,whose data were retrospectively collected. A 1∶4 matching study was conducted,therefore there were 132 patients undergoing MHV were included. The collected date included the clinical outcomes in the perioperative, perinatal,and SMTP period event-free survival (EFS) was determined using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The average follow-up time was (5.8±3.6) years,and the two groups had similar baseline . The clinical outcomes difference of perinatal and SMTP between the two groups were not significant. There were 17 patients in BHV group and 60 in MHV group with pregnancy and birth experiences (PBE),which also showed no significant difference for adverse events both in the maternity and in the fetus. The rates of valve-related adverse events of BHV replacement patients with and without PBE were 5.9% and 0% at 3 years after the operation, and 11.8% and 5.9% after 5 years. PBE was not identified as an adverse prognostic factor for EFS (P=0.43). CONCLUSION: Either artificial BHV or MHV replacement can achieve ideal SMTP effect in CAW. BHV seems not superior to MHV. Pregnancy and birth experience will not increase the risk of BHV relevant adverse events.

The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

Prognosis research of delayed facial palsy after microvascular decompression for hemifacial spasm.

BACKGROUND: Although microvascular decompression (MVD) surgery has been widely accepted as an effective treatment for hemifacial spasm (HFS), delayed facial palsy (DFP) is not an unusual complication, but it has only been sporadically described in the literature. The purpose of this study was to examine the probability of occurrence, the risk/predisposing factors, and the prognosis and timing of DFP. METHODS: A prospective cohort study was conducted that included patients diagnosed with HFS and treated by MVD at our institution. All patients were followed up at the outpatient department or by telephone from December 2009 to December 2014. Categorical variables were analyzed using the Pearson's Chi-square test or Fisher's exact test. Continuous variables were compared using the independent Student's t test. The Spearman rank test was used to determine the correlation between the time of onset and the duration of DFP. The risk/predisposing factors were analyzed by the logistic regression method. RESULTS: We enrolled 248 patients who were treated by MVD for HFS. During the follow-up period, 16 patients (6.5 %) developed DFP. Fifteen of those patients had a complete recovery, and in one patient the facial palsy did not resolve. The average onset time was 10.2 days (range, 2-30 days) after surgery, and the mean duration of DFP after MVD, with exclusion of the permanent facial palsy patient, was 59.7 days (range, 7-220 days). The time of onset was correlated with the duration of DFP after MVD (p = 0.036). Furthermore, hypertension contributed to DFP (odds ratio [OR] 4.226, 95 % confidence interval [CI] 1.089-16.401, p = 0.037). CONCLUSIONS: Although the degree of facial palsy was variable, most patients experienced a complete recovery without requiring any special treatment. DFP may be a self-healing disease that resolves spontaneously without any treatment. The time of onset was correlated with the duration of DFP; i.e., an earlier development of DFP corresponded with a shorter duration, whereas a later development of DFP corresponded with a longer duration. Our results also suggest that hypertension contributes to DFP.

Effectiveness and safety of ShenXiong glucose injection for acute ischemic stroke: a systematic review and GRADE approach.

BACKGROUND: To appraise critically whether published trials of ShenXiong glucose injection for patients with acute ischemic stroke (AIS) are of sufficient quality, and in addition to rate the quality of evidence by using the GRADE approach (grading of recommendations, assessment, development, and evaluation, GRADE). METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, Chinese TCM (traditional Chinese medicine) Database, CNKI, VIP, WanFang Databases until January 2015. The limits were patients with AIS and randomized controlled trials (RCTs) or quasi-RCTs. Studies by which patients suffering intracerebral haemorrhage were excluded. RESULTS: Twelve studies fulfilled the inclusion criteria. We found significant benefits of ShenXiong glucose injection compared with conventional treatment in improving activities of daily living function at 4 weeks (MD = 34.12, 95 % CI: 29.07, 39.17), neurological function deficit at 2 weeks (MD = -5.39, 95% CI: -6.90, -3.87), 4 weeks (MD = -5.16, 95 % CI: -6.49, -3.83), and clinical effects at 4 weeks (RR = 1.17, 95% CI: 1.10, 1.24). No trials reported the effects of ShenXiong glucose injection on the risk of early, deterioration, or quality of life. No adverse events were reported within the whole follow-up period. CONCLUSIONS: The use of ShenXiong glucose injection may improve rehabilitation for patients with acute ischemic stroke, however, as the GRADE approach indicated low to moderate quality of available evidence as well as insufficient information about harm and patients preference, the recommendations were not provided for ShenXiong glucose injection taking as a therapeutic intervention to patients with acute ischemic stroke.

Heterogeneous Cardiac- and Neural Crest-Derived Aortic Smooth Muscle Cells have Similar Transcriptional Changes after TGFß Signaling Disruption.

Smooth muscle cells (SMCs) of cardiac and neural crest origin contribute to the developing proximal aorta and are linked to disease propensity in adults. We analyzed single-cell transcriptomes of SMCs from mature thoracic aortas in mice to determine basal states and changes after disrupting transforming growth factor-ß (TGFß) signaling necessary for aortic homeostasis. A minority of Myh11 lineage-marked SMCs differentially expressed genes suggestive of embryological origin. Additional analyses in Nkx2-5 and Wnt1 lineage-marked SMCs derived from cardiac and neural crest progenitors, respectively, showed both lineages contributed to a major common cluster and each lineage to a minor distinct cluster. Common cluster SMCs extended from root to arch, cardiac subset cluster SMCs from root to mid-ascending, while neural crest subset cluster SMCs were restricted to the arch. The neural crest subset cluster had greater expression of a subgroup of TGFß-dependent genes suggesting specific responsiveness or skewed extracellular matrix synthesis. Nonetheless, deletion of TGFß receptors in SMCs resulted in similar transcriptional changes among all clusters, primarily decreased extracellular matrix molecules and modulators of TGFß signaling. Many embryological markers of murine aortic SMCs were not confirmed in adult human aortas. We conclude: (i) there are multiple subtypes of cardiac- and neural crest-derived SMCs with shared or distinctive transcriptional profiles, (ii) neural crest subset SMCs with increased expression of certain TGFß-inducible genes are not spatially linked to the aortic root predisposed to aneurysms from aberrant TGFß signaling, and (iii) loss of TGFß responses after receptor deletion is uniform among SMCs of different embryological origins.

Short-Term Disruption of TGFß Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced Dissection.

Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGFß signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGFß-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.

Corrosion Resistance of Amorphous-Nanocrystalline Composite Structure Materials.

The purpose of this paper is to investigate the corrosion resistance of different nanoscale microstructures in the same material system and propose a novel method to obtain high-performance materials. During the last 2 decades, microstructure refinement and microalloying have become the main methods to prepare high-performance materials. The tensile strength of nanocrystalline solid solutions can reach 2.3 gigapascal, which is more than 1 fold the strength of traditional steel. However, there are few studies about the corrosion resistance of different nanoscale microstructures. In this paper, coatings with different microstructures (nanocrystalline, amorphous, and amorphous-nanocrystalline composite) have been successfully prepared by electrodeposition in the same material system (nickel-phosphorus alloy). Electrochemical test and high-pressure corrosion immersion test were carried out. The results show that the material loss of amorphous-nanocrystalline coating (P = 9.2 wt %) is about 1/4 that of crystalline coating at 8 MPa. In the range of 0.1 and 8 MPa, the average acceleration effect of hydrostatic pressure on the corrosion rate was calculated to be 1.611 × 10-6 g·cm-2·d-1·MPa-1.