IiAGL6 participates in the regulation of stamen development and pollen formation in Isatis indigotica.

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.

Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing.

Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.

Selenium attenuates the association of co-exposure to arsenic, cadmium, and lead with cognitive function among Chinese community-dwelling older adults.

The effects of interactions between the toxic and essential metal mixtures on cognitive function are poorly understood. This study aims to identify the joint association of arsenic (As), cadmium (Cd), and lead (Pb) with cognitive function in older adults and the moderating role of selenium (Se), zinc (Zn), and copper (Cu) in this association. This study included 1000 community-dwelling older adults. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Blood concentrations of As, Cd, Pb, Se, Zn, and Cu were measured using inductively coupled plasma mass spectrometry. Linear regression and Bayesian kernel machine regression (BKMR) models were applied to assess the individual and joint associations of As, Cd, and Pb with cognitive function and to examine whether Se, Zn, and Cu (individually and as a mixture) modified these associations. In the adjusted single-metal models, both Cd (ß = - 0.37, 95% CI: - 0.73 to - 0.01) and Pb (ß = - 0.44, 95% CI: - 0.86 to - 0.02) were associated with MMSE scores, while Se (ß = 0.71, 95% CI: 0.30 to 1.13) exhibited a positive relationship with MMSE scores. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the toxic metal mixture (As, Cd, and Pb) exhibited a significant negative association with MMSE scores in a dose-response pattern, with Pb being the greatest contributor within the mixture. The negative association of Pb alone or the toxic metal mixture with MMSE scores became weaker at higher concentrations of Se within its normal range, especially when Se levels were greater than the median (89.18 µg/L). Our findings support that Se can attenuate the negative associations of exposure to single Pb or the As, Cd, and Pb mixtures with cognitive function. Future prospective studies are needed to replicate our findings.

Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy.

Messenger RNA (mRNA) is being developed by researchers as a novel drug for the treatment or prevention of many diseases. However, to enable mRNA to fully exploit its effects in vivo, researchers need to develop safer and more effective mRNA delivery systems that improve mRNA stability and enhance the ability of cells to take up and release mRNA. To date, lipid nanoparticles are promising nanodrug carriers for tumor therapy, which can significantly improve the immunotherapeutic effects of conventional drugs by modulating mRNA delivery, and have attracted widespread interest in the biomedical field. This review focuses on the delivery of mRNA by lipid nanoparticles for cancer treatment. We summarize some common tumor immunotherapy and mRNA delivery strategies, describe the clinical advantages of lipid nanoparticles for mRNA delivery, and provide an outlook on the current challenges and future developments of this technology.

Determination of nine nucleosides in Rhizoma Paridis by quantitative analysis of multi-components via a single marker method.

In this work, a new quantitative analysis method of multi-components analysis via a single marker strategy coupled with high-performance liquid chromatography (HPLC) analysis, was proposed to analyze nine nucleosides (cytidine, uridine, 2'-deoxyuridine, inosine, guanosine, 2'-deoxyguanosine, thymidine, adenosine, and 2'-deoxyadenosine) as quality control markers in Rhizoma Paridis. Guanosine was set as the internal reference substance, whose content in Rhizoma Paridis was determined using conventional external standard method. Then, relative correction factors between guanosine and the other eight nucleosides were measured respectively. The amounts of the other eight components were calculated according to the relative correction factors by the quantitative analysis of multi-components via a single marker method. Finally, the result of vector angle cosine analysis showed that there was no significant difference of the contents between the external standard method and the quantitative analysis of multi-components via a single marker method, indicating that the quantitative analysis of multi-components via a single marker method can be applied for the quality control of Rhizoma Paridis. As far as we know, this is also the first report to analyze nucleosides by the quantitative analysis of multi-components via a single marker method, providing an efficient and promising quality assessment method for other traditional Chinese medicine containing nucleosides.

Upregulation of aurora kinase A promotes vascular smooth muscle cell proliferation and migration by activating the GSK-3ß/ß-catenin pathway in aortic-dissecting aneurysms.

AIMS: Aurora kinase A (AURKA) is a mitotic serine/threonine kinase that contributes to the regulation of cell-cycle progression. AURKA has been shown to further enhance Wnt/ß-catenin signaling; however, in the context of driving aortic-dissecting aneurysm (ADA), the molecular details of this phenomenon remain poorly understood. MATERIALS AND METHODS: A total of 43 specimens of ADA tissues and eleven healthy aortic tissues as controls were collected from the hospital. Pathological changes were observed by hematoxylin and eosin staining. AURKA expression in aortic tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry staining. The proliferative and migratory effects of AURKA were observed in cultured vascular smooth muscle cells (VSMCs). KEY FINDINGS: AURKA expression was significantly increased in aorta samples from ADA patients relative to those from normal donors, and the expression was even higher in ruptured ADA tissues. AURKA overexpression promoted and AURKA knockdown inhibited, respectively, the proliferation, and migration of VSMCs. Angiotensin II (AngII) treatment of VSMCs significantly increased AURKA expression. The knockdown of AURKA partially reversed AngII-induced VSMC proliferation and migration. Finally, the downregulation of AURKA inhibited cell proliferation by inactivating the p-GSK-3ß/ß-catenin pathway. SIGNIFICANCE: The GSK-3ß/ß-catenin signaling pathway participates in the AURKA-regulated proliferation and migration of VSMCs. The expression of AURKA may be involved in the phenotypic conversion of VSMC and the occurrence and development of ADA and could be a potential molecular target for ADA therapy.

Tuberous sclerosis complex presenting as primary intestinal lymphangiectasia: A case report.

BACKGROUND: Primary intestinal lymphangiectasia (PIL) is a rare congenital protein-losing enteropathy caused by dysplasia of the small intestinal lymphatics. The cause of the disease is unknown. Through a literature review, we found that PIL and tuberous sclerosis complex (TSC) have some common symptoms and molecular pathways. CASE SUMMARY: Here, we present the case of a patient with a three-year history of primary intestinal lymphangiectasia. The patient most recently visited the hospital with abdominal distension and swelling of the left leg. His mother told us that she was diagnosed with TSC one year previously, which alerted us because the patient had multiple regions of pigmentation. To evaluate the condition of the child and make a definite diagnosis, multiple imaging examinations were performed, as was TSC gene analysis. The results met the diagnostic criteria for TSC. The patient was discharged after symptomatic treatment. Through a review of the literature, it can be seen that changes at the molecular gene level of TSC can lead to abnormal lymphatic vessels. CONCLUSION: In summary, when patients with hypomelanotic macules or enamel hypoplasia are diagnosed with PIL, TSC gene screening may be important for further diagnosis.

Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice.

Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.

Postnatal nectin-3 knockdown induces structural abnormalities of hippocampal principal neurons and memory deficits in adult mice.

The early postnatal stage is a critical period of hippocampal neurodevelopment and also a period of high vulnerability to adverse life experiences. Recent evidence suggests that nectin-3, a cell adhesion molecule, mediates memory dysfunction and dendritic alterations in the adult hippocampus induced by postnatal stress. But it is unknown whether postnatal nectin-3 reduction alone is sufficient to alter hippocampal structure and function in adulthood. Here, we down regulated hippocampal expression of nectin-3 and its heterophilic adhesion partner nectin-1, respectively, from early postnatal stage by injecting adeno-associated virus (AAV) into the cerebral lateral ventricles of neonatal mice (postnatal day 2). We found that suppression of nectin-3, but not nectin-1, expression from the early postnatal stage impaired hippocampus-dependent novel object recognition and spatial object recognition in adult mice. Moreover, AAV-mediated nectin-3 knockdown significantly reduced dendritic complexity and spine density of pyramidal neurons throughout the hippocampus, whereas nectin-1 knockdown only induced the loss of stubby spines in CA3. Our data provide direct evidence that nectins, especially nectin-3, are necessary for postnatal hippocampal development of memory functions and structural integrity.

Ambient air pollution and adverse birth outcomes: a systematic review and meta-analysis.

Several reviews have assessed the relationship between exposure to ambient air pollution and adverse birth outcomes during pregnancy, but the results remain controversial. The objective of this study was to assess this correlation quantitatively and to explore sources of heterogeneity. We included all published case-control or cohort studies that evaluated the correlation between ambient air pollution and low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). Analytical methods and inclusion criteria were provided on the PROSPERO website (CRD42018085816). We evaluated pooled effects and heterogeneity. Subgroup analyses (grouped by exposure period, study settings, study design, exposure types, data source, Newcastle-Ottawa quality score (NOS), and adjustment for smoking or meteorological factors) were also conducted and publication bias was examined. The risk of bias in systematic reviews (ROBIS) tool was used to evaluate the overall risk of bias in this review. Forty studies met the inclusion criteria. We observed pooled odds ratios (ORs) of 1.03-1.21 for LBW and 0.97-1.06 for PTB when mothers were exposed to CO, NO2, NOx, O3, PM2.5, PM10, or SO2 throughout their pregnancy. For SGA, the pooled estimate was 1.02 in relation to NO2 concentrations. Subgroup analysis and sensitivity analysis decreased the heterogeneity to some extent, such as the subgroups of continuous measures (OR=0.98 (0.97-0.99), I2=0.0%) and NOS>7 (OR=0.98 (0.97-0.99), I2=0.0%) in evaluating the association between PTB and NO2. This review was completed with a low risk of bias. High concentrations of air pollution were significantly related to the higher risk of adverse birth outcomes. However, the sources of heterogeneity among studies should be further explored.

Identification of a novel strain, Streptomyces blastmyceticus JZB130180, and evaluation of its biocontrol efficacy against Monilinia fructicola.

Peach brown rot, caused by Monilinia fructicola, is one of the most serious peach diseases. A strain belonging to the Actinomycetales, named Streptomyces blastmyceticus JZB130180, was found to have a strong inhibitory effect on M. fructicola in confrontation culture. Following the inoculation of peaches in vitro, it was revealed that the fermentation broth of S. blastmyceticus JZB130180 had a significant inhibitory effect on disease development by M. fructicola. The fermentation broth of S. blastmyceticus JZB130180 had an EC50 (concentration for 50% of maximal effect) of 38.3 µg/mL against M. fructicola, as determined in an indoor toxicity test. Analysis of the physicochemical properties of the fermentation broth revealed that it was tolerant of acid and alkaline conditions, temperature, and ultraviolet radiation. In addition, chitinase, cellulase, and protease were also found to be secreted by the strain. The results of this study suggest that S. blastmyceticus JZB130180 may be used for the biocontrol of peach brown rot.

An Observation of the Role of Autophagy in Patients with Endometriosis of Different Stages during Secretory Phase and Proliferative Phase.

BACKGROUND: Autophagy exists widely in various physiological and pathological conditions. Lots of investigations have verified that the autophagic activity is always related to the occurrence and the development of cancer. Endometriosis (EMs) is a disease that endometrium-like tissues abnormally grow outside the uterus and also considered to possess the characters of tumor because of its malignant biological behavior. INTRODUCTION: Recently, several studies have already revealed that autophagy may play a potential role in proliferative-phase EMs. However, the function of autophagic activity in secretory-phase EMs is still unclear. METHODS: In our work, we explored autophagic activity between normal endometrium and EMs lesion endometrium during different menstrual phases and EMs stages. The clinical endometrium samples from 73 women were selected in this study, including 30 healthy individuals and 43 patients with EMs (endometrium samples include eutopic and its matched ectopic endometrium). All the participants were divided into two groups according to the menstrual cycle, namely proliferative-phase and secretive- phase group. Among the patients with EMs, 22 individuals in proliferative phase and the other 21 individuals in secretory phase were further classified into the groups of Stage I-II and Stage III-IV according to revised-American Fertility Society (r-AFS). Two autophagy-related proteins microtubuleassociated protein 1 light chain 3 beta-II (LC3B-II) and sequestosome protein (P62), which are believed to be the indicators of autophagy activity, were chosen in the study. Immunohistochemical (IHC) staining, Western blot assay and Real-Time quantitative Polymerase Chain Reaction (RTqPCR) were used to examine the expression of LC3B-II and P62 in protein and mRNA level accordingly. RESULT: It showed that the expression of LC3B-II both in protein and mRNA level decreased and that of P62 increased in secretory phase of the healthy group (P<0.05), but showed no significant difference in ectopic and its eutopic endometrium group during proliferative and secretory phase (P>0.05). In addition, the expression of LC3B-II in ectopic endometrium group was significantly lower than that of its eutopic endometrium group (P<0.05), and the expression of P62 was significantly higher accordingly (P<0.05). At the same time, both LC3B-II and P62 levels remained same between eutopic endometrium group and control group (P>0.05). Furthermore, compared to Stage I-II EMs group, the expression of LC3B-II was significantly lower (P<0.05) and P62 was significantly higher (P<0.05) in Stage III-IV EMs during secretory phase. CONCLUSION: Taken together, the periodicity-losing in EMs and the decreased autophagic activity in ectopic endometrium may exert a potential role in the pathogenesis of EMs. Down-regulated autophagy of ectopic endometrium in secretory phase may be related to the progression of EMs.

Long-Term Outcomes of Caustic Esophageal Stricture with Endoscopic Balloon Dilatation in Chinese Children.

Caustic esophageal stricture (CES) in children still occurs frequently in developing countries. We aimed to evaluate the long-term outcomes of endoscopic balloon dilatation (EBD) in treating CES in children and the influencing factors associated with outcome. We retrospectively reviewed the data of all patients who had a diagnosis of CES and underwent EBD from August 1, 2005, to December 31, 2014. The primary outcome was EBD success, which was defined as the maintenance of dysphagia-free status for at least 12 months after the last EBD. The secondary outcome was to analyze influencing factors associated with EBD success. Forty-three patients were included for analysis (29 males; mean age at first dilatation 44 months with range 121 months). 26 (60.5%) patients had long segment (>2 cm) stricture. A total of 168 EBD procedures were performed. Twenty-six (60.5%) patients were considered EBD success. Seventeen (39.5%) patients failed EBD and required stent placement and/or surgery. Patients in the EBD success group had significantly shorter stricture segments when compared to the EBD failure group (t = 2.398, P = 0.018, OR = 3.206, 95% OR: 1.228-8.371). Seven (4.4%) esophageal perforations occurred in 6 patients after EBD. Stents were placed in 5 patients, and gastric tube esophagoplasty was performed in 14 patients. In conclusion, 26 (60.5%) of 43 children with CES had EBD success. Length of stricture was the main influencing factor associated with EBD treatment outcome.

Significance and prognosis of epithelial-cadherin expression in invasive breast carcinoma.

The objective of the present study was to investigate and analyze the epithelial-cadherin (E-cadherin) expression in invasive ductal carcinoma of the breast, and to analyze the associations between the expression and clinicopathological characteristics of lymph node metastasis and the prognosis of breast cancer. The immunohistochemical streptavidin-peroxidase method was used to detect the E-cadherin expression in 30 cases of breast fibroadenoma and in 450 cases of invasive breast cancer, and then the χ2test and Kaplan-Meier method were used to analyze the data. The 30 cases of breast fibroadenoma showed positive expression of E-cadherin. Specifically, results found that E-cadherin was highly expressed in 49.04% (77/157) of patients with non-metastatic breast cancer, while low expression was found in 50.96% (80/157). Additionally, E-cadherin was highly expressed in 29.69% (87/293) of patients with lymph node metastasis of breast cancer, with low expression in 70.31% (206/293); these differences were significantly different (χ2=16.53; P<0.001). E-cadherin was expressed in 35.48% (22/62), 33.73% (84/249), 63.83% (30/47) and 30.43% (28/92) of patients with luminal A type, luminal B type, human epidermal growth factor receptor-2positive and triple-negative breast cancer (TNBC), respectively. It was found that patients with high expression of E-cadherin had a better prognosis than the low expression group with regards to TNBC, and this result was significantly different (χ2=4.48; P=0.034). In conclusion, low E-cadherin expression was associated with lymph node metastasis in invasive breast cancer, and the patients with low expression also had a poor prognosis compared with those in the high expression group. The present results suggested that E-cadherin could be used in a prognostic index for patients with lymph node metastasis and TNBC.

[Pollutant Emissions from Diesel Buses Fueled with Waste Cooking Oil Based Biodiesel].

Two diesel buses respectively certified to meet China Ⅲ and China Ⅴ emission standards were used as prototype vehicles, fixed on a heavy-duty chassis dynamometer and driven according to a typical city bus driving cycle to analyze the pollutant emissions and volatile organic compounds (VOCs). The buses were fueled with diesel and waste cooking oil based biodiesel with 10 vol% blend ratio (B10). The emissions of total hydrocarbon(THC), CO, particulate matter (PM), and the number of solid particles with a diameter of 23 nm to 2.5 µm (referred to as "solid particulate number of PM2.5") from the bus certified to meet China Ⅴ (referred to as "China V bus") were 39.3%, 19.9%, 77.4%, and 28.4% lower than those from the other bus certified to meet China Ⅲ (referred to as "China Ⅲ bus"), while NOx emissions were 31.7% higher. Moreover, alkanes, alkenes, aromatic hydrocarbons, and oxygenated compounds in VOCs emitted from the China V bus were lower than those emitted from the China Ⅲ bus, suggesting lower atmospheric reactivity and smaller potential of secondary organic aerosol formation. Compared with the emission results of two diesel-fueled buses, the B10-fueled buses emitted smaller amounts of THC, CO, PM, and solid particulate number of PM2.5, lower oxygenated compounds but higher alkenes; slightly higher NOx emissions than China Ⅲ but slightly lower NOx emissions than China V. Consequently, the atmospheric reactivity of VOCs in exhaust gas from the bus fueled with B10 was higher than that from the diesel-powered bus.

Cortical Activation Changes in Hirayama Disease After Anterior Cervical Decompression and Fusion.

BACKGROUND: Spinal cord injury may cause cortical reconstruction. We, therefore explored the changes in cortical activation before and after anterior cervical decompression and fusion surgery in patients with Hirayama disease (HD). METHODS: In total, 17 cases with HD underwent anterior cervical decompression and fusion surgery. Blood oxygenation level-dependent functional magnetic resonance imaging scan was performed preoperatively, 3 months, 6 months, and 1 year after surgery. Activated voxels were compared between both hands after adjusting for head motion, slice timing, spatial normalization, and image smoothing. Grip strength also was tested in both hands. RESULTS: A retrospective review indicated that the grip strength of the asymptomatic hand was significantly stronger than the symptomatic hand at the time point before the surgery, 3 months after surgery, 6 months after surgery, and 1 year after surgery (P < 0.001). The grip strength of both symptomatic and asymptomatic hands continuously increased within 6 months after surgery (P < 0.05), but it stopped at 1 year after the surgery. The symptomatic limb tends to produce bilateral activation in the primary motor area (M1) during motor tasks. Both contralateral and ipsilateral M1 activation were stronger in symptomatic hand tasks preoperatively (P < 0.05). Both contralateral and ipsilateral activation in M1 during symptomatic hand tasks began to reduce after surgery, and statistical significance was observed 6 months after surgery (P < 0.05). Contralateral activation was relatively even over 6 months of the surgery (P > 0.05). CONCLUSIONS: After surgery, pathologic reconstruction may have occurred in the primary motor cortex. Recovery of motor function in the symptomatic limb was accompanied by decreased ipsilateral and contralateral M1 activation, as well as symptom improvement. These findings suggested that postoperative cortical activation changes may reflect functional recovery in HD.

Risk Factors of Adjacent Segment Disease After Anterior Cervical Arthrodesis: A Retrospective Study of Sagittal Measurement of Thoracic Inlet Parameters.

BACKGROUND: To explore the predictive parameters for adjacent segment disease (ASD) after anterior cervical arthrodesis at the sagittal measurement of thoracic inlet. METHODS: We included 212 subjects treated with anterior cervical fusion surgery to identify predictive parameters for ASD. We applied multivariate logistic regression to find the relevant parameters. RESULTS: Two hundred patients completed the final follow-up. The results of logistic regression analysis showed that T1 slope of less than 19.50 could be a predictive parameter of ASD after the anterior cervical arthrodesis (P < 0.05). CONCLUSIONS: Sagittal balance of thoracic inlet is vital to avoid the. cervical degenerative disease, while T1 slope of less than 19.50 appears to be an independent risk factor for the ASD, keeping the T1 slope of more than 19.5 is reasonable.

Bevacizumab and risk of intracranial hemorrhage in patients with brain metastases: a meta-analysis.

Administration of bevacizumab to patients with brain metastases (BM) is controversial due to concerns about the increased risk of intracranial hemorrhage (ICH). This meta-analysis assessed whether the risk of ICH increases in BM patients receiving treatments that contain bevacizumab versus without. PubMed, Embase, Cochrane Library and annual meeting abstracts of the American Society of Clinical Oncology up to 13 November 2016 were searched for studies that referred to ICH complications due to bevacizumab in patients with BM. Eight studies involving 8713 patients were included in this analysis. Compared with the control arm without bevacizumab, the bevacizumab treatment arm did not exhibit a significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI) 0.69-2.09; P = 0.53]. Subgroup analyses with retrospective studies showed a similar result, although subgroup analyses with prospective studies failed. This meta-analysis revealed that bevacizumab does not significantly increase the risk of ICH in solid tumor patients with BM.

Prevention of Atrial Fibrillation by Using Sarcoplasmic Reticulum Calcium ATPase Pump Overexpression in a Rabbit Model of Rapid Atrial Pacing.

BACKGROUND Recent research suggests that abnormal Ca2+ handling plays a role in the occurrence and maintenance of atrial fibrillation (AF). Therefore, Ca2+ release and ingestion depend on properties of the ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+ATPase2a (SERCA2a). This study aimed to detect whether SERCA2a gene overexpression has a preventive effect on atrial fibrillation caused by rapid pacing right atrium. MATERIAL AND METHODS Forty-eight New Zealand white rabbits were randomly divided into a control group, AF group, AAV9/GFP group, and AAV9/SERCA2a group. The right atrium was rapidly paced at 600 beats/min for 30 days after an intraperitoneal injection of an adeno-associated virus expressing the SERCA2a gene and GFP. The AF induction rate and the effective refraction period (ERP) were measured after 0, 4, 8, 12, and 24 h of pacing. Western blot analysis was used to test for the expression of SERCA2a. Changes in atrial tissue structure were observed by H&E staining and electron microscopy. RESULTS The AF induction rate was higher in the AF groups than in the AAV9/SERCA2a group at different time points of pacing. After 12 h of pacing, ERP was significantly prolonged in the AAV9/SERCA2a group compared to the AF and AAV9/GFP groups (p<0.05). SERCA2a protein expression was significantly lower in the AF and AAV9/GFP groups compared to the control group (p<0.05), while expression was significantly higher in the AAV9/SERCA2a group than in the AF and AAV9/GFP groups (p<0.05). The myocardial structure of the AAV9/SERCA2a group was significantly improved compared with the AF group, indicating that SERCA2a overexpression relieved the structural remodeling of atrial fibrillation. CONCLUSIONS SERCA2a overexpression is capable of suppressing ERP shortening and AF induced by rapid pacing atrium. SERCA2a gene therapy is expected to be a new anti-atrial fibrillation strategy.

Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines / Efeitos citotóxicos de anestesia local com lidocaína/ropivacaína em linhagens celulares de melanoma humano

Abstract Background: Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Methods: Melanoma cell lines, A375 and Hs294T, were exposed to 1 h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Results: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p < 0.001), concentration- (p < 0.001), and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72 h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10% ± 2% and 14% ± 2% in A375 and Hs294T, respectively after 72 h of exposure. Ropivacaine 0.75% after 72 h reduced viable cells to 15% ± 3% and 25% ± 3% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to the combination was 10% ± 2% and 18% ± 2% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to melphalan was 8% ± 1% and 12% ± 2%, in A375 and Hs294T, respectively. Conclusion: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

Resumo Justificativa: Os anestésicos locais (ALs) são geralmente considerados como seguros, mas citotoxicidade foi relatada em vários anestésicos locais usados em seres humanos, a qual não é bem investigada. No presente estudo, a citotoxicidade de lidocaína e ropivacaína e da combinação de lidocaína e ropivacaína foi avaliada em linhagens celulares de melanoma humano. Melfalano, um agente alquilante de mostarda nitrogenada, foi usado como um agente de controle para a comparação da atividade citotóxica. Métodos: Linhagens celulares de melanoma, A375 e Hs294T foram expostas por uma hora a concentrações diferentes dos agentes mencionados acima. A viabilidade celular após a exposição foi determinada por citometria de fluxo. Resultados: Os ALs investigados mostraram citotoxicidade prejudicial nas linhagens celulares de melanoma estudadas dependente do tempo (p < 0,001), da concentração (p < 0,001) e do agente. Em ambas as linhagens de células A375 e Hs294T, níveis mínimos de viabilidade celular foram encontrados após 72 horas de exposição a esses agentes. Lidocaína a 2% provocou uma redução das células vitais para 10% ± 2% e 14% ± 2% em A375 e Hs294T, respectivamente, após 72 horas de exposição. Ropivacaína a 0,75% após 72 horas reduziu as células viáveis para 15% ± 3% e 25% ± 3%, em A375 e Hs294T, respectivamente. A viabilidade celular mínima após exposição de 72 horas para a combinação foi de 10% ± 2% e 18% ± 2% em A375 e Hs294T, respectivamente. A viabilidade celular mínima após exposição de 72 horas ao melfalano foi de 8% ± 1% e 12 ± 2, em A375 e Hs294T, respectivamente. Conclusão: Os ALs têm atividade citotóxica em linhagens de celulares de melanoma humano de modo dependente do tempo, da concentração e do agente. A apoptose nas linhagens celulares foi mediada por meio da atividade das caspases-3 e caspases-8.