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Pulmonary aspergilloma is chronic and invasive, potentially leading to life-threatening massive hemoptysis. The role of surgery for treating pulmonary aspergilloma and its effect on long-term survival needs more study.We reviewed 166 patients with aspergillomas treated at Shanghai Pulmonary Hospital from 2004 to 2017. Surgery indications included destroyed lung parenchyma, recurrent hemoptysis, despite appropriate medical treatment, and isolated pulmonary nodules suspected to be aspergilloma. Pulmonary aspergillomas are classified as simple (in an isolated thin-walled cavity, ≤3 mm) or complex (a thick-walled cyst,3 mm) based on computed tomographic scan findings.Aspergilloma was complex in 100 patients (60.2%) and simple in 66 (39.8%). The median (interquartile range) size of complex aspergillomas (2.5 [0.3-8.0] cm) was larger than that (2.0 [0.2-6.0] cm) of simple types (P.001). Hemoptysis occurred in 72 patients (72%) with complex disease and in 35 (53%) with simple disease (P = .014). Video-assisted thoracoscopic surgery was performed in 42 patients (63.6%) with simple aspergillomas, and 75 patients (75%) with of complex aspergillomas underwent thoracotomy. Prolonged air leakage (7 days) was the most common (17 [10.2%]) postoperative complication. A bronchopleural fistula developed postoperatively in 1 patient (0.6%). One patient (0.6%) died of respiratory failure within 30 days postoperatively. Two patients (1.2%) experienced recurrence during follow-up. The overall 10-year survival rates were 87.7% for complex aspergillomas and 94.97% for simple aspergillomas (P = .478). Diabetes (12 [7.2%]; hazard ratio, 13.15; 95% CI, 1.12-154.46) was associated with a worse prognosis.The perioperative morbidity and mortality of pulmonary aspergillomas are acceptable. Overall survival rates of simple and complex types are comparable.

Age-related macular degeneration (AMD), a degenerative disease of the outer retina, is the leading cause of blindness among the elderly. A hallmark of geographic atrophy (GA), an advanced type of nonneovascular AMD (dry AMD), is photoreceptor and retinal pigment epithelium (RPE) cell death. Currently, there are no FDA-approved therapies for GA due to a lack of understanding of the disease-causing mechanisms. Increasing evidence suggests that chronic inflammation plays a predominant role in the pathogenesis of dry AMD. Dead or stressed cells release danger signals and inflammatory factors, which causes further damage to neighboring cells. It has been reported that type I interferon (IFN) response is activated in RPE cells in patients with AMD. However, how RPE cells sense stress to initiate IFN response and cause further damage to the retina are still unknown. Although it has been reported that RPE can respond to extracellularly added dsRNA, it is unknown whether and how RPE detects and senses internally generated or internalized nucleic acids. Here, we elucidated the molecular mechanism by which RPE cells sense intracellular nucleic acids. Our data demonstrate that RPE cells can respond to intracellular RNA and induce type I IFN responses via the RIG-I (DExD/H-box helicase 58, DDX58) RNA helicase. In contrast, we showed that RPE cells were unable to directly sense and respond to DNA through the cGAS-STING pathway. We demonstrated that this was due to the absence of the cyclic GMP-AMP synthase (cGAS) DNA sensor in these cells. The activation of IFN response via RIG-I induced expression of cell death effectors and caused barrier function loss in RPE cells. These data suggested that RPE-intrinsic pathways of nucleic acid sensing are biased toward RNA sensing.

Urban subway system, as an important type of urban transportation infrastructure, can provide mass mobility service and help address urban sustainability challenges such as traffic congestion and air pollution. The continuous construction of subways, however, causes large amounts of construction materials and embodied greenhouse gas (GHG) emissions. In this study, we characterized the patterns of subway development, construction material stocks, and embodied emissions covering all 219 cities in the world in which subways are found by July 2020. The global subway length reached 16,419 km in 2020, and the construction material stocks amounted to 2.5 gigatons, equaling to an embodied emission of 560 megatons. In particular, China’s subway system contributes to ~40% of the total global stocks, with a pattern of moderate and steady stocks growth before 2010 and a rapid expansion afterwards, implying the late-development advantages and infrastructure-based urbanization mode. Our results demonstrated that identifying the spatiotemporal characteristics of subway materials stocks development is imperative for benchmarking future resource demand, informing sustainable subway planning, prospecting urban mining and waste management opportunities and challenges, and mitigating the associated environmental impacts for global GHG emission reduction.

Bridges are subjected to long-term deformations in addition to deformations under design loads. In high-speed railway bridges, long-term bridge deformation and potential degradation of materials may adversely impact the operation safety and riding comfort of the railway. While a high-speed railway network is being established in China, it is significant to understand the effects of long-term bridge deformation on track deformation for effective asset management. This study aims to develop an analytical model to investigate the roles of long-term bridge deformations and bridge-track interlayer degradation. Mechanical analysis is conducted to develop a track-bridge deformation model and derive closed-form solutions that can be applied in design and evaluation of high-speed railway bridges. The analytical study is validated against a three-dimensional finite element model, and used to investigate the effects of key parameters (e.g. bridge deformation amplitude, span length, fastener stiffness, and mortar layer stiffness). This study provides a method to quantitatively evaluate track deformation due to bridge deformations and interlayer degradation. With the developed formulae, real-time condition assessment of high-speed railway track can be performed based on real-time monitoring of bridge deformations.

Hypoxic pulmonary hypertension (HPH) is a progressive and irreversible disease that reduces survival. Echinacoside is a phenylethanoid glycoside from Tibetan herbs known for its vasorelaxant effect and for inhibiting the proliferation of rat pulmonary arterial smooth muscle cells. This study aimed to investigate the effect of echinacoside on HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber (4500 m) for 28 days to obtain the HPH model. Echinacoside (3.75, 7.5, 15, 30 and 40 mg/kg) was administered by intraperitoneal injection from the 1st to the 28th day. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index, hemoglobin, hematocrit, red blood cell concentration and morphological change of pulmonary arteries were evaluated. Vascular perfusion assay was used to assess the pulmonary artery function. Echinacoside reduced mPAP, hemoglobin, hematocrit, right ventricular hypertrophy index and mean wall thickness% of pulmonary arteries in HPH rats. It significantly increased maximum vasoconstriction percentage of pulmonary arteries induced by noradrenaline in a dose-dependent manner. In addition, it improved the responsiveness of pulmonary arteries to acetylcholine and sodium nitroprusside. Therefore, Echinacoside might be an effective treatment against HPH, since it regulated pulmonary artery endothelium and smooth muscle layer function and improved the remodeling of pulmonary artery.

Diabetes mellitus (DM) is a highly prevalent chronic systemic disease, which may cause cognitive decline and degenerative change of the brain. Neuronal differentiation defects of neural stem cells (NSCs) played an important role in the development and progression of diabetes-associated cognitive decline (DACD), but the intrinsic pathological mechanism remains largely unclear. In the present study, we demonstrated that expression level of HDAC3 was upregulated in diabetic mice with reduced learning and memory abilities and in cultured NSCs after advanced glycation end products (AGEs) induction. In addition, AGEs interfered with normal differentiation of the cultured NSCs, and knocking down the expression of HDAC3 could partially attenuate the inhibitory effect of AGEs on NSCs differentiation. Findings in this study demonstrate that HDAC3 may serve as an experimental clue for revealing the pathogenesis of DACD.

Diffuse leptomeningeal glioneuronal tumor with the first symptom of acute rapid blindness in both eyes are rare in adolescents. We present a case of an adolescent female without a history of cancer who developed a dramatic loss of vision and eventually blindness, and was diagnosed as diffuse leptomeningeal glioneuronal tumor by cerebrospinal fluid cytology and enhanced MRI. In order to save vision, under the condition of ineffective dehydration treatment, timely emergency surgery to implant Ommaya sac drainage cerebrospinal fluid. According to the pathophysiological mechanism of cerebral edema, we added Edaravone to scavenge oxygen free radicals, Alprostadil to improve microcirculation, Monosialotetrahexosylganglioside nutrient nerve, Butylphthalide to promote collateral circulation, combined with hyperbaric oxygen and acupoint injection of Anisodine. Finally, the patient's vision returned to normal. Conclusion: when dehydration treatment is ineffective, timely surgery to reduce intracranial pressure, combined with comprehensive treatment, can effectively save vision.

External prestressing technology has been successfully adopted for enhancing the load-carrying capacity of beams in bridge engineering. Previous studies on the shear behaviour of externally prestressed concrete (EPC) beams mainly focused on the ultimate shear strength. The post-cracking shear behaviour of EPC beams remains unclear. This study aims to investigate the post-cracking shear behaviour of EPC beams. To this end, nine EPC beams with different design parameters were tested to failure. The investigated parameters included the prestressing condition, shear span to depth ratio, shear reinforcement ratio, and bend angle of external tendons. In contrast to reinforced concrete beams, the EPC beams demonstrated shear tension sliding with concrete spalling failure. The applied prestressing increased the concrete shear contribution by 68%. The percentage of the concrete shear contribution out of the total shear strength of the test beams ranged from 45% to 79%. The post-cracking shear strength reserve ability index, defined as the ratio of the shear strength and shear cracking strength, ranged from 1.72 to 2.96 in the EPC beams. A new ductility index, defined as the ratio of the ultimate deflection and the deflection corresponding to first shear cracking, was used to evaluate the post-cracking deformability of EPC beams. The ductility index of the EPC beams ranged from 3.0 to 7.6, indicating considerable post-cracking deformability. The beam’s stiffness at first shear cracking was 39–81% of the beam’s initial stiffness; the beam’s stiffness at the ultimate state was 18–41% of the beam’s initial stiffness. Finally, the current shear provisions were evaluated by the test results.

Juanfen Mo,1 Li Zheng,1 Zhenzhen Gao,2 Jiayuan Wu,1 Yi Bao1,2 1The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of ChinaCorrespondence: Yi BaoThe Key Laboratory, The Department of Oncology, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Zhejiang, 314000, People’s Republic of ChinaTel +865 738 207 3185Fax +865 738 208 2936Email ybao2011@gmail.comIntroduction: Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells, which strongly express CD161 and are involved in defending against infectious pathogens and inflammatory diseases. They are activated by inflammatory cytokines, secrete various cytokines and cytotoxic molecules, and express chemokine receptors and integrins. However, the underlying mechanisms of MAIT cells in colon cancer are still not fully understood.Methods: The phenotype and frequency of circulating MAIT cells were investigated by flow cytometry in colon cancer patients and healthy donors. CD161 was examined in cancerous and paracancerous nontumor tissues of colon cancer patients by immunohistochemistry. The serum levels of IFN-γ and IL-17A were analyzed by ELISA. Finally, MAIT cells were also detected in peripheral blood and tumor tissues in a CT26 tumor-bearing mice model.Results: The percentages of CD4+CD8− MAIT cells, CD4−CD8+ MAIT cells, and CD4−CD8− MAIT cells increased in the peripheral blood of colon cancer patients compared with healthy donors. The expression of CD161 protein in colon cancer cancerous tissues was higher than that in the paracancerous nontumor tissues. The killer cell lectin-like receptor B1 (KLRB1), a coding gene for CD161, was positively associated with the gene expressions of immune inhibitory receptors, such as CTLA4, HAVCR2, PDCD1, and CD274 in colon cancer. Furthermore, the serum levels of IFN-γ and CEA were positively correlated with CD8+ MAIT cells in the peripheral blood of colon cancer patients.Conclusion: Taken together, our data suggest that the circulating MAIT cells and the expression of CD161 protein in the tumor tissues increased in colon cancer patients, and MAIT cells may participate immune activities in colon cancer.Keywords: MAIT cells, colon cancer, KLRB1, inflammation, immune activities

BackgroundPyroptosis is essential for tumorigenesis and progression of neoplasm. However, the heterogeneity of pyroptosis and its relationship with the tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remain unclear. The purpose of the present study was to identify pyroptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.MethodsFirst, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model established by LASSO regression was verified by the ICGC database. Then, the clinical significance, functional status, immune infiltration, cell–cell communication, genomic alteration, and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.ResultsTwo heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in the C2 subgroup was lower than that in the C1 subgroup. Pyroptosis-related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters via the pyroptosis-related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while the characteristics of C2 were alterations in SPEN and ROS1 mutation. Finally, a robust and promising pyroptosis-related prediction model for ccRCC was constructed and validated.ConclusionTwo heterogeneous pyroptosis subtypes were identified and compared in multiple omics levels, and five pyroptosis-related signatures were applied to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.

RationalePatients with clear cell renal cell cancer (ccRCC) may have completely different treatment choices and prognoses due to the wide range of heterogeneity of the disease. However, there is a lack of effective models for risk stratification, treatment decision making and prognostic prediction of renal cancer patients. The aim of the present study was to establish a model to stratify ccRCC patients in terms of prognostic prediction and drug selection based on multi-omics data analysis.MethodsThis study was based on the multi-omics data (including mRNA, lncRNA, miRNA, methylation and WES) of 258 ccRCC patients from TCGA database. Firstly, we screened the feature values that had impact on the prognosis and obtained two subtypes. Then, we used 10 algorithms to achieve multi-omics clustering, and conducted pseudo-timing analysis to further validate the robustness of our clustering method, based on which the two subtypes of ccRCC patients were further subtyped. Meanwhile, the immune infiltration was compared between the two subtypes, and drug sensitivity and potential drugs were analyzed. Furthermore, to analyze the heterogeneity of patients at the multi-omics level, biological functions between two subtypes were compared. Finally, Boruta and PCA methods were used for dimensionality reduction and cluster analysis to construct a renal cancer risk model based on mRNA expression.ResultsA prognosis predicting model of ccRCC was established by dividing patients into high- and low-risk groups. It was found that overall survival (OS) and progression-free interval (PFI) were significantly different between the two groups (pConclusionThe model could precisely predict the prognosis of ccRCC patients and may have implications for drug selection for ccRCC patients.

BackgroundPytoptosis is essential for tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the heterogeneity of pyroposis and its relationship with the tumor microenvironment (TME) remain unclear. The aim of the present study was to identify proptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.MethodsFirst, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model establsihed by LASSO regression was verified by ICGC database. Then, the clinical significance, functional status, immune infiltration, cell-cell communication, genomic alteration and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.ResultsTwo heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype, and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in C2 subgroup was lower than that in C1 subgroup. Pyroptosis related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters via Pyroptosis related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while C2 was characterized by more significant alterations in SPEN and ROS1 mutation. Finally, we constructed and validated a robust and promising signature based on the pyroptosis-related risk score for assessing the prognosis in ccRCC.ConclusionWe identified two heterogeneous pyroptosis subtypes and 5 reliable risk signatures to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.

Polydatin (PD), an active component of Chinese herbs, is reported to have many biological functions, such as cardioprotective actions, anti-inflammatory activities, and antitumor effects. In this study, we investigated the effects of PD on body weight control, glucose and lipid metabolic regulation, and anti-inflammation in a high-fat-diet- (HFD-) induced obese mice model. After treatment of PD (100 mg/kg/d for 4 weeks), HFD mice reduced body weight, retroperitoneal fat mass, and adipose cell sizes; significantly lowered serum total cholesterol triglyceride (TG) and low-density lipoprotein (LDL) levels; and increased high-density lipoprotein (HDL) levels compared with the HFD control mice. Further studies showed that PD downregulated the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involving in the regulation of adipocyte differentiation, in the retroperitoneal fat of HFD mice. Additionally, PD significantly upregulated the mRNA and protein expressions of leptin, an adipocyte-derived anorexic hormone that regulates food intake and energy expenditure, in the adipose tissues of HFD mice. Moreover, PD reduced the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in the retroperitoneal and epididymal tissues of HFD mice, suggesting that PD prevented adipose tissue inflammation. In conclusion, PD may serve as a pharmaceutic candidate for obesity-related lipid metabolism, anti-inflammation, and body weight loss.

Purpose Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC. Patients and methods The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naive NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses. Results Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67-6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10-7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33-8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites. Conclusion T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.

Ischemia and reperfusion injury following severe trauma or cardiac arrest are major causes of organ damage in intensive care patients. The brain is particularly vulnerable because hypoxia rapidly damages neurons due to their heavy reliance on oxidative phosphorylation. Therapeutic hypothermia can reduce ischemia-induced brain damage, but cooling procedures are slow and technically difficult to perform in critical care settings. It has been previously reported that injection of naturally occurring adenosine 5’-monophosphate (AMP) can rapidly induce hypothermia in mice. We studied the underlying mechanisms and found that AMP transiently reduces the heart rate, respiratory rate, body temperature, and the consciousness of adult male and female C57BL/6J mice. Adding AMP to mouse or human neuronal cell cultures dose-dependently reduced the membrane potential (ΔΨm) and Ca(2+) signaling of mitochondria in these cells. AMP treatment increased intracellular AMP levels and activated AMP-activated protein kinase (AMPK), which resulted in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and of mitochondrial and cytosolic Ca(2+) signaling in resting and stimulated neurons. Pretreatment with an intraperitoneal injection of AMP almost doubled the survival time of mice under hypoxic (6% O(2)) or anoxic (

Rationale: Although sunitinib has been shown to improve the survival rate of advanced renal cell carcinoma (RCC) patients, poor drug response is a major challenge that reduces patient benefit. It is important to elucidate the underlying mechanism so that the therapeutic response to sunitinib can be restored. Methods: We used an Illumina HumanMethylation 850K microarray to find methylation-differentiated CpG sites between sunitinib-nonresponsive and -responsive RCC tissues and Sequenom MassARRAY methylation analysis to verify the methylation chip results. We verified glutaminyl peptide cyclotransferase (QPCT) expression in sunitinib-nonresponsive and -responsive RCC tissues via qRT-PCR, western blot and immunohistochemical assays. Then, cell counting kit 8 (CCK-8), plate colony formation and flow cytometric assays were used to verify the function of QPCT in RCC sunitinib resistance after QPCT intervention or overexpression. Chromatin immunoprecipitation (ChIP) was performed to clarify the upstream regulatory mechanism of QPCT. A human proteome microarray assay was used to identify downstream proteins that interact with QPCT, and co-immunoprecipitation (co-IP) and confocal laser microscopy were used to verify the protein chip results. Results: We found that the degree of methylation in the QPCT promoter region was significantly different between sunitinib-nonresponsive and -responsive RCC tissues. In the sunitinib-nonresponsive tissues, the degree of methylation in the QPCT promoter region was significantly reduced, and the expression of QPCT was upregulated, which correlated with a clinically poor response to sunitinib. A knockdown of QPCT conferred sunitinib sensitivity traits to RCC cells, whereas an overexpression of QPCT restored sunitinib resistance in RCC cells. Mechanistically, reducing the methylation degree of the QPCT promoter region by 5-aza-2'-deoxycytidine (decitabine) in RCC cells could increase the expression of QPCT and NF-κB (p65) bound to the QPCT promoter region, positively regulating its expression, while the hypermethylation in the QPCT promoter region could inhibit the binding of NF-κB (p65). QPCT could bind to HRAS and attenuate the ubiquitination of HRAS, thus increasing its stability and leading to the activation of the ERK pathway in RCC cells. Conclusion: QPCT may be a novel predictor of the response to sunitinib therapy in RCC patients and a potential therapeutic target.

Introduction:A rapid, and accurate Ultra Performance Liquid Chromatography (UPLC) method was developed to simultaneously analyze Methocarbamol, Paracetamol and the related substancesMaterials and Methods:Waters ACQUITY UPLC® BEH Phenyl C18 column was used in conjunction with UV detection at 225nm. Gradient elution with 0.05M, pH 6 phosphate buffer and acetonitrile flow at 0.3mL /min rate were used to separate the substances. The retention times for 4-Aminopheno, Paracetamol, Guaifenesin, Methocarbamol, and 4-Chloroacetanilide were 1.319 minute, 2.224 minute, 4.467 minute, 4.769 minute and 5.433 minute respectively. The concentration was linear in the range of 2-100 µg/ml for Methocarbamol, and 1-100 µg/mL for Paracetamol. The percentage recoveries were between 99.28±1.23% to 100.57±0.99% for Methocarbamol, and between 99.08±1.23% to 101.23±1.39% for Paracetamol.Results and Discussion:The validated optimal protocol is robust and accurate for simultaneous analysis of Methocarbamol, Paracetamol and the related substances, applicable for bulk powder as well as pharmaceutical formulation.Conclusion:In this paper, a highly sensitive, accurate, and precise UPLC method with UV-Vis detection was developed and validated for quality control of MET and PAR in bulk as well as in pharmaceutical preparations.

Introduction: This study aimed at developing a technology to measure the hardness of Ibuprofen (IBU) tablets and optimize the IBU formulation using Near-infrared (NIR) spectroscopy. Materials and Methods: Tablets (400 mg±5%, 10mm in diameter) consisting of IBU, microcrystalline cellulose SH-103, carboxymethyl starch sodium, magnesium stearate, silicon dioxide were formed of various hardness (2kg, 4kg, 6kg, 8kg, 10kg, 12kg). The reflectance NIR spectra of various tablets were employed to establish 9 calibrations models, which were further used to predict tablet hardness by Partial least squares (PLS) and principal component regression (PCR) analysis. Results and Conclusion: Cross-validation with independent samples shows that PLS is the optimal predictive model. Which R2=0.9832, RSECV=0.334 and RSE=0.0669. This study established a new, simple, rapid, nondestructive and reliable methodology to optimize the IBU tablet hardness.

The incidence of synchronous multiple primary lung cancer (SMPLC) has been increased in recent years. Because of a variance in clinical management and outcome, it is important to distinguish SMPLC from a primary tumor with intrapulmonary metastases. Here, we reported a diagnosis and treatment procedure regarding a case of a 58-year-old woman who presented with synchronous multiple tumor lesions in separate lungs. Using a next generation sequencing technology, a discordant EGFR gene profile from the separate lungs was revealed for this patient. After standard treatment procedures, the therapeutic effects were evaluated by response evaluation criteria in solid tumors (RECIST). This case shows an essential role in the combination of molecular features, together with pathological analysis, during the management of SMPLC, but challenges still required considering during dealing the cases of SMPLC.

Peritoneal fibrosis (PF) is a crucial cause of the loss of peritoneal function in patients with peritoneal dialysis. To better understand the underlying mechanism of PF, we selected AV310809, which is one of the most highly upregulated lncRNA in fibrotic peritoneal tissue, for functional analysis. We used co-expression analysis to explore the potential relationship between AV310809 and coding genes. qPCR, WB and IF were applied to evaluate the expression and localization of AV310809, epithelial markers and proteins involved in the Wnt2/β-catenin signaling pathway. The interaction between AV310809 and β-catenin was examined using an RNA pulldown assay. The expression level of AV310809 was upregulated in fibrotic peritoneum and TGF-β1 induced EMT in HPMCs. Ectopic overexpression of AV310809 promoted EMT and activated the Wnt2/β-catenin signaling pathway. Furthermore, we demonstrated that AV310809 could interact with β-catenin and blocking β-catenin inhibited the augmentation of EMT by AV310809. These findings indicated that AV310809 promoted TGF-β1-induced EMT in HPMCs through the activation of the Wnt2/β-catenin signaling pathway, possibly by targeting β-catenin. We suggest that AV310809 may be a new therapeutic target for the management of peritoneal dialysis-associated PF.

Background. Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The idea of therapeutic angiogenesis in ischemic myocardium is a promising strategy for MI patients. Buyang Huanwu decoction (BHD), a famous Chinese herbal prescription, exerted antioxidant, antiapoptotic, and anti-inflammatory effects, which contribute to cardio-/cerebral protection. Here, we aim to investigate the effects of BHD on angiogenesis through the caveolin-1 (Cav-1)/vascular endothelial growth factor (VEGF) pathway in MI model of mice. Materials and Methods. C57BL/6 mice were randomly divided into 3 groups by the table of random number: (1) sham-operated group (sham, n=15), (2) AMI group (AMI+sham, n=20), and (3) BHD-treated group (AMI+BHD, n=20). 2,3,5-Triphenyltetrazolium chloride solution stain was used to determine myocardial infarct size. Myocardial histopathology was tested using Masson staining and hematoxylin-eosin staining. CD31 immunofluorescence staining was used to analyze the angiogenesis in the infarction border zone. Western blot analysis, immunofluorescence staining, and/or real-time quantitative reverse transcription polymerase chain reaction was applied to test the expression of Cav-1, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), and/or phosphorylated extracellular signal-regulated kinase (p-ERK). All statistical analyses were performed using the SPSS 20.0 software and GraphPad Prism 6.05. Values of P<0.05 were considered as statistically significant. Results and Conclusion. Compared with the AMI group, the BHD-treated group showed a significant improvement in the heart weight/body weight ratio, echocardiography images, cardiac function, infarct size, Mason staining of the collagen deposition area, and density of microvessel in the infarction border zone (P<0.05). Compared with the AMI group, BHD promoted the expression of Cav-1, VEGF, VEGFR2, and p-ERK in the infarction border zone after AMI. BHD could exert cardioprotective effects on the mouse model with AMI through targeting angiogenesis via Cav-1/VEGF signaling pathway.

Diffuse leptomeningeal glioneuronal tumor has various clinical manifestations and is easily misdiagnosed. This article aims to describe the clinical features of a patient with diffuse leptomeningeal glioneuronal tumor misdiagnosed as optic neuromyelitis lineage disease (NMOSD), analyze the causes of misdiagnosis, and identify the disease with similar clinical manifestations. Adolescent women with decreased vision and headache, nausea, and vomiting were initially diagnosed as NMOSD. Immunotherapy was ineffective; enhanced MRI and cerebrospinal fluid cytology examination were completed and compared with classic meningeal carcinoma, NMOSD, multiple sclerosis, and Vogt-Koyanagi-Harada (VKH) syndrome. Diffuse leptomeningeal glioneuronal tumor was finally diagnosed in adolescent women with no history of tumor. Compared with NMOSD: no history of infection, no AQP4, MOG antibody, no spinal segmental abnormalities, immunotherapy was ineffective; compared with multiple sclerosis: no history of infection, no plaque, no oligoclonal antibody, immunotherapy was ineffective; compared with VKH syndrome: no history of infection, no fever, no treatment for immunotherapy; and compared with classic meningeal carcinoma: adolescents, no extracranial tumor lesions, super high protein, more different sugar excess. Patients with acute visual impairment should consider not only NMOSD, but also diffuse leptomeningeal glioneuronal tumor (DLGNT) and other diseases. DLGNT could not be excluded when CSF cytology and MRI plain scan were negative. The positive rate of malignant cells can only be increased by repeatedly sending fresh cerebrospinal fluid for examination; DLGNT needs to be differentiated from NMOSD, multiple sclerosis, VKH syndrome, and other diseases. Early diagnosis and molecular targeted therapy can improve the quality of life and prolong life.

Peritoneal fibrosis is recognised as the main cause of the technical failure of peritoneal dialysis (PD), and currently, there are no specific and effective anti-fibrosis therapies. We have found that miR-200a is down-regulated in a rat model of PD-related peritoneal fibrosis (PF) and could inhibit transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells by target ZEB1/2. However, its treatment role in vivo is still largely unclear. In this study, we examined the therapeutic potential for miR-200a on PD-related PF in a rat model of PD induced by daily infusion of 4.25% dextrose-containing dialysate. Male Sprague-Dawley rats were divided into four groups: control group, PD group, PD + miR-agomir-NC group, and PD + miR-200a-agomir group (n = 5 in each group). MiR-200a agomir was delivered into the peritoneum by intra-peritoneal injection on days 10 and 20 after PD. We found that treatment with miR-200a agomir significantly reduced the collagen volume fraction (CVF) of the peritoneum and prevented peritoneal dysfunction. The up-regulation of the EMT marker (decreased E-cadherin and increased α-smooth muscle actin) and extracellular matrix (fibronectin and collagen I) was significantly ameliorated by miR-200a in the PD + miR-200a-agomir group. Furthermore, we demonstrated that miR-200a inhibition of PF in vivo was associated with the suppression of ZEB1 and 2, which were proved to be the target of miR-200a in our previous study. In conclusion, results from the present study suggest that treatment with miR-200a may represent a novel and effective therapy for PD-related PF.

High-performance fiber-reinforced cementitious composite (HPFRCC) has potential to greatly improve the fire resistance and seismic behavior of concrete structures. This paper reports an experimental investigation on post-fire seismic behavior of two-bay two-story frames with HPFRCC joints. Four reinforced concrete frames were fabricated; three of them were tested in compartment fire for 60 min. The fire was regulated following ISO-834 temperature curve. Two different fire scenarios (one- and two-bay fire) were investigated. Two frames were made of monotonic conventional concrete; the other two frames had HPFRCC joints. Each frame was tested under a constant vertical load and a pseudo-static cyclic horizontal load with increased magnitude until the frame failed. The effects of the HPFRCC and fire scenarios on the failure mechanism, hysteretic loops, envelope curve, stiffness degradation, and energy dissipation of the frames were evaluated. The experimental results revealed that the fire exposure reduced the load capacity and deformability of the frames. In the two-bay fire scenario, the use of HPFRCC joints increased the post-fire load capacity by 11%, ultimate deformation by 6%, initial stiffness by 30%, and energy dissipation by 21%. The cyclic behavior of the frame in one-bay fire was better than that in two-bay fire. The frames with HPFRCC joints demonstrated better cyclic behaviors than the virgin reinforced concrete frame.

Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (n = 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (n = 204), EGFR-AS1 was significantly upregulated in RCC tissues (P < 0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low: P = 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.

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Background: Conventional chondrosarcoma, a rare type of bone tumor, is resistant to chemotherapy and radiation therapy. Thus, additional characteristics of this disease are needed to open other treatment modalities. The clinical investigation of chondrosarcoma is limited to small-series and single-institution studies. The Surveillance, Epidemiologic, and End Results (SEER) is the most complete and comprehensive database worldwide. This SEER database study aimed to collect clinicopathological features and determine the prognosis of patients with conventional chondrosarcoma. Methods: Clinicopathologic and survival data of 782 patients from 2010 to 2016 and 353 patients from 2007 to 2009 were downloaded and analyzed. Overall survival was analyzed using the Kaplan–Meier method and verified by univariable Cox regression. Independent prognostic factors were assessed using the multi-variable Cox regression hazards model. A nomogram was established and used to calculate the one-, three-, and five-year survival rates. Competitive risk models were established to identify the prognostic risk factors related to competitive endpoint events in patients with conventional chondrosarcoma. Results: In total, 361 extremities, 360 axial bones, and 61 cranial samples were collected from the 2010–2016 cohort. The median survival time of patients with conventional chondrosarcoma was 35 months, and the independent prognostic factors were sex, grade, surgery, AJCC_M age, and tumor size. Thereafter, a nomogram was established basing from those independent prognostic factors. The competitive risk model revealed no competitive risk for the cancer-specific endpoint event. The data from 2007 to 2009 were used to validate the results from 2010 to 2016 with general consistency. Conclusion: This retrospective study determined the prognostic factors in patients with conventional chondrosarcoma by using the Cox regression hazards model. A nomogram was established to help oncologists assess this rare malignant tumor with low heterogeneity.

Background: Conventional chondrosarcoma, a rare type of bone tumor, was resistant to chemotherapy and radiation therapy, so more characteristics were needed. In clinic, the use of small series and single-institution studies have limited the investigation of chondrosarcoma. The Surveillance, Epidemiologic, and End Results is the most complete and comprehensive database worldwide. Based on this database, the study aimed to collect clinicopathological features and detect the prognosis of patients with conventional chondrosarcoma. Methods: Clinicopathologic and survival data of 782 patients from 2010 to 2016 and 353 patients from 2007 to 2009 were downloaded and analyzed. Overall survival was analyzed using the Kaplan-Meier method and verified by univariable Cox regression, and independent prognostic factors were assessed using the multi-variable Cox regression hazards model. Then, nomogram was established and the one-, three-, and five-year survival rates could be calculated with the nomogram. Competitive risk models were conducted to identify prognostic risk factors related to competitive endpoint events in patients with conventional chondrosarcoma. Results: In total, 361 extremities, 360 axial bones, and 61 cranial samples were collected from the 2010 to 2016 cohort. The median survival time of patients with conventional chondrosarcoma was 35 months, and the independent prognostic factors were sex, grade, surgery, AJCC_M age, and tumor size. Thereafter, a nomogram was established based on those independent prognostic factors. The competitive risk model revealed no competitive risk for the cancer specific endpoint event. Those data from 2007 to 2009 were used to validate the results from 2010 to 2016 with general consistency. This retrospective study determined the prognostic factors in patients with conventional chondrosarcoma using the Cox regression hazards model. A nomogram was established to help oncologists assess this rare malignant tumor with low heterogeneity.Conclusions: In the study, independent prognostic risk factors for conventional chondrosarcoma were identified, and a nomogram predicting three- and five- year overall survival rates were established, which may help physicians to predict the prognosis of patients with chondrosarcoma.

DEAD-box protein 39 (DDX39) has been demonstrated to be a tumorigenic gene in multiple tumor types, but its role in the progression and immune microenvironment of clear cell renal cell cancer (ccRCC) remains unclear. The aim of the present study was to investigate the role of DDX39 in the ccRCC tumor progression, immune microenvironment and efficacy of immune checkpoint therapy. The DDX39 expression level was first detected in tumors in the public data and then verified in ccRCC samples from Changzheng Hospital. The prognostic value of DDX39 expression was assessed in the Cancer Genome Atlas (TCGA) and ccRCC patients from Changhai Hospital. The role of DDX39 in promoting ccRCC was analyzed by bioinformatic analysis and in vitro experiments. The association between DDX39 expression and immune cell infiltration and immune inhibitory markers was analyzed, and its value in predicting the immune checkpoint therapy efficacy in ccRCC were evaluated in the public database. DDX39 expression was elevated in Oncomine, GEO and TCGA ccRCC databases, as well as in Changzheng ccRCC samples. In TCGA ccRCC patients, increased DDX39 expression predicted worse overall survival (OS) (p

Microglia-mediated neuroinflammation is tightly correlated with the etiology and progression of neurodegenerative disorders, including Parkinson's disease (PD). Nilotinib, a c-Abl inhibitor used for chronic myeloid leukemia, has been proven effective in relieving PD progression. However, whether nilotinib could affect neuroinflammation is largely unknown. In this current study, we investigated the role of nilotinib in microglia-mediated neuroinflammatory response in Parkinson's disease. Lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and mouse brains were used as models for Parkinson's disease. Our results demonstrated that nilotinib significantly suppressed LPS-induced neuroinflammation by reducing the production of pro-inflammatory factors including iNOS, COX-2, IL-1β, IL-6 and TNF-α in BV2 cells. Moreover, pretreatment of nilotinib attenuated the neurotoxicity of LPS-treated microglial conditioned medium to MES23.5 dopaminergic (DA) neurons. Mechanismly, nilotinib inhibited NF-κB signaling pathway and suppressed the nuclear translocation of p65 upon LPS stimulation. In LPS-injected mouse brains, nilotinib administration markedly suppressed the activation of microglia and down-regulated COX-2 as well as IL-1β expression. Most importantly, nilotinib effectively protected against microglial activation-mediated mouse DA neuronal loss. Taken together, our study suggests that nilotinib exerts anti-neuroinflammatory effect and protects DA neurons from activated microglia-induced inflammatory damage through suppressing NF-κB signaling pathway, indicating its potential application in further clinical trials.

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which has been determined in various cancers, including renal cell carcinoma, acute promyelocytic leukemia, colorectal cancer, endometrial cancer, and glioma. However, its role in retinoblastoma (RB) has not yet been explored. METHODS: The expression level of TRIB3 was detected in RB tissues and cell lines using qRT-PCR. The effects of TRIB3 on cell proliferation and invasion capacities were analyzed with MTT, crystal violet, and transwell assays. Western blot and rescue assays were conducted to explore the underlying mechanism. RESULTS: This study found that TRIB3 was upregulated in human RB tissues compared to adjacent normal tissues both at the mRNA and protein levels. Overexpression of TRIB3 significantly promoted cell proliferation and invasion of RB cells, while TRIB3 knockdown inhibited these processes. Moreover, the mechanism deciphering experiments showed that TRIB3 overexpression can increase AKT and mTOR phosphorylation. Conversely, TRIB3 knockdown decreased the phosphorylation of AKT and mTOR. Additionally, MK2206, a potent AKT inhibitor, blocked the promotive effects of TRIB3 in RB cells. CONCLUSION: This study demonstrated that TRIB3 acts as an oncogene and plays a crucial role in the proliferation and invasion of RB cells via regulating the AKT/mTOR signaling pathway. Therefore, TRIB3 may serve as a potential target in the diagnosis and/or treatment of RB.

Background: The intracerebral hemorrhagic stroke (ICH) is associated with high mortality and severe disability in survivors, which causing about 42% of the disability-adjusted life years lost and 50% of all stroke patients dead within 1 year. Although early functional training is recommended to facility rehabilitation after the stroke, the benefit and safety are still controversial. Introduction: This systematic review aims to investigate whether early physical rehabilitation could have a beneficial effect for the patients with ICH compared with standard rehabilitation care. Methods and analysis: Pubmed, Embase, and Cochrane library will be searched to include randomized control trials which investigate the rehabilitation effective of the early mobilization for patients with ICH compared with routine nursing or standard care. Rev-Man version 5.3 will be used to perform all calculations related to the meta-analysis. Dichotomous data will be calculated in terms of a fixed or random effect model and expressed by the relative risk (RR) with 95% confidence interval (CI). The Cochrane collaborations tool in the following aspects was used to assess the risk of bias (ROB) in included studies. The inconsistency index (I2) and Chi-Squared will be applied for heterogeneity detection between clinical trials. A value of P

Diabetic coronary heart disease (DM-CHD) poses a major threat to the world. The newly described T cell subset-Th9 cells and related cytokine interleukin (IL)-9 play important roles in the pathogenesis of diabetes and atherosclerosis. B lymphocyte-induced maturation protein 1 (Blimp-1) has been indicated to negatively regulate Th9 development in allergic asthma, but its role in DM-CHD remains unclear. Hence, this study was designed to investigate the role of Blimp-1 in DM-CHD and to elucidate whether the mechanism was associated with regulation of Th9 cell differentiation. Our results showed that serum Blimp-1 mRNA level was decreased whereas proportion of Th9 cells (IL-9+ CD4+ T cells) and serum level of Th9-related IL-9 were increased in DM-CHD patients. Furthermore, serum Blimp-1 mRNA level was negatively correlated with IL-9 level in DM-CHD patients. Importantly, administration of lentiviruses expressing Blimp-1 (LV-Blimp-1) significantly inhibited Th9 cell differentiation and alleviated the severity of atherosclerotic lesions in the aorta and coronary artery, dyslipidemia, inflammation, vascular endothelial dysfunction, and oxidative stress in DM-CHD model rats. Collectively, Blimp-1 exerts a protective effect in DM-CHD rats and the mechanism might involve inhibition of Th9 cell differentiation.

Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as highly prospective therapeutic modalities in cancer therapy. Notwithstanding, a critical challenge still remains in the exploration of an effective strategy to maximize the synergistic efficacy of PTT and PDT due to low photoconversion efficiency. Herein, inspired by the phospholipid bimolecular structure of the cell membrane, bionic cell membrane polymeric vesicles with photothermal/photodynamic synergy for prostate cancer therapy at one wavelength's excitation are constructed in one step by the coordination of hexadecyl trimethyl ammonium bromide (CTAB) from the surface of hydrophobic gold nanorods (AuNRs) with indocyanine green (ICG) and polycaprolactone (PCL), achieving their self-assembly in aqueous solutions. Importantly, the aggregation of the assembly improves the stability of the vesicles, realizing the synergistic effect of PTT and PDT for prostate cancer therapy. After being assembled within polymeric vesicles, bifunctional photosensitizer ICG can generate reactive oxygen species (ROS) and photothermal effect under light treatment. Their ROS not only induce PDT efficacy but also destroy the integrity of the lysosomal membrane, promoting the translocation of ICG and another photosensitizer called gold nanorods (AuNRs) into the cytosol. Moreover, their photothermal effects produced by both photosensitizers are able to engender greater damage to the tumor cells because of the close distance with organelles. This structure manifests good cellular uptake, highly effective tumor accumulation, high photothermal conversion efficiency, and excellent properties of enhanced photobleaching resistance, which are beneficial to ICG-based fluorescence tumor imaging. Using the same near-infrared (NIR) wavelength for excitation, the AuNR/ICG vesicles can reduce the side effect rate of photodamage on the skin. In addition, by generating reactive oxygen species (ROS) and double photothermal effect, the vesicles under NIR excitation can promote the apoptosis of PC3 tumor cells. Taken together, the spontaneous self-assembled AuNR/ICG vesicles exhibit huge potential in advanced-stage prostate cancer therapy, especially for the prostate-specific membrane antigen (PSMA)-negative castration-resistant subtype.

Objective To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. Methods A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8–14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. Results The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P

COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient's symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.

Diffuse leptomeningeal glioneuronal tumor has a high degree of malignancy and high mortality. The purpose of this paper is to describe the characteristics of atypical diffuse leptomeningeal glioneuronal tumor and analyze the causes of misdiagnosis as viral meningoencephalitis. An adolescent female patient presented with headache, nausea, vomiting, sharp vision loss and cognitive dysfunction. After poor therapeutic effect of standard antiviral treatment, further inspection found that malignant cells were detected by cerebrospinal fluid (CSF) cytology; and enhanced magnetic resonance imaging (MRI) showed extensive enhancement of the leptomeningeal. In conclusions, when patient with unexplained high intracranial pressure, it is necessary to be alert to the diagnosis of diffuse leptomeningeal glioneuronal tumor. Multiple examinations of fresh CSF are helpful to increase the positive detection rate of tumor cells. Early diagnosis and active treatment are conducive to improving survival rate.