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IntroductionN-methyl-D-aspartate receptor (NMDAR) is one of the main receptor of the excitatory neurotransmitter glutamate in the brain, which is the key determinant of the excitatory/inhibitory balance of neural network. GluN2A/GRIN2A is one of the subunits of NMDAR and plays an important role in epilepsy. Approximately 78% of patients with GluN2A/Grin2a mutations have epilepsy, and the underlying mechanism of this association is not well characterized.MethodsWe constructed a mouse model of hyperthermic seizure, and conducted in vitro and in vivo electrophysiological and behavioral studies to clarify the pathogenic characteristics and mechanism of GluN2A/GRIN2A-V685G mutation. In addition, the drug efavirenz (EFV), which is used to treat HIV infection, was administrated to mutant animals to assess whether it can restore the loss of function.ResultsMutant mice showed no significant change in the mRNA or protein expressions of NMDAR compared with wild type (WT) mice. Mice with GluN2A/GRIN2A-V685G mutation exhibited shorter latency to seizure, increased frequency of seizure-like events, decreased peak current and current area of NMDAR excitatory postsynaptic current, and decreased event frequency of micro-inhibitory postsynaptic current, compared to WT mice. They also exhibited decreased threshold, increased amplitude, increased input resistance, and increased root number of action potential. EFV administration reversed these changes. The loss-of-function (LoF) mutation of NMDAR changed the excitatory/inhibitory balance of neural network, rendering animal more prone to seizures.DiscussionEFV was indicated to hold its potential in the treatment of inherited epilepsy.

The weapon-target allocation (WTA) problem is a fundamental subject of defense-related applications research, and previous studies assume that the parameters in the model are determinate. For the real battlefield, asymmetric information usually leads to the failure of the above assumption, and there are uncertain factors whose frequency is hard to pinpoint. Based on uncertainty theory, we study a WTA problem in indeterminate battlefield in this paper. First, we analyze the uncertain factors in indeterminate battlefield and their influence on WTA problem. Then, considering the target threat value, the protected asset value and the extra cost of interception as uncertain variables, the uncertain multi-objective dynamic WTA (UMDWTA) model is established, where three indices including the value of destruction of targets, the value of surviving assets and the cost of operation are regarded as objective functions, and on this basis, an equivalent transformation is presented to convert the UMDWTA model into a determinate multi-objective programming (MOP) problem by expected value and standard deviation principle. To solve the proposed model efficiently, an improved multi-objective evolutionary algorithm based on decomposition (MOEA/D) is designed, which employs three new evolutionary operators and the weight vectors adaptation mechanism to improve the convergence and uniformity of the Pareto front obtained. Finally, a case of the UMDWTA problem is carried out to be solved by the designed algorithm, and the results verify the feasibility of the proposed model.

During the solar eclipse, the perturbation of ionospheric D layer changes the characteristics of the Earth's Ionospheric Waveguide (EIWG) on which the very low frequency (VLF, 3-30 kHz) wave propagation depends. Therefore, the amplitude and phase of the VLF signal transmitted through the waveguide will be abnormal. In this article, based on the VLF transmitter signals observed in Suizhou (31.57°N, 113.32°E) during the total solar eclipse on December 26, 2019 and the days before and after, the variation characteristics of VLF transmitter signals along the north-south propagation path are analyzed in detail. Responses of the amplitude and phase of the signal during the solar eclipse are closely related to the solar obscuring rate. There is a positive correlation between the signal fluctuation and the solar obscuring rate, and the peak time of the two has a delay of ~5 min. By adopting the amplitude and phase of the observed signals and performing the Long Wavelength Propagation Capability (LWPC) propagation simulations, the electron density of the ionosphere over the propagation path is calculated. The results show that the electron density profile above the path during the solar eclipse changes significantly. The electron density decreases with a maximum drop of ~53.5% at the 70 km height, and the reflection height of the signal increases correspondingly. The obtained results are useful to better understand the propagation characteristics of VLF transmitter waves and the corresponding response features of the ionospheric D layer to solar radiation flux variations, especially during the solar eclipse.

BackgroundChina’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.MethodsTissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.ResultsIn cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations.ConclusionsThese findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

Flavan-3-ols are a group of flavonoids that exert beneficial effects. This study aimed to enhance key metabolic processes related to flavan-3-ols biosynthesis. The engineered Saccharomyces cerevisiae strain E32 that produces naringenin from glucose was further engineered for de novo production of two basic flavan-3-ols, afzelechin (AFZ) and catechin (CAT). Through introduction of flavonoid 3-hydroxylase, flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase (DFR), and leucoanthocyanidin reductase (LAR), de novo production of AFZ and CAT can be achieved. The combination of FaDFR from Fragaria × ananassa and VvLAR from Vitis vinifera was optimal. (GGGGS)2 and (EAAAK)2 linkers between DFR and LAR proved optimal for the production of AFZ and CAT, respectively. Optimization of promoters and the enhanced supply of NADPH further increased the production. By combining the best engineering strategies, the optimum strains produced 500.5 mg/L AFZ and 321.3 mg/L CAT, respectively, after fermentation for 90 h in a 5 L bioreactor. The strategies presented could be applied for a more efficient production of flavan-3-ols by various microorganisms.

BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.

Background Malignant cerebral edema (MCE) is a common and feared complication after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). This study aimed to establish a nomogram to predict MCE in anterior circulation large vessel occlusion stroke (LVOS) patients receiving EVT. Methods In this retrospective cohort study, 381 patients with anterior circulation LVOS receiving EVT were screened from 636 hospitalized patients with LVOS in two stroke medical centers. Clinical baseline data and imaging data were collected within 2–5 days of admission to the hospital. The patients were divided into two groups based on whether MCE occurred after EVT. Multivariate logistic regression analysis was used to evaluate the independent risk factors for MCE and to establish a nomogram. Results Sixty-six patients out of 381 (17.32%) developed MCE. The independent risk factors for MCE included admission NIHSS ≥ 16 (OR, 1.851; 95% CI: 1.029–3.329; P = 0.038), ASPECT score (OR, 0.621; 95% CI: 0.519–0.744; P

Anthocyanins are natural pigments found in various plants. As multifunctional natural compounds, anthocyanins are widely used in food, pharmaceuticals, health products, and cosmetics. At present, the anthocyanins are heterologously biosynthesized in prokaryotes from flavan-3-ols, which is rather expensive. This study aimed to metabolically engineer Saccharomyces cerevisiae for anthocyanin production. Anthocyanin production has been extensively studied to understand the metabolic pathway enzymes in their natural hosts, including CHS (chalcone synthase); FLS (flavonol synthase); CHI (chalcone isomerase); F3H (flavanone 3-hydroxylase); F3′H (flavonoid 3′-hydroxylase); F3′5′H (flavonoid 3′,5′-hydroxylase); DFR (dihydroflavonol 4-reductase); ANS (anthocyanidin synthase); LAR (leucoanthocyanidin reductase); and UFGT (flavonoid 3-O-glucosyltransferase). The anthocyanin transporter MdGSTF6 was first introduced and proven to be indispensable for the biosynthesis of anthocyanins. By expressing MdGSTF6, FaDFR, PhANS0, and Dc3GT and disrupting EXG1 (the main anthocyanin-degrading enzyme), the BA-22 strain produced 261.6 mg/L (254.5 mg/L cyanidin-3-O-glucoside and 7.1 mg/L delphinidin-3-O-glucoside) anthocyanins from 2.0 g/L dihydroflavonols, which was known to be the highest titer in eukaryotes. Finally, 15.1 mg/L anthocyanins was obtained from glucose by expressing the de novo biosynthesis pathway in S. cerevisiae, which is known to be the highest de novo production. It is the first study to show that through the introduction of a plant anthocyanin transporter and knockout of a yeast endogenous anthocyanin degrading enzyme, the anthocyanin titer has been increased by more than 100 times.

Dihydromyricetin (DHM) is a traditional plant-extracted flavonoid with some health benefits. This study aimed to metabolically engineer the strains for DHM bioproduction. Two strains of BK-11 and BQ-21 were integrated with flavonoid 3-hydroxylase (F3H) or both F3H and flavonoid 3'-hydroxylase (F3'H). The resulting strains have expressed the enzymes of GmCPR and SlF3'5'H, and then, the promoters of INO1p and TDH1p were used to enhance further the DHM production from naringenin in Saccharomyces cerevisiae. Through multiple-copy integration, 709.6 mg/L DHM was obtained by adding 2.5 g/L naringenin in a 5 L bioreactor, implying that the synergistic effect between F3'H and flavonoid 3'5'-hydroxylase is likely to promote the DHM production. An yield of 246.4 mg/L DHM was obtained from glucose by deleting genes for branch pathways and integrating PhCHS, MsCHI, Pc4CL, and FjTAL. To our knowledge, this is the highest production reported for the de novo biosynthesis of DHM.

Methylprednisolone is an effective drug in the treatment of autoimmune disease, such as multiple sclerosis (MS), due to long‐acting anti‐inflammatory, antiallergic and immunosuppressant. Previous studies have noted the importance of myeloid‐derived suppressor cells (MDSC) in MS progression. However, it is still not known whether methylprednisolone could influence the ratio and function of MDSC during MS treatment. In the current study, we found an increased ratio of MDSC at the onset of EAE in mice model; but methylprednisolone pulse therapy (MPPT) did not alter the percentage and suppressive function of MDSC during disease attenuation. However, the percentage of G‐MDSC in PBMC significantly increased in patients with MS. Surprisingly, relapsing MS patients showed a significant increase in both M‐MDSC and G‐MDSC after MPPT. The disease remission positively correlated expansion of MDSC and expression of arginase‐1. Additionally, MPPT reduced the expression of inhibitory glucocorticoid (GCs) receptor β subunit on MDSC while elevating serum levels of immune regulatory S100A8/A9 heterodimer. Thus, MDSC dynamics and function in mouse EAE differ from those in human MS during MPPT. Our study suggested that GCs treatment may help relieve the acute phase of MS by expanding MDSC through up‐regulating of GR signalling and S100A8/A9 heterodimers.

Pathology arising from the intrathoracic portion of the trachea (distal trachea), the carina and the main bronchi is usually neoplastic and is mainly treated with surgery. Resection of the intrathoracic portion of the trachea, the carina and the main bronchi for neoplastic lesions does not necessitate lung resection and is traditionally being conducted via open surgery. Video-assisted thoracic surgery (VATS) is witnessing an exponential growth and is the treatment of choice for early-stage non-small cell lung cancer (NSCLC). The experience accumulated over the past two decades along with the introduction of reliable and ergonomic technology, has led to the expansion of its indications. In this article we provide a detailed description of lung sparing distal tracheal, carinal and main bronchi resection for primary neoplasms of the airway, without involvement of the lung, with the uniportal video-assisted technique. The chest is entered through the fourth intercostal space, mid-axillary line. Dissection of the paratracheal space anteriorly, the tracheoesophageal groove posteriorly and the subcarinal space and division of the azygos arch are essential to mobilize the distal trachea and carina. Lateral dissection should be avoided beyond the points of division of the airway, as it may hinder the blood supply to the anastomosis. Any tension to the anastomosis should be relieved by release maneuvers. Ventilation is achieved through an endobronchial catheter, inserted into the left main bronchus through which a high-frequency jet ventilation catheter can be also inserted through it. The rationale of applying a minimally invasive technique for the conduction of tracheal and carinal resections, is to exploit its advantages, namely less pain, earlier mobilization and lower morbidity. Uniportal video-assisted resections of the distal trachea, carina and the main bronchi, are safe when conducted by experienced surgical and anesthetic teams.

Phenotypic switching of the vascular smooth muscle cells (VSMCs) is closely related to an in-stent restenosis (ISR). This study aimed to investigate whether S-(–)-equol prevented the phenotypic switch of the VSMCs as a potential treatment of an ISR. The carotid arteries of female Sprague Dawley (SD) rats with or without a carotid injury and ovariectomy were harvested after 4 weeks of treatment with S-(–)-equol. Stenosis of the carotid artery and two phenotype-related proteins-α smooth muscle actin (αSMA) and osteopontin (OPN)-were determined. The proliferation and migration capacities of VSMCs were determined by the CCK-8 and transwell assays, respectively. The expressions of αSMA, OPN, MAPKp38, p-MAPKp38, NF-κBp65, and p-NF-κBp65 were detected by a western blot. S-(–)-equol alleviated carotid stenosis and prevented the VSMC phenotypic switch in female SD rats with a carotid artery injury and a bilateral ovariectomy. S-(–)-equol inhibited the phenotypic switch of VSMCs, which was induced by PDGF-BB, and enhanced the proliferation and migration of VSMCs. The effects of S-(–)-equol on VSMCs were confirmed to be related to the inactivation of the GPER-MAPKp38-NF-κBp65 signaling in vitro and in vivo. Our results indicate that S-(–)-equol affects carotid stenosis by preventing the phenotypic switch of VSMCs via the GPER-MAPKp38-NF-κBp65 signaling pathway.

The primary reason for detecting emerging topics is to reduce researchers’ time in finding current related topic while maintaining awareness of current trends in a particular field. Nowadays, the amount of information is growing rapidly, but tracking the development of a research field by manually reading the literature is challenging. This study takes Library and Information Science (LIS) as a case study to present a new method for detecting emerging topics. This novel method could be applied to analyse various types of documents and detect emerging topics automatically. This method utilizes a Latent Dirichlet Allocation (LDA) model to generate topics and calculate probabilities. It discovers emerging topics by detecting probability burst in consecutive time spans. Association rule mining and lexical similarity computation are adopted to represent the topics. This work tests the method by comparing the results of emerging topics from the LIS data in the baseline paper. The validation demonstrates that the proposed approach is feasible.

Anthocyanins are natural pigments found in various plants. As multifunctional natural compounds, anthocyanins are widely used in food, pharmaceuticals, health products, and cosmetics. At present, the anthocyanins are heterologously biosynthesized in prokaryotes from flavan-3-ols, which is rather expensive. This study aimed to metabolically engineer

Thrombus components are dynamically influenced by local blood flow and blood immune cells. After a large-vessel occlusion stroke, changes in the cerebral thrombus are unclear. Here we assessed a total of 206 cerebral thrombi from patients with ischemic stroke undergoing endovascular thrombectomy. The thrombi were categorized by time to reperfusion of 8 h (T8). The cellular compositions in thrombus were analyzed, and relevant clinical features were compared. Both white blood cells and neutrophils were increased and then decreased in thrombus with time to reperfusion, which were positively correlated with those in peripheral blood. The neutrophil extracellular trap (NET) content in thrombus was correlated with the degree of neurological impairment of patients. Moreover, with prolonged time to reperfusion, the patients showed a trend of better collateral grade, which was associated with a lower NET content in the thrombus. In conclusion, the present results reveal the relationship between time-related endovascular immune response and clinical symptoms post-stroke from the perspective of thrombus and peripheral blood. The time-related pathological changes of cerebral thrombus may not be the direct cause for the difficulty in thrombolysis and thrombectomy. A low NET content in thrombi indicates excellent collateral flow, which suggests that treatments targeting NETs in thrombi might be beneficial for early neurological protection.

BackgroundInherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links.MethodsTissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics.ResultsOur FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system.ConclusionsThe lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

The sensor–weapon–target allocation (S-WTA) is a typical collaborative task allocation problem involved in network-centric warfare (NCW). The existing related studies have a limitation to the nature of cooperation and uncertainty in an air defense battle scenario, and most existing models have the assumption that they are determinate, i.e., the parameters in them are known certainly. For the actual battlefield environment, the asymmetric information in it could lead to the failure of the above assumption, and there are many uncertainties whose frequency can not be evaluated objectively. Based on uncertainty theory, this paper studied the S-WTA problem in an indeterminate battlefield environment. First, we analyze the uncertain factors existing in the actual battlefield environment and their influence on the S-WTA problem, and by considering the threat value of the target, the deviation parameters of the sensor tracking performance and weapon interception performance as uncertain variables, we then establish an uncertain S-WTA (USWTA) model, where the destruction value to targets is regarded as an objective function and four categories of typical constraints are set. Further, an equivalent transformation is presented to convert the unsolvable model into a determinate one by the expected value principle. To solve the proposed model efficiently, a permutation-based representation for the allocation scheme of the USWTA problem is introduced firstly, which can construct a feasible solution efficiently, and on this basis, a constructive heuristic algorithm based on maximum marginal return rule (MMRCH) is designed to construct a feasible solution with high quality. Additionally, a local search (LS) operation is proposed to explore for the better solution locally and further improve the quality of solution obtained by MMRCH. Finally, a set of instances are set to be solved by the designed algorithm, and the simulation experiment demonstrates the superiority of the designed algorithm and the feasibility of the proposed model.

Cerebral small vessel disease (cSVD)—a common cause of stroke and vascular dementia—is a group of clinical syndromes that affects the brain's small vessels, including arterioles, capillaries, and venules. Its pathogenesis is not fully understood, and effective treatments are limited. Increasing evidence indicates that an elevated total serum homocysteine level is directly and indirectly associated with cSVD, and endothelial dysfunction plays an active role in this association. Hyperhomocysteinemia affects endothelial function through oxidative stress, inflammatory pathways, and epigenetic alterations at an early stage, even before the onset of small vessel injuries and the disease. Therefore, hyperhomocysteinemia is potentially an important therapeutic target for cSVD. However, decreasing the homocysteine level is not sufficiently effective, possibly due to delayed treatment, which underlying reason remains unclear. In this review, we examined endothelial dysfunction to understand the close relationship between hyperhomocysteinemia and cSVD and identify the optimal timing for the therapy.

Flavan-3-ols are a group of flavonoids that exert beneficial effects. This study aimed to enhance key metabolic processes related to flavan-3-ols biosynthesis. The engineered

The aim of this study is to examine the antidepressant-like effect of EGCG and get deeper insights into implications of modulating serotonin (5-HT) in the colon and brain. A total of 24 stochastically-selected rats were subdivided into three groups: one group served as the control group, and other two groups were subjected to chronic unpredictable mild stress interventions (CUMS group and CUMS + EGCG group respectively). Before conducting a designed set of behavior tests, all rats were weighed and then forced swimming test (FST) and open field test (OPT) were performed in all rats for the measurement and analysis of central and colonic serotonin levels. In order to determine the extent of CUMS-induced injuries and examine neurological deficits, the method of Nissl staining was implemented accordingly. Meanwhile, haematoxylin-eosin (H&E) staining was employed to detect the structure of the colon. The study found that, due to the involvement of CUMS, the body weight of experimental rats declined, their time of immobility in FST was greater, and the avoidance of central sections in OPT was also greater and more obvious. However, through intervention of the EGCG treatment, either weight loss or depression-related behavior induced by the involvement of CUMS was alleviated in the experimental rats. Comparison of both CUMS and CUMS + EGCG groups indicated that EGCG administration may decrease the level of serotonin (5-HT) in the colon but increase the level of serotonin (5-HT) in the hippocampus. However, it should be noted that the level of 5-HT in peripheral blood did not show any significant difference between both groups. Furthermore, CUMS caused the morphological changes of the hippocampus and structural changes of the colon were noteworthy. Summarily, the investigation results of this experimental study indicated that the intervention of EGCG treatment might have considerable implications in several aspects such as anti-depression, regulation of 5-HT concentration, enhancement of intestinal hyper-permeability, and neuroprotection in the hippocampus.

BACKGROUND: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology, and both exhibit population heterogeneity. MUC16 is overexpressed in various cancers and often associated with poor prognosis. Present work was to investigate the clinical significance of MUC16 in non-small cell lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution caused by coal use. METHODS: Clinicopathologic characteristics and MUC16 expression were analyzed and evaluated in our subject population. Vectors were constructed for MUC16 gene knockout and overexpression, then we examined how MUC16 affected lung cancer cell behaviors, including proliferation, migration, invasion and chemoresistance. RESULTS: FLC showed significant association with early-onset (P

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and accumulating evidences suggest a key role of amyloid-β (Aβ) peptide in the pathogenesis of AD. According to the amyloid cascade hypothesis, the imbalance of producing and clearing Aβ is the beginning of neurodegeneration and dementia. Consequently, immunotherapy becomes popular through using antibodies against Aβ. However, many studies of monoclonal antibodies were stopped because adverse effects appeared or there were no evident benefits observed. Some antibody fragments have many advantages over monoclonal antibodies, such as small sizes, lack of the crystallizable fraction (Fc) and so on. There are three main antibody fragments, including single chain variable fragments (scFvs), Fab fragments and single-domain antibody fragments. Nanoparticles can facilitate the entry of drug molecules across the blood-brain barrier, making them become excellent carriers. Various kinds of nanoparticles have been applied in the treatment of AD. The combination of nanoparticles and antibody fragments against amyloid-β can be used in the diagnosis and treatment of Alzheimer’s disease. In this review, we summarize the progress of antibody fragments against amyloid-β in AD, focusing on the combined application with nanoparticles in the diagnosis and treatment of AD.

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non‐small‐cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para‐carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up‐regulated and 260 were downregulated compared to para‐carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)‐receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL‐induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

Background The cellular immunity of lung cancer patients is mainly the immune response of T cells, which plays an important role in tumour cell killing and immune surveillance. Transforming growth factor 1 (TGF-β1) is secreted by tumour cells that can suppress the immune response and is an important group of immune down-regulation factors. Our study aims to investigate the effect of TGF-β1 on the morphology and cellular immune function of A549 and peripheral blood mononuclear cells (PBMCs). Methods A549 cell line was cultured, PBMCs were cultured with different concentrations of TGF-β1, and the morphology of A549 cells and PBMCs were seen. The levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and TNF and the numbers of CD3, CD4, CD8, CD4/CD8, and CD3 CD25 and CD4 CD25 in PBMCs were detected. Results During co-culture of A549 with PBMCs, TGF-β1 can induced A549 showing epithelial-to-mesenchymal transition, enhanced its ability of migration and infiltration. Simultaneously, TGF-β1 can depressing the growth and proliferation of PBMCs, inhibiting T-cell activation, and accelerating the PBMCs apoptosis. TGF-β1 can inhibits A549 Th1 related-cytokines, enhance Th2 related-cytokines, cause the disorder of Th1/Th2, resulting in the Th1 cellular dominate immunity decline. Conclusions TGF-β1 may affect the secretion of related cytokines, hinder the activation of T lymphocytes, destroy the immune surveillance and killing effect of the body, and thus inhibit the cellular immunity.

Circadian rhythm dysfunction is primary symptom of depression and is closely related to depression onset. The role of the lateral habenula (LHb) of the thalamus in the pathogenesis of depression has been a research topic of great interest. The neuronal activity of this structure has circadian characteristics, which are related to the regulation of circadian rhythms. However, in depression model of rats, the role of clock genes in the LHb has not been assessed. To address this gap, we used a clomipramine (CLI) injection-induced depression model in rats to assess the daily expression of rhythmic genes in the LHb and depression-like behavior in rats at multiple time points. In determining the role of the Per2 gene in the development of depression-like behavior in the LHb, we found that the expression of this clock gene differed in a circadian manner. Per2 expression was also significantly decreased in CLI-treated rats in late afternoon (17:00) and in the middle of the night (1:00). Furthermore, silencing Per2 in the LHb of normal rats induced depression-like behavior at night, suggesting that Per2 may play an important role in the pathogenesis of depression. Collectively, these results indicate that decreased Per2 expression in the LHb may be related to increased depression-like behavior at night in depression model of rats.

Background The Xuanwei area of Yunnan Province, China is one of the regions with the highest incidence of lung cancer in the world. Local residents use bituminous coal as fuel for cooking and heating, which causes serious indoor air pollution. After the local government carried out furnace and stove reform work, the high incidence of lung cancer in residents continued. We herein wonder if there are specific mechanisms at protein level for the development of lung cancer in the area. Methods We investigated the changes of protein profiling in tumor of the patients from Xuanwei area. Tandem Mass Tag (TMT) were employed to screen the differential proteins between carcinoma and para-carcinoma tissues. Results We identified a total of 422 differentially-expressed proteins, among which 162 proteins were significantly upregulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially-expressed proteins were related to ECM-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, TXN2 and HP, showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumor in nude mice. Conclusion This study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A) upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis in a case-based analysis and investigation of its biological function though a series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276 lung cancer tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with clinical stage and metastasis status in lung cancer patients. Patients with high expression levels of this lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011 in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples; 13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of death than those with lower levels (HR = 1.52; 95% CI = 1.01–2.26, in merged samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung cancer cell proliferation in vitro and in vivo. Further analyses using digital gene expression tag profiling revealed that lnc-RAB1A-2 could affect the expression of fibroblast growth factor 1 (FGF1), a gene involved in the PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung cancer development.

In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB [P65], Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP.

The aim of this study was to investigate the function of miR-1244 in cisplatin-treated non-small cell lung cancer (NSCLC). The results of quantitative PCR analysis revealed that the expression levels of miR-1244 in cisplatin‑treated A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC tissue samples from cisplatin-treated patients was also lower than that in non-cisplatin-treated NSCLC patients. Notably, the overall survival times of cisplatin-treated NSCLC patients with high miR-1244 expression were superior to those patients with low miR-1244 expression. We found that overexpression of miR-1244 suppressed cell viability and increased LDH toxicity in cisplatin-treated A549 and NCI-H522 cells. Additionally, overexpression of miR-1244 induced the apoptosis of cisplatin-treated A549 and NCI-H522 cells. Furthermore, overexpression of miR-1244 promoted caspase-3 activity and p53 and Bax protein expression, and suppressed myocyte enhancer factor 2D (MEF2D) and cyclin D1 protein expression in cisplatin‑treated A549 and NCI-H522 cells. Small interfering RNA (siRNA) targeting MEF2D suppressed the protein expression of MEF2D, and was able to decrease the proliferation, promote caspase-3 activity, p53 and Bax protein expression and inhibit cyclin D1 protein expression in cisplatin-treated A549 and NCI-H522 cells following the overexpression of miR-1244. In summary, we found that miR-1244 affected cisplatin-treated NSCLC via MEF2D expression.

Purpose: To examine the mortality rate and causes of death of phenobarbital (PB) monotherapy and sodium valproate (VPA) monotherapy in patients with convulsive epilepsy in rural northeast China and compare the differences in the results between the two antiepileptic drugs. Methods: Patients with convulsive epilepsy were recruited by trained public health workers in a project for epilepsy prevention and treatment. Patients were enrolled between January 2010 and December 2018 and were treated with PB or VPA. Mortality rate (MR), the proportional mortality ratio (PMR) for each cause, standardized mortality ratio, and years of potential life lost (YPLL) for sex, age, and cause were estimated based on the 2018 Chinese rural population. Results: A total of 3,916 patients with convulsive epilepsy enrolled in the study, of whom 3,418 received PB and 498 received VPA. There were 325 reported deaths (300 from the PB group) during the follow-up period. The MRs were 9.96 and 5.73% in the PB and VPA groups, respectively. The overall SMRs were 12.92 (95% confidence intervals [CI]: 11.50-13.93) and 7.39 (95% CI: 4.78-10.91), for the PB and VPA groups, respectively. Cerebrovascular disease and heart disease were the major causes of death in both treatment groups. The average YPLL for the PB group (21.9 years) was higher than that for the VPA group (13.4 years). Conclusion: This is the first epidemiological study to examine the MR of patients with epilepsy in rural northeast China. Our study is somewhat different from previous studies reported in China, and we provide new relevant data from northeast China.

Among autoimmune encephalitis, patients with anti-N-methyl D- aspartate receptor (NMDAR) encephalitis typically present epileptic seizures, memory deficits and psychiatric symptoms. However, the signal mechanisms leading to the functional disorders of autoantibodies are largely unclear. In this study, anti-NMDAR antibody was administered into dentate gyri against the NR1 subunit of the NMDAR. The purpose of the study examined the effects of pro-inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on neuronal NMDAR currents of the hippocampus in rats with anti-NMDAR encephalitis and we further determined the role played by TNF-α and IL-6 in modulating learning performance. In results, we observed a decrease in amplitude of the NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) in the hippocampal neurons of animals treated with anti-NMDAR. In those rats with anti-NMDAR, we also observed impaired learning performance in the Morris water maze and spatial working memory test. Of note, cerebral infusion of TNF-α and IL-6 worsened NMDAR-EPSCs and this was accompanied with exaggeration of impaired learning performance. In conclusion, our findings suggest that the role played by neuroinflammation in exacerbating the memory impairment found in animals treated with anti-NMDAR. Anti-inflammation is a potential target in improving the memory impairment induced by anti-NMDA encephalitis.

With the development of China’s sports power development strategy, the quality of sports competitions also needs to be further improved. Only in this way can we better play its role in promoting sports and sports. The application of big data technology is an important way to improve the quality of sports competitions. Big data technology can not only comprehensively mine and collect sports competition data, but also perform objective, comprehensive and efficient analysis and processing of massive technologies. This will not only provide better protection for athletes, but also provide spectators with a better watching experience, thus laying a good foundation for comprehensively improving the quality of sports competitions.

Aim To examine the clinical characteristics, laboratory tests, imaging and electroencephalography presentation, treatment, and prognosis of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis and improve the awareness of this disease. Method We performed a retrospective analysis of the clinical data of 41 patients who were diagnosed with anti-LGI1 encephalitis. Their clinical characteristics, laboratory tests, and imaging and electroencephalography data were collected, and the treatment results and prognosis were evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. Results A total of 41 patients were included in the study, the average follow-up time is 33.0 months.The initial symptoms included cognitive impairment (n = 16, 39.0%),faciobrachial dystonic seizures (FBDS) (n = 12, 29.3%), grand mal seizures (n = 5, 12.2%) hallucinations (n = 4, 9.8%), loss of consciousness (n = 2, 4.9%), nausea and vomiting (n = 1, 2.4%),and head discharge-like sensation and radiate one limb (n = 1, 2.4%). There were 20 and 21 patients in the good (mRS ≤ 2) and poor (mRS > 2) prognosis groups, respectively. In the good prognosis group, the initial symptoms included faciobrachial dystonic seizures (FBDS) (n = 6, 30.0%), cognitive impairment (n = 6, 30.0%), hallucinations (n = 4, 20.0%), grand mal seizures (n = 3, 15.0%), loss of consciousness (n = 2, 10.0%), and nausea and vomiting (n = 1, 5.0%). There were 10 patients with hyponatremia. Magnetic resonance imaging (MRI) showed limbic system involvement in 12 patients (60.0%).17 patients (85.0%) recovered, 2 (10.0%) showed significant improvement, and 1 (5.0%) died after a mean follow-up period of 36.9 months. In the poor prognosis group, the initial symptoms included FBDS (n = 6, 28.5%), cognitive impairment (n = 10, 47.6%), grand mal seizures (n = 2, 9.5%), and electric shock-like sensation in the left limbs (n = 1, 4.7%). There were 20 patients with hyponatremia. MRI showed limbic system involvement in 11 patients (52.4%). 11 patients (52.4%) recovered, 8 (38.1%) showed significant improvement, and 2 (9.5%) died after a mean follow-up period of 29.0 months. Conclusions The clinical characteristics of anti-LGI1 encephalitis include hyponatremia, FBDS, epileptic seizures, hallucinations, cognitive impairment, and loss of consciousness, while the rarely seen characteristics are nausea, vomiting, and other autonomic dysfunctions and electric shock-like sensation. The appearance of hallucinations often indicates a good prognosis.Hyponatremia and elevated cerebrospinal fluid protein levels can be used as indicators that affect the prognosis of patients.Limbic system involvement has nothing to do with prognosis.Attention should be paid to early diagnosis and timely first-line immunotherapy.

Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this meta-analysis were to evaluate the efficacy and tolerability of vortioxetine compared with duloxetine in MDD. Randomized controlled trials (RCTs) published in PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were systematically reviewed to compare vortioxetine with duloxetine in terms of efficacy and tolerability in patients with MDD. Results were expressed as the risk ratio (RR) with 95 % confidence intervals (CIs), and weighted mean difference (WMD). Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies. A total of five RCTs involving 2287 patients met the inclusion criteria and were included in this meta-analysis. Pooled results showed that duloxetine was associated with a higher response rate than vortioxetine, as well as showing a similar remission rate with vortioxetine. The changes from baseline in the Montgomery–Asberg Depression Rating Scale (MADRS), 24-item Hamilton Rating Scale for Depression (HAM–D24), Clinical Global Impression–Improvement scale (CGI–I), CGI–Severity scale (CGI–S), Sheehan Disability Scale (SDS), and Hamilton Anxiety Rating Scale (HAM–A) scores were significantly greater in the duloxetine group than in the vortioxetine group. The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group. Duloxetine was more effective but less well-tolerated than vortioxetine in MDD. Considering the potential limitations of this meta-analysis, more large-scale RCTs are needed to confirm these findings.

The transcription factor SOX4 has functional importance in foetal lung maturation and tumorigenesis in a number of cancers. However, its biological functions in the progression of lung tumorigenesis remain unclear. In this study, we found that the expression levels of SOX4 mRNA and protein were significantly higher in Xuanwei female lung cancer tissues than in benign lung lesions. The patients with high expression of the SOX4 protein had a higher pathological grade, lymph node (LN) metastasis, poor tumor differentiation and worse prognosis than those patients with low expression of SOX4. Knockdown of the SOX4 gene in the Xuanwei female lung cancer cell line XWLC-05 resulted in apoptotic morphological changes, decreased cell proliferation, invasion and migration. Furthermore, knockdown of the SOX4 gene resulted in obvious sub-G1 peaks and induction of apoptosis through upregulation of caspase-3 expression, while in cells treated with a caspase-3 inhibitor, apoptosis induced by silencing SOX4 expression was inhibited. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor suppressor gene in the regulation of Xuanwei female lung cancer cell proliferation, apoptosis and metastases, and it may be a potential target for effective lung cancer therapy. J. Cell. Biochem. 116: 1007–1018, 2015. © 2015 Wiley Periodicals, Inc.

Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.

Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients.From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured.A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50 ± 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 ± 6.94) pg/mL (P0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 ± 8.597) ng/mgCr were significantly higher than those of patients from other regions (25.673 ± 7.986) ng/mg Cr (P0.05), with statistically significant difference.The accumulation of inorganics and the activation of NF-κB-iNOS signaling pathway may contribute to Xuanwei lung cancer. .背景与目的 室内空气污染不仅会诱发哮喘，也会导致慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD），甚至促进肺癌发生。随着宣威肺癌的病因学研究，发现室内空气污染最终造成肺部无机颗粒物的沉积，这些物质可以造成肺泡细胞损伤、信号通路激活，最终促进肿瘤的发生。本研究旨在探讨宣威肺癌患者肺部中无机杂质的赋存以及核转录因子（nuclear factor κB, NF-κB）-诱导型一氧化氮合成酶（inducible nitric oxide synthase, iNOS）信号通路的激活情况。方法 选取48例2013年12月-2014年11月在昆明医科大学第三附属医院行手术治疗的宣威肺癌患者与其他地区的肺癌患者作为研究对象，用透射电镜（transmission electron microscope, TME）对患者术后标本进行超微结构的观察，探究无机颗粒物的赋存情况；对患者的血清行细胞因子检测；对术后的标本行免疫组化以及蛋白质印迹（Western blot），了解NF-κB-p65蛋白以及iNOS蛋白的表达；对肺癌组织中和尿液中的8-OHdG赋存进行检测。结果 在宣威肺癌患者癌旁组织的肺泡II型细胞、巨噬细胞中可见到大量纳米级无机物赋存；对无机物进行元素分析，含有硅（Silicon, Si）成分；宣威地区患者血清中白介素（interleukin, IL）-1β（31.50±19.16）pg/mL较其他地区肺癌患者（11.33±6.94）pg/mL高，差异有统计学意义（P0.01）；宣威肺癌与其他地区肺癌患者的术后病理组织中癌组织有NF-κB-p65和iNOS表达，较非宣威地区明显升高；癌旁和正常组织之间未见明显差异；宣威肺癌组织和尿液8-OHdG较非宣威地区肺癌患者高，肺癌患者尿液中的8-OhdG（40.124±8.597）ng/mgCr与其他地区患者（25.673±7.986）ng/mgCr相比，差异有统计学意义（P0.05）。结论 肺部无机物的赋存以及NF-κB-iNOS信号通路的激活可能促进了宣威肺癌的发生。.

The mismatch between pleural space and remnant lung after bilobectomy has been considered as the main reason for the high incidence of postoperative complications in non-small cell lung cancer (NSCLC) patients. The aim of this study is to analyze the differences in postoperative complications between bilobectomy and lobectomy in the right lung of NSCLC patients.This study included 528 NSCLC patients who underwent right pulmonary lobectomy. A total of 352 cases that underwent upper or lower right lobectomy (108 upper and 244 lower) were the control group, and 176 cases that underwent bilobectomy (57 upper and middle and 119 lower and middle) were the observation group. A retrospective case-control study was performed on a series of matched NSCLC patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation method, cardiac comorbidity, type of postoperative management, and pathological type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac-respiratory complications (hospital-acquired pneumonia, low oxygen concentration, pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or infarction, and cardiac insufficiency) and occurrence of space-related complications (atelectasis, air leak more than 5 days, and pneumothorax) were compared between the bilobectomy and lobectomy groups.The prevalence of 30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the lobectomy group. No statistical significance was observed between the two groups. The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176) was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory complication rate of the lower and middle pulmonary lobectomy patients in the bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352), respectively. No statistically significant difference between the two groups was observed.The postoperative cardiac-respiratory complications of NSCLC patients with right bilobectomy are higher than those of the right lobectomy patients, but the prevalence of 30-day death and space-related complication was not statistically different between the two groups.背景与目的 双肺叶切除后剩余肺叶与胸膜腔空间不匹配是右侧非小细胞肺癌（non-small cell lung cancer, NSCLC）患者术后高并发症发病率的主要原因。本研究旨在比较右侧NSCLC双肺叶切除与单肺叶切除患者术后并发症发生率之间的差异。方法 本研究共纳入行右侧肺叶切除NSCLC 528例，右肺单肺叶切除病例352例（108例上叶与244例下叶）为对照组，右肺双肺叶切除病例176例（57例中上叶与119例中下叶）为观察组。两组病例行回顾性病例-对照配对研究。两组病例按照年龄、性别、术前预计FEV1%、LEVF%、手术方式、术前心脏伴随疾病、术后管理方式、病理类型、肿瘤大小等情况进行按1:2进行配对。比较两组患者术后30天内死亡率、空间相关并发症（肺不张、漏气大于5天、气胸）发生率与心肺并发症（院内获得性肺炎、低氧气血症、肺栓塞、脑卒中、心律失常、心肌缺血或梗塞、心功能不全）发生率之间的差异。结果 双肺叶切除组病例术后30天死亡率为3.4%（6/176），单肺叶切除组病例为2.3 %（8/352），两者间差异无统计学意义；双肺叶切除组病例术后心肺并发症总体发病率为23.8%（42/176）高于单肺叶切除组10.7%（38/352），差异具有统计学意义；双肺叶切除组中下叶切除病例的心肺并发症发病率为26.5%（31/119）远高于单肺叶切除组4.9%（12/244）；而空间相关并发症双肺叶切除组与单肺叶切除组分别为20.4%（36/176）和17.3%（61/352），两者间差异无统计学意义。结论 右侧NSCLC双肺叶切除患者术后心肺相关并发症发生率高于单肺叶切除患者， 30天内死亡率与空间相关并发症发生率无明显差异。

Silicon nanoparticles are widely used in daily life. Therefore, they attract increased attention because of their potential biotoxicity to the lungs when inhaled. The aims of this study are to explore the organism distribution and genotoxicity of silica nanoparticles in human bronchial epithelial cells (BEAS-2B).The biodistribution of silica with different particle sizes in human bronchial epithelial cells was observed by transmission electron microscopy (TEM). DNA damage was detected by single-cell gel electrophoresis (comet assay).TEM revealed that SiO₂ nanoparticles with different sizes can be uptaken by cells and be localized in the cytoplasm and the nucleus. Compared with micro-silica, nano-silica in BEAS-2B cells can inflict more severe DNA damage (P0.05).The particle size of silica nanoparticles can be used to determine their distribution in biological cells. Compared with micro-silica, nano-silica has higher genotoxicity.

China's Xuan Wei County in Yunnan Province have the world's highest incidence of lung cancer in nonsmoking women-20 times higher than the rest of China. Previous studies showed, this high lung cancer incidence may be associated with the silica particles embedded in the production combustion from the C1 coal. The aim of this study is to separate the silica particles from production combustion from the C1 bituminous coal in Xuan Wei County of Yunnan Province, and study in vitro toxicity of naturally occurring silica particles on BEAS-2B.①Separating the silica particles from combustion products of C1 bituminous coal by physical method, observing the morphology by Scanning Electron Microscope, analysis elements by SEM-EDX, observed the single particle morphology by Transmission Electron Microscope, analyed its particle size distribution by Laser particle size analyzer, the surface area of silica particles were determined by BET nitrogen adsorption analysis; ②Cell viability of the experimental group (silica; naturally occurring), control group (silica; industrial produced and crystalline silica) was detected by assay used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, and the reactive oxygen species (ROS), lactate dehydrogenase (LDH) were determined after 24 h-72 h exposed to these particles.①The physical method can separate silica particles from production combustion from the C1 bituminous coal, which have different size, and from 30 nm to 120 nm particles accounted for 86.8%, different morphology, irregular surface area and containing trace of aluminum, calcium and iron and other elements; ②Under the same concentration, the experiment group have higher toxicity on BEAS-2B than control groups.Physical method can separate silica particles from production combustion from the C1 bituminous coal and not change the original morphology and containing trace; ②Naturally occurring silica nanoparticles have irregular morphology, surface area, and containing complex trace elements may has greater toxicity than the silica nanoparticle of industrial produced and crystalline silica.

Purpose To evaluate the effectiveness and safety of carotid artery stent (CAS) placement for treatment of long segment stenosis in patients with Takayasu arteritis. Materials and Methods Between January 2002 and February 2012, all patients with Takayasu arteritis found to have long segment (≥80mm) carotid artery stenoses at a single institution were retrospectively analyzed. Five patients treated by CAS placement with either long or multiple self-expandable stents were included. All patients had focal neurologic symptoms, including three strokes and two transient ischemic attacks (TIAs). Six self-expanding stents were used in five patients. The mean follow-up period was 19.2 months (range, 6–30 mo); all patients had clinical evaluation, laboratory examination, and vascular imaging follow-up. Results Improvement in clinical symptoms was shown after successful angioplasty. There were no perioperative or in-hospital deaths. Four patients exhibited persistent relief, and repeated angiography or computed tomography (CT) angiography showed normal flow. One patient stopped taking her medications after CAS placement and became symptomatic 8 months later as a result of a severe in-stent stenosis. Conclusions CAS placement was shown to be a feasible option for treating long segment (≥80mm) stenosis of carotid arteries in patients with Takayasu arteritis with encouraging results.

Background and Objectives: Spontaneous vertebral artery dissection (sVAD) is a rare condition and can potentially cause a stroke, particularly in young to middle-aged people. Patients and Methods: The clinical manifestations, medical imaging characteristics, treatment, and prognosis of 16 patients with sVAD were analyzed. Results: None of the 16 patients had a history of head or neck trauma. The most common clinical manifestation was headache with symptoms of posterior-circulation ischemia (63%). Diagnosis of VAD was definitive in one patient at autopsy, and in the remaining it was established by magnetic resonance angiography, computer tomography angiography, or digital subtraction angiography. Treatment modalities included: thrombolysis with urokinase (1), antiplatelet therapy (6), and endovascular stenting (9). There was one death and the remaining 15 patients were followed up for 3-48 months and did not have recurrence of cerebral events. Conclusions: Rapid and accurate diagnosis of sVAD and proper treatment are crucial for good outcomes. This study shows that antiplatelet therapy and endovascular treatment are effective treatments for sVAD.