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Assessing water exchange capability is an essential step to understand the vulnerability of waterbody to potential pollution. To characterize the spatiotemporal variations of water exchange rate in Hong Kong waters, a three-dimensional hydrodynamic and transport model was implemented. In this study, water residence time (T re ) representing the water exchange rate was <10 days in open waters but exceeded 60 days in weakly-flushed Tolo Harbour. Sensitivity experiments revealed that river discharge accelerated water exchange in western areas, especially during the wet season, causing 45 % ~ 37 % declines in regional T re . Conversely, tidal currents were the primary limiting factor, particularly during winter. Furthermore, the seasonal reversal of vertical T re difference in Mirs Bay demonstrated how intrusion water facilitates water exchange by dilution effects. This comprehensive assessment of coastal water exchange capability not only enhances understanding of local marine pollution distribution but also informs coastal management strategies, which can be applied to other coastal water areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the features and influencing factors of language in children with various types of speech disorders. Methods: A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin-comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi-square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors. Results: There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs. 96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F =5.46, 4.69, 3.68, all P <0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P <0.01) and the overall language score was lower than that of children with stuttering ( P <0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ 2 =7.93, 10.28; both P <0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder ( OR =1.87, 2.18, 2.01; 95% CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P <0.01). Negative family history are protective factors for the progress of language ability ( OR =0.37, 95% CI 0.17-0.81, P <0.05). Conclusions: Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability., Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes., Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus., Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Gan, Zhang, Liu, Wang, Lu, Jiang, Duan, Yuan and Li.)

Objective: To detect the cell-free DNA of Mycobacterium tuberculosis (Cf-TB) in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM), and to assess the diagnostic value of this method for TBM. Methods: We prospectively included patients with suspected meningitis from the Department of Tuberculosis, Beijing Chest Hospital, Department of Neurology, Beijing Chaoyang Hospital and Department of Neurology, 263 Hospital of the People's Liberation Army from September 2019 to March 2022. A total of 189 patients were included in this study. Among them, 116 were male and 73 were female, aged from 7 to 85 years, with an average of (38.5±19.1) years. The CSF specimens of the patients were collected for Cf-TB, MTB culture and Xpert MTB/RIF. SPSS 20.0 was used for statistical analysis and the difference was statistically significant with P <0.05. Results: Among the 189 patients, there were 127 patients in the TBM group and 62 patients in the non-TBM group. The sensitivity of Cf-TB was 50.4% (95% CI 41.4%-59.3%), the specificity was 100% (95% CI 92.7%-100.0%), the positive predictive value was 100% (95% CI 92.9%-100.0%), and the negative predictive value was 49.6% (95% CI 40.6%-58.6%). Using clinical diagnosis as the gold standard, the sensitivity of Cf-TB was 50.4% (64/127), which was significantly higher than that of MTB culture (8.7%, 11/127) and Xpert MTB/RIF (15.7%,20/127) (all P <0.001). Using etiology as the gold standard, the sensitivity of Cf-TB was 72.7% (24/33), which was significantly higher than that of MTB culture [33.3%, 11/33, ( χ 2 =10.28, P =0.001)] and was similar to Xpert MTB/RIF (60.6%, 20/33) ( χ 2 =1.091, P =0.296). Conclusion: The sensitivity of the Cf-TB test was significantly higher than that of CSF MTB culture and Xpert MTB/RIF. Cf-TB may provide evidence for earlier diagnosis and treatment of TBM.

Background and Objective: This paper proposes a novel strategy to localize anomalies in the arterial network based on its response to controlled transient waves. The idea is borrowed from system identification theories in which wave reflections can render significant information about a target system. Cardiovascular system studies often focus on the waves originating from the heart pulsations, which are of low bandwidth and, hence, can hardly carry information about the arteries with the desired resolution., Methods: Our strategy uses a relatively higher bandwidth transient signal to characterize healthy and unhealthy arterial networks through a frequency response function (FRF). We tested our novel approach on data simulated using a one-dimensional cardiovascular model that produced pulse waves in the larger arteries of the arterial network. Specifically, we excited the blood flow from the brachial artery with a relatively high bandwidth flow disturbance and collected the subsequent pressure waveform at peripheral positions. To better differentiate FRFs of healthy and unhealthy networks, we used a FRF that removes the effects of heart pulsations., Results: Results demonstrate the ability of the proposed FRF to detect and follow-up on the development of a common carotid artery (CCA) stenosis. We tested distinct geometrical variations of the stenosis (size, length and position) and observed differences between the FRFs of healthy and unhealthy networks in all cases; such differences were mainly due to geometrical variations determined by the stenosis., Conclusions: We have provided a theoretical proof of concept that demonstrates the ability of our novel strategy to detect and track the development of CCA stenosis by using peripheral pressure waves that can be measured non-invasively in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Euryale ( Euryale ferox Salisb.) is an aquatic crop used as both food and drug in Asia, but its utilization is seriously limited due to low yield. Previously, we hypothesized that Euryale small auxin up RNA s ( EuSAUR s) regulate seed size, but the underlying biological functions and molecular mechanisms remain unclear. Here, we observed that the hybrid Euryale lines (HL) generate larger seeds with higher indole-3-acetic acid (IAA) concentrations than those in the North Gordon Euryale (WT). Histological analysis suggested that a larger ovary in HL is attributed to longer cells around. Overexpression of EuSAUR62 in rice ( Oryza sativa L.) resulted in larger glumes and grains and increased the length of glume cells. Immunofluorescence and protein interaction assays revealed that EuSAUR62 modulates IAA accumulation around the rice ovary by interacting with the rice PIN-FORMED 9, an auxin efflux carrier protein. Euryale basic region/leucine zipper 55 (EubZIP55), which was highly expressed in HL, directly binds to the EuSAUR62 promoter and activated the expression of EuSAUR62 . Constant light increased the expression of both EubZIP55 and EuSAUR62 with auxin-mediated hook curvature in HL seedlings. Overall, we proposed that EuSAUR62 is a molecular bridge between light and IAA and plays a crucial role in regulating the size of the Euryale seed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Bao, Jing, Wang, Duan, Zhang, Tao and Wu.)

Hydraulic modeling of a foul sewer system (FSS) enables a better understanding of the behavior of the system and its effective management. However, there is generally a lack of sufficient field measurement data for FSS model development due to the low number of in-situ sensors for data collection. To this end, this study proposes a new method to develop FSS models based on geotagged information and water consumption data from smart water meters that are readily available. Within the proposed method, each sewer manhole is firstly associated with a particular population whose size is estimated from geotagged data. Subsequently, a two-stage optimization framework is developed to identify daily time-series inflows for each manhole based on physical connections between manholes and population as well as sewer sensor observations. Finally, a new uncertainty analysis method is developed by mapping the probability distributions of water consumption captured by smart meters to the stochastic variations of wastewater discharges. Two real-world FSSs are used to demonstrate the effectiveness of the proposed method. Results show that the proposed method can significantly outperform the traditional FSS model development approach in accurately simulating the values and uncertainty ranges of FSS hydraulic variables (manhole water depths and sewer flows). The proposed method is promising due to the easy availability of geotagged information as well as water consumption data from smart water meters in near future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.

Objective: To analyze the clinical manifestations, radiographic characteristics and prognosis of Mycobacterium xenopi pulmonary disease, in order to improve diagnosis and treatment of the disease. Methods: Using " Mycobacterium xenopi, pulmonary disease" as the search term, from February 15, 2007 to February 21, 2021, a total of 1 264 cases were retrieved in the PubMed database. In the Wanfang database, using " Mycobacterium xenopi, pulmonary disease" as the search term, from February 15, 2007 to February 21, 2021, no related document was retrieved. In the CNKI database, " Mycobacterium xenopi, pulmonary disease" was used as the search term, and one relevant case report was retrieved, but did not meet the diagnostic criteria of Mycobacterium xenopi pulmonary disease issued by American Thoracic Society in 2007. The 1 264 cases from the literature and 3 cases of our institution were used for review. Results: Our 3 cases were elderly males complaining of cough and expectoration, and had underlying lung diseases. The imaging examination showed cavitary lesions. All of them had positive sputum smear for acid-fast bacillus and negative Xpert MTB/RIF examination. Mycobacterium xenopi was isolated at least 2 times from sputum samples. Although prescribed with chemotherapy, case 1 and case 2 died 4 years and 2 years later, respectively, after the diagnosis. Case 3 got sputum conversion, symptom improvement and radiographic responses after 30-month chemotherapy. Conclusions: The clinical manifestations of Mycobacterium xenopi pulmonary disease are atypical. For patients with positive sputum smear for acid-fast bacillus and negative Xpert MTB/RIF examination and conventional mycobacterial culture, Mycobacterium xenopi pulmonary disease should be considered. The disease deserves further attention from clinicians due to poor prognosis.

During the past three decades, harmful algal blooms (HAB) events have been frequently observed in marine waters around many coastal cities in the world including Hong Kong. The increasing occurrence of HAB has caused acute influences and damages on water environment and marine aquaculture with millions of monetary losses. For example, the Tolo Harbour is one of the most affected areas in Hong Kong, where more than 30% HAB occurred. In order to forewarn the potential HAB incidents, the machine learning (ML) methods have been increasingly resorted in modelling and forecasting water quality issues. In this study, two different ML methods - artificial neural networks (ANN) and support vector machine (SVM) - are implemented and improved by introducing different hybrid learning algorithms for the simulations and comparative analysis of more than 30-year measured data, so as to accurately forecast algal growth and eutrophication in Tolo Harbour in Hong Kong. The application results show the good applicability and accuracy of these two ML methods for the predictions of both trend and magnitude of the algal growth. Specifically, the results reveal that ANN is preferable to achieve satisfactory results with quick response, while the SVM is suitable to accurately identify the optimal model but taking longer training time. Moreover, it is demonstrated that the used ML methods could ensure robustness to learn complicated relationship between algal dynamics and different coastal environmental variables and thereby to identify significant variables accurately. The results analysis and discussion of this study also indicate the potentials and advantages of the applied ML models to provide useful information and implications for understanding the mechanism and process of HAB outbreak and evolution that is helpful to improving the water quality prediction for coastal hydro-environment management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A series of chiral thiourea bearing multiple H-bond donors derived from hydroquinine has been reported. The aza-Henry reaction of isatin-derived ketimines and long-chain nitroalkanes catalyzed by these chiral thioureas can achieve high enantioselectivity (78-99% ee) and excellent diastereoselectivity (up to 99:1). This work is the first report on long-chain nitroalkanes as substrates with excellent diastereoselectivity in metal-free catalytic systems., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Since the establishment of the world-class Three Gorges Dam (TGD) across the Yangtze River, China, the downstream reach has experienced a long-term adjustment with regard to the river morphology and hydrodynamics, imposing a profound impact on the environmental conditions of human living and aquatic ecosystem. This study presents an investigation on the river channel morphological characteristics and hydrodynamic environment of a large bifurcation-confluence complex downstream of the TGD through detailed field survey and numerical modeling. Results show that the main stem, before being bifurcated into two sub-channels (the North Channel and the South Channel), experiences a meander, leading to the severe bed scouring near the outer bank (pools) resulted from a high flow mass flux and bed shear stress. Because of being bifurcated, the river width with largely growing may result in the reduction of flow velocity and sediment deposition (riffles), and thereby two plugbars are formed near the entrance of two sub-channels. In the meantime, the velocity-reversal phenomenon (flow velocity and friction velocity) is identified when low flows are transited into high flows. The flow mass flux, however, is always larger in pool regions, which is highly related to water depth. As a result, the topographic steering of flows by riffles, bars and floodplains may have more impact on flow path under low flow conditions, while the bankline shape would become more important under high flows. Furthermore, the topographic steering could play a key role in the pattern of flow separations near the confluence. More interestingly, the confluence flow separation only occurs under low flow conditions and its occurring location shifts upwards the tributary (the North Channel), which differs from observations in previous studies. The visualized numerical results of friction velocity distribution indicate that sediment is more likely to deposit in the North Channel (entrance) with lower friction velocity, implying the potential closure of the sub-channel., Competing Interests: Declaration of competing interest We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. This study has no conflicts of interest to other bodies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Emotional abnormality in major depressive disorder (MDD) is generally regarded to be associated with functional dysregulation in the affective network (AN). The present study examined the changes in characteristics of AN connectivity of MDD patients before and after repetitive transcranial magnetic stimulation (rTMS) treatment over the left dorsolateral prefrontal cortex, and to further assess how these connectivity changes are linked to clinical characteristics of patients. Functional connectivity (FC) in the AN defined by placing seeds in the bilateral amygdale was calculated in 20 patients with MDD before and after rTMS, and in 20 healthy controls (CN). Furthermore, a linear regression model was used to obtain correlations between FC changes and Hamilton depression scale (HAMD) changes in MDD before and after rTMS. Before rTMS, compared with CN, MDD exhibited significantly lower FC between left insula (INS.L), right superior and inferior frontal gyrus (SFG.R and IFG.R), right inferior parietal lobule (IPL.R), and amygdala, and showed an increment of FC between the bilateral precuneus and amygdala in AN. After rTMS, MDD exhibited a significant increase in FC in the INS.L, IFG.R, SFG.R, IPL.R, and a significant reduction in FC in the precuneus. Interestingly, change in FC between INS.L and left amygdala was positively correlated with change in HAMD scores before and after rTMS treatment. rTMS can enhance affective network connectivity in MDD patients, which is linked to emotional improvement. This study further suggests that the insula may be a potential target region of clinical efficacy for MDD to design rationale strategies for therapeutic trials., (Copyright © 2020 Chen, Gu, Zhai, Duan, Zhai and Zhang.)

Purpose: To investigate the value of dual-energy spectral computed tomography (CT) imaging in the differential diagnosis of small bowel adenocarcinoma (SBA) from primary small intestinal lymphoma (PSIL)., Materials and Methods: We retrospectively analyzed the images of 27 SBA cases and 15 PSIL cases. These patients underwent spectral CT imaging in the arterial phase (AP) and venous phase (VP). CT attenuation values of tumors at different energy levels were measured to generate spectral attenuation curve and to calculate curve slope (λ HU ). Iodine concentration (IC) in tumors at AP and VP were measured and normalized to that of aorta as normalized iodine concentration (NIC). Independent samples t test was used to analyze the spectral CT parameters; Receiver operating characteristic curves were generated to evaluate the diagnostic efficacy of each parameter., Results: There were significant differences between SBA and PSIL in IC (2.09 ± 0.71 vs 1.33 ± 0.15 mg/ml), NIC (0.20 ± 0.06 vs 0.13 ± 0.02) and slope (λ HU ) (2.78 ± 1.06 vs 1.86 ± 0.30) in AP and (1.86 ± 0.68 vs 1.37 ± 0.18 mg/ml for IC; 0.47 ± 0.13 vs 0.33 ± 0.02 for NIC and 2.00 ± 0.56 vs 1.50 ± 0.26 for λ HU ) in VP (all p < 0.05). For the CT value measurement, there were significant differences between SBA and PSIL in the 40-60keV energy range (p < 0.05), but not in the 70-140keV range (p > 0.05). Using 1.38 mg/ml as a threshold value for iodine concentration at AP, one could obtain the area-under-curve of 0.93 for receiver operating characteristic study and sensitivity of 94% and specificity of 85% for differentiating SBA from PSIL. The sensitivity and specificity values were significantly higher than the respective values of 62% and 60% with the conventional CT numbers at 70keV., Conclusion: Quantitative parameters obtained in spectral CT, especially iodine concentration in AP, provide high accuracy for differentiating SBA from PSIL., (Copyright © 2019. Published by Elsevier Inc.)

The aim of this study was to investigate the effectiveness of cognitive behavioral therapy (CBT) on improving the cognitive function in minor depression (MiD) and major depression (MaD). The study will constitute a placebo-controlled single-blind parallel-group randomized controlled trial. The selected participants will be randomly allocated into one of two parallel groups with a 1:1 ratio: the CBT-based group and the general health education group. CBT significantly alleviated depressive symptoms of MiD and MaD at 12 weeks (p < 0.001), and the treatment effect was maintained for at least 12 months (p < 0.001). Interestingly, CBT significantly promotes more cognitive function of MiD and partial cognitive function of MaD at 12 weeks in the intervention group than in the control group (p < 0.01). CBT can alleviate depressive symptoms of both minor and MaDs. The effectiveness of CBT is different on improving the cognitive function in MiD and MaD.

A new method of quantitative computed tomography (CT) measurements of pulmonary vessels are applicable to morphological studies and may be helpful in defining the progression of emphysema in smokers. However, limited data are available on the relationship between the smoking status and pulmonary vessels alteration established in longitudinal observations. Therefore, we investigated the change of pulmonary vessels on CTs in a longitudinal cohort of smokers.Chest CTs were available for 287 current smokers, 439 non-smokers, and 80 former smokers who quit smoking at least 2 years after the baseline CT. CT images obtained at the baseline and 1 year later were assessed by a new quantitative CT measurement method, computing the total number of pulmonary vessels (TNV), mean lung density (MLD), and the percentage of low-attenuation areas at a threshold of -950 (density attenuation area [LAA]%950). Analysis of variance (ANOVA) and the independent sample t test were used to estimate the influence of the baseline parameters. The t paired test was employed to evaluate the change between the baseline and follow-up results.The current smokers related to have higher whole-lung MLD, as well as less and lower TNV values than the non-smokers (P <.05). But no significant differences in LAA%950 were found between smokers and non-smokers. After one year, the increase in LAA%950 was more rapid in the current (additional 0.3% per year, P <. 05-.01) than in the former smokers (additional 0.2% per year, P = .3). Additionally, the decline in TNV was faster in the current (additional -1.3 per year, P <.05-.01) than that in the former smokers (additional -0.2 per year, P = .6). Current smoke, pack-years, weight, and lung volume independently predicted TNV at baseline (P <.001) in multivariate analysis.The findings of this study reveal that the decline in the pulmonary vessels in smokers can be measured and related to their smoking status.

Background: TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown., Results: Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections., Conclusions: Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.

Objective: To compare image quality of two adaptive statistical iterative reconstruction (ASiR and ASiR-V) algorithms using objective and subjective metrics for routine liver CT, with the conventional filtered back projection (FBP) reconstructions as reference standards., Methods: This institutional review board-approved study included 52 patients with clinically suspected hepatic metastases. Patients were divided equally into ASiR and ASiR-V groups with same scan parameters. Images were reconstructed with ASiR and ASiR-V from 0 (FBP) to 100% blending percentages at 10% interval in its respective group. Mean and standard deviation of CT numbers for liver parenchyma were recorded. Two experienced radiologists reviewed all images for image quality blindly and independently. Data were statistically analyzed., Results: There was no difference in CT dose index between ASiR and ASiR-V groups. As the percentage of ASiR and ASiR-V increased from 10 to 100% , image noise reduced by 8.6 -57.9% and 8.9-81.6%, respectively, compared with FBP. There was substantial interobserver agreement in image quality assessment for ASiR and ASiR-V images. Compared with FBP reconstruction, subjective image quality scores of ASiR and ASiR-V improved significantly as percentage increased from 10 to 80% for ASiR (peaked at 50% with 32.2% noise reduction) and from 10 to 90% (peaked at 60% with 51.5% noise reduction) for ASiR-V., Conclusion: Both ASiR and ASiR-V improved the objective and subjective image quality for routine liver CT compared with FBP. ASiR-V provided further image quality improvement with higher acceptable percentage than ASiR, and ASiR-V60% had the highest image quality score. Advances in knowledge: (1) Both ASiR and ASiR-V significantly reduce image noise compared with conventional FBP reconstruction. (2) ASiR-V with 60 blending percentage provides the highest image quality score in routine liver CT.

Nasopharyngeal carcinoma (NPC) is the most frequently occurring carcinoma of the head and neck. The complexity of NPC makes it difficult for it to be diagnosed and treated at an early stage. Certain long non-coding RNAs (lncRNAs) are closely associated with the carcinogenesis of NPC. In the present study, the expression of lncRNA ZNF674-1 in NPC tissues and an NPC cell line was analyzed and was revealed to be downregulated compared with normal tissues and cells. When the expression of lncRNA ZNF674-1 was reduced in NPC cells, the proliferation, migration and invasion of these cells was promoted, whereas the apoptosis of these cells was decreased. On the contrary, when overexpressed, the expression of lncRNA ZNF674-1 inhibited the proliferation, invasion and migration of cells, but promoted cell apoptosis. The results of the present study reveal that the lncRNA ZNF67-1 may restrain the carcinogenesis of NPC, and may also serve as a potential biomarker for the early diagnosis and treatment of NPC.

Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4 + CD25 + FoxP3 + (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.

Objective: To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma., Methods: This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RIC AP-VP : [RIC AP-VP =(IC AP -IC VP )/IC AP ]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison., Results: 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RIC AP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all p<0.05). Using 0.188 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.87 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.71 with CT value at 70keV and improved to 0.81 at 40keV., Conclusion: Dual-energy Spectral CT provides additional quantitative parameters than conventional CT to improve the differentiation between small hepatocellular carcinoma with and without microvascular invasion., Clinical Application/relevance: Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The mechanism of nasopharyngeal carcinoma (NPC) remains unclear. The present study investigated the abnormal expression of long non-coding (lnc)RNAs in NPC tissues and one NPC cell line to identify the involvement of lncRNAs in the tumorigenesis of NPC. Using a quantitative reverse transcription polymerase chain reaction (RT-qPCR), the expression of lncRNA C22orf32-1 in NPC tissues and an NPC cell line was verified. The effects of lncRNA C22orf32-1 on NPC cells were investigated with a cell proliferation assay, cell scratch assay, Transwell assay and a cell apoptosis assay. The expression levels of lncRNA C22orf32-1 in NPC tissues and an NPC cell line were upregulated. lncRNA C22orf32-1 promoted the proliferation, migration and invasion of NPC cells, and reduced the apoptosis of NPC cells. The data demonstrated that lncRNA C22orf32-1 may facilitate the tumorigenesis of NPC, and may be used for the early diagnosis and treatment of NPC.

The underlying mechanism of modified electroconvulsive therapy (MECT) treatment for drug-resistant and catatonic schizophrenia remains unclear. Here, we aim to investigate whether MECT exerts its antipsychotic effects through elevating N-acetylaspartate (NAA) concentration measured by proton magnetic resonance spectroscopy (H-MRS). Multiple-voxel H-MRS was acquired in the bilateral prefrontal cortex (PFC) and thalamus to obtain measures of neurochemistry in 32 MECT, 34 atypical antipsychotic-treated schizophrenic patients, and 34 healthy controls. We found that both MECT and atypical antipsychotic treatments showed significant antipsychotic efficacy. MECT and atypical antipsychotic treatments reversed the reduced NAA/creatine ratio (NAA/Cr) in the left PFC and left thalamus in schizophrenic patients compared with healthy controls. Furthermore, the NAA/Cr ratio after treatments was significant higher in the MECT group, but not in the medication group. Our findings demonstrate that eight times of MECT elevated the relative NAA concentration to display neuroprotective effect, which may be the underlying mechanism of rapid antipsychotic efficacy.

Rationale and Objective: This study aimed to investigate the clinical value of spectral computed tomography (CT) in the detection of cholesterol gallstones from surrounding bile., Materials and Methods: This study was approved by the institutional review board. The unenhanced spectral CT data of 24 patients who had surgically confirmed cholesterol gallstones were analyzed. Lipid concentrations and CT numbers were measured from fat-based material decomposition image and virtual monochromatic image sets (40-140 keV), respectively. The difference in lipid concentration and CT number between cholesterol gallstones and the surrounding bile were statistically analyzed. Receiver operating characteristic analysis was applied to determine the diagnostic accuracy of using lipid concentration to differentiate cholesterol gallstones from bile., Results: Cholesterol gallstones were bright on fat-based material decomposition images yielding a 92% detection rate (22 of 24). The lipid concentrations (552.65 ± 262.36 mg/mL), CT number at 40 keV (-31.57 ± 16.88 HU) and 140 keV (24.30 ± 5.85 HU) for the cholesterol gallstones were significantly different from those of bile (-13.94 ± 105.12 mg/mL, 12.99 ± 9.39 HU and 6.19 ± 4.97 HU, respectively). Using 182.59 mg/mL as the threshold value for lipid concentration, one could obtain sensitivity of 95.5% and specificity of 100% with accuracy of 0.994 for differentiating cholesterol gallstones from bile., Conclusions: Virtual monochromatic spectral CT images at 40 keV and 140 keV provide significant CT number differences between cholesterol gallstones and the surrounding bile. Spectral CT provides an excellent detection rate for cholesterol gallstones., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Unlabelled: : Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metabolism. Here we have demonstrated for the first time that AD-MSC infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in db/db obese mice and diet-induced obesity mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia and associated cardiovascular diseases., Significance: Mesenchymal stem cells (MSCs) are considered one of the most promising types of stem cells for translational application because of their rich tissue sources, multilineage differentiation capacity, and easy amplification in vitro and unique immunobiological properties. This study demonstrated that adipose-derived MSCs (AD-MSCs) infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in obese mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue were demonstrated to contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia., (©AlphaMed Press.)

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: Neurocognitive impairment is a contributor to major depressive disorder (MDD). However, MDD patients show great variability in the level and course of deficits. The present longitudinal study was to identify predictors of neurocognitive impairment in first-episode MDD patients., Methods: Neurocognitive performance was analyzed in a cohort of 100 patients at 2years after a first-episode MDD. Subgroups, deficit type vs. non-deficit type, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. The analysis was performed using the multivariate logistic regression to obtain a model for neurocognitive impairment determination. The predicted probabilities of multivariate logistic regression were analyzed using receiver operating characteristic (ROC) curve., Results: Fifty-two percent of MDD participants presented general neurocognitive impairment. The regression analyses demonstrated that clinical and sociodemographic characteristics were not predictive variables. A model composed of processing speed, executive function, and attention, dexterity correctly classified 85.8% of the MDD patients with deficit type. ROC curve indicated that the changes of these three cognitions could identify MDD with deficit type from MDD with non-deficit type. In addition, ROC curve also indicated that processing speed and executive function could identify MDD from CN subjects. Finally, processing speed performance was negatively correlated with Hamilton Depression Scale scores in both MDD with deficit and non-deficit type., Conclusion: The present study provides novel insights on frequency and neurocognitive profile of subtypes of patients showing impairment. Our results suggest that processing speed impairment is a trait dimension of the disorder related to specific cognitive dysfunctions and the severity of depression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To study transfection efficiency of Ad5F11p-GFP and its influence on biological characteristics of CIK and NK-92 cells in order to predict the application of Ad5F11p vector in immunotherapy., Methods: Two kinds of immune cells, cytokine-induced killer (CIK) cells and natural-killer (NK) cell line NK-92 cells, were transfected by Ad5F11p-GFP at different multiplicity of transfection (MOI), and untransfected immune cells were used as negative control. GFP expression was determined by flow cytometry, the cell morphology was observed with microscope, the cell proliferation was analyzed by trypan blue staining, specific cytotoxicity of NK-92 cells was determined by LDH assay., Results: About 90% of transfection efficiency for NK-92 cells could be achieved at a MOI of 25, while the transfection efficiency for CIK was less than 40% at a MOI of 200. In addition, the transfection efficiency basically unchanged at the same MOI for 48 h and 96 h, and the immune cells transfected with the virus trended to form agglomeration, displaying slower proliferation, increase of IFN-γ release and enhancement of tumor killing activity., Conclusion: Ad5F11p- modified NK-92 shows a good prospect for adoptive immunotherapy.

Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-α stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

GalNAc-transferase-7 (GALNT7) is essential for the regulation of cell proliferation and has been implicated in tumorigenesis. However, the role of GALNT7 in the development and progression of nasopharyngeal carcinoma (NPC) remains unclear. Our previous study showed that GALNT7 was a putative target of miR-494, which was confirmed by luciferase reporter assay. In the present study, we demonstrated that in vitro knockdown of GALNT7 significantly inhibited the proliferation, colony formation, migration, and invasion of NPC-derived cells. In vivo tumorigenicity assay showed that miR-494 and GALNT7-small interfering RNA (siRNA) reduced tumor growth in nude mice. Taken together, our results provided new evidence for an oncogenic role of GALNT7 in NPC.

Emotional and cognitive dysregulation in major depressive disorder (MDD) have been consistently considered to be attributed to structural and functional abnormalities in affective network (AN) and cognitive control network (CCN). This study was to investigate the functional connectivity (FC) patterns and altered functional interactions between both networks in MDD. We investigated resting-state functional connectivity magnetic resonance imaging in the AN and the CCN in 25 MDD and 35 healthy controls (HC). The seeds were from voxel-based morphometry (VBM) analysis results. Then FC within the AN was assessed from a seed placed in the left amygdala (AMG) and FC within CCN was determined by placing seeds in the right dorsolateral prefrontal cortex (DLPFC). Compared with HC, MDD showed reduced FC between left AMG and bilateral precuneus and right anterior cingulated cortex (ACC) within AN and reduced FC between right DLPFC and left cuneus, left lingual gyrus, and right ACC within CCN. An interaction hub of altered FC in MDD between AN and CCN located in the right ACC. Interestingly, the altered FC between right ACC and left AMG was negatively correlated with depressive symptom score while the altered FC between right ACC and DLPFC was positively correlated the executive function in MDD. The right ACC not only supports the cognitive and emotional processes, but also is an altered functional interaction hub between AN and CCN in MDD. It further suggest multiple sources of dysregulation in AN and CCN implicate both top-down cognitive control and bottom-up emotional expression dysfunction in MDD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To assess the frequency and clinical relevance of rapidly growing mycobacterium (RGM) isolates in a tuberculosis referral center in Beijing, China., Methods: All isolates were identified by using targeted gene sequencing. RESULTS of species identification for 228 nontuberculous Mycobacterium (NTM) isolates from respiratory samples were analyzed, and available medical files of patients from whom NTM were isolated were reviewed retrospectively. Diagnostic criteria for RGM pulmonary disease issued by the American Thoracic Society (ATS) were used to determine clinical relevance., Results: Isolates of Mycobacterium abscessus (M.abscessus) and Mycobacterium fortuitum (M.fortuitum) accounted for 28.9% (66 isolates) and 8.8% (20 isolates)of NTM isolates, respectively. Sixty-six M. abscessus isolates from 32 patients had evaluable medical files, including 28 cases diagnosed as definite M. abscessus lung disease, and 4 as probable M. abscessus lung disease. Eight M. fortuitum isolates from 8 cases had evaluable medical files, and all of them were diagnosed as unlikely lung disease. Mycobacteria Growth Indicator Tube (MGIT) was more effective to diagnose M. abscessus lung disease, as compared with Lowestein-Jensen medium (23/24 vs 18/28)., Conclusions: RGM is a common NTM in our institute. M. abscessus is mostly associated with RGM lung disease, but M. fortuitum is not.

Background Aims: Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI)., Methods: Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2)., Results: In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells., Conclusions: We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Unlike its reported role in the cardiovascular diseases, little information is available for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the cerebrovascular function. We investigated the different effects of ALDH2 genotypes on the risk of cerebral infarction between the genders, because different genders had different smoking and/or dinking status which are also risk factors for cerebral infarction. 247 healthy Chinese Han people (controls, group 1), 287 Chinese Han male patients with cerebral infarction (group 2), and 82 Chinese Han female patients with cerebral infarction (group 3) were involved in this study. The frequencies of the ALDH2*2 allele in group 3 were significantly higher than those in other groups (with P = 0.001 and P = 0.002, respectively). The difference of ALDH2*2 allele frequency between group 1 and group 2 was not significant (P = 0.652). After adjustment for smoking and drinking status, the male patients without smoking or drinking status (group 4) had higher ALDH2*2 allele frequency than group 1, but the difference was still not significant (P = 0.139). Thus, we conclude that ALDH2*2 allele may be a significant negative risk factor for cerebral infarction in Chinese women [odds ratio (OR) = 2.207, 95% CI 1.416-3.439]. But for Chinese male patients, the negative effects of ALDH2*2 allele on cerebral infarction which might be concealed by other risk factors were not significant.

Nasopharyngeal carcinoma has very high incidence and high mortality worldwide. MiRNA is related to the tumorigenesis and metastasis of a variety of tumors. In the present study, we verify that the expression of miR-494 in NPC tissues and NPC-derived cells was down-regulated, respectively. The proliferation, colony formation, migration, and invasion of NPC-derived cells were suppressed, while the cell apoptosis was promoted, when miR-494 was over-expressed in these cells. GALNT7 and CDK16 were confirmed to be the direct targets of miR-494. These results suggested that miR-494 play an inhibitory role in the tumorigenesis of NPC.

We have demonstrated that photoluminescence (PL) is a non-damaging and powerful tool for the characterization of heavily-doped semiconductor nanostructures such as n-ZnO nanowires. The PL shows a redshift and a Gaussian-shaped low-energy wing, indicating a broadening mechanism governed by the impurity band. The electron concentration can be estimated from the PL linewidth.

Hippocampal pathology has been considered to underlie clinical, functional and cognitive impairments in schizophrenia. While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the hippocampus during the early phases of schizophrenia (SCZ), very little is known about whether functional connectivity (FC) between the hippocampus and other brain regions also exhibit progressive changes. In this study, resting state functional MRI (fMRI) was used to examine changes in hippocampal connectivity at baseline and follow-up scans comparing 68 patients with first episode SCZ and 62 matched controls. At baseline and follow-up, in the bilateral hippocampal network, SCZ mainly showed decreased FC with bilateral cerebellum posterior lobe, frontal gyrus temporal gyrus, precuneus, and cingulate cortex compared to controls. Furthermore, in the bilateral hippocampus, there was a significant interaction effect of group and time for FC with cerebellum posterior lobe, temporal gyrus, frontal gyrus, and posterior cingulate cortex. Interestingly, longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus negatively correlated with positive symptom scores in SCZ. These results provide novel evidence for the progressive changes of FC between hippocampus and other brain regions in SCZ. It further suggests that longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus can contribute to the formation and emergence of positive symptom of SCZ., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Human mesenchymal stem cells (hMSCs) are currently investigated for a variety of therapeutic applications. However, MSCs isolated from primary tissue cannot meet clinical grade needs and should be expanded in vitro for several passages. Although hMSCs show low possibility for undergoing oncogenic transformation, they do, similar to other somatic cells, undergo cellular senescence and their therapeutic potential is diminished when cultured in vitro. However, the role of senescent MSCs in tumor progression remains largely elusive. In the current study, by establishing senescent human umbilical cord mesenchymal stem cells (s-UCMSCs) through the replicative senescence model and genotoxic stress induced premature senescence model, we show that s-UCMSCs significantly stimulate proliferation and migration of breast cancer cells in vitro and tumor progression in a co-transplant xenograft mouse model compared with 'young' counterparts (defined as MSCs at passage 5, in contrast to senescent MSCs at passage 45). In addition, we identified IL-6, a known pleiotropic cytokine, as a principal mediator for the tumor-promoting activity of s-UCMSCs by induction of STAT3 phosphorylation. Depletion of IL-6 from s-UCMSCs conditioned medium partially abrogated the stimulatory effect of s-UCMSCs on the proliferation and migration of breast tumor cells.

Recently, many researchers have reported that the genetic polymorphisms of CYP2C19 may account for the interpatient variability of the clinical course in cancers including primary liver cancer (PLC). Besides the genetic polymorphisms of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially HBV and/or HCV) also account for the interpatient variability of the clinical course in PLC. This research covered the above two factors and divided the patients with PLC into two groups (one group with HBV infection and another without any HV infection) to find out whether the genetic polymorphisms of CYP2C19 have different effects in the progressing of PLC in different groups of patients. Eight hundred sixty-four cancer-free Han people (controls, named group 1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients without any HV infection (group 3) were involved in this study. A wild-type allele (CYP2C19*1) and two mutated alleles (CYP2C19*2 and CYP2C19*3) were identified. The frequencies of the mutant alleles and genotypes were then compared with each other. The frequencies of the homozygous and heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P = 0.014, 95 % confidence interval (CI)). The differences were statistically significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus, we conclude that people which were not infected with HV but with the homozygous or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have higher possibilities of getting PLC than people with other allelic genotypes (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788). However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95 % CI = 0.738 ~ 1.810).

Early onset schizophrenia (EOS) is often associated with poorer outcomes, including lack of school education, higher risk of mental disability and resistance to treatment. But the knowledge of the neurobiological mechanism of EOS is limited. Here, using proton magnetic resonance spectroscopy, we investigated the possible neurochemical abnormalities in prefrontal cortex (PFC) and thalamus of first-episode drug-naïve patients with EOS, and followed up the effects of atypical antipsychotic treatment for 6 months on neurochemical metabolites and clinical symptoms. We measured the ratios of N-acetylaspartate (NAA), choline (Cho) to creatine (Cr) in 41 adolescents with first episode of EOS and in 28 healthy controls matched for age, gender, and years of education. The EOS patients presented with abnormally low NAA/Cr values in the left PFC and left thalamus with a reduced tendency in the right PFC compared with healthy controls. No significant differences were detected between groups for Cho/Cr in PFC and thalamus in any hemisphere. After atypical antipsychotic treatment for 6 months, the reduced NAA/Cr in the left PFC and left thalamus in EOS patients was elevated to the normal level in healthy controls, without any alteration in Cho/Cr. We also found that there was no significant correlation between the neurochemical metabolite ratios in the PFC and thalamus in patients with EOS, and clinical characteristics. Our results suggest that there was neurochemical metabolite abnormalities in PFC and thalamus in EOS patients, atypical antipsychotic treatment can effectively relieve the symptoms and restore the reduced NAA in PFC and thalamus., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate drug-induced liver injury (DILI) in tuberculosis (TB) patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS), and therefore to provide data for using second-line anti-tuberculosis drugs and risk prediction of liver damage., Methods: A retrospective analysis was performed for TB patients treated with regimens containing Pto and (or) PAS in Beijing Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified, and associated factors including patients' age and gender, time of onset, severity, clinical manifestations and prognosis of DILI were analyzed. The 2 groups were compared with χ(2) test. P < 0.05 was considered to be significant., Results: A total of 1714 cases were admitted, among whom 226 experienced liver damage during treatment, of which 97 cases were excluded because of underlying alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714), being 9.2% (59/641) in females, and 6.5% (70/1073) in males (χ(2) = 4.143, P < 0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2% (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious clinical symptoms of hepatotoxicity. Among different regimens, combination of Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05., Conclusions: DILI caused by Pto and PAS should be taken into account, especially in female patients and for multi-drug combination therapy. Liver function should be monitored even in patients without related clinical manifestations for early identification and treatment, and therefore avoiding severe liver damage.

Objective: To analyze the clinical manifestations and efficacy of a combination antibiotic therapy including cefoxitin for Mycobacterium abscessus (M.abscessus) group lung disease., Methods: We retrospectively analyzed the clinical manifestations of 16 patients with M.abscessus group lung disease, and the responses of 5 cases treated with whole-course clarithromycin and moxifloxacin, initially intensified with intravenous amikacin and cefoxitin therapy for the first 12 weeks., Results: Radiological study showed that 14 patients with M.abscessus group pulmonary disease were classified as nodular bronchiectasis form, and 1 patient as upper lobe cavity form and 1 patient was unclassifiable. The radiological characteristics of M.abscessus group pulmonary disease included multiple micronodules (14/16), bronchiectasis (14/16), tree in bud sign (13/16), cavity (5/16), consolidation (5/16), nodules (5/16), and collapse of lung (3/16). Five cases were treated with a combination antibiotic therapy including cefoxitin. After 3 months treatment for the initial phase, 2 of them got improvement in symptoms, CT manifestations and sputum conversion. Two of them improved in symptoms and CT manifestations, but not in sputum conversion. One case showed no improvement in the initial phase, and continuation therapy also failed to improve symptoms, CT abnormalities or sputum conversion., Conclusions: Nodular bronchiectasis is the main manifestation of M.abscessus group lung disease. The main imaging characteristics included multiple micronodules, bronchiectasis and tree in bud sign. A therapeutic regimen including cefoxitin may be moderately effective in treating M.abscessus group lung disease.

Parkinson's disease (PD) is a common neurodegenerative condition causing significant disability and thus negatively impacting quality of life. The recent advent of stem cell-based therapy has heralded the prospect of a potential restorative treatment option for PD. In particular, mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. Furthermore, hepatocyte growth factor (HGF), which shows mitogenic and morphogenetic activities in a variety of cells, including MSC, and may be implicated in the pathophysiology of PD. As such, HGF may represent a new therapeutic target for the disease. In this study, we successfully isolated and facilitated the transduction of an adenoviral vector expressing HGF (Ad-HGF) into isolated hUC-MSCs. Following transduction, the hUC-MSCs can differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter. Our data suggest that hUC-MSCs have the ability to differentiate into dopaminergic neurons after transduction with Ad-HGF, providing encouraging evidence to further explore this approach to the treatment of PD.

This study was purposed to investigate the effects of 2-deoxy-D-glucose (2-DG) on sensitizing HL-60 cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and its possible mechanism. The proliferative inhibition of HL-60 cells treated with different concentrations of 2-DG and TRAIL was measured by MTT assay. The cells were treated with 2-DG, TRAIL, and 2-DG combined with TRAIL at the concentration < IC50 value, i.e. 10 mmol/L for 2-DG and 100 ng/ml for TRAIL. Apoptosis was analyzed by flow cytometry with PI staining; the expression of RIP1, GRP78, and PARP was analyzed by Western blot; the activity of caspase-3 was detected by special detection kit. The results showed that the combined treatment of HL-60 cells for 48 h induced an apoptotic rate of (45.1 ± 4.3)%, which was significantly higher than that of treated with 2-DG or TRAIL alone; at the same time, the combined treatment potentiated the expression of GRP78 and caspase-3 activity, and down-regulated the expression of RIP1. It is concluded that 2-DG can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be correlated with excessive endoplasmic reticulum stress response, down-regulation of RIP1, and increase of caspase-3 activity.