Abnormal energy metabolism, oxidative stress, and polyunsaturated fatty acid metabolism in depressed adolescents associated with childhood maltreatment: A targeted metabolite analysis.

The purpose of this study was to explore the metabolomic differences between Major depressive disorder (MDD) and healthy individuals among adolescents and the association between childhood maltreatment (CM) and differentially abundant metabolites. The exploratory study included 40 first-episode drug-naïve adolescents with MDD and 20 healthy volunteers. We used the Beck Depression Inventory (BDI-13) to assess the severity of depression and the Childhood Trauma Questionnaire (CTQ) to assess the presence of childhood maltreatment. The plasma samples from all participants were collected for targeted metabolomics analysis using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS) methods. Spearman correlation was applied to analyse the correlations between clinical variables and metabolites. We found 11 increased metabolites and 37 decreased metabolites that differed between adolescents with MDD and healthy individuals. Pathway enrichment analysis of differentially abundant metabolites showed abnormalities in energy metabolism and oxidative stress in MDD. Importantly, we found that creatine, valine, isoleucine, glutamic acid and pyroglutamic acid were negatively correlated with the BDI-13, while isocitric acid, fatty acid and acylcarnitine were negatively associated with CTQ, and 4-hydroxyproline was positively related to CTQ in adolescents with MDD. These studies provide new ideas for the pathogenesis and potential treatment of adolescents with MDD.

Resting-state EEG dynamic functional connectivity distinguishes non-psychotic major depression, psychotic major depression and schizophrenia.

This study aims to identify dynamic patterns within the spatiotemporal feature space that are specific to nonpsychotic major depression (NPMD), psychotic major depression (PMD), and schizophrenia (SCZ). The study also evaluates the effectiveness of machine learning algorithms based on these network manifestations in differentiating individuals with NPMD, PMD, and SCZ. A total of 579 participants were recruited, including 152 patients with NPMD, 45 patients with PMD, 185 patients with SCZ, and 197 healthy controls (HCs). A dynamic functional connectivity (DFC) approach was employed to estimate the principal FC states within each diagnostic group. Incremental proportions of data (ranging from 10% to 100%) within each diagnostic group were used for variability testing. DFC metrics, such as proportion, mean duration, and transition number, were examined among the four diagnostic groups to identify disease-related neural activity patterns. These patterns were then used to train a two-layer classifier for the four groups (HC, NPMD, PMD, and SCZ). The four principal brain states (i.e., states 1,2,3, and 4) identified by the DFC approach were highly representative within and across diagnostic groups. Between-group comparisons revealed significant differences in network metrics of state 2 and state 3, within delta, theta, and gamma frequency bands, between healthy individuals and patients in each diagnostic group (p < 0.01, FDR corrected). Moreover, the identified key dynamic network metrics achieved an accuracy of 73.1 ± 2.8% in the four-way classification of HC, NPMD, PMD, and SCZ, outperforming the static functional connectivity (SFC) approach (p < 0.001). These findings suggest that the proposed DFC approach can identify dynamic network biomarkers at the single-subject level. These biomarkers have the potential to accurately differentiate individual subjects among various diagnostic groups of psychiatric disorders or healthy controls. This work may contribute to the development of a valuable EEG-based diagnostic tool with enhanced accuracy and assistive capabilities.

Mapping Violent Behaviors and Psychiatric Symptoms Among Male Psychiatric Inpatients from a Network Perspective.

Psychiatric symptoms are common risk factors of violent behaviors among psychiatric patients. This study explored the interrelationship between violence and psychiatric symptoms in male psychiatric inpatients. This is a cross-sectional survey conducted in 2019. All patients admitted to the Male Psychiatry Unit of the Second Xiangya Hospital were consecutively recruited. The presence of five violent behaviors and eleven psychiatric symptoms were collected by reviewing medical records and were included as categorical variable in the network analyses. A total of 673 participants were included. The most central symptoms were "flight of ideas", "property-oriented violence", "emotional high", "verbal violence", "physical violence attempt", and "physical violence" in the network of psychiatric symptoms and violent behaviors. The bridge symptoms connecting violence and psychiatric symptoms were "verbal violence", "property-oriented violence", "hyperbulia", and "emotional high" according to the indices of bridge expected influence. The directed acyclic graph analysis revealed that "emotional high" and "hyperbulia" were the key psychiatric symptoms triggering violence, while "verbal violence" and "property-oriented violence" were the most upstream violent behavior. Verbal and property-oriented violence should be addressed in the risk assessment among male psychiatric inpatients. In addition, emotional high and hyperbulia are the potential treatment targets for violent behaviors.

The bridge symptoms of childhood trauma, sleep disorder and depressive symptoms: a network analysis.

BACKGROUND: This study aimed to elucidate the characteristics of symptom network of childhood trauma (CT) and sleep disorder (SD) in Chinese adolescents, with the influence of depressive symptoms taken into account. METHOD: A total of 1301 adolescent students were included, and their CT, SD and depressive symptoms were measured using the Pittsburgh sleep quality index (PSQI), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and The Patient Health Questionnaire-9 (PHQ-9), respectively. Central symptoms and bridge symptoms were identified based on centrality indices and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. RESULTS: In CT and SD symptom network, emotional abuse and sleep quality symptoms had the highest centrality values, and two bridge symptoms, i.e., emotional abuse and sleep disturbance symptoms, were also identified. In symptom network for CT, SD, and depressive symptoms, sleeping difficulty symptoms, daily dysfunction symptoms, and emotional abuse appeared to be potential bridge symptoms. In symptom network of CT, SD, and depressive symptoms (excluding the symptom of sleeping difficulty), daily dysfunction symptoms, emotional abuse, and sleep disturbance symptoms appeared to be bridge symptoms. CONCLUSIONS: In this study, emotional abuse and poor sleep quality were found to be central symptoms in the CT-SD network structure among Chinese adolescent students, with daytime dysfunction as the bridge symptom in the CT-SD-depression network structure. Systemic multi-level interventions targeting the central symptoms and bridge symptoms may be effective in alleviating the co-occurrence of CT, SD and depression in this population.

Functional connectivity alterations in reward-related circuits associated with non-suicidal self-injury behaviors in drug-naïve adolescents with depression.

Non-suicidal self-injury (NSSI) behaviors are a major public health concern among adolescents with depression. Such behaviors may be associated with the reward system. However, the underlying mechanism in patients with depression and NSSI still remains unclear. A total of 56 drug-naïve adolescents with depression, including 23 patients with NSSI (the NSSI group) and 33 patients without NSSI (the nNSSI group), and 25 healthy controls (HCs) were recruited in this study. Seed-based functional connectivity (FC) was used to explore the NSSI-related FC alterations in the reward circuit. Correlation analysis was conducted between the altered FCs and clinical data. Compared with the nNSSI group, the NSSI group showed greater FC between left nucleus accumbens (NAcc) and right lingual gyrus and between right putamen accumbens and right angular gyrus (ANG). The NSSI group also had declined FC between right NAcc and left inferior cerebellum, between left cingulate gyrus (CG) and right ANG, between left CG and left middle temporal gyrus (MTG), and between right CG and bilateral MTG (voxel-wise p < 0.01, cluster-wise p < 0.05, Gaussian random field correction). The FC between right NAcc and left inferior cerebellum was found positively correlated with the score of addictive features of NSSI (r = 0.427, p = 0.042). Our findings indicated that the regions in the reward circuit with NSSI-related FC alterations included bilateral NAcc, right putamen and bilateral CG, which may provide new evidence on the neural mechanisms of NSSI behaviors in adolescents with depression.

SHFM1 deficiency suppresses esophageal squamous cell carcinomas progression via modulating NF­κB signaling and enhancing nature killer cell­mediated tumor surveillance.

Excessive proliferation, metastasis and immune escape are considered to be hallmarks of cancer contributing to tumor progression. Split hand and foot malformation 1 (SHFM1) is highly expressed in various cancers and has been reported to increase malignant behaviors. However, the biological functions of SHFM1 in esophageal squamous cell carcinomas (ESCC) progression remain to be elucidated. An integrated bioinformatics analysis was performed to identify candidate genes in ESCC progression based on GSE microarrays. SHFM1 was found to be profoundly upregulated in ESCC tissues compared with normal tissues and SHFM1 expression was positively associated with poor prognosis. The biological effects of SHFM1 on cell growth, metastasis and immune escape were investigated following depletion or overexpression of SHFM1 in vitro. A xenograft mouse model was established to investigate the effect of SHFM1 on ESCC progression in vivo. SHFM1 overexpression promoted ESCC cell proliferation and migration in vitro as well as tumorigenesis in vivo, while SHFM1 knockdown restored those phenotype changes. Additionally, the present study demonstrated that the effects of SHFM1 on malignant behaviors of ESCC cells were achieved by activating the NF-κB signaling accompanied by increased P65 phosphorylation and nuclear translocation. Furthermore, SHFM1 was also found to regulate the sensitivity of cancer cells to natural killer (NK) cells. Specifically, inhibition of SHFM1 enhanced cell-mediated cell apoptosis and increased NK toxicity, which might involve the downregulation of c-Myc and programmed death-ligand 1, key targets in cancer immunotherapy. In conclusion, these findings suggested that SHFM1 probably promoted ESCC progression by activating the NF-κB pathway and enhancing the resistance of ESCC cells to NK cell cytotoxicity, indicating that SHFM1 may be a promising target for ESCC treatment.

Polymer-Dispersed Liquid Crystal Films on Flexible Substrates with Excellent Bending Resistance and Spacing Stability.

Polymer-dispersed liquid crystals (PDLCs) are very attractive due to their electrically switchable properties. However, current PDLC films still have problems such as high driving voltages, low contrast ratio (CR), and poor bending resistance and spacing stability. To solve these problems, a PDLC film with a system of coexisting polymer spacer columns and polymer network was proposed. First, based on the adhesive systems of IBMA and UV6301, the effects of IBMA concentration and LC content on the morphology of the polymer network and the electro-optical properties of PDLC were investigated, respectively. Then, the effects of the process conditions of mask polymerization such as temperature, time, and UV light intensity on the morphology and electro-optical properties of the polymer spacer columns were systematically investigated. It was found that PDLC films with the coexistence system exhibit both excellent electro-optical properties and outstanding bending resistance and spacing stability. Thus, it provides new practical possibilities for the preparation of high-performance PDLC films used in flexible devices.

Influence of academic stress and school bullying on self-harm behaviors among Chinese middle school students: The mediation effect of depression and anxiety.

Objective: The purpose of this study was to explore the relationship between academic stress, school bullying and self-harm behaviors among Chinese middle school students and to further explore the impact of anxiety and depression on this relationship. Methods: The students (aged 12-16 years) in a middle school in Changsha city were invited to respond to a questionnaire through an online platform. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess the severity of anxiety and depressive symptoms, respectively. The experience of being bullied, academic stress, and self-harm behaviors were assessed using several questions on the basis of previous studies. Results: A total of 1,313 middle school students completed the study, and 3.40% and 4.10% of them reported suicide attempts (SAs) and non-suicidal self-injury (NSSI), respectively. Univariate logistic regression analysis revealed that anxiety symptoms (OR = 1.23, 95% CI: 1.18-1.28; OR = 1.25, 95% CI: 1.19-1.31), depressive symptoms (OR = 1.20, 95% CI: 1.16-1.25; OR = 1.26, 95% CI: 1.20-1.31), school bullying (OR = 3.8, 95% CI: 2.11-6.89; OR = 2.76, 95% CI: 1.39-5.47), and academic stress (OR = 2.20, 95% CI: 1.27-3.80; OR = 3.80, 95% CI: 1.20-7.25) were common factors of NSSI and SAs. In addition, depressive symptoms showed a mediating effect on the association of school bullying and academic stress with SAs or NSSI, and anxiety symptoms showed a mediating effect on the association of school bullying and academic stress with NSSI only. Conclusion: Appropriate strategies are needed to reduce academic pressure and prevent school bullying. Meanwhile, negative emotions such as depression and anxiety should be evaluated and intervened in to prevent self-harm behaviors among middle school students.

Anticipating Unipolar Depression and Bipolar Depression in young adult with first episode of depression using childhood trauma and personality.

Objective: Relevant research focusing on young adults with Unipolar Depression (UD) and Bipolar Depression (BD) is limited. The current research aims to investigate childhood trauma and personality traits in young adults with UD and BD. Methods: Two hundred and thirty-five patients in a first depressive episode (diagnosed UD and BD), 16-25 years old, were recruited from Second Xiangya Hospital. And 79 healthy controls (HC) were recruited from the community to form the comparison group. Patients' childhood trauma was measured by the Childhood Trauma Questionnaire (CTQ), and personality was measured by Eysenck Personality Inventory (EPI). The Kruskal-Wallis test was used to compare depression, anxiety, CTQ, and EPI scores between the HC (n = 79), UD (n = 131), and BD (n = 104) groups. Factors independently associated with mood disorders and BD were determined using binary logistic regression analyses. Results: Compared with HC, mood disorders had more severe anxiety and depression symptoms, and higher CTQ. Emotional abuse (OR = 1.47; 95% CI = 1.08-2.01), emotional neglect (OR = 1.24; 95% CI = 1.05-1.46), and neuroticism (OR = 1.25; 95% CI = 1.16-1.35) were associated with significantly increased odds of mood disorders. Whereas, higher extraversion scores were a protective factor for mood disorders. Compared with UD, BD had more severe anxiety symptoms, and higher CTQ, than extraversion and neuroticism personality scores. Anxiety (OR = 1.06; 95% CI = 1.02-1.08) and extraversion (OR = 1.05; 95% CI = 1.03-1.09) were associated with significantly increased odds of BD. Conclusion: Interventions to prevent childhood trauma may improve young adults' mental health. Using childhood trauma and personality to anticipate BD and UD creates more accurate treatment for young adults with first depression.

The Association Between Suicide Attempts, Anxiety, and Childhood Maltreatment Among Adolescents and Young Adults With First Depressive Episodes.

Objective: Adolescents and young adults are susceptible to high-risk behaviors such as self-harm and suicide. However, the impact of childhood maltreatment on suicide attempts in adolescents and young adults with first episode of depression remains unclear. This study examined the association between suicide attempts and childhood maltreatment among adolescents and young adults with first depressive episodes. Methods: A total of 181 adolescents and young adults with first depressive episodes were included. The Child Trauma Questionnaire (CTQ), Beck Anxiety Inventory (BAI), and Patient Health Questionnaire-2 (PHQ-2) were used to assess childhood maltreatment and the severity of anxiety and depressive symptoms, respectively. The suicide item in the MINI-International Neuropsychiatric Interview (M.I.N.I.) 5.0 was used to assess the suicide attempts. Logistic regression analyses were used to explore the associated factors of suicide attempts. Results: The prevalence of SA in the total sample was 31.5% (95% CI = 24.9-38.1%). Multivariate logistic regression analyses revealed that the diagnosis of bipolar disorder (OR = 2.18, 95% CI = 1.07-4.40), smoking (OR = 2.64, 95% CI = 1.10-6.37), anxiety symptoms (OR = 1.05, 95% CI = 1.02-1.08), and childhood maltreatment (OR = 1.04, 95% CI = 1.01-1.07) were potential associated factors of SA. In addition, anxiety symptoms had a mediating effect on the relationship between childhood maltreatment and SA. Conclusion: Adolescents and young adults with first depressive episodes and having experiences of childhood maltreatment are at a high risk of suicide. The severity of anxiety symptoms may mediate the relation between childhood maltreatment and suicide attempts in this group of patients.

Processing Characteristics and Parametric Effects on Picosecond Laser Nanoscaled Patterning of Poly(methyl methacrylate).

Characteristics of picosecond laser processing for poly(methyl methacrylate) (PMMA) are studied in this text. Poly(methyl methacrylate) (PMMA) can be applied to micro- or nano-scale electronic devices. Short-pulsed laser is usually used for noncontact processing of nanoscale patterning of poly(methyl methacrylate) (PMMA). This study considers optical energy of laser to be transferred into decomposition energy of poly(methyl methacrylate) (PMMA). Using the condition of the energy balance at the decomposition interface, the variation of the ablation rate with the logarithm of the laser fluence is calculated for poly(methyl methacrylate) (PMMA) and agrees with the measured data. This study also discusses parametric effects of poly(methyl methacrylate) (PMMA) on the variation of the ablation rate with the logarithm of the laser fluence.

Prevalence and risk factors of asthma in mainland China: The CARE study.

BACKGROUND: There are limited population based data on the prevalence of asthma in China. The China Asthma and Risk factors Epidemiologic (CARE) survey was designed to understand the prevalence and risk factors for asthma in mainland China. OBJECTIVES: The CARE survey aims to demonstrate the prevalence and risk factors of asthma in mainland China among adolescents (age >14 years) and adults. METHODS: The survey was performed between February 2010 and August 2012 in eight provinces/cities of seven areas in mainland China. The inhabitants (age, >14 years) recruited in this survey were through multi-stage cluster random sampling. Asthma diagnosis was based on medical history and lung function tests. Multivariable logistic regression was used to analyzed the risk factors for asthma. RESULTS: The study included 164 215 subjects (men, 79 692 [48.53%]; women, 84 523 [51.47%]). 2034 (1.24%) were asthmatic patients. Among all asthmatic patients, 521 (25.61%) were newly diagnosed. Univariable regression analysis showed that risk factors for asthma included smoking, first-degree relatives with asthma, allergic rhinitis, chronic bronchitis, COPD, pollinosis, allergic pneumonia, concomitant allergic diseases, BMI and raising pets. Multivariable logistic regression indicated that asthma risk factors included women, age stratification, smoking, first-degree relatives suffering from asthma or pollinosis, combined with allergic rhinitis, eczema or GERD. CONCLUSIONS: We speculated that the prevalence of asthma is increasing in mainland China among individuals aged >14 years in the past 10 years. A number of risk factors were identified. The risk factors of asthma would be further elucidated in our future work. CLINICAL IMPLICATIONS: Our CARE study highlights that asthma epidemic in mainland China should be paid more attention.

LncRNAs BCYRN1 promoted the proliferation and migration of rat airway smooth muscle cells in asthma via upregulating the expression of transient receptor potential 1.

BACKGROUND: Long noncoding RNAs (lncRNAs) played important roles in several biological processes through regulating the expression of protein. However, the function of lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) has not been reported. METHODS: Male Sprague-Dawley (SD) rats were divided into control and asthma groups and the ovalbumin (OVA) model was constructed. The expression of BCYRN1 and transient receptor potential 1 (TRPC1) were detected in the ASMCs separated from these rats. Then 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay, Roche real-time cell analyzer (RTCA) DP assay and Transwell cell migration assay were performed to detect the effect of BCYRN1 on the viability/proliferation and migration of ASMCs. RNA pull-down assays and RNA immunoprecipitation assay were used to identify and verify the binding between BCYRN1 and TRPC1. Inspiratory resistance and expiratory resistance were measured in OVA challenged rats with BCYRN1 knockdown. RESULTS: We foundthe high expression of BCYRN1 and TRPC1 in asthma groups and ASMCs treated with PDGF-BB. Overexpression of BCYRN1 greatly promoted the proliferation and migration of ASMCs. In addition,TRPC1 overexpression reversed the function of si-BCYRN1 indecreasing the viability/proliferation and migration of ASMCs treated with PDGF-BB. BCYRN1 could up-regulate the protein level of TRPC1 through increasing the stability of TRPC1. Finally, we found that BCYRN1 knockdown reduced the inspiratory resistance and expiratory resistance in OVA challenged rats. CONCLUSION: Our study indicated that BCYRN1 promotedthe proliferation and migration of rat ASMCs in asthma via upregulating the expression of TRPC1.

Schisandrin B inhibits the proliferation of airway smooth muscle cells via microRNA-135a suppressing the expression of transient receptor potential channel 1.

Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.

[An epidemiological survey on management and insights of asthma in China in 2009 to 2010].

OBJECTIVE: Through the analysis of relevant data of China Asthma and Risk factors Epidemiologic investigation (CARE study), we understand the status quo of management and insights of asthma patients in our country. METHODS: Using multi-stage random cluster sampling method, epidemiological survey was performed on the prevalence rate in 8 provinces (cities) of China residents who aged over 14 years from 2009 to 2010. Detailed epidemiological data was collected via face-to-face home visit interview among 2 034 asthmatics who were diagnosed in the last epidemiology survey. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS12.0 software was conducted for statistical analysis and the status of asthma control was investigated. RESULTS: This survey has shown that 22.71% (462/2 034) asthmatics had ever taken a lung functional test in the past year. A total of 294 (14.45%) people had peak flow meters but only 1.62% (33/2 034) regularly used it daily. There were 22.42% (456/2 034) asthmatics aware that bronchial asthma is characterized by chronic airway inflammation. 14.85% (302/2 034) asthmatics understood that the treatment goal of this disease is long-term good control or complete control. This survey has found that 59.64% (1 213/2 034) patients complained that asthma has affected their work, life and entertainment, including 8.90% (181/2 034) asthmatics dependent on instruments in daily life and 4.57% attempting to suicide. This suggested that allergic asthma has seriously decreased the quality of life. CONCLUSION: Therefore it is necessary to educate the asthmatics, guide the patients to the long-term management and standardized therapy and raise the level of disease understanding, thus reducing the burden of disease to society. Gaining better insight of patient's attitude about self-care is critical to the improvement of asthma management.

An Implantable RFID Sensor Tag toward Continuous Glucose Monitoring.

This paper presents a wirelessly powered implantable electrochemical sensor tag for continuous blood glucose monitoring. The system is remotely powered by a 13.56-MHz inductive link and utilizes an ISO 15693 radio frequency identification (RFID) standard for communication. This paper provides reliable and accurate measurement for changing glucose level. The sensor tag employs a long-term glucose sensor, a winding ferrite antenna, an RFID front-end, a potentiostat, a 10-bit sigma-delta analog to digital converter, an on-chip temperature sensor, and a digital baseband for protocol processing and control. A high-frequency external reader is used to power, command, and configure the sensor tag. The only off-chip support circuitry required is a tuned antenna and a glucose microsensor. The integrated chip fabricated in SMIC 0.13-µm CMOS process occupies an area of 1.2 mm ×2 mm and consumes 50 µW. The power sensitivity of the whole system is -4 dBm. The sensor tag achieves a measured glucose range of 0-30 mM with a sensitivity of 0.75 nA/mM.

DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer.

BACKGROUND: Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein belongs to the membrane-associated cytoskeleton protein 4.1 family, as an efficient suppressor of EMT in lung cancer. METHODS: The relationship between DAL-1 and EMT markers were analyzed by using immunohistochemistry in the clinical lung cancer tissues. Quantitative real-time PCR and western blot were used to characterize the expression of the EMT indicator mRNAs and proteins in DAL-1 overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co-immunoprecipitation. RESULTS: DAL-1 levels were strongly reduced even lost in lymph node metastasis and advanced pathological stage of human lung carcinomas. Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E-cadherin, ß-catenin Vimentin and N-cadherin expression, meanwhile changed the morphological shape of lung cancer cells, and whereas silencing DAL-1 had an opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated its expression that could be the reason for impairing EMT and decreasing cell migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding protein. CONCLUSIONS: These results suggest that tumor suppressor DAL-1 could also attenuate EMT and be important for tumor metastasis in the early transformation process in lung cancer.

Epidemiology of bronchial asthma and asthma control assessment in Henan Province, China.

BACKGROUND: Prevalence of bronchial asthma, asthma treatment assessment, and estimation of the control level among asthma patients in Henan Province, China are reported in this paper. METHODS: We selected 10 among the 109 cities and districts in Henan province using a multistage stratified cluster random sampling method. A total of 500 households from each city and district were chosen. Approximately 20,000 residents from a total of 5,000 households were randomly selected to answer a questionnaire recommended by the China Asthma Alliance. Asthma patients were asked to answer a detailed questionnaire using the symptom-based guidelines to assess the levels of disease control. RESULTS: The overall prevalence of asthma was 0.73% ± 0.12%. Urban and rural residents had asthma prevalence rates of 1.1% ± 0.23% (88/7,924) and 0.48% ± 0.12% (57/11,792), respectively. Among the asthma patients, only 33.8% (52) received regular medication, 25% (13) used oral glucocorticoids, and 71.1% (37) used oral theophylline. The classified control levels of patients were as follows: 33.1% controlled, 49.7% partially controlled, and 17.2% uncontrolled. A total of 38.5% and 27.5% of regularly and irregularly treated asthma patients reached controlled level, respectively. The two groups significantly differed in asthma control level. CONCLUSION: Asthma prevalence is low in Henan Province, China. Urban residents have higher prevalence of asthma than rural residents do. Patients with asthma receive insufficient medication, resulting in suboptimal asthma control. Improvement in diagnosis and treatment of asthma patients is urgently needed.

[An epidemiological survey of current asthma control status in China].

OBJECTIVE: Base on the China asthma and risk factors epidemiologic investigation (CARE study), we analyzed the current status of asthma control in China. METHODS: With the multi-stage random cluster sampling method, epidemiological survey was performed among Chinese residents who aged over 14 years in 8 provinces (cities) from 2010 to 2011. Detailed clinic data of 2 034 asthma patients were collected via face-to-face home visit . Asthma was diagnosed based upon the history, clinical signs and lung function tests. The SPSS 12.0 was conducted for statistics analysis. RESULTS: This survey found that the prevalence rate of asthma in China was 1.24% (2 034/164 215), including 973 male and 1 061 female patients, with a mean age of (56 ± 18) years old. Consistent with the Global Initiative for Asthma (GINA) guidelines, 40.51% (824/2 034) and 42.58% (866/2 034) of our patients achieved control and partial control, respectively. According to the asthma control test (ACT) estimates, 15.63% (318/2 034) and 49.46% (1 006/2 034) of patients achieved full control (ACT 25) and well control(ACT 20-24), respectively. In the past year, 22.62% (460/2 034) of patients reported hospitalized and 26.99% (549/2 034) of patients reported emergency room visit at least one time due to asthma exacerbation. 61.80% (1 257/2 034) of patients were on daily us of medication. Inhaled corticosteroids (ICS) plus a long-acting ß2 agonist (LABA) or solely ICS were used in 6.39% and 14.75% of patients, respectively. Theophylline treatment accounted for 29.11% (592/2 034). Oral glucocorticoid and oral leukotriene modifier (LTRA) treatment accounted for 9.49% (193/2 034) and 3.10% (63/2 034), respectively. According to the survey, 34.51% (702/2 034) of asthma patients reported a history of smoking . The percentage of asthma control in non smoking patients was higher than in smoking patients [43.24% (576/1 332) and 35.33% (248/702), respectively]. Meanwhile, the rates of both hospitalization and emergency due to asthma exacerbation in smoking asthma patients were significantly higher than nonsmoking asthma patients (27.35% and 31.77%, 20.12% and 24.47%, respectively). CONCLUSIONS: The situation of asthma control has been improved in China. However, compared with GINA guidelines, there is still a considerable gap. Smoking is one of the crucial factors that affect asthma control.

Tumor necrosis factor-α sensitizes breast cancer cells to natural products with proteasome-inhibitory activity leading to apoptosis.

The inflammatory microenvironment plays an important role in the process of tumor development. Tumor necrosis factor-α (TNF-α), a key pro-inflammatory cytokine, has a significant role in this process. Natural medicinal products such as Withaferin A (WA) and Celastrol (Cel) have shown anti-cancer and anti-inflammatory properties that can be attributed to multiple mechanisms including, but not limited to, apoptosis induction due to the inhibition of proteasomal activities. This study aimed to investigate the effects of TNF-α in combination with WA or Cel in vitro in MDA-MB-231 breast cancer cells. TNF-α, when combined with WA or Cel, activated caspase-3 and -9 and downregulated XIAP in a dose-dependent manner, leading to induction of apoptosis in MDA-MB-231 breast cancer cells. The combination also caused accumulation of the proteasomal target protein IκBα, resulting in inhibition of the nuclear translocation of nuclear factor-κB (NF-κB). Taken together, these results suggest that TNF-α could sensitize breast cancer cells MDA-MB-231 to WA and Cel, at least in part, through inhibiting the activation of NF-κB signaling, leading to XIAP inhibition with subsequent upregulation of caspase-3 and -9 activities. Thus, the anti-cancer activities of TNF-α are enhanced when combined with the natural proteasome inhibitors, WA or Cel.