Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

BACKGROUND: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. METHODS: Murine models of NSCLC with distinct driver mutations (KrasG12D/P53+/-/Lkb1-/- (KPL); KrasG12D/P53+/- (KP); and KrasG12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. RESULTS: ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. CONCLUSIONS: CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.

Staging study of single-channel sleep EEG signals based on data augmentation.

Introduction: Accurate sleep staging is an essential basis for sleep quality assessment and plays an important role in sleep quality research. However, the occupancy of different sleep stages is unbalanced throughout the sleep process, which makes the EEG datasets of different sleep stages have a class imbalance, which will eventually affect the automatic assessment of sleep stages. Method: In this paper, we propose a Residual Dense Block and Deep Convolutional Generative Adversarial Network (RDB-DCGAN) data augmentation model based on the DCGAN and RDB, which takes two-dimensional continuous wavelet time-frequency maps as input, expands the minority class of sleep EEG data and later performs sleep staging by Convolutional Neural Network (CNN). Results and discussion: The results of the CNN classification comparison test with the publicly available dataset Sleep-EDF show that the overall sleep staging accuracy of each stage after data augmentation is improved by 6%, especially the N1 stage, which has low classification accuracy due to less original data, also has a significant improvement of 19%. It is fully verified that data augmentation by improving the DCGAN model can effectively improve the classification problem of the class imbalance sleep dataset.

Effect of foliage applied chitosan-based silicon nanoparticles on arsenic uptake and translocation in rice (Oryza sativa L.).

In this study, chitosan-based silicon nanoparticles (Chsi-NPs) are prepared that primarily consists of C (57.9%), O (31.3%), N (5.6%), and Si (3.5%) and are 10-180 nm in size. We then explore the effect on the foliage applied on rice planted on soil contaminated with 104 mg·kg-1 arsenic (As); low (3 mg·L-1)and high (15 mg·L-1) doses of the foliar Chsi-NPs are administered during the rice grain filling stage. The results showed that the higher dose foliar Chsi-NPs treatment reduced the As concentration in the grain by 61.2% but increased As concentration in the leaves by 47.1% compared to the control treatment. The foliar spraying of the Chsi-NPs inhibited As transport to the grain by facilitating the attachment of As to the cell wall, with higher doses of the foliar Chsi-NPs treatment increased by 8.7%. The foliar spraying of Chsi-NPs increased the malondialdehyde levels by 18.4%, the catalase activity by 49.0%, and the glutathione activity by 99.0%. These results indicated that the foliar Chsi-NPs application was effective for alleviating As toxicity and accumulation in rice. This study provides a novel method for effectively alleviating As accumulation in rice.

Strategies towards PM2.5 attainment for non-compliant cities in China: A case study.

The northern part of the Yangtze River Delta (YRD) region in China suffers from high concentrations of fine particular matter (PM2.5) during the past years yet received much less attention compared to the other parts of the YRD region. In this study, we integrated observational data, control policies and strategies, and air quality simulations to develop PM2.5 attainment demonstration by year 2030 for the city of Bengbu, which represents a typical non-compliant city in the northern YRD region. In 2018, the annual average PM2.5 concentration in Bengbu was 51.8 µg/m3, which was 48 % higher than the standard of 35 µg/m3 set by the National Ambient Air Quality Standards (NAAQS). Different future emission scenarios were developed for year 2025 as mid-term and year 2030 as long-term. Integrated meteorology and air quality modeling system together with monitoring data was applied to predict the air quality under the future emission scenarios. Results show that when a conservative emission reduction ratio of 40 % was assumed for surrounding regions, the annual average PM2.5 concentration in Bengbu could meet the target value by 2030, in which case emissions of SO2, NOx, PM2.5, VOCs, and NH3 need to be reduced by 70.6 %, 43.5 %, 47.2 %, 33.4 %, and 47.5 %, respectively. PM2.5 concentration in Bengbu is not only controlled by local emission reductions but also affected by emission reductions of surrounding regions as well as contribution from long-range transport. More attentions need to be paid to the control of VOCs emissions in the near future to avoid increase of ozone concentrations while reducing PM2.5. Our results provide scientific support for the local government to formulate future air pollution prevention and control strategies, sub-regional joint-control among surrounding cities, as well as trans-regional joint-control between the north China and the YRD region.

The casual effects of COVID-19 lockdown on air quality and short-term health impacts in China.

The outbreak of coronavirus (COVID-19) has forced China to lockdown many cities and restrict transportation, industrial, and social activities. This provides a great opportunity to look at the impacts of pandemic quarantine on air quality and premature death due to exposure to air pollution. In this study, we applied the difference-in-differences (DID) model to quantify the casual impacts of COVID-19 lockdown on air quality at 278 cities across China. A widely used exposure-response function was further utilized to estimate the short-term health impacts associated with changes in PM2.5 due to lockdown. Results show that lockdown has caused drastic reduction in air pollution level in terms of all criteria pollutants except ozone. On average, concentrations of PM2.5, PM10, NO2, SO2 and CO are estimated to drop by 14.3 µg/m3, 22.2 µg/m3, 17.7 µg/m3, 2.9 µg/m3, and 0.18 mg/m3 as the result of lockdown. Cities with more confirmed cases of COVID-19 are related to stronger responses in air quality, despite that similar lockdown measures were implemented by the local governments. The improvement of air quality caused by COVID-19 lockdown in northern cities is found to be smaller than that of southern cities. Avoided premature death associated with PM2.5 exposures over the 278 cities was estimated to be 50.8 thousand. Our results re-emphasize the effectiveness of emission controls on air quality and associated health impacts. The high cost of lockdown, still high level of air pollution during lockdown and smaller effects in northern cities implies that source-specific mitigation policies are needed for continuous and sustainable reduction of air pollution.

[Textual research on Xilei Powder].

Xilei Powder is a commonly used prescription for the treatment of oral ulcers, and is originally used to treat scarlet fever. Scarlet fever is a warm-toxin disease from the perspective of the theory of warm disease. It is a warm infectious disease caused by epidemic. Xilei Powder was recorded in the Chinese Pharmacopoeia from 1953 edition to 2010 edition. As China joined Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), Xilei Powder was removed from the Chinese Pharmacopoeia of 2015 edition due to the limitation of the use of animal drugs, such as ivory and rhinoceros horn. Xilei Powder has been widely used to treat such diseases as otolaryngology, fever, gynecological diseases, digestive diseases, and tumors. Does Xilei Powder have a unique place in clinical application? Can stable and effective alternative drugs be derived from original prescription? Due to the lack of theoretical studies on Xilei Powder, by consulting ancient books, monographs and papers, we comprehensively summarized and studied historical evolution and prescription connotation of Xilei Powder, and analyzed its drug origin and clinical application, in the hope to promote the theoretical study and clinical application.

Clinical significance of 21-gene recurrence score assay for hormone receptor-positive, lymph node-negative breast cancer in early stage.

OBJECTIVE: To identify the relationship between clinical pathological characteristics and the recurrence score (RS) on a 21-gene expression assay in patients with hormone receptor-positive, node-negative breast cancer, as well as the effect of RS on adjuvant decision-making. METHODS: The retrospective study was conducted among luminal breast cancer patients admitted to Xijing Hospital between October 10, 2016, and September 14, 2018. Real-time PCR was used for 21-genome detection. Based on the calculated RS, participants were classified into low-risk, moderate-risk, and high-risk groups. Single-factor analysis and multiple logistic regression analysis were performed to explore independent predictors of high RS. Moreover, the effect of RS on adjuvant decision-making was studied. RESULTS: Two hundred twenty-two patients with luminal breast cancer, aged 48.3 ±â€¯9.66, were enrolled. Among them, 33.8% had low (13 ±â€¯3.34), 45.5% intermediate (23 ±â€¯3.65), and 20.7% high (37 ±â€¯3.44) RS. According to the single-factor analysis, age, tumor size, Ki-67, molecular subtype, CK5/6 expression, E-cadherin level, and histological grade were positively associated with high RS. Multiple logistic analyses showed that tumor size and histological grade were independent variables that might predict high RS in patients with hormone receptor-positive, node-negative breast cancer. For adjuvant decision-making, the proportion of adjuvant chemotherapy in the intermediate-/high-risk groups was higher than that in the low-risk group, P < 0.001. Compared with the data worldwide, the changes of treatment selection in the present study were similar to those in Japan (23.0% vs. 26%) and America (23.0% vs. 23.0%). Considering the pathology types, 14.3% of patients with invasive breast cancer with lower RS changed treatment recommendations, predominantly from chemo-endocrine to endocrine treatment alone, whereas the percentage in intermediate/high RS groups was 8.1%. CONCLUSIONS: Tumor size and histological grade were independent variables, predicting high risk in patients with hormone receptor-positive, node-negative breast cancer; 21-gene RS assessment was potentially a critical tool in guiding adjuvant decision-making in China.

Prevalence and risk factors of hepatitis B infection among mothers and children with hepatitis B infected mother in upper Dolpa, Nepal.

BACKGROUND: Hepatitis B Virus (HBV) infection is a worldwide public health problem. In Nepal, the prevalence of HBV is found to be low (0.9%), although high prevalence (≥8%) of HBV infection is depicted among subgroup/population in the mountain region by various studies. This study assessed the prevalence and the risk of HBV infection among mothers, as well as among the youngest child under 5 years old living with hepatitis B positive mothers in Dolpa, the most remote mountain district of Nepal. METHODS: The cross sectional study survey was conducted between June and July 2014. All mothers with their youngest child under 5 years old were invited to participate in the survey and tested for hepatitis B surface antigen (HBsAg). The HBsAg positive mothers were further tested by 5-panel HBV test card. Children living with HBsAg positive mothers were also tested for HBsAg. RESULTS: One hundred fifty-one mothers, comprising 37% of the total study population in the selected Village Development Committees (VDCs), were surveyed in the mobile health camps. The seroprevalence of HBsAg among mothers and their youngest child under 5 years old living with HBsAg positive mothers were 17% (95% CI, 11.01-22.99%) and 48% (95%CI, 28.42-67.58%) respectively. The majority of HBV infected mothers were indigenous (84%) followed by Dalit (4%) and other castes (12%). Among HBV infected mothers, 40% were hepatitis B envelope antigen (HBeAg) positive. The prevalence of HBsAg was higher among children living with HBeAg positive mothers as compared to HBeAg negative (60% vs 40%) and male children compared to female (60% vs 33%). Thirty-six percent of children were vaccinated with a full course of the hepatitis B vaccine. Of these vaccinated children, 56% were HBsAg sero-positive. CONCLUSIONS: The HBV infection rate is high among mothers and children living with HBsAg positive mothers in the indigenous population of the most remote mountain community of Nepal.

[Identification of a myeloid differentiation factor 88 (MyD88) in Oncomelania hupensis against Schistosoma japonicum infection].

OBJECTIVE: To identify a myeloid differentiation factor 88 (MyD88) in Oncomelania hupensis, and characterize the role of MyD88 against Schistosoma japonicum infection. METHODS: The complete cDNA of MyD88 in O. hupensis was obtained by using rapid amplification of cDNA ends (RACE), and homologues sequences and conserved domains were aligned and the structure of MyD88 was predicted either. A phylogenetic tree of MyD88 was further constructed with other species. In addition, the mRNA expression level of O. hupensis MyD88 before and after S. japonicum infection was investigated by real-time quantitative PCR (RT-qPCR). RESULTS: The cDNA of O. hupensis MyD88 consisted of 1 406 bp open reading frame (ORF), encoding 468 amino acid residues, which contained death domain and Toll/interlrukin-1 receptor (TIR) domain, the typical features of MyD88 family proteins. The predicted amino acid sequence of O. hupensis MyD88 shared 38%-52% identity with other mollusc. O. hupensis MyD88 was phylogenetically closeted to Biomphalaria glabrata MyD88. The O. hupensis MyD88 existed in all selected tissues and expressed highly in hemocyte, up-regulated after S. japonicum infection in all selected tissues except cephalopodium, especially higher in whole snail and hemocyte. CONCLUSIONS: MyD88-dependent signaling pathway is present in O. hupensis and plays an important role in innate immune response against S. japonicum infection.

Epidemiology of pathogens and drug resistance of ventilator-associated pneumonia in Chinese neonatal intensive care units: a meta-analysis.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units. However, limited literature has been reviewed to synthesize the findings about the incidence, case fatality rate, pathogen distribution, and drug resistance of neonatal VAP in China. METHODS: A search of electronic databases was undertaken to identify the incidence, case fatality rate, pathogen distribution, and drug resistance of neonatal VAP based on the inclusion and exclusion criteria. Meta-analysis was carried out using R3.0.2 software. RESULTS: A total of 16,587 participants were included in our final analysis. The incidence and case fatality rates were 42.8% and 16.4%, respectively. Gram-negative bacteria were detected in 77.6% of cultures, followed by gram-positive bacteria (18.8%) and fungi (3.7%). Gram-negative bacteria were sensitive to meropenem, imipenem, and ciprofloxacin, with resistance rates of 1.5%-25.0%, 4.9%-29.0%, and 8.5%-24.7%, respectively. Gram-positive bacteria have resistance rates as high as 72.7%-99.1% to penicillin, 62.6%-90.9% to erythromycin, and 80.3%-91.9% to oxacillin. CONCLUSIONS: The incidence and case fatality rates of neonatal VAP are high in China. VAP was mainly caused by gram-negative bacteria that were resistant to most common antibiotics. The future study of drug-resistance mechanisms should be intensified, and effective measures of hospital infection control should be considered to prevent the outbreak of drug-resistant strains.

The relationship between TTF-1 expression and EGFR mutations in lung adenocarcinomas.

OBJECTIVE: To explore the relationship between TTF-1 and EGFR mutations in lung adenocarcinoma tissues to guide clinical treatment timely and effectively. MATERIALS AND METHODS: we collected 664 tissue samples from patients with histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All tumor tissues were collected prior to administering therapy. TTF-1 was detected by immunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the correlation between TTF-1 expression and the presence of EGFR mutations was analyzed using χ2 test or Fisher's exact test with SPSS software version 18.0. RESULTS: Of the 664 lung adenocarcinoma tissue samples, 18 were partially positive for TTF-1 (+-), and 636 were positive for TTF-1 (+) resulting in a total positive rate of 98.49% (+,+-)(including partial positive). In only 10 cases was the TTF-1 negative (-); the negative rate was 1.51%. There were 402 cases without an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was 39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon 21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and 20 detected by DNA direct sequencing no mutations.A Fisher's exact test was used to determine the correlation between EGFR mutations and TTF-1 expression.for the whole, TTF-1 positive expression(including partial positive) has correlation with EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is significant (p = 0.008). CONCLUSION: In lung adenocarcinomas, positive and partial positive TTF-1 expression has a significant positive correlation with EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine with EGFR mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas.

New evidences for fractalkine/CX3CL1 involved in substantia nigral microglial activation and behavioral changes in a rat model of Parkinson's disease.

Activated microglia are instrumental to neurodegeneration in Parkinson's disease (PD). Fractalkine, as an exclusive ligand for CX3CR1 expressed on microglia, has recently been reported to be released out by neurons, and induce microglial activation as a neuron-to-glia signal in the spinal cord. However, the role of fractalkine-induced microglial activation in PD remains unknown. In our study, we injected 1-methyl-4-phenylpyridinium (MPP(+)) into unilateral substantia nigra (SN) which induced ipsilateral endogenous fractalkine expression on neuron and observe the increase of CX3CR1 expression in response to MPP(+) by Western blotting analysis. Moreover, pre-administration of anti-CX3CR1 neutralizing antibody which potentially blocked microglial activation can promote rotation behaviors. To further investigate the role of fractalkine in PD, we injected exogenous fractalkine in unilateral SN, and observed microglial activation, dopaminergic cell depletion, and motor dysfunction. All these effects can be totally abolished by cerebroventricular administration of anti-CX3CR1. Intracerebroventricular administration of minocycline, a selective microglia inhibitor, can prevent fractalkine-induced rotation behaviors, and inhibit dopaminergic neurons from degeneration in the way of dose-dependent. Our studies demonstrate that fractalkine-induced microglial activation plays an important role in the development of PD, and provide an evidence of fractalkine and CX3CR1 as new therapeutic targets for PD treatment.

[Cost-benefit analysis of comprehensive parasitic disease control project in Rongxian County, Guangxi Zhuang autonomous region].

OBJECTIVE: To evaluate the cost-benefit of comprehensive parasitic disease control project in Rongxian County of Guangxi, so as to provide the evidence for formulating the control strategy of soil-transmitted nematode. METHODS: The data of the overall input and output for soil-transmitted nematode control were collected from 2007 to 2009, and the cost-benefit was analyzed. RESULTS: The infection rates of soil-transmitted nematode dropped from 30.10% in 2007 to 12.30% in 2009. The overall cost of soil -transmitted nematode control was 969 185.6 Yuan from 2007 to 2009. The direct benefits arising from avoiding the incidence of the disease for populations reached 88.415 million Yuan in three years. The ratio of benefit-cost was 91:1. CONCLUSIONS: The soil -transmitted nematode infection brings a heavy financial burden on both the patients and society. The implementation of comprehensive control measures can effectively control the prevalence of the diseases and produce good social and economic benefits.