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The sulfate process for bamboo pulp production encounters silicon interference during the pulping stage, necessitating desilication before the alkali recovery section. This study investigated the desilication of bamboo pulping black liquor (BPBL), demonstrating that silicon was removed effectively by adding Mg/Al compound desilication agent to the BPBL via burning at high temperature. The desilication extent can reach 84% when the desilication agent is added in the proportion of Mg/Al (magnesium sulfate and sodium metaluminate) in the ratio 1.25:0.75. Subsequently, less-silicon white mud (LSWM) can be prepared after black liquor (BL) combustion desilication. LSWM was compared with normal WM as a blank sample, and the morphology and physicochemical properties of two kinds of WM were characterized. X-ray diffractometry revealed that both types of WM are primarily composed of calcite crystalline CaCO3 and hydrated CaSiO3. Scanning electron microscopy, X-ray photoelectron spectroscopy, and particle size analysis demonstrated the reduced content of CaSiO3 generated in the LSWM. This result indicated that the Mg/Al compound desilication agent removed the silicon from the green liquor (GL), thereby reducing the residual silicon in WM. This reduction is beneficial to the calcination recovery and comprehensive utilization of WM.

Introduction: Malignant ascites is a common complication of advanced hepatocellular carcinoma (HCC) that seriously affects the quality of life and survival of patients and has poor clinical efficacy. In the early stages, the authors found that the combination of the Shengqing Jiangzhuo decoction (SQJZD)and Endostar can effectively alleviate the clinical symptoms of malignant ascites in patients with HCC and reduce the amount of malignant ascites. The purpose of this study was to investigate the mechanism of action of SQJZD in HCC-related malignant ascites. Methods: A malignant ascites BALB/c mouse model was established by the intraperitoneal inoculation of H22 cells. The mice were randomly divided into model, Endostar, and high-, medium-, and low-dose traditional Chinese medicine (TCM) combined with Endostar groups. Normal mice from the same batch were used as the normal group. The Endostar and TCM + Endostar groups were intraperitoneally injected with Endostar, whereas the model and normal groups were intraperitoneally injected with equal amounts of normal saline. Different doses of SQJZD were administered to each TCM group, and equal amounts of distilled water were administered to the normal, model, and Endostar groups. Results: The malignant ascites volume and body weight were higher in the model group than in the normal group. After treatment, the volume and body weight of mice with malignant ascites decreased, especially in the SQJZD combined with Endostar group. Compared with that in the normal group, the number of regulatory T cells (Tregs) in the peripheral blood and spleen of mice in the model group was significantly decreased; the number of regulatory dendritic cells (DCregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) in the peripheral blood were not significantly changed; and the number of DCregs, MDSCs, and TAMs in the spleen was increased. Compared with those in the model group, the numbers of Tregs, DCregs, MDSCs, and TAMs in the peripheral blood increased in the Endostar or SQJZD combined with Endostar groups, whereas the numbers of Tregs, DCregs, MDSCs, and TAMs in the spleen decreased. Western blotting revealed that the percentage of p-STAT3-positive cells in the liver and spleen of mice increased in the model group, whereas the percentage of p-STAT3-positive cells in the liver and spleen decreased in mice treated with Endostar or SQJZD combined with Endostar. Conclusions: SQJZD combined with Endostar may attenuate immunosuppression and enhance the antitumor immune response by regulating the STAT3 pathway to alleviate malignant ascites in HCC.

Temperature changes had a huge impact on the growth of aquaculture organisms, which mainly involved two parameters: the changing amplitude and the changing speed. Wide-adaptability and narrow-adaptability were divided by the amplitude, while fast-adaptability and slow-adaptability proposed in this article were divided based on the speed. Investigating the impact of the changing speed on artificial farming was vital. In this study, two fish species of wide-adaptability, Hippocampus kuda and Oryzias melatigma, were selected as research objects, explored the effects of temperature changing speeds on them under 2 changing amplitudes of 2°C and 4°C. The similarities and differences in their responses to temperature changes were analyzed and compared from the aspects of feeding, metabolism, physiology, immunity, and growth. The results showed that all 3 changing speeds (0.5°C/h, 1°C/h, and direct input) had no effect on the growth of O. melatigma under the 2°C amplitude, while there were significant differences in various aspects of H. kuda in the treatments with the speeds between 0.5°C/h and direct input, such as a significant difference in growth, in food intake, and in response speeds and response levels of several enzymes and related genes. Under 4°C amplitude, the impact of all 4 changing speeds (0.5°C/h, 1°C/h, 2°C/h and direct input) on both fish was more pronounced. H. kuda showed a significant difference of growth among 3 groups, and the critical safe speed was about 0.5°C/h in its heating treatments. And the growth decrease only occured the heating treatment of direct input in O. melatigma. Furthermore, some genes responded quickly and efficiently to the low-speed changes of temperature in H. kuda, but were inhibited in the treatments with high-speed changes. However, they can still express rapidly and efficiently in the high-speed treatments of O. melatigma, included several stress-related genes, lipid metabolic-related genes, and immune-related genes. Seen from these differences, the energy source used in H. kuda to resist stress was single and short-lived. So, under a long-term stress, H. kuda gradually transformed from normal physiological stress into pathological stress, leading to the outbreak of diseases. Therefore, for precise aquaculture of H. kuda, stricter and more precise control of environmental temperature is necessary to prevent rapid and big temperature changes from affecting the growth and survival of the seahorse.

As an effective methods of plasma heating, neutral beam injection (NBI) systems based on negative hydrogen ion sources will be utilized in future magnetic-confinement nuclear fusion experiments. Because of the collisions between the fast negative ions and the neutral background gas, the positive ions are inevitable created in the acceleration region in the negative NBI system. These positive ions are accelerated back into the ion source and become high energy backstreaming ions. In order to explore the characters of backstreaming ions, the track and power deposition of backstreaming H+ beam is estimated using the experimental and simulation methods at NNBI test facility. Results show that the flux of backstreaming positive ions is 1.93 % of that of negative ion extraction from ion source, and the magnet filed in the beam source has an effect on the backstreaming positive ions propagation.

Summary: Background: The prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet. Methods: Data were obtained from the China Pulmonary Health study (2012–2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria. Findings: The age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3–6.9), 7.2% (5.9–8.8), 1.1% (0.7–1.8), and 3.1% (2.5–3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents’ events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment. Interpretation: Significant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population. Funding: Chinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was

Abstract In this study, a certain percentage of lignin in original bamboo kraft black liquor (BKBL) was separated, and the residual BKBL with low lignin content was expected to be fed into the alkali recovery boiler to reduce the heat transfer load of the alkali recovery boiler. With the decrease in lignin content, the rheological properties/volumetric isothermal expansivity (VIE) of BKBL change. When the lignin content was 70% remaining in the original BKBL, the viscosity of BKBL with low lignin content is close to that of the passivated BKBL at the same solids content, the dynamic viscoelasticity is superior, and the VIE decreases by 57.2%. When the amount of desilication agent is 1.5%, the viscosity of BKBL with low lignin content did not change much, and the VIE increased sharply and was 62.7% higher than that of the passivated BKBL. Therefore, the combination of partial lignin separation process and sodium aluminate desilication process can effectively improve the ability of alkali recovery boiler to deal with BKBL and reduce the influence of “silicon interference”.

Objective We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. Methods Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. Results After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 − 0.71); specificity 0.72 (0.71 − 0.73), PPV 0.25 (0.24 − 0.26) and NPV 0.94 (0.94 − 0.95). Conclusion We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

The presence of silicon in non-wood raw materials is known to interfere with the causticization of green liquor and the calcination of white mud, which has provided motivation for advances in alkali recovery technology. Therefore, reducing the silicon content of green liquor is the fundamental way to solve the problem. However, there are certain defects in conventional green liquor desilication, so this study provides a basis for desilication from green liquor via black liquor combustion and studies the desilication effect of a compound desilication agent on bamboo pulping black liquor. The results show that the desilication effect was better and the desilication rate could reach 84% when the Mg/Al proportion in compound desilication agent was 1:0.6. Meanwhile, the content of residual aluminum in green liquor decreased, which can avoid the influence of residual desilication agent on subsequent stages. Scanning electron microscopic images show that green-liquor-silicon-insoluble (GLSI) substance is a granular precipitate, and the X-ray diffraction analysis shows that GLSI substance has a complex structure similar to 3Al2O3•2SiO2•MgO. This implies that the desilication mechanism consists of chemical precipitation and physical adsorption.

Abstract Background While reducing inequity in health service utilization is an important goal of China’s health system, it has been widely acknowledged that a huge number of rural migrant workers cannot be effectually protected against risks with the New Rural Cooperative Medical Insurance (NCMS). Method Data of the 2016 China Labor-force Dynamic Survey and the Chinese Urban Statistical Yearbook were used. The multilevel regression approach was implemented with a nationally representative sample of rural migrant workers with NCMS. Our study adopted the concentration index and its decomposition method to quantify the inequality of their health service utilization. Result The multilevel model analysis indicated that impact variables for health service utilization were not concentrated, especially the contextual and individual characteristics. The concentration indices of the probability of two weeks outpatient and the probability of inpatient were -0.168 (95%CI:-0.236,-0.092) and -0.072 (95%CI:-1.085,-0.060), respectively. The horizontal inequality indices for the probability of two-week outpatient and the probability of inpatient were -0.012 and 0.053, respectively. Conclusion The health service utilization of rural migrant workers with NCMS is insufficient. Our study highlighted that substantial inequalities in their health service utilization did exist. In addition, their need of health service utilization increased the pro-poor inequality. Based on the findings, our study offered notable implications on compensation policies and benefit packages to improve the equality among rural migrant workers with NCMS.

Abstract Background As a common female pelvic tumor, uterine fibroids remain the leading cause for hysterectomy in China. Hysterectomy provides a good surgical treatment of uterine fibroids, and it guarantees the removal of all uterine fibroids without lower risk of recurrence. This study compares the cost effectiveness of total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH) for women with uterine fibroids from a societal perspective. Methods An economic analysis was conducted in 392 patients (TLH n = 75; TAH n = 317), including all relevant costs over a 12-month time horizon. Primary outcome was major surgical complications; secondary outcomes were postoperative discomfort symptoms and time of return to normal activities. Clinical, outcomes and costs data were collected from medical records, telephone survey and financial information system. Generalized linear models were used to assess costs and outcomes differences between the two groups. Incremental cost effectiveness ratio (ICER) was used to estimate the cost effectiveness. Results Mean direct costs were $2,925.71 for TLH, $2,436.24 for TAH, respectively. Mean indirect costs were $1,133.22 for TLH, $1,394.85 for TAH, respectively. Incremental societal costs were $256.86 (95%CI: 249.03–264.69). Mean differences in outcome were: 4.53% (95%CI: 4.35–4.71) for major surgical complications; 6.75% (95%CI: 6.45–7.05) for postoperative discomfort symptoms; 1.27 (95%CI: 1.23–1.30) weeks for time to return to normal activities. ICER of TLH was $5,669.16 (95%CI: 5,384.76–5,955.56) per complication averted, $3,801.54 (95%CI: 3,634.81–3,968.28) per postoperative discomfort symptoms averted and $202.96 (95%CI: 194.97–210.95) per week saved to return to normal activities. Conclusions TLH is cost effective compared with TAH in preventing additional complications based on our estimated conservative threshold in China. The findings provide useful information for researchers to conduct further cost effectiveness analysis based on prospective study which can provide stronger and more evidence, in China. In addition, the data may be useful for Chinese health care policy-makers and medical insurance payers to make related health care decisions.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. Methods Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Results In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. Conclusions These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.

Idiopathic pulmonary fibrosis is a fatal lung disease with limited treatment options. Here the authors show that tartrate-resistant acid phosphatase 5 (Acp5) promotes lung fibrosis by enhancing beta-catenin signaling and that inhibition of Acp5 can reverse stablished pulmonary fibrosis.

Abstract Background Hypoxic pulmonary hypertension (PH) is a refractory pulmonary vascular remodeling disease, and the efficiency of current PH treatment strategies is unsatisfactory. Tribbles homolog 3 (TRB3), a member of the pseudokinase family, is upregulated in diverse types of cellular stresses and functions as either a pro-proliferative or pro-apoptotic factor depending on the specific microenvironment. The regulatory mechanisms of TRB3 in hypoxic PH are poorly understood. Methods We performed studies using TRB3-specific silencing and overexpressing lentiviral vectors to investigate the potential roles of TRB3 on hypoxic pulmonary artery smooth muscle cells (PASMCs). Adeno-associated virus type 1(AVV1) vectors encoding short-hairpin RNAs against rat TRB3 were used to assess the role of TRB3 on hypoxic PH. TRB3 protein expression in PH patients was explored in clinical samples by western blot analysis. Results The results of whole-rat genome oligo microarrays showed that the expression of TRB3 and endoplasmic reticulum stress (ERS)-related genes was upregulated in hypoxic PASMCs. TRB3 protein expression was significantly upregulated by hypoxia and thapsigargin. In addition, 4-PBA and 4μ8C, both inhibitors of ERS, decreased the expression of TRB3. TRB3 knockdown promoted apoptosis and damaged the proliferative and migratory abilities of hypoxic PASMCs as well as inhibited activation of the MAPK signaling pathway. TRB3 overexpression stimulated the proliferation and migration of PASMCs but decreased the apoptosis of PASMCs, which was partly reversed by specific inhibitors of ERK, JNK and p38 MAPK. The Co-IP results revealed that TRB3 directly interacts with ERK, JNK, and p38 MAPK. Knockdown of TRB3 in rat lung tissue reduced the right ventricular systolic pressure and decreased pulmonary medial wall thickness in hypoxic PH model rats. Further, the expression of TRB3 in lung tissues was higher in patients with PH compared with those who have normal pulmonary artery pressure. Conclusions TRB3 was upregulated in hypoxic PASMCs and was affected by ERS. TRB3 plays a key role in the pathogenesis of hypoxia-induced PH by binding and activating the ERK, JNK, and p38 MAPK pathways. Thus, TRB3 might be a promising target for the treatment of hypoxic PH.

ObjectiveTo address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.MethodsStudies were conducted in asthmatic patients and macrophage-specific Mbd2 knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with Mbd2 siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.ResultsAsthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of Mbd2 protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying Mbd2 siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production.ConclusionsThe above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.

Background Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results Chronic cough was found in 3.6% (95% CI 3.1–4.1) of Chinese adults, 2.4% (95% CI 1.9–3.1) of those aged 20–49 years and 6.0% (95% CI 5.3–6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

Tartrate-resistant acid phosphatase 5 (TRAP/ACP5) has been shown to involve the development and prognosis of multiple tumors in previous studies; however, the mechanism in lung cancer is still unclear, and thus this study investigated the role of ACP5 in the progression of lung adenocarcinoma. After a series of in vitro and in vivo experiments, we observed that ACP5 expression was increased in lung adenocarcinomas (40/69, 57.97%); importantly, an increased ACP5 level was associated with patient age (p = 0.044) and lymph node metastasis (p = 0.0385). ACP5 overexpression significantly enhanced A549 and NCI-H1975 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and reduced cell apoptosis. Knocking down the expression of ACP5 could rescue the above cell phenotypes. Furthermore, enhancing ACP5 expression promoted lung adenocarcinoma cell hyperplasia and intrapulmonary metastasis in a mouse model. Additionally, mechanistic studies revealed that ACP5 might regulate p53 phosphorylation at Ser392, thereby enhancing the ubiquitination of p53, which then underwent degradation. Reducing the levels of p53 intensified the transcription of SMAD3, which promotes EMT in lung adenocarcinoma cells. In summary, the present study provides a theoretical basis and important scientific evidence on the key role of ACP5 in lung adenocarcinoma progression by inducing EMT via the regulation of p53/SMAD3 signaling. Keywords: ACP5, lung adenocarcinoma, epithelial-mesenchymal transition, p53, SMAD3, metastasis

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by the infiltration of macrophages in the fibrotic region. Currently, no therapeutic strategies effectively control disease progression, and the 5‐year mortality of patients after diagnosis is unacceptably high. Thus, developing an effective and safe treatment for IPF is urgently needed. The present study illustrated that methyl‐CpG‐binding protein 2 (MECP2), a protein responsible for the interpretation of DNA methylome‐encoded information, was abnormally expressed in lung and bronchoalveolar lavage fluid samples of IPF patients and mice with onset of pulmonary fibrosis. And further studies verified that the overexpression of MECP2 occurred mainly in macrophages. Inhibition of Mecp2 expression in macrophages robustly abrogated alternatively activated macrophage (M2) polarization by regulating interferon regulatory factor 4 expression. Accordingly, cationic liposomes loading Mecp2 small interfering RNA (siRNA) were raised for the treatment of pulmonary fibrosis. It was noted that the liposomes accumulated in the fibrotic region after intratracheal injection, especially in macrophages. In addition, intratracheal administration of Mecp2 siRNA‐loaded liposomes significantly reversed the established pulmonary fibrosis with few side‐effects and high safety coefficients. Collectively, these results are essential not only for further understanding the DNA methylation in pathogenesis of IPF but also for providing a potent therapeutic strategy for IPF treatment in the clinic practice.

BackgroundPatients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.MethodsCOPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator.ResultsCOPD with concomitant features of asthma was found in 1.62% (95% CI 1.31–2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0–17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.ConclusionsCOPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.

Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.

Cellulose nanocrystals (CNCs) are nanoscale particles made from cellulose. They have many unique properties such as being lightweight, stiff, and renewable, making them promising for a variety of applications in a wide range of industries, including materials science, energy storage, and biomedicine. In this paper, a two-stage (swelling-SA-catalyzed) method including IL pretreatment and solid acid hydrolysis process was developed to extract CNCs with high purity and good thermal stability from microcrystalline cellulose (MCC). In the first stage, the swelling of MCC in ionic liquid was studied with the assistance of ultrasonication, and it was found that the amorphous regions became more disordered while the crystalline areas were selectively retained under the conditions of 30 min of reaction time, 45 °C of temperature, 2% of ionic liquid water content and 1:4 mass ratio of cellulose to ionic liquid. CNCs were extracted using solid acid hydrolysis, with a 45 wt% solid acid to cellulose ratio and a 5.0 h hydrolysis process at 45 °C. The morphology, crystallinity, surface characteristics and thermo stability of the sample were characterized by atomic force microscopy (AFM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA), respectively. Results demonstrated the highly thermostable CNCs were successful extracted with rodlike shape of 300 ± 100 nm in length and 20 ± 10 nm in width. Solid acid recovery and reuse were also studied, revealing a promising candidate that can reduce the environmental impact associated with chemical products.

Abstract With the increased use of immune checkpoint inhibitors (ICIs) in lung cancer, which are of great benefit to patients, more and more immune‐related adverse events (irAEs) are being reported. Checkpoint inhibitor pneumonitis (CIP) is one of the most challenging adverse events, which pose a huge challenge to clinical diagnosis and treatment, and its incidence in the real world is greatly underestimated. Currently, the treatment of CIP mainly depends on the use of glucocorticoids. As for steroid‐resistant CIP, there is no unified standardized treatment strategy. Herein, we report a case of steroid‐resistant CIP induced by pembrolizumab in a patient with advanced non‐small cell lung cancer (NSCLC), in which their symptoms were successfully controlled with pirfenidone.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible disease characterized by excessive fibroblast to myofibroblast differentiation with limited therapeutic options. Curdione, a sesquiterpene compound extracted from the essential oil of Curcuma aromatica Salisb, has anti-inflammatory and anti-tumor effects. However, the role of curdione in IPF is still unclear. Methods The effects of curdione were evaluated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. C57BL/6 mice were treated with BLM on day 0 by intratracheal injection and intraperitoneal administered curdione or vehicle. In vitro study, expression of fibrotic protein was examined and the transforming growth factor (TGF)-β-related signaling was evaluated in human pulmonary fibroblasts (HPFs) treated with curdione following TGF-β1 stimulation. Results Histological and immunofluorescent examination showed that curdione alleviated BLM-induced lung injury and fibrosis. Specifically, curdione significantly attenuated fibroblast to myofibroblast differentiation in the lung in BLM induced mice. Furthermore, curdione also decreased TGF-β1 induced fibroblast to myofibroblast differentiation in vitro, as evidenced by low expression of α-SMA, collagen 1 and fibronectin in a dose dependent manner. Mechanistically, curdione suppressed the phosphorylation of Smad3 following TGF-β1 treatment, thereby inhibiting fibroblast differentiation. Conclusions Overall, curdione exerted therapeutic effects against pulmonary fibrosis via attenuating fibroblast to myofibroblast differentiation. As curdione had been shown to be safe and well-tolerated in BLM-induced mouse model, curdione might be useful for developing novel therapeutics for IPF.

Abstract Background Monitoring inequalities in chronic disease prevalence and their preventive care can help build effective strategies to improve health equality. Using hypertension and diabetes as a model, this study measures and decomposes socioeconomic inequalities in their prevalence and preventive care among Chinese adults aged 45 years and older in Shaanxi Province, an underdeveloped western region of China. Methods Data of 27,728 respondents aged 45 years and older who participated in the fifth National Health Services Survey conducted in 2013 in Shaanxi Province were analyzed. The relative indexes of inequalities based on Poisson regressions were used to assess disparities in the prevalence of hypertension and diabetes and their preventive care between those with the lowest and the highest socioeconomic status, and the concentration index was used to measure the magnitude of the socioeconomic-related inequality across the entire socioeconomic spectrum. The contribution of each factor to the inequality was further estimated via the concentration index decomposition. Results Our results indicate a higher prevalence of hypertension and diabetes among the rich than the poor individuals aged 45 years and older in Shaanxi Province, China. Among individuals with hypertension or diabetes, significant inequalities favoring the rich were observed in the use of preventive care, i.e. in adequate use of medication and of blood pressure/blood glucose monitoring. Furthermore, economic status, educational level, employment status, and urban-rural areas were identified as the key socioeconomic indicators for monitoring the inequalities in the patient preventive care. Conclusions Our study suggests that the existence of clear inequities in the prevalence of chronic diseases and preventive care among adults aged 45 and older in Shaanxi Province, China. These inequalities in chronic diseases could be as much a cause as a consequence of socioeconomic inequalities.

Abstract Background Ensuring equal access to preventive care has always been given a priority in health system throughout world. This study aimed to decompose inequality in utilization of preventive care services into its contributing factors and then explore its changes over the period of China’s 2009–2015 health system reform. Methods The concentration index (CI) and decomposition of the CI was performed to capture income-related inequalities in preventive services utilization and identify contribution of various determinants to such inequality using data from China Health and Nutrition Survey. Then, changes in inequality from 2009 to 2015 were estimated using Oaxaca-type decomposition technique. Results The CI for preventive services utilization dropped from 0.2240 in 2009 to 0.1825 in 2015. Residential location and household income made the biggest contributions to income-related inequalities in these two years. Oaxaca decomposition revealed changes in residential location, regions and medical insurance made positive contributions to decline in inequality. However, alternation in household income, age and medical services utilization pushed the equality toward deterioration. Conclusion The pro-rich inequality in preventive healthcare services usage is evident in China despite a certain decline in such inequality during observation period. Policy actions on eliminating urban-rural and income disparity should be given the priority to equalize preventive healthcare.

Abstract Background A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter

Abstract Background Pulmonary hypertension (PH) is a progressive and fatal disease. While cigarette smoke can change DNA methylation status, the role of such molecular alterations in smoke-associated PH is unclear. Methods A PH rat model was developed by exposing animals to cigarette smoke for 3 months. Right ventricular systolic pressure was measured with a right heart catheter. Histological changes (right ventricular hypertrophy index, medial wall thickness in pulmonary arteries (PAs)) and DNMT1 protein levels in rat PAs or primary human PA smooth muscle cells (HPASMCs) exposed to cigarette smoke extract were assessed. Methylation sequencing and MassArray® were used to detect genomic and RASEF promoter methylation status, respectively. After DNMT1 knockdown and cigarette smoke extract exposure, HPASMCs behavior (proliferation, migration) and RASEF methylation status were examined; RASEF mRNA expression was evaluated by real-time-polymerase chain reaction. RASEF overexpression viral vectors were used to assess the impact of RASEF on rat PH and HPASMCs remodeling. Results Higher right ventricular systolic pressure, medial wall thickness, and right ventricular hypertrophy index values were observed in the smoking group rats. Smoke exposure increased DNMT1 expression and RASEF methylation levels in rat PAs and HPASMCs. Cigarette smoke extract induced HPASMCs behavioral changes and RASEF hypermethylation followed by silencing, while DNMT1 knockdown markedly inhibited these changes. RASEF overexpression distinctly inhibited PH and HPASMCs remodeling, possibly through phospho-AKT (Ser473), PCNA, and MMP9 downregulation. Conclusions Cigarette smoke caused PA remodeling in PH rats related to RASEF hypermethylation. These results expand our understanding of key epigenetic mechanisms in cigarette smoke-associated PH and potentially provide a novel therapeutic target for PH.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease that has a poor prognosis. Scutellarein, which is extracted from the traditional Chinese medicine Erigeron breviscapus , is used to treat a variety of diseases; however, the use of scutellarein for the treatment of pulmonary fibrosis and the related mechanisms of action have not been fully explored. Methods: This study was conducted using a well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM). The antifibrotic effects of scutellarein on histopathologic manifestations and fibrotic marker expression levels were examined. The effects of scutellarein on fibroblast differentiation, proliferation, and apoptosis and on related signaling pathways were next investigated to demonstrate the underlying mechanisms. Results: In the present study, we found that scutellarein alleviated BLM-induced pulmonary fibrosis, as indicated by histopathologic manifestations and the expression levels of fibrotic markers. Further data demonstrated that the ability of fibroblasts to differentiate into myofibroblasts was attenuated in scutellarein-treated mice model. In addition, we obtained in vitro evidence that scutellarein inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling, inhibited cellular proliferation by repressing PI3K/Akt signaling, and increased apoptosis of fibroblasts by affecting Bax/Bcl2 signaling. Discussion: In general, scutellarein might exert therapeutic effects on pulmonary fibrosis by altering the differentiation, proliferation, and apoptosis of fibroblasts. Although scutellarein has been demonstrated to be safe in mice, further studies are required to investigate the efficacy of scutellarein in patients with IPF.

Abstract Background China’s New Cooperative Medical Scheme (NCMS) enables insured citizens to enjoy the same benefit package by paying a flat-rate premium. However, it still remains uncertain whether economically disadvantaged enrollees receive insurance benefits that at least match those of non-disadvantaged enrollees. This article, therefore, estimates the distribution of benefits under the NCMS across economic groups and compares the magnitude of economic-related inequity changes in the NCMS benefits. Methods Data were drawn from two-wave large-scale representative and comparable cross-sectional household health survey datasets conducted in Shaanxi Province in 2008 and 2013. In total, 9506 (2008) and 38,010 (2013) NCMS enrollees were included. The benefits from the NCMS are measured in two ways: via the probability of receiving reimbursements and via the absolute amount of the obtained reimbursements. Two-part models were used to estimate the benefit distribution and to adjust benefits for health care needs. Concentration curve, dominance test of the concentration curve, and concentration index (CI) were used to estimate the overall degree of economic-related inequality. The degree of horizontal inequity was estimated via indirectly standardized measures based on the “equal treatment for equal needs” concept. Results Our results indicate that economically affluent groups were more likely to receive reimbursements from the NCMS, and these reimbursements were also higher. Positive need-adjusted CIs for the probability of receiving reimbursements (CIs: 0.2027/0.1056 in 2008/2013) and the absolute amount of reimbursements (CIs: 0.3002/0.1660 in 2008/2013) further suggest the existence of clear pro-rich horizontal inequities in the benefits distribution under the NCMS. Encouragingly, a decreasing trend could be observed from 2008 to 2013, which suggests that horizontal inequities in NCMS benefits that favored the rich decreased over the investigated period, while the level of insurance benefits improved. Conclusions Our study suggests that the benefits of NCMS are concentrated toward economically affluent groups. Although any trade-off between policy feasibility and equity has become a challenge for the formulation of social health insurance funding and benefit packages in developing countries, inequality can be gradually reduced through continuous adjustment of the medical insurance scheme, thus effectively targeting economically disadvantaged enrollees.

Abstract This population-based cross-sectional study aims to explore the effect of China’s Rural Hospital Delivery Subsidy (RHDS) policy on the utilization of women’s hospital delivery between rural and urban areas. A total of 2398 women were drawn from the Fourth and Fifth National Health Service Surveys, from the Shaanxi province. A generalized linear mixed model was used to analyze the influence of the RHDS policy on the hospital delivery rate. Concentration index and decomposition methods were used to explore the equity of hospital delivery utilization. Prior to introduction of the RHDS policy, the difference in hospital delivery rates was −0.09 (95% CL: −0.16, −0.01) between rural and urban women when adjusting the influence of socioeconomic factors on hospital delivery; after implementation of the policy, the difference was reduced to 0.02 (95% CL: −0.01, 0.06). The horizontal inequity index was reduced from 0.084 to 0.009 for rural women and from 0.070 to 0.011 for urban women. China’s Rural Hospital Delivery Subsidy policy had some positive effect on reducing the gap between rural and urban women’s hospital delivery rate and inequity. However, there is still a pro-rich inequity of hospital delivery utilization for both rural and urban women.

Abstract Background Although the awareness of mental health problems in late life is rising, the association between financial transfers to the older generations from children and mental health at older ages in China has received little attention. This study examines the association between financial transfers from children and depressive symptoms among the mid-aged and elderly residents (from 45 years of age and older) in China. Methods We used the data from the China Health and Retirement Longitudinal Study (CHARLS, 2013) (n = 10,935) This included data on financial transfers from all non-co-resident children to their parents, and the individual scores on depressive symptoms as measured by the 10-item Center for Epidemiologic Studies–Depression Scale (CESD-10). A two-level - individual and community levels - mixed linear model was deployed to explore their association. Results Financial transfers from children to parents was the major component of inter-generational financial transfers in Chinese families. A higher financial support from non-co-resident children was signivicantly and positively related to fewer depressive symptoms (coef. = − 0.195,P-value

Abstract Background China has three basic health insurance schemes: Urban Employee Basic Medical Insurance (UEBMI), Urban Resident Basic Medical Insurance (URBMI) and New Rural Cooperative Medical Scheme (NRCMS). This study aimed to compare the equity of health-related quality of life (HRQoL) of residents under any two of the schemes. Methods Using data from the 5th National Health Services Survey of Shaanxi Province, China, coarsened exact matching method was employed to control confounding factors. We included a matched sample of 6802 respondents between UEBMI and URBMI, 34,169 respondents between UEBMI and NRCMS, and 36,928 respondents between URBMI and NRCMS. HRQoL was measured by EQ-5D-3L based on the Chinese-specific value set. Concentration index was adopted to assess health inequality and was decomposed into its contributing factors to explain health inequality. Results After matching, the horizontal inequity indexes were 0.0036 and 0.0045 in UEBMI and URBMI, 0.0035 and 0.0058 in UEBMI and NRCMS, and 0.0053 and 0.0052 in URBMI and NRCMS respectively, which were mainly explained by age, educational and economic statuses. The findings demonstrated the pro-rich health inequity was much higher for the rural scheme than that for the urban ones. Conclusion This study highlights the need to consolidate all three schemes by administrating uniformly, merging funds pooling and benefit packages. Based on the contributing factors, strategies aim to facilitate health conditions of the elderly, narrow economic gap, and reduce educational inequity, are essential. This study will provide evidence-based strategies on consolidating the fragmented health schemes towards reducing health inequity in both China and other developing countries.