Causal effects of gut microbiota in the development of lung cancer and its histological subtypes: A Mendelian randomization study.

BACKGROUND: Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. METHODS: Two-sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome-wide association studies. The researchers ran two groups of MR analyses, including the genome-wide statistical significance threshold (5 × 10-8 ) and the locus-wide significance level (1 × 10-5 ). RESULTS: Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus-wide significance level. Of the 42 groups, 12 were in LC, nine in non-small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome-wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. CONCLUSION: Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC.

Ozone Pollution and Acute Exacerbation of Asthma in Residents of China: An Ecological Study.

Purpose: The evidence for a causal relationship between high-level ozone (O3) exposure and acute exacerbation of asthma among adults is limited, and the conclusions are less definitive. Patients and methods: Here we collected the daily data on asthma cases, O3 exposure, and meteorological factors from 2010 to 2016 in Shijiazhuang, China. We investigated the risk of asthma exacerbation associated with high-level ozone exposure using a polynomial distributed lag model (PDLM). Using a generalized additive model (GAM), we estimated the interactive effects between O3 and other pollutants as well as meteorological factors on asthma exacerbation. Results: A total of 7270 patients with asthma were enrolled from 22 governmental hospitals in 13 counties. Each 10 µg/m3 increase in O3 concentration on the exacerbation of asthma was associated with a 1.92% (95% CI = 0.80-3.03%) higher risk of asthma exacerbation on day lag 7. The cumulative risk of O3 on asthma exacerbation increased by 18.9% (95% CI = 12.8-25.4%) on the 14th day. High consecutive levels of O3 increase the risk of asthma exacerbation, and the interactive effect of O3 and sulfur dioxide (SO2) appears before the exacerbation onset. Conclusion: These findings suggested that O3 should be an important risk factor for asthma exacerbation, and health benefits in reducing asthma exacerbation risk would be gained with continued efforts to improve the air quality in China.

Instantaneous sap flow velocity simulation of Euonymus bungeanus based on neural network optimization model.

The sap flow of trees is complex and difficult to express with multivariate linear or empirical models. A simple and feasible method on the basis of understanding sap flow variation to simulate its variation with environmental factors is of special importance for quantitatively analyzing forest ecohydrological processes and regional water demand. In this study, with one of the shelter forest species Euonymus bungeanus in the east sandy land of Yellow River in Ningxia as the research object, we continuously measured the trunk sap flow velocity by thermal diffusion sap flow meter, and analyzed the effects of environmental factors on stem sap flow. We used the particle swarm optimization (PSO) and sparrow search algorithm (SSA) optimized neural network model to predict sap flow velocity of E. bungeanus. Results showed that the main environmental factors influencing sap flow were solar radiation, vapor pressure deficit, air temperature, and relative humidity, with the influencing importance of 32.5%, 25.3%, 22.0% and 16.1%, respectively. The response process between sap flow and environmental factors presented a hysteresis loop relationship. The optimized BP, Elman and ELM neural network models improved the comprehensive evaluation index (GPI) by 1.5%, 30.0% and 5.3%, respectively. Compared with the PSO-Elman and SSA-ELM optimization models, the SSA-BP optimization model had the best prediction results with an improvement of 1.0% and 23.2% in GPI, respectively. Therefore, the prediction results of the BP neural network model based on the sparrow search algorithm could be used as an optimal model for predicting instantaneous sap flow velocity of E. bungeanus.

Fatigue at sea during and after the COVID-19 pandemic: A comparative study of two matched samples of seafarers.

This paper examines seafarers' experience of fatigue during and after the pandemic. A multi-phase mixed methods research design was used, including two quantitative surveys (Nduring-pandemic=501 and Nafter-pandemic=412) and 36 in-depth interviews. Applying propensity score matching the two samples to approximate the conditions of a randomized controlled experiment, the study shows that surprisingly seafarers reported higher levels of fatigue after the pandemic. Qualitative interviews with seafarers and ship managers reveal the underlying reason - the intensified ship inspection regime together with policy and regulatory updates/revisions in the immediate aftermath of the pandemic increased seafarers' workload and made seafarers more fatigued. The results of the two surveys also show that while fatigue risk factors differed between the two periods, fatigue risk can be managed and mitigated in both periods by implementing fatigue risk management policies and practices. Policy and management implications for improving seafarers' occupational health and safety are discussed at the end of the paper.

Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040.

Esophageal cancer is a familiar malignancy with high incidence and mortality, and the overall prognosis is poor. The numbers of cases of and deaths from esophageal cancer have risen rapidly in recent decades. It is one of the most malignant cancers, with more than 0.6 million new cases and 0.54 million deaths worldwide in 2020. Here, we present the global epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040 at different geographical levels of continents, regions and countries, and analyze them by gender, race, geographic region and human development index. We summarize the prospects for the esophageal cancer burden and risk factors in different areas, which will be useful for global esophageal cancer clinical therapy and cancer control planning.

Association between waist circumference change and incident chronic obstructive pulmonary disease among Chinese adults: a 10-year cohort study.

The aim of our study was to investigate waist circumference (WC) change and the risk of incident chronic obstructive pulmonary disease (COPD) among Chinese adults. A total of 8164 participants aged > 18 years who attended health examinations with repeat measurements of WC and lung function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)] from 2010 to 2019 were recruited. WC change was categorized as ≤ - 2.5%, - 2.5 to 2.5%, 2.5% to 5% and > 5% according to sex. Modified Poisson regression models were used to assess the association of WC gain and the risk of COPD. During the 10-year follow-up, a total of 917 COPD cases were identified. From baseline to follow-up, the mean FEV1 decreased from 3.20 to 2.79L among male participants and 2.28-1.95L among female participants. Compared with participants who did not have abdominal obesity, at either, baseline or follow-up, participants with abdominal obesity of both sexes after the follow-up were associated with a greater risk of COPD regardless of abdominal obesity at baseline. The risk of incident COPD increased 19% among male participants (RR = 1.19, 95%CI = 1.04-1.48) and 14% among female participants (RR = 1.14, 95%CI = 1.01-1.40) when WC gain increased > 5% during the 10-year follow-up. The COPD risk decreased 18% among male participants with a WC change ≤ - 2.5% (RR = 0.82, 95%CI = 0.67-0.99). The risk of incident COPD was positively associated with increasing WC among Chinese adults of both sexes.

A Study on Epidemic Information Screening, Prevention and Control of Public Opinion Based on Health and Medical Big Data: A Case Study of COVID-19.

The outbreak of the coronavirus disease 2019 (COVID-19) represents an alert for epidemic prevention and control in public health. Offline anti-epidemic work is the main battlefield of epidemic prevention and control. However, online epidemic information prevention and control cannot be ignored. The aim of this study was to identify reliable information sources and false epidemic information, as well as early warnings of public opinion about epidemic information that may affect social stability and endanger the people's lives and property. Based on the analysis of health and medical big data, epidemic information screening and public opinion prevention and control research were decomposed into two modules. Eight characteristics were extracted from the four levels of coarse granularity, fine granularity, emotional tendency, and publisher behavior, and another regulatory feature was added, to build a false epidemic information identification model. Five early warning indicators of public opinion were selected from the macro level and the micro level to construct the early warning model of public opinion about epidemic information. Finally, an empirical analysis on COVID-19 information was conducted using big data analysis technology.

Identification of circular RNA circVPS33A as a modulator in house dust mite-induced injury in human bronchial epithelial cells.

BACKGROUND: House dust mite has been well documented as a major source of allergen in asthma. Circular RNAs (circRNAs) vacuolar protein sorting 33A (circVPS33A, circ_0000455) is overexpressed in a murine asthma model. Herein, we sought to identify its critical action in Dermatophagoides pteronyssinus peptidase 1 (Der p1)-induced dysfunction of BEAS-2B cells. METHODS: The levels of circVPS33A, microRNA (miR)-192-5p, and high-mobility group box 1 (HMGB1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Actinomycin D treatment and Ribonuclease R (RNase R) assay were used to characterize circVPS33A. Cell viability, proliferation, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. Direct relationship between miR-192-5p and circVPS33A or HMGB1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. RESULTS: CircVPS33A was highly expressed in asthma plasma and Der p1-treated BEAS-2B cells. Knocking down circVPS33A suppressed Der p1-induced injury in BEAS-2B cells. CircVPS33A targeted miR-192-5p. MiR-192-5p directly targeted HMGB1, and miR-192-5p-mediated repression of HMGB1 alleviated Der p1-driven cell injury. Furthermore, circVPS33A modulated HMGB1 expression through miR-192-5p. CONCLUSION: Our findings demonstrated that circVPS33A regulated house dust mite-induced injury in human bronchial epithelial cells at least partially depending on the modulation of the miR-192-5p/HMGB1 axis.

Tumor size and lymph node metastasis are prognostic markers of small cell lung cancer in a Chinese population.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by rapid growth, early metastatic spread, and poor prognosis. This study aimed to explore the prognosis factors of survival in Chinese SCLC patients.A total of 78 patients with stage IIIA SCLC (mean age: 53.9 years, 65 males and 13 females) were enrolled in this retrospective study. At least of 5 years follow-up was performed.The survival time of these patients ranged from 1 month to 66 months with a median survival time of 11 months. Kaplan-Meier method with log-rank test was performed and showed that survival time in patients with tumor size ≤4 cm (median: 16 months) was significantly longer (P < .001) than that in patients with tumor size > 4 cm (median: 8 months); the median survival time of the patients with single lymph node metastasis was significantly longer than that in patients with multiple lymph node metastasis (P = .043). Combined multiple lymph node metastasis and tumor size >4 cm presented the worst survival outcome than others. Multivariate analysis by Cox Hazard model shows that the lymph node metastasis and tumors size were prognostic factors independent of age, sex, smoke, surgery, and treatment regimen (P < .05).Results showed that larger tumor size and multiple lymph node metastasis were associated with the poor survival in SCLC.

The effect of temperature-control microwave on HELA and MG-63 cells.

CONTEXT: Hyperthermia has now been used to treat many kinds of solid malignancies. However, the applied thermal parameters about heat temperature and time varied all over the world, and no consensus about the optimal formula had been reached. Microwave ablation, as one of thermal ablation methods, is usually applied based on the fixed parameters of power and duration. As a result, too high temperature or overheating might not be avoided and excessive heating might cause some additional side effects to normal tissues. AIMS: To explore the optimal parameters of power and duration for the HELA and MG-63 cells in vitro. SETTINGS AND DESIGN: With a temperature-controlled microwave workstation, a microwave thermal ablation experiment was performed in vitro. SUBJECTS AND METHODS: The HELA and MG-63 cells were heated with 40°C, 45°C, 50°C, 55°C, and 60°C lasting for 5-30 min, respectively. Then, the cell viability was detected using four methods: Flow cytometer assay, nicotinamide adenine dinucleotide-diaphorase staining, Calcein-acetoxymethyl ester staining immediately after treatment, and CCK-8 assay 24 h later. RESULTS: The temperature-controlled microwave has an excellent ablation effect on both cell lines. Furthermore, when the thermal stimulation reached 55°C 25 min and 55°C 20 min for the HELA and MG-63 cells, respectively, or 60°C 5 min for both, all the viability indexes indicated immediately devitalization. CONCLUSION: It presented a preliminary minimum lethal dose of heat was validated on the cellular level in vitro, which should be verified and corrected further in vivo.

[Analysis of Efficacy of Surgical Treatment for IIIa Small Cell Lung Cancer].

BACKGROUND: Small cell lung cancer (SCLC) accounts for nearly 15% of all cases of cancer. As a type of highly invasive tumors, SCLC has high degree of malignancy, early and extensive metastasis, and is sensitive to chemotherapy and radiotherapy. The early treatment response rate of SCLC is high but it can also relapse rapidly without any treatment. Its median survival time is merely four to six months. Although many studies on SCLC have been conducted in recent years, its clinical treatment strategies have remained unchanged. The treatment of SCLC is still confined to chemotherapy regimens of etoposide plus cisplatin (EP) and other classic treatments because the surgical treatment of SCLC, particularly for IIIa treatment, has yet to reach a consensus. This study investigated the prognostic factors and clinical therapy effect in the comprehensive treatment of IIIa SCLC after surgical treatment. METHODS: This study was conducted through the retrospective analysis of the clinical data of 78 patients with SCLC who underwent surgical treatment in Beijing Chest Hospital affiliated to Capital Medical University between January 1995 and December 1995. Through follow-up, we performed statistical analysis of each patient's gender, age, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) staging, surgical methods, and adjuvant radiation and chemotherapy. RESULTS: The median survival in this clinical trial team was 13.93 months. Among the participants, 47 patients accepted neoadjuvant chemotherapy and their median survival were 14.25 months. By contrast, 31 patients accepted postoperative adjuvant chemotherapy and their median survival were 13.83 months. No statistical difference was observed between the two groups. Moreover, 28 patients were of single Lymph node metastasis and their median survival was 17.1 months. By contrast, 50 patients were of multiple lymph node metastasis and their median survival was 11.9 months. Significant statistical difference was observed between the two groups (P<0.01). CONCLUSIONS: In performing further evaluation of the status and value of surgical treatment in the comprehensive treatment of SCLC, several patients benefitted from IIIa SCLC surgery with comprehensive treatment.

miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma.

Osteosarcoma, the most common primary tumor of the bones, causes many deaths due to its rapid proliferation and drug resistance. Recent studies have shown that cyclin D1 plays a key regulatory role during cell proliferation, and non-coding microRNAs (miRNAs) act as crucial modulators of cyclin D1 (CCND1). The aim of the current study was to determine the role of miRNAs in controlling CCND1 expression and inducing cell apoptosis. CCND1 has been found to be a target of miR-15a and miR-16-1 through analysis of complementary sequences between microRNAs and CCND1 mRNA. The upregulation of miR-15a and miR-16-1 in the cell line SOSP-9607 induces apoptosis and cell cycle arrest. Osteosarcoma cells transfected with miR-15a and miR-16-1 show slower proliferation curves. Moreover, the transcription of CCND1 is suppressed by miR-15a and miR-16-1 via direct binding to the CCND1 3'-untranslated region (3'-UTR). The data presented here demonstrate that the CCND1 contributes to osteosarcoma cell proliferation, suggesting that repression of CCND1 by miR-15a and miR-16-1 could be used for osteosarcoma therapy.

[Effect of silencing p53 and p21 on delaying senescence of nucleus pulposus cells].

UNLABELLED: OBJECTIVE The senescence and death of nucleus pulposus (NP) cells are the pathologic basis of intervertebral disc degeneration (IVD). To investigate the molecular phenotypes and senescent mechanism of NP cells, and to identify the method of alleviating senescence of NP cells. METHODS: The primary NP cells were harvested from male Sprague Dawley rats (8-10 weeks old); the hypoxia inducible factor 1alpha(HIF-1alpha, HIF-1beta matrix metalloproteinase 2 (MMP-2), and collagen type II as phenotypic markers were identified through immunocytochemical staining. RT-PCR and Western blot were used to test the silencing effect of NP cells after the NP cells were transfected with p53 and p21 small interference RNA (siRNA). Senescence associated-beta-galactosidase (SA-beta-gal) staining was used to test the senescence of NP cells, flow cytometry to test the change of cell cycle, the growth curve analysis to test the NP cells proliferation. RESULTS: Immunocytochemical staining showed that NP cells expressed HIF-1alpha HIF-1beta, MMP-2, and collagen type II. RT-PCR and Western blot showed that the relative expressions of mRNA and protein of p53 and p21 were significantly inhibited in NP cells at passage 35 after transfected with p53 and p21 siRNA. The percentage of SA-Pbetagal-positive NP cells at passage 35 was significantly higher than that at passage 1 (P < 0.001). And the percentage of SA-Pbetagal-positive NP cells in the p53 siRNA transfection group and p21 siRNA transfection group were significantly lower than that in control group (P < 0.001). The flow cytometry showed that the GC1phase of NP cells in p53 siRNA transfection group and p21 siRNA transfection group was significantly shorter than that in control group (P < 0.05), but the S phase of NP cells in p53 siRNA transfection group and p21 siRNA transfection group were significantly longer than that in control group (P < 0.05). In addition, the growth curve showed that the growth rate of NP cells could be promoted after transfection of p53 and p21 siRNA. CONCLUSION: he senescence of NP cells can be alleviated by silencing of p53 and p21. The effect of alleviating senescence can even ameliorate the progress of IVD and may be a useful and potential therapy for IVD.

Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and matrix metalloproteinase-2 in sacral chordomas.

Hypoxia-inducible factor-1α (HIF-1α) has been reported to transactivate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2), which are frequently overexpressed in numerous types of cancer and are known to be significant regulators of angiogenesis. Few studies have investigated the role of these factors in solid tumors, particularly chordomas, which are rare tumors that are thought to originate from notochordal remnants. To clarify whether HIF-1α is involved in angiogenesis in chordoma tissues, we examined the expression of HIF-1α, VEGF and MMP-2 with immunohistochemistry using a tissue microarray containing 35 chordoma samples. The results indicated that HIF-1α, VEGF and MMP-2 are expressed in the majority of chordoma samples. VEGF expression was significantly correlated with HIF-1α and MMP-2 expression, as well as with microvessel density (MVD). However, the prognosis of the chordoma patients was not significantly associated with the expression of these factors, but was associated with MVD. The results therefore showed that there is a correlation between the expression of HIF-1α, VEGF and MMP-2 in chordomas and that the angiogenic process is a potential therapeutic target for chordomas.

The healing process of intracorporeally and in situ devitalized distal femur by microwave in a dog model and its mechanical properties in vitro.

BACKGROUND: Limb-salvage surgery has been well recognized as a standard treatment and alternative to amputation for patients with malignant bone tumors. Various limb-sparing techniques have been developed including tumor prosthesis, allograft, autograft and graft-prosthesis composite. However, each of these methods has short- and long-term disadvantages such as nonunion, mechanical failures and poor limb function. The technique of intracorporeal devitalization of tumor-bearing bone segment in situ by microwave-induced hyperthermia after separating it from surrounding normal tissues with a safe margin is a promising limb-salvage method, which may avoid some shortcomings encountered by the above-mentioned conventional techniques. The purpose of this study is to assess the healing process and revitalization potential of the devitalized bone segment by this method in a dog model. In addition, the immediate effect of microwave on the biomechanical properties of bone tissue was also explored in an in vitro experiment. METHODS: We applied the microwave-induced hyperthermia to devitalize the distal femurs of dogs in situ. Using a monopole microwave antenna, we could produce a necrotic bone of nearly 20 mm in length in distal femur. Radiography, bone scintigraphy, microangiography, histology and functional evaluation were performed at 2 weeks and 1, 2, 3, 6, 9 and 12 months postoperatively to assess the healing process. In a biomechanical study, two kinds of bone specimens, 3 and 6 cm in length, were used for compression and three-point bending test respectively immediately after extracorporeally devitalized by microwave. FINDINGS: An in vivo study showed that intracorporeally and in situ devitalized bone segment by microwave had great revitalization potential. An in vitro study revealed that the initial mechanical strength of the extracorporeally devitalized bone specimen may not be affected by microwave. CONCLUSION: Our results suggest that the intracorporeal microwave devitalization of tumor-bearing bone segment in situ may be a promising limb-salvage method.

[Protective function of melatonin to acute lung injury and its mechanisms in rats caused by oleic acid].

OBJECTIVE: To observe the expression of P-selectin (Ps), intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-kappa B (NF-kappaB) in lung tissues of acute lung injury (ALI) rat model induced by oleic acid (OA) and to explore the protective effects of melatonin (MT) in lung tissues in rats. METHODS: All rats were randomly divided into four groups: control group, OA group, MT + OA group and SB203580 + OA group. Rat model of ALI was established by intravenous injection of oleic acid (OA). Lung coefficient was measured, lung tissues were imbedded by paraffin to observe morphological changes and the expression of Ps, ICAM-1 and NF-kappaB in lung tissues by means of immunohistochemistry staining. RESULTS: Compared with control group, the lung coefficient increased significantly in OA group (P < 0.05). Alveolar septum thickened significantly in OA group, there had many infiltrated inflammatory cells and collapsed alveoli of lung; positive expression of Ps, ICAM-1 and NF-kappaB were very obvious (P < 0.05); the administration of MT and SB203580 mitigated above changes significantly (P < 0.05). CONCLUSION: MT possesses obviously protective effect on lung tissues during ALI, its protective mechanism might be related to the inhibition of the expression of Ps, ICAM-1 and NF-kappaB.

[Protective effects of melatonin in acute lung injury rats caused by LPS].

OBJECTIVE: To observe the expression of p-p38 mitogen-activated protein kinase in lung tissues of acute lung injury rat model induced by lipopolysaccharide (LPS) and to explore the protective effects of melatonin (MT) in lung tissues in rats. METHODS: Seventy-two rats was randomly assigned to three groups, control group, LPS group and LPS + MT group. Rat model of ALI was established by instilling LPS intratracheally. We used immunohistochemical SP and Western blot method to detect the expression of p-p38 mitogen-activated protein kinase in lung tissues and used light microscope to observe morphological changes. RESULTS: There were rare p-p38 mitogen-activated protein kinase positive cells scattered in alveolar and airway epithelial cells in control group (P < 0.01). The positive p-p38 mitogen-activated protein kinase cells in LPS group increased obviously than those in control group (P < 0.01), and were mainly distributed in infiltrative inflammatory cells, airway epithelial cells, alveolar epithelial cells and pleurames epithelial cells. In MT group, the p-p38 mitogen-activated protein kinase positive cells in airway and lung tissues were much less than those in the LPS group (P < 0.05). The Western blot results were consistent with those of immunohistochemical method. CONCLUSION: The expression of p-p38 mitogen-activated protein kinase increases in alveolar and airway epithelial cells in acute lung injury rat models induced by LPS. The activation of p-p38 mitogen-activated protein kinase is found in most lung tissues, suggesting that p-p38 mitogen-activated protein kinase participates in the signal transduction in inflammatory and noninflammatory cells. MT is an effective antioxidant, which relieves the inflammation in acute lung injury rats, possibly through the inhibition of the pathway of p38 MAPK over activation.