Study on the dynamic response and roadways stability during mining under the disturbance of hard roof break.

Under the condition that the working face was directly covered with hard roof, the abrupt breaking of hard roof release significant amount of energy, thus prone to triggering dynamic disasters such as roadway instability or rockburst. This paper based on the engineering background of the Xieqiao Coal Mine's 11,618 working face, a numerical simulation method was put forward to study the dynamic response of roadway under the disturbance of hard roof breaking and proposed an evaluation index IC for roadway stability. Research indicates that the elastic energy released during the periodic weighting of the hard roof is higher than that released during the first weighting. Under the dynamic disturbance caused by hard roof breaking, the peak stresses of the roadway was slight decreased, accompanied by a significant increase in the range of stress concentration and plastic zone expansion. Roadway deformation patterns are significantly influenced by hard roof breaking, with noticeable increases in deformation on the roof and right side. During the period of hard roof breaking, the possibility of instability of the roadway increase significantly due to the disturbance caused by the dynamic load. The research results reveal the instability mechanism of roadway under the condition of hard roof, and provide a more reliable basis for evaluating the stability of roadway.

Harnessing cGAS-STING axis for therapeutic benefits in systemic lupus erythematosus.

The cyclic GMP-AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)-mediated synthesis of pro-inflammatory cytokines, such as type-I interferon (IFN-I). For decades, IFN-I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS-STING pathway by self-DNA would propagate the autoimmune responses via upregulating IFN-I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS-STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Fossil and Nonfossil Sources of Winter Organic Aerosols in the Regional Background Atmosphere of China.

Carbonaceous aerosols (CA) from anthropogenic emissions have been significantly reduced in urban China in recent years. However, the relative contributions of fossil and nonfossil sources to CA in rural and background regions of China remain unclear. In this study, the sources of different carbonaceous fractions in fine aerosols (PM2.5) from five background sites of the China Meteorological Administration Atmosphere Watch Network during the winter of 2019 and 2020 were quantified using radiocarbon (14C) and organic markers. The results showed that nonfossil sources contributed 44-69% to total carbon at these five background sites. Fossil fuel combustion was the predominant source of elemental carbon at all sites (73 ± 12%). Nonfossil sources dominated organic carbon (OC) in these background regions (61 ± 13%), with biomass burning or biogenic-derived secondary organic carbon (SOC) as the most important contributors. However, the relative fossil fuel source to OC in China (39 ± 13%) still exceeds those at other regional/background sites in Asia, Europe, and the USA. SOC dominated the fossil fuel-derived OC, highlighting the impact of regional transport from anthropogenic sources on background aerosol levels. It is therefore imperative to develop and implement aerosol reduction policies and technologies tailored to both the anthropogenic and biogenic emissions to mitigate the environmental and health risks of aerosol pollution across China.

Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.

Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

Comparison of Biatain Ag and Biatain Alginate Ag dressings on skin graft donor sites: a prospective clinical trial.

OBJECTIVE: The aim of this study was to compare Biatain Ag and Biatain Alginate Ag (both Coloplast, Denmark) as skin graft donor site dressings. METHOD: A single-centre, prospective, randomised clinical study was conducted. In patients who had undergone a skin graft operation, adjacent split-thickness skin graft donor sites were dressed with Biatain Ag and Biatain Alginate Ag, respectively. The primary outcomes were time to re-epithelialisation and pain score after the operation. The secondary outcomes were scar scores of the donor site after the operation, haematoma rates, infection rates, and exudation rates before wound healing. Results were compared using the Wilcoxon test and the Chi-squared test. RESULTS: A total of 16 paired wounds in 16 patients were studied. The donor sites dressed with Biatain Ag needed more time for >90% re-epithelialisation than those dressed with Biatain Alginate Ag. On day 3 postoperatively, the pain scores with Biatain Ag were significantly less severe than those with Biatain Alginate Ag. On days 6, 9 and 12, the pain scores of both dressings did not differ significantly. The scar scores of the donor site dressed with Biatain Ag were significantly worse than those dressed with Biatain Alginate Ag at 6 months. With respect to infection rates, no significant differences were detected between these two groups. However, the exudation rates of the donor site dressed with Biatain Ag were significantly lower than those dressed with Biatain Alginate Ag. CONCLUSION: As skin graft donor site dressings, both Biatain Ag and Biatain Alginate Ag have advantages.

Cervical lymphadenitis caused by Mycobacterium avium in a patient treated with Janus kinase inhibitors.

A woman diagnosed with rheumatoid arthritis and treated with Janus kinase (JAK) inhibitors presented with a gradually enlarging bilateral submandibular lymph nodes swelling that had lasted several weeks. A lymph node biopsy showed epithelioid granulomatous lymphadenitis with caseous necrosis. Mycobacteria grew in acid-fast bacteria culture and were identified as Mycobacterium avium by polymerase chain reaction. The patient was diagnosed with cervical lymphadenitis caused by M. avium. A computed tomography scan showed no evidence of a mass or infection at other sites, including the lungs; therefore, the mass was excised without any antimicrobial treatments. Her neck mass had not recurred at 9 months after the excision. JAK inhibitors have emerged as an important new class of oral therapy for rheumatoid arthritis and other diseases. Physicians should be aware of the relatively rare complications, such as cervical lymphadenitis caused by nontuberculous mycobacteria, when using JAK inhibitors.

[Composition Characteristics and Sources of Non-polar Organic Compounds in PM2.5 in the Background Atmosphere of Yangtze River Delta].

In order to explore the composition and source characteristics of non-polar organic compounds (NPOCs) in atmospheric fine particulate matter in the Yangtze River Delta region, 129 PM2.5 samples were collected at the Regional Atmospheric background station in Lin'an from December 2019 to November 2020. Including polycyclic aromatic hydrocarbons (PAHs), n-alkanes, and hopanes, the main sources of organic aerosols were investigated using molecular tracers, eigen ratios, and orthogonal matrix factorization models. The results showed that the average annual mass concentration of PM2.5 in Lin'an was approximately (32.36±20.44) µg·m-3, and the average annual mass concentration of NPOCs was approximately (59.05±40.39) ng·m-3, showing the seasonal characteristics of being high in winter and low in summer. n-alkanes mainly came from fossil fuels and biomass (grass, wood, etc.) burning, followed by cuticle wax emission from higher plants. PAHs mainly came from the mixed contribution of non-fossil sources such as coal burning motor vehicle emissions and biomass combustion. Hopanes were mainly derived from motor vehicle emissions, which were also affected by coal burning in winter. Backward trajectory cluster analysis and potential source analysis showed that Lin'an was mainly affected by external air mass transport. Combined with the orthogonal matrix-factor decomposition model, NPOCs observed during the sampling period were analyzed, and non-fossil sources such as coal burning sources, transportation emission sources, and biomass combustion were obtained. In winter, transportation sources were the main source, accounting for 59%. In spring and summer, coal burning was the main source, accounting for 58% and 57%, respectively. In autumn, biomass combustion and other non-fossil sources dominated, accounting for 64%.

Research advances of N6-methyladenosine in diagnosis and therapy of pancreatic cancer.

BACKGROUND: N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance. METHODS: Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy". RESULTS: Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy. CONCLUSION: Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.

The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Therapeutic Effect.

Exosomes participate in many physiological and pathological processes by regulating cell-to-cell communication. This affects the etiology and development of diseases, such as osteoarthritis (OA). Although exosomes in the OA tissue microenvironment are involved in the progression of OA, exosomes derived from therapeutic cells represent a new therapeutic strategy for OA treatment. Recent studies have shown that exosomes participate in OA treatment by regulating the proliferation, apoptosis, inflammation, and extracellular matrix synthesis of chondrocytes. However, studies in this field are scant. This review summarizes the therapeutic properties of exosomes on chondrocytes in OA and their underlying molecular mechanisms. We also discuss the challenges and prospects of exosome-based OA treatment.

Protocadherin alpha 3 inhibits lung squamous cell carcinoma metastasis and epithelial-mesenchymal transition.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. OBJECTIVE: To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism. METHODS: Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis. RESULTS: Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition. CONCLUSIONS: PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.

AI-Driven Synthetic Biology for Non-Small Cell Lung Cancer Drug Effectiveness-Cost Analysis in Intelligent Assisted Medical Systems.

According to statistics, in the 185 countries' 36 types of cancer, the morbidity and mortality of lung cancer take the first place, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer (International Agency for Research on Cancer, 2018), (Bray et al., 2018). Significantly in many developing countries, limited medical resources and excess population seriously affect the diagnosis and treatment of alung cancer patients. The 21st century is an era of life medicine, big data, and information technology. Synthetic biology is known as the driving force of natural product innovation and research in this era. Based on the research of NSCLC targeted drugs, through the cross-fusion of synthetic biology and artificial intelligence, using the idea of bioengineering, we construct an artificial intelligence assisted medical system and propose a drug selection framework for the personalized selection of NSCLC patients. Under the premise of ensuring the efficacy, considering the economic cost of targeted drugs as an auxiliary decision-making factor, the system predicts the drug effectiveness-cost then. The experiment shows that our method can rely on the provided clinical data to screen drug treatment programs suitable for the patient's conditions and assist doctors in making an efficient diagnosis.

Potential Role of Life Stress in Unexplained Sudden Cardiac Arrest.

BACKGROUND: The etiology of sudden cardiac arrest (SCA) in individuals without known cardiovascular heart disease remains elusive in nearly half of all patients after systematic testing. We investigated the relationship between stressful life events and SCA risk in cases of explained and unexplained SCA (USCA) events. METHODS: Individuals who previously experienced SCA were enrolled prospectively and divided into a USCA or explained SCA (ESCA) subgroup dependent on whether a diagnosis was ascribed after SCA. Participants completed either the 1997 Recent Life Changes Questionnaire, Student Stress Scale, or Social Re-adjustment Rating Scale for Non-Adults recalling events during the year preceding their SCA, depending on age at SCA presentation; all measure stress in life change units (LCUs). SCA group scores were compared with an age- and sex-matched control group. RESULTS: We compared 36 SCA group participants (22 USCA, 14 ESCA, age 47 ± 15 years, age at SCA 40 ± 14 years, 50% male) with 36 control participants (age 47 ± 15 years, 50% male). There was no significant difference in LCU score between the control group and the SCA group (248 ± 181 LCU vs 252 ± 227 LCU; P > .05). The ESCA subgroup had significantly lower mean LCU scores than the USCA subgroup (163 ± 183 LCU vs 308 ± 237 LCU; P = .030). CONCLUSIONS: Stressful life events, especially those producing chronic stress, might predispose otherwise healthy individuals to lethal arrhythmias. Further investigation into the role of stress in SCA precipitation is warranted.

CONTEXTE: La cause de l'arrêt cardiaque subit (ACS) chez les personnes n'ayant pas de maladie cardiovasculaire connue demeure nébuleuse dans près de la moitié des cas, même après des examens systématiques. Nous avons étudié la relation entre les événements stressants de la vie et le risque d'ACS chez des patients présentant un ACS expliqué (ACSe) ou inexpliqué (ACSi). MÉTHODOLOGIE: Des sujets ayant déjà subi un ACS ont été recrutés de manière prospective et répartis en deux sous-groupes (ACSe et ACSi), selon qu'un diagnostic a pu ou non être posé après l'ACS. On a demandé aux participants de répondre au questionnaire RLCQ (Recent Life Changes Questionnaire, questionnaire sur les changements de vie récents, version de 1997), au questionnaire SSS (Student Stress Scale, échelle d'évaluation du stress vécu par les étudiants) ou au questionnaire SRRS (Social Readjustment Rating Scale, échelle d'évaluation du réajustement social) pour les non-adultes en repensant aux événements survenus dans l'année précédant l'ACS, selon leur âge au moment de l'ACS; tous ces questionnaires mesurent le stress en unités de changement de vie (UCV). Les scores des patients ayant subi un ACS ont été comparés à ceux de sujets témoins appariés selon l'âge et le sexe. RÉSULTATS: Nous avons comparé 36 sujets ayant subi un ACS (22 ACSi et 14 ACSe; âge : 47 ± 15 ans; âge au moment de l'ACS : 40 ± 14 ans; proportion d'hommes : 50 %) à 36 sujets témoins (âge : 47 ± 15 ans; proportion d'hommes : 50 %). Il n'y avait pas de différence significative quant au score UCV entre le groupe témoin et le groupe ACS (248 ± 181 UCV vs 252 ± 227 UCV; p > 0,05). Les sujets du sous-groupe ACSe avaient un score UCV moyen significativement plus faible que ceux du sous-groupe ACSi (163 ± 183 UCV vs 308 ± 237 UCV; p = 0,030). CONCLUSIONS: Les événements stressants, plus particulièrement ceux qui entraînent un stress chronique, peuvent prédisposer des personnes autrement en bonne santé aux arythmies mortelles. Une étude plus poussée du rôle du stress dans la survenue précipitée d'un ACS s'impose.

Chemoselective electrochemical reduction of nitroarenes with gaseous ammonia.

Valuable aromatic nitrogen compounds can be synthesized by reduction of nitroarenes. Herein, we report electrochemical reduction of nitroarenes by a protocol that uses inert graphite felt as electrodes and ammonia as a reductant. Depending on the cell voltage and the solvent, the protocol can be used to obtain aromatic azoxy, azo, and hydrazo compounds, as well as aniline derivatives with high chemoselectivities. The protocol can be readily scaled up to >10 g with no decrease in yield, demonstrating its potential synthetic utility. A stepwise cathodic reduction pathway was proposed to account for the generations of products in turn.

Effects of the micro/nanostructure of electrospun zein fibres on cells in simulated blood flow environment.

In order to prevent thrombosis, reduce intima hyperplasia, and to maintain long-term patency after implantation of an artificial blood vessel, the formation of intact endothelial cells layer on an inner surface of graft is desirable. The present study aimed to improve endothelial cell adhesion by regulating the morphology of the inner surface of artificial blood vessels. Zein fibre membranes with three fibre diameters (small, ~100 nm; medium, ~500 nm; and large, ~1000 nm) were constructed by electrospinning. A flow chamber device was designed to simulate the blood flow environment. The morphology and adhesion of human umbilical vein fusion cells (EA.hy926) on the surface of the fibre membranes were studied under a shear stress of approximately 15 dynes/cm2. The results showed that oriented electrospun zein fibre surfaces with both medium- and large-diameter fibres can regulate the morphology of endothelial cells (EA.hy926), which are aligned by the fibre direction. The three fibre membranes improved the adhesion of endothelial cells significantly compared to that on the flat membrane. When the fibre direction was fixed parallel to the fluid direction, the medium-diameter oriented-fibre membrane could significantly improve the ability endothelial cells to resist shear stress, and there was a significant difference at 1, 2 and 4 h time points compared with the shear stress resistance on the small-diameter and large-diameter oriented-fibre membranes. When the fibre direction was perpendicular to the fluid direction, again the medium-diameter oriented-fibre membrane improved the ability of endothelial cells to resist shear stress significantly at 1 and 2 h time points. It was concluded that by changing the diameter and arrangement of electrospun fibres, cell morphology control and shear stress resistance can be achieved.

Two different treatment regimens of ranibizumab 0.5 mg for neovascular age-related macular degeneration with or without polypoidal choroidal vasculopathy in Chinese patients: results from the Phase IV, randomized, DRAGON study.

PURPOSE: To evaluate the efficacy and safety of monthly and pro re nata (PRN, guided by visual acuity stabilization and disease activity criteria) ranibizumab regimens in Chinese patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This double-masked study randomized nAMD patients (1:1) to ranibizumab monthly from baseline to Month (M) 11 to a PRN regimen from M12 to M23 (monthly group, n = 167) versus ranibizumab three monthly doses followed by a PRN regimen up to M23 (PRN group, n = 166). Subgroups were assessed based on the presence/absence of PCV (indicated by indocyanine green angiography). RESULTS: Of 334 randomized patients, 41.7% had PCV at baseline. Mean average best-corrected visual acuity (BCVA) change from M3 to M4 through M12 was 3.3 letters with monthly and 1.7 letters with PRN (mean difference: 1.6; 95% CI: -2.95, -0.20, primary end-point). Mean change in BCVA from baseline (monthly/PRN, 53.8/53.7) to M12 and M24 was 12.3 and 11.3 letters in monthly and 9.6 and 9.3 letters in PRN group. Corresponding values for patients with PCV/without PCV were 12.7/12.1 letters (M12) and 12.3/10.6 letters (M24) in monthly and 9.4/9.4 letters (M12) and 9.7/8.7 letters (M24) in PRN groups. The mean number of injections was 11.4 (monthly) and 8.2 (PRN) from Day 1 to M11 and 4.8 (monthly) and 5.0 (PRN) from M12 to M23. No new safety findings were reported. CONCLUSIONS: The study results support the use of either ranibizumab monthly or PRN regimens in Chinese patients with nAMD, regardless of presence of PCV.

[Study on anti-inflammatory mechanism of Lonicera fulvotometosa on acute lung injury model in rats].

To study the effect of Lonicera fulvotometosa(LFH) on expression of genes related to inflammatory pathways in the lung tissue of rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS), explore the lung-protective effects and inflammatory mechanisms of L. fulvotometosa water extract, and provide experimental and theoretical basis for the clinical application of LFH. Forty SD rats were randomly divided into 4 groups: normal group, model group(LPS, 5 mg·kg~(-1)), LFH group(7.2 g·kg~(-1)) and dexa-methasone group(Dexa, 5 mg·kg~(-1)). The rats in LFH group received intragastric administration of water extract once a day for 5 days; rats in dexamethasone group received intraperitoneal injection for 2 hours before modeling. Except the normal group, the rats in other groups were injected intraperitoneally with LPS(5 mg·kg~(-1)) to induce ALI rats model. Serum, bronchoalveolar lavage fluid(BALF) and lung tissues were collected 6 hours after modeling. The lung tissues were taken for pathological observation; enzyme-linked immunosorbent assay(ELISA) was used to detect changes of inflammatory factors in serum and BALF; Real-time quantitative polymerase chain reaction(RT-qPCR) was applied to detect mRNA expression of tumor necrosis factor alpha inducible protein 3(TNFAIP3), interleukin(IL) 1 R1, interleukin(IL) 6 R and nuclear factor κB inhibitor α(NFKBIA) in the lung tissues. The degree of lung injury was lighter in LFH group than that in the LPS group. As compared with the LPS group, the levels of interleukin-1ß(IL-1ß), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum and BALF, malondialdehyde(MDA) and myeloperoxidase(MPO) in lung tissues were significantly reduced in LFH group and Dexa group, while glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) in lung tissues were significantly increased; the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues of the LFH group was significantly lower than that of the LPS group. The water extract of LFH can significantly reduce the content of inflammatory factors in rats with ALI, and down-regulate the mRNA expression of TNFAIP3, IL1 R1, IL6 R and NFKBIA in the lung tissues, showing significant anti-inflammatory effect. Its mechanism may be related to the regulation of NF-κB signaling pathway, and the pulmonary inflammation response may be reduced by down-regulating the expression of downstream-related inflammatory factors.

[Study on molecular of anti-tumor mechanism of Forsythia suspensa based on molecular docking and network pharmacology].

In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.