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ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.
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Although surgery,radiotherapy and chemotherapy have made great progress,pancreatic cancer is still the most fatal malignant tumor,with a 5-year overall survival rate of only about 4% . Many studies have demonstrated that the local recurrence of pancreatic cancer is an important cause of high mortality,and the failure rate after local excision is still as high as 50~80% . There-fore,how to improve the local control rate of pancreatic cancer has been a hot spot of concern. Due to the adjacent organs and tissues (such as bone marrow,spinal cord,kidney,liver,intestine,etc. ),the dose of external irradiation(EBRT) is limited. Increasing local control rates and reducing treatment side effects are trends in future treatments. Intraoperative radiotherapy has the advantages of do-simetry and direct vision treatment to be increasingly used in the treatment of pancreatic cancer,becoming an important part of com-prehensive treatment. This article summarizes the clinical research results of intraoperative radiotherapy for pancreatic cancer in recent years,in order to provide the reference for clinicians.
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Radiation therapy is one of the main therapeutic means of thoracic malignant tumors .When re-ceived certain radiation ,lung may cause the common complication of chest tumor radiotherapy -Radiation -in-duced Lung Injury ( RILI) ,which restricts the radiation dose for the tumor region and may affect patient outcomes . RILI is closely associated with multiple cytokines ,such as interleukin family,tumor necrosis factor,transforming growth factor,etc.Currently,research on RILI control methods has also made some breakthrough ,this article elab-orates on this individually .
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Thoracic radiotherapy is an important means of local treatment for non -small cell lung cancer (NSCLC).Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)have the effect of systemic therapy.Studies have shown that NSCLC patients with EGFR exons 19,21 mutation have a synergistic effect in the combination therapy .Radiotherapy activates EGFR signaling pathway ,inducing cell proliferation and DNA damage repair,leading to radiation resistance .Therefore,EGFR-TKIs have the effect in increasing radiosensitivity .Lung injury is one of the most common side effects when the two therapies combined .Studies suggest that radiotherapy combined with EGFR-TKIs may have conflicting functions in the development of pulmonary fibrosis ,the discrep-ancy between these studies may depend on the differences in the experimental systems ,the differences in pulmo-nary fibrosis models,as well as the differences between different species and individuals .Therefore,a more com-plete understanding of the etiology for pulmonary fibrosis is necessary to the development of improved treatments .
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Objective To study radiation -induced lung damage after lung ionizing radiation and the temporal and spatial release of pro -inflammatory cytokines of interleukin -6(IL-6),interleukin-8(IL-8) and interleukin-10(IL-10)in the irradiated lung tissue.Methods BALB/C male mice weighted around 25 g were randomly divided into two groups:radiation group ( R) and control group ( C) ,with 30 mice in R group and10 mice in C group.The thorax of mice was irradiated by 6 MV X-ray with 25 Gy in 5 fractions.The mice were sac-rificed at 12 weeks post irradiation.Lung tissues were collected and embedded in paraffin .After HE staining,lung histopathological changes were detected by immunohistochemistry to detect IL -6,IL-8 and IL-10 expression in lung tissue.Results Immunohistochemistry results showed that the expressions of IL -6,IL-8 and IL-10 were mainly expressed in macrophages and inflammatory cells .The results showed that the expressions of IL -6 and IL-8 in R group were significantly higher than that in C group .IL-10 expression level was lower than C group.Conclusion After 12 weeks exposing to radiation ,cytokines of IL-6,IL-8 and IL-10 in lung tissue are associated with radiation -induced lung injury .
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About 2/3 patients with chest tumor requires radiation therapy .Normal lung tissues inevitably receive a certain amount of radiation during the treatment ,which results in the most frequent complication in tho-racic tumor radiotherapy:radiation-induced lung injury(radiation-induced lung injury,RILI).Usually,radio-logical changes are more common than clinical manifestations .RILI has become the bottleneck in radiotherapy which restricts the improvement of efficacy .At present ,there is no accurate and reliable method to predict the oc-currence of RILI .Once RILI occurs ,the condition is irreversible and treatment in recent decades has been stag-nant.In the present review ,we summarized the RILI predictors and RILI treatment methods .
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90%) was a forepart change of gemcitabine-induced lung injury in the first month in G group, but the exudation, proliferation and fibrosis dominated in the 1,3 and 6 months in R+CG group. Hydroxyproline content of lung-irridiated tissue was increased from the 5th month and lasted to months 6,7 and 8, and its content in the R+CG group was higher than that in the other groups(P