Fibrosis is an important pathoIogicaI change in a variety of diseases and with compIicated causes. Fibrosis diseases in different organs have different causes,but the common manifestations of fibrobIast are proIiferation and coIIagen deposition that couId eventuaIIy Iead to normaI tissue damage and Ioss of function. Fibrosis in such important organs as the heart or Iung couId be Iife-threatening. There are different reguIating factors and drugs to fibrosis. Chinese medicine treatment is stiII the main method cIinicaIIy for Iiver fibrosis. Because there is no effective cure for puImonary fibrosis,treatment focuses on anti-infIammation by aIIeviating Iesion and improving kidney function. Despite the tremendous progress in fibrosis treatment,there is stiII a Iack of targeted drugs that couId cure a specific disease in a specific area. With the deveIopment of gene technoIogy,gene therapy wiII become an important treatment for this disease. This paper introduces anti-myocardiaI fibrosis drugs according to the mechanism.

Objective To investigate the anti-fatigue activity of fermented grain-containing blueberry anthocyanins ( LANHE,LH) in mice.Methods Experiments were conducted in two phases .In the first phase , forty mice were randomly divided into four groups:control group(distilled water,dw) and three LH administration groups (8.75,17.5 and 35.08 ml/kg body mass).In the second phase, mice were randomly divided into two groups:high-dose LH group (35.08 ml/kg body mass) and control group (dw 35.08 ml/kg body mass).After four weeks, a forced swimming test was performed and the biochemical parameters related to fatigue were examined .Results and Conclusion The administration groups showed a significant increase of swimming time to exhaustion compared with the control group , especially the high-dose group ( P<0.001).There was no significant change in the blood lactate between the two groups , but at 20 min after swimming, the lactic acid(LA) contents of the high-dose group were lower than in the control group (P>0.05).LH could significantly increase the liver glycogen contents and decrease the serum contents (P<0.05).These data indicate that LH has anti-fatigue activity and can elevate the exercise tolerance in mice .

Objective To study the effects of semaphorin 5A (SEMA5A) gene silencing by lentivirus?mediated short hairpin RNA(shRNA)on biological activity of malignant melanoma cell line A375. Methods Two pairs of interference sequences for SEMA5A gene(shRNA1 and A375?shRNA2)and a pair of control interference sequences were designed to build lentiviral vectors, which were then transfected into HEK293T cells to gain lentivirus. A375 cells were divided into three groups:experimental group(A375?shRNA1 and A375?shRNA2 cells)transfected with the lentivirus containing shRNA1 or shRNA2, negative control group (A375?con cells) transfected with that containing the control shRNA, and blank control group(A375 cells)receiving no transfection. The A375 cells with stable knockdown of SEMA5A gene expression were screened by puromycin. Subsequently, reverse transcription?PCR and Western?blot analysis were performed to detect mRNA and protein expressions of Semaphorin 5A in these cells, and methyl thiazolyl tetrazolium(MTT)assay was applied to evaluate the growth of cells. The scratch assay and invasion assay were conducted to estimate migration and invasion ability of cells. Results The lentivirus containing the SEMA5A?targeting shRNAs or control shRNA was successfully transfected into A375 cells, and stably transfected cells were gained after puromycin selection. The expressions of semaphorin 5A mRNA and protein in the A375?shRNA2 cells were significantly reduced compared with those in the A375?con and A375 cells(all P < 0.05). MTT assay showed that the growth of A375?shRNA2 cells was significantly slower than that of A375?con and A375 cells(both P<0.05), while there was no significant difference in the growth rate between A375?con and A375 cells(P>0.05). The scratch assay showed that there was no obvious cell migration into the scratch in the experiment group, whereas the scratch was almost covered by cells in the negative control group and blank control group. The invasion assay showed that the number of A375?shRNA2 cells passing through the Transwell chamber was significantly smaller than that of A375 and A375?con cells(both P<0.05), while there was no significant difference between that of A375 and A375?con cells(P > 0.05). Conclusion The silencing of SEMA5A gene by lentivirus?mediated shRNA could effectively down?regulate the expression of semaphorin 5A, and inhibit the growth, invasion and migration of A375 cells.

Objective To systematially observe the different patterns and leves of military stress on modified multitle-platform method the level of stress-related hormones in rats .Methods A sleep deprivation model was established by water environment modified multiple-platform method(MMPM).A restraint stress model was established by self-made bondage cage.Chronic unpredictable mild stress ( CUMS) model was established by action control , cage damp, cage tilt, night lightening, water and food fasting , empty bottles stimulation and group feeding methods .Cortisol, catecholamines and 5-HT levels were detected to observe the different military stress loads and modes on the level of stress hormones .Results The level of serum cortisol increased significantly ( P <0.05 ) after 5 days of sleep deprivation .The level of serum catecholamines increased significantly (P<0.05) after 1 day of sleep deprivation.The cortisol concentration increased and the level of 5-HT decreased in serum after 4 weeks CUMS.The level of catecholamines increased significantly (P<0.05) after 2-8 weeks of CUMS, increased significantly (P<0.05) after 1 week of restraint stress , and returned to normal after 3-4 weeks of restraint stress .The level of serum cortisol increased significantly after 3 -4 weeks of restraint stress . Conclusion Cortisol levels gradually increased with the level of stress in different military stress modes , which can serve as an index to evaluate the level of different stress modes .

Objective To study the possibility of the plasma level of heat shock protein 70(HSP70) being used as a bi-ological marker of military stress .Methods Soldiers who returned from a 6-month-navigation were chosen as subjects , the HSP70 level of plasma was measured with the ELISA assay and stress questionnaires and Self -rated Health Measurement Scale (SRHMS) were used to measure the stress level .Results The soldiers′plasma level of HSP70 was 31.40%higher than that of the control .The stress questionnaire indicatesd that the level of thinking and anxiety , negative mood and somat-ic symptoms were higher than normal .The SRHMS indicated that the level of physiological health ,mental health and social health was lower than normal .The plasma level of HSP70 was associated with the level of military stress .Conclusion The plasma level of HSP70 may be used as an important predictor of military stress .It can predict the level of military stress injury.

Objective To study the role of glucagon-like peptide-1 (GLP-1) analogue liraglutide played in the proliferation of CD4+CD25 T cells in normal people and newly-onset type 1 diabetic patients,and to evaluate the possible immune regulatory role of liraglutide in the therapy of type 1 diabetes.Methods CD4+ CD25-T cells of 10 normal people and 10 newly-onset type 1 diabetic patients were separated from peripheral blood by MACS immunomagnetic beads and stimulated by Human T-Activator CD3/CD28 Dynabeads to proliferate.CFSE labeling technique was used to evaluate the proliferation of CD4+ CD25-T cells by flow cytometry.Liraglutide of different concentrations(0,25,50,and 100 nmol/ml) was added to the proliferation system,then the proliferation of CD4+CD25-T cell was measured.Results (1) Liraglutide suppressed the proliferation of CD4+ CD25-T cells from either normal people or type 1 diahetic patients with dose-dependent manner (P ＜ 0.05).(2) Under the different concentrationsofliraglutide,the proliferation ofCD4+CD25 T cells from diabetic patients was mueh more robust than that of normal people (P＜0.01).(3) The inhibitory effects of liraglutide on CD4+ CD25-T cells proliferation in normal people and diabetic patients were similar (P＞0.05).Conclusion The proliferation of CD4+ CD25 T cells in type 1 diabetic patients was more robust than normal people,which indicated cellular immune dysfunction in type 1diabetes.Liraglutide inhibits the proliferation of CD4+ CD25-T cells of type 1 diabetic patients in vitro.The immunosuppression effect of liraglutide may have potential value in the treatment of type 1 diabetes.

Objective:To correlate acute ischemic stroke with leukoaraiosis with intracranial and extracranial artery stenosis.Methods:A total of 300 patients with acute ischemic stroke admitted to Shaoxing Second Hospital from January to December 2017 were included in this study. All patients underwent magnetic resonance (MRI) examination. According to the examination results, these patients were divided into control (acute ischemic stroke, n = 100) and acute ischemic stroke with leukoaraiosis, n = 200). Carotid artery plaque size and blood sugar level were recorded in each group. Intracranial and extracranial large artery stenosis rates were compared between the two groups. Severity of leukoaraiosis was correlated with intracranial and extracranial artery stenosis. Results:The percentage of patients developing hypertension in the observation group was significantly higher than that in the control group [66.0% (132/200) vs. 44.0% (44/100), χ2 = 13.31, P < 0.01]. The incidence of coronary heart disease in the observation group was significantly higher than that in the control group [49.0% (98/200) vs. 31.0% (31/100), χ2 = 8.81, P < 0.01]. The incidence of carotid artery plaque in the observation group was significantly higher than that in the control group [49.5% (99/200) vs. 34.0% (34/100), χ2 = 6.49, P = 0.01]. The incidence of carotid artery stenosis in the observation group was significantly higher than that in the control group [23.5% (47/200) vs. 12.0% (12/100), χ2 = 5.58, P = 0.01]. There was no significant difference in the incidence of anterior cerebral artery stenosis between observation and control groups [5.5% (11/200) vs. 4.0% (4/100), χ2 = 0.32, P = 0.57]. The size of carotid artery plaque in the observation group was significantly larger than that in the control group [(1.86 ± 0.42) cm vs. (1.39 ± 0.27) cm, t = 10.18, P < 0.01]. The incidence of intracranial and extracranial artery stenosis in the observation group was significantly higher than that in the control group [41.0% (82/200) vs. 24.0% (24/100), χ2 = 8.43, P < 0.01]. The severity of leukoaraiosis was positively correlated with the degree of intracranial and extracranial artery stenosis ( r = 0.79, P < 0.01). Conclusion:Patients with acute ischemic stroke with leukoaraiosis have a high intracranial and extracranial artery stenosis and the severity of leukoaraiosis is positively correlated with intracranial and extracranial artery stenosis.

Objective:To observe the morphological characteristics of lungs in patients with critical corona virus disease 2019 (COVID-19), and to analyze the clinical-pathological relationship.Methods:Two critical patients with COVID-19 who died in Beijing You′an Hospital, Capital Medical University on February 13 and 14, 2020, respectively, were examined by bilateral lungs biopsy. The obtained samples were dehydrated, paraffin embedded, sectioned, stained with hematoxylin-eosin as routine methods, and then observed under light microscope.Results:The pulmonary morphology changes of patients with COVID-19 showed diffuse alveolar damage. Case one was an elderly patient with underlying diseases and her lesions were mainly exudation and hyaline membrane formation, which showed an acute exudation stage of diffuse alveolar damage. Case two was a patient without underlying diseases and his pathological changes were diffuse inflammatory cell infiltration, extensive fibrosis of alveolar wall, filling of necrotizing inflammatory cellulosic exudate in alveolar airspace, extensive destruction of alveoli and pulmonary consolidation, which was characterized by organized stage of diffuse alveolar damage complicated with bacterial pneumonia. The injury of paracronchial submucosal gland was not observed in the two patients.Conclusions:Diffused alveolar damage is the main pathological feature of critical COVID-19. Diffused alveolar damage can induce or aggravate the underlying diseases of elderly patients in the early stage. Extensive destruction of alveoli, pulmonary consolidation and secondary infection are the main causes of respiratory failure in the late stage.

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

Objective To determine the expression of caspase-14 in skin lesions of patients with chronic actinic dermatitis (CAD),and to explore the effect of ultraviolet B (UVB) radiation on its mRNA and protein expression in HaCaT cells.Methods In 2016,skin samples were collected from lesions of 10 patients with CAD (test group),10 patients with eczema (positive control group) and from normal skin of 10 healthy controls after cosmetic surgery (negative control group) in the Department of Dermatology,First Affiliated Hospital of Kunming Medical University.Immunohistochemical staining was performed to determine the expression of caspase-14 in the normal skin,CAD and eczema lesions.Cultured HaCaT cells were divided into several groups:UVB groups irradiated with 0,30,60,90 mJ/cm2 UVB separately,and 5-AzaC groups irradiated with 0,30,60,90 mJ/cm2 UVB separately followed by the treatment with the methylase inhibitor 5-AzaC for 24 hours.Then,the cells were collected,and real-time fluorescence-based quantitative PCR (RT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of caspase-14 respectively in HaCaT cells in the UVB groups and 5-AzaC groups.Statistical analysis was carried out with SPSS22.0 software by using chi-square test for the comparison of rates,and t test and two-factor analysis of variance for the comparison of means.Results In the CAD and eczema lesions,caspase-14 was mainly expressed in the spinous and granular layers,but not in the stratum comeum.However,caspase-14 was markedly expressed in the stratum corneum of the normal skin tissues.Of the 10 CAD samples,5 were positive for caspase-14,and 9 of 10 normal skin samples were positive for caspase-14.The positive rate of caspase-14 significantly differed between the two above groups (x2 =7.30,P ＜ 0.05).RT-PCR and Western blot analysis showed significant changes in the mRNA and protein expression of caspase-14 in HaCaT cells after irradiation with different doses of UVB (F =87.54,23.46,both P ＜ 0.05),which showed a decreasing trend along with the increase in the dose of UVB.After exposure to 0,30,60 and 90 mJ/cm2 UVB,the mRNA and protein expression of caspase-14 was significantly higher in the 5-AzaC groups than in the UVB groups (all P ＜ 0.05).Conclusions In CAD lesions,the expression of caspase-14 markedly decreased,and was absent in the stratum corneum.UVB radiation can downregulate the mRNA and protein expression of caspase-14 in HaCaT cells.