BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

OBJECTIVE To explore the mechanism of action of epigallocatechin-3-gallate(EGCG) in inhibiting laryngeal cancer cells. METHODS The expression of epidermal growth factor receptor(EGFR) in laryngeal cancer cell lines AMC-HN-8, TU686 and TU212 was detected by Western blotting, and the inhibitory effects of cetuximab and EGCG on three laryngeal cancer cells were detected by CCK-8 assay. A lentiviral vector containing EGFR promoter and Luc reporter gene was constructed to generate a TU686-EGFR-Luc cell line that could steadily express Luc activity. Luciferase assay was performed to evaluate the effect of EGCG on the transcription activity of EGFR promoter. Cell cycle and apoptosis of EGCG-treated laryngeal carcinoma cells were analyzed by flow cytometry, and changes of the levels of EGFR and downstream ERK1/2, cell cycle-associated proteins P53 and P27, apoptosis-associated proteins BCL2 and PART, and autophagy marker LC3A/B were further examined. RESULTS The laryngeal carcinoma cell lines were insensitive to cetuximab but could be effectively suppressed by EGCG. EGCG effectively inhibited the transcription activity of EGFR promoter. Treatment of TU686 cells at sub-IC50 dose EGCG resulted in significant cell cycle arrest at S phase with partial apoptosis. Significant inhibition of expression and activation of EGFR and downstream signaling pathway were observed. CONCLUSION EGCG can effectively downregulate EGFR and suppress laryngeal carcinoma cells, further investigation on in vivo effect and mechanisms are anticipated.

Objective To investigate whether fenoldopam(FNDP)(an agonist of type 1 dopamine receptor)has a protective effect on thoracic aortic aneurysm(TAA)in mice.Methods Three-week-old male C57BL/6J mice were treated with β-aminopropionitrile(BAPN)to induce TAA.The mice were divided into three groups:the con-trol group,the BAPN group,and the BAPN+FNDP group(FNDP injected intraperitoneally).The incidence and survival rate of TAA were recorded.Gross anatomy of the whole aortae was observed.Elastin staining was per-formed to assess morphological change,while immunohistochemistry was employed to evaluate the expressions of matrix metalloproteinase 2(MMP2),matrix metalloproteinase 9(MMP9)and cluster of differentiation 68(CD68)respectively.Gelatin zymography was conducted to assess MMP2 and MMP9 activity.Reverse transcription-poly-merase chain reaction(RT-PCR)was performed to measure the mRNA expression levels of dopamine receptor D1(D1DR),dopamine receptor d2(D2DR),dopamine receptor d3(D3DR),dopamine receptor d5(D5DR),in-terleukin-1β(IL-1β),interleukin-6(IL-6),tumour necrosis factor-α(TNF-α),monocyte chemoattractant pro-tein-1(MCP-1),alpha-smooth muscle actin(α-SMA)and smooth muscle protein 22-alpha(SM22α).Results Compared to the control group,the BAPN group exhibited significant formation of TAA.Elastic fiber disruption was also observed in the thoracic aortic wall,along with a significant decrease in the mRNA levels of D1DR and D5DR.The BAPN+FNDP group showed a significant reduction in the incidence of TAA formation and the rate of aneu-rysm rupture compared to the BAPN group.The disruption and rupture of elastic fibers in the thoracic aortic wall were significantly improved in the BAPN+FNDP group.The levels of MMP2 and MMP9 in the thoracic aortic wall significantly decreased,and the enzymatic activity of MMP2 in the serum was significantly reduced.Moreover,macrophage infiltration in the thoracic aortic wall was significantly reduced and the mRNA levels of IL-1β,IL-6,TNF-α and MCP-1 also significantly decreased after FNDP treatment.There was no statistically significant differ-ence in the mRNA levels of α-SMA and SM22α.Conclusion FNDP shows an inhibitory effect on TAA progres-sion in mice,suggesting a potential of FNDP as a therapeutic agent for TAA.

Objective To analyze the current status of cognition and satisfaction of medical staff in public hospitals in Hangzhou towards medical prevention integration,in order to provide reference and reference for promoting the development of medical prevention integration.Methods A questionnaire survey was conducted on 421 medical staff from three public hospitals in Hangzhou using stratified random sampling.Results Only 29.5%of medical staff expressed a strong or relatively good under-standing of medical prevention integration work;The overall satisfaction score of medical staff with medical prevention integration is(3.54±0.74).The results of logistic regression analysis show that age,professional title,education level,and monthly in-come are important factors affecting the satisfaction of medical staff with medical prevention integration(P＜0.05).Conclusion The awareness and satisfaction of medical staff in public hospitals in Hangzhou regarding the integration of medical and preven-tive measures need to be strengthened.It is recommended to improve basic construction,optimize health policies,promote infor-mation integration,and strengthen work cohesion.

With the expanded application of heavy metal cadmium, soil cadmium pollution is more and more serious. In this study, using Salix matsudana as a phytoremediation candidate, we observed changes of gene expression and metabolic pathway after 1, 7 and 30 days under 2.5 mg/L and 50 mg/L cadmium stress. The result of transcriptome sequencing showed that we obtained 102 595 Unigenes; 26 623 and 32 154 differentially expressed genes (DEG) in the same concentration and different stress time; 8 550, 3 444 and 11 428 DEG with different concentrations at the same time; 25 genes closely related to cadmium stress response were screened. The changes of genes expression (such as metallothionein, ABC transporter, zinc and manganese transporter) depended on both concentration of cadmium and exposure time. The expression of several genes was obviously up-regulated after cadmium stress, for example 3,6-deoxyinosinone ketolase (ROT3) in brassinolide synthesis pathway and flavonoid synthase (FLS), flavanone-3-hydroxylase (F3H) in the synthesis pathway of brassinolide. In addition, GO analysis shows that GO entries were mainly enriched in metabolic processes including cellular processes, membranes, membrane fractions, cells, cellular fractions, catalytic activation and binding proteins in response to cadmium stress, whose number would increase along with cadmium concentration and exposure time. The reliability of transcriptome information was verified by qPCR and physiological experimental data. Response mechanisms of S. matsudana after cadmium stress were analyzed by transcriptome sequencing, which provided theoretical guidance for remediation of cadmium pollution in soil by S. matsudana.
Biodegradation, Environmental ; Cadmium ; toxicity ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; drug effects ; Plant Proteins ; genetics ; Reproducibility of Results ; Salix ; drug effects ; genetics ; Stress, Physiological ; genetics ; Transcriptome ; drug effects

Drugs targeting immune checkpoint are used for cancer treatment, but resistance to single drug may occur. Combination therapy blocking multiple checkpoints simultaneously can improve clinical outcome. Therefore, we designed a recombinant protein rPC to block multiple targets, which consists of extracellular domains of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). The coding sequence was inserted into expression vector and stably transfected into HEK293 cells. The culture supernatant was collected and rPC was affinity-purified. Real-time quantitative PCR was used to evaluate the expression levels of ligands for PD-1 and CTLA-4 in several human cancer cell lines. The binding of rPC with cancer cells was examined by immunofluorescence cell staining, the influence of rPC on cancer cell growth was assayed by CCK-8. The results showed that rPC could be expressed and secreted by stably transfected HEK293 cells, the purified rPC could bind to lung cancer NCI-H226 cells which have high levels of ligands for PD-1 and CTLA-4, no direct impact on cancer cell growth could be observed by rPC treatment. The recombinant protein rPC can be functionally assayed further for developing novel immunotherapeutic drugs for cancer.
Animals ; CTLA-4 Antigen ; genetics ; Cell Proliferation ; HEK293 Cells ; Humans ; Lung Neoplasms ; metabolism ; Programmed Cell Death 1 Receptor ; genetics ; Protein Binding ; Protein Domains ; genetics ; Recombinant Fusion Proteins ; genetics ; isolation & purification ; metabolism

Objective ToinvestigatethevalueofpreoperativeMRIforplacentapreviainpredictionofmassivepostpartumhemorrhage. Methods AretrospectiveanalysisoftheclinicalhistoryandprenatalMRIfeaturesof362patientswithplacentapreviawereperformed. Ofthese,54casesexperiencedseverepostpartum hemorrhage.Results Univariateanalysisshowedthattheageofpregnantwomen (χ2＝3.951,P＝0.047),gestationalage(χ2＝6.257,P＝0.012),numberofcesareansections(χ2＝36.372,P＝0.001)andgemellary pregnancy(χ2＝7.933,P＝0.005)wereassociated with massivepostpartum hemorrhage.Amongthe MRIsigns,Uterinebulging (OR,46.712;95%CI,13.067－166.987),placentalprotrusionsign (OR,22.787;95% CI,4.595－113),andintroplacentalT2dark band(OR,14.757;95%CI,7.149－30.461)indicatedhighriskwithmassivepostpartumhemorrhage.Myometrialthinningorlocalized interruption,unevenplacentalsignal,abnormalbloodvesselsbelowtheplacenta,abundantbloodvesselsinloweruterusandcervix, cervicalshorteningandothersignsfortheevaluationofseverepostpartumhemorrhagewerealsostatisticallysignificant.Conclusion MRIcanpredictmostoftheseverepostpartumhemorrhagebeforesurgeryandisveryhelpfultoimprovethepatientprognosis.

With the progress of medical technology, the development of new drugs and the improvement of the therapeutic effect of graft-versus host disease in the last two decades, the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been greatly improved. However, graft failure is still a rare but serious complication of allo-HSCT. HLA incompatibility, virus infection, elderly donor, uncontrolled primary disease, damage of bone marrow hematopoietic microenvironment, ABO blood group incompatibility, T cell depletion, reduced intensity conditioning, and low nucleated cell number are all risk factors for graft failure. In recent years, with the implementation of HLA haplo-identical hematopoietic stem cell transplantation, the role of donor-specific antibodies in graft failure has attracted attention increasingly. This article reviews the recent studies involving the mechanism, risk factors and prevention measures of graft failure in allo-HSCT.
Graft vs Host Disease ; epidemiology ; Hematopoietic Stem Cell Transplantation ; statistics & numerical data ; Humans ; Risk Factors ; Transplantation Conditioning ; Transplantation, Homologous ; standards ; statistics & numerical data

Objective To explore the MRI findings of placental protusion sign in predicting postpartum hemorrhage in patients with placenta previa.Methods Totally 354 placenta previa patients with whole clinical data underwent MR scaning 2 weeks before operation.Association of postpartum hemorrhage and placental protusion sign was analyzed.Results Among 354 patients with placental previa,the age of the pregnant women (x2 =4.34,P=0.04),gestational age at delivery (x2 =5.19,P=0.02) and the number of cesarean sections (x2 =44.85,P＜0.01) had associated with postpartum hemorrhage.Eight cases had placental protusion sign in MRI,while 6 cases occurred postpartum hemorrhage.The incidence of postpartum hemorrhage was 75.00％ (6/8) and 12.72％ (44/346) in patients with placenta accreta and with placental abruption,respectively (x2 =20.14,P＜0.01).The sensitivity,specificity,odds ratio (95％ confidence interval) and positive likelihood ratio of predicting postpartum hemorrhage was 12.00％ (6/50),99.34％ (302/304),20.59 (4.03,105.23) and 15.68,respectively.Conclusion MRI placental protrusion sign has important clinical reference value in predicting postpartum hemorrhage.

OBJECTIVETo assess the predictive value of Neuropad test on occurrence of diabetic foot ulceration (DFU) among type 2 diabetic patients.

METHODSWe divided 725 cases of type 2 diabetic patients into the high-risk and the non-high-risk groups of DFU based on the results of vibration perception thresholds(VPT) examination, which was widely used as a criteria for predicting DFU. Receiver operating characteristic (ROC) analysis was used to compare the effectiveness of Neuropad with 10 g Semmes-Weinstein monofilament (10 g SWMF) testing in predicting the risk of DFU.

RESULTSAmong 725 patients of type 2 diabetes, 6.1% were at a high risk of DFU. Compared to non-high-risk group, patients in high-risk group had older age, longer diabetes duration, higher values of complete colour change time (CCC time) of Neuropad and higher abnormal rate of 10 g SWMF (P<0.01). CCC time of Neuropad was shown to be better in predicting the risk of DFU than 10 g SWMF, and the area under the ROC curve was about 0.8, and the best cut-off value was 22.25 min.

CONCLUSIONNeuropad is an effective means for predicting of the risk of DFU, and can be used to prevent diabetic foot ulceration.

Adult ; Aged ; Diabetic Foot ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Neurologic Examination ; methods ; Predictive Value of Tests ; Risk Assessment