Objective: To evaluate the effect of hypoxia on migration, invasion and adhesion to endothelial cells of human pulmonary adenocarcinoma A549 cells. Methods: Wound-healing and Transwell invasion assays were performed to study the effect of hypoxia on migration and invasion of A549 cells. Cell adhesion test was used to detect the adhesion of A549 cells to a monolayer of human umbilical vein endothelial cells (HUVECs). Immunofluorescence assay was used to evaluate the effect of hypoxia on distribution of E-cadherin, β-catenin, and F-actin. The luciferase reporter gene assay was performed to detect the transcription of hypoxia-inducible factor-1 (HIF-1) alpha. Results: Hypoxia promotes A549 cell migration, invasion, and adhesion to endothelial cells, and modulated the distribution of E-cadherin and β-catenin and rearrangement of actin cytoskeletal protein, and up-regulated HIF-1-dependent reporter gene expression in A549 cells. Conclusion: Hypoxia promoted A549 cell migration, invasion, and adhesion to endothelial cells by upregulating HIF-1-dependent gene expression, subsequently affecting the redistribution of E-cadherin and β-catenin and rearrangement of F-actin cytoskeletal protein.

Objective: To systematically investigate the prevalence of anxiety among healthcare professionals during the COVID-19 pandemic, so as to provide the development of evidence-based psychological interventions among healthcare professionals. Methods: The publications pertaining to the prevalence of anxiety among healthcare professionals during the COVID-19 pandemic were retrieved in national and international electronic databases from January 1, 2020 through November 30, 2021, including CNKI, Wanfang Data, VIP, SinoMed, PubMed and Web of Science. The quality of publications was evaluated using the United States Healthcare Research and Quality (AHRQ) quality assessment of included cross-sectional studies, and the pooled prevalence of anxiety was estimated among healthcare professionals using the software Open Meta Analyst version 3.0. The publication bias were evaluated with funnel plots and Begg rank correlation test. Results: Totally 598 publications were retrieved, and 36 eligible publications were enrolled in the final analysis, including 33 Chinese publications and 3 English publications. There were 5 high-quality, 29 moderate-quality and 2 low-quality publications. All investigations pertaining to the prevalence of anxiety among healthcare professionals were conducted in 2020. Totally 19 872 healthcare professionals were investigated, and the prevalence of anxiety was 28.8% (95%CI: 24.0%-33.6%). Subgroup analysis showed that the prevalence of anxiety was 31.9% (95%CI: 17.6%-46.2%) among healthcare professionals from western China, 29.6% (95%CI: (17.8%-41.4%) from central China, and 25.3% (95%CI: 20.2%-30.3%) from eastern China. The prevalence of anxiety was 4.9% (95%CI: 3.3%-6.4%) among male healthcare professionals and 22.9% (95%CI: 17.7%-28.0%) among male healthcare professionals, and the prevalence of anxiety was 21.6% (95%CI: 13.2%-29.9%) among nurses, 5.2% (95%CI: 2.8%-7.5%) among doctors and 4.8% (95%CI: 2.2%-7.4%) among other healthcare professionals. The prevalence of mild, moderate and severe anxiety was 18.6% (95%CI: 14.0%-23.2%), 5.5% (95%CI: 4.1%-6.8%) and 1.9% (95%CI: 1.3%-2.5%), respectively. No publication bias was detected as revealed by funnel plots and Begg rank correlation test, and stable meta-analysis results and heterogeneity test were observed. Conclusions The prevalence of anxiety is 28.8% among healthcare professionals during the COVID-19 pandemic, and mild anxiety is predominant. A high prevalence rate of anxiety is seen female healthcare professionals and nurses, who should be given a high priority and timely psychological interventions

Sixteen compounds were isolated from the ethanol extract of Illigera rhodantha by silica gel, ODS, and Sephadex LH-20 column chromatographies. These compounds were identified as (2R,3R)-2,3-dihydroxy-2-methylbutane-1,4-diyldibenzoate (1), p-hydroxyphenethyl trans-ferulate (2), 4-O-benzoyl-2-C-methyl-D-erythritol (3), N-trans feruloyl-3-methyldopamine (4), tribulusamide A (5), cryptomeridiol (6), teuclatriol (7), oleanolic acid (8), icario A₂ (9), vanillic acid (10), p-hydroxybenzoic acid (11), gallic acid (12), ethyl gallate (13), chrysophanol (14), D-1-O-methyl-inositol (15), and hexadecanoic acid (16) based on their spectral data and physico-chemical properties. Compound 1 is an undescribed compound, of which its absolute configurations were determined by Mosher and ROESY methods; all the compounds except 10, 11 and 14 were isolated from Illigera genus for the first time. Compared with the positive control indomethacin, compounds 4-6, 8 and 9 inhibited significantly against the NO production in LPS-induced RAW 264.7 cells.

Aim To investigate the effect that catalpol intervenes macrophage polarization mediated by mouse mesangial cells(MMCs) stimulated by advanced glycation end products(AGEs).Methods RAW264.7 macrophages and MMCs were co-cultured in vitro and divided into model group(100 mg·L-1 AGEs), control group(100 mg·L-1 BSA), catalpol(0.1, 1.0, 10.0 μmol·L-1) group, and aminoguanidine(1.0 μmol·L-1) group which was set as positive control.After being incubated with catalpol for 1 h, MMCs were stimulated by AGEs for 23 h.The proliferation-inhibition rate of MMCs was measured by MTT assay.MCP-1 in supernatant liquid of MMCs was detected by ELISA method.The expression of iNOS, CD16/32, TNF-α, COX-2, CD206 and Arg-1 was detected by Western blot.Simultaneously, the percentage of iNOS and CD206 was also measured by flow cytometry.Results AGEs could increase the level of MCP-1 secreted by MMCs.The expression of iNOS, TNF-α, CD16/32 and COX-2 protein of macrophage was up-regulated after MMCs stimulated by AGEs, while the expression of CD206 and Arg-1 was down-regulated.After being intervened by catalpol, these effects could be reversed.All the changes were concentration-related.Conclusions Catalpol can inhibit macrophages M1-type polarization process and promote M2-type polarization, which may be mediated through MCP-1 secreted by MMCs after AGEs stimulation.Catalpol can ameliorate inflammation and relieve diabetic kidney injury.

OBJECTIVEThe aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA (dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics.

DATA SOURCESThe data used in this review were obtained from the current RNAi-related research reports.

STUDY SELECTIONdsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system.

DATA EXTRACTIONThe currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included.

DATA SYNTHESISSince the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality.

CONCLUSIONSIt is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.

Animals ; Antigens, Neoplasm ; Gene Silencing ; Genes, abl ; Genetic Therapy ; Humans ; Neoplasm Proteins ; genetics ; RNA Interference

OBJECTIVETo study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibroblast-like synoviocytes (FLS).

METHODSThe rat model of collagen-induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 micromol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50, 100, and 200 pmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected.

RESULTSGen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10+/-0.04, significantly lower than that in the model group (2.12+/-0.03, P<0.01). Besides, after Gen's action on FLS, the expression of p-ERK was down-regulated. It was only 0.34+/-0.02 in the high dose Gen group, significantly lower than that in the model group (2.68+/-0.14, P<0.01). There was no change in the expression of ERK (P>0.05).

CONCLUSIONSGen could inhibit the proliferation of FLS in CIA rats. Its mechanism of action was mainly correlated to down-regulating the tyrosine kinase of MAPK signal transduction pathway and inhibiting phosphorylation of ERK.

Animals ; Arthritis, Experimental ; metabolism ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Female ; Genistein ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; cytology ; drug effects ; metabolism

Objective To investigate the effect of recombinant adenovirus mediatied human endostatin (rAD-GFP-ES)on rats with collagen typeⅡinduced arthritis(CIA),and explore the mechanism of inflamma- tion and cytokines inhibition on rats CIA.Methods The rAD-GFP-ES was amplified and purified.The model of rat CIA was induced by intradermal injection of typeⅡcollagen combined with complete Freund's adjuvant(CFA). On the second day after the injection,the therapeutic administration of rAD-GFP-ES(1?10~(11)pfu?kg~(-1)?week~(-1)?4 weeks)were performed to the rats.The mean arthritis index(AI)was scored every week since then.The relative concentrations of ES,IL-I?,TNF-?in sera collected at the fourth week were evaluated by western blotting. Results①The titer of the purified rAD-GFP-ES and rAD-GFP was 6.6?10~(12)pfu/ml and 4.8?10~(12)pfu/ml,re- spectively(A_(260nm)/A_(280nm)＞1.3).②The concentration of ES in sera of the group treated with rAD-GFP-ES was 2.4-lold higher compared to the normal group.③The mean arthritis index of the group treated with rAD-GFP- ES was much lower than that of the model group.The administration of rAD-GFP-ES could significantly de- creas the production of IL-1?and TNF-?in sera.Conclusions①The rAD-GFP-ES is efficiently expressed in vivo.②The rAD-GFP-ES has an inhibitory effect on the arthritis index of rat CIA.③IL-1?and TNF-?are involved in the pathogenesis of RA.The rAD-GFP-ES has an inhibitory effect on the expression of IL-1?and TNF-?in rat CIA.

Objective To evaluate the olfactory function and its influence factors by using Sniffin ’ Sticks test, and to compare the quality of Parkinson ’s disease (PD) recognition between Sniffin’ Sticks and 16 kinds of odor identification in Sniffin ’ Sticks(SS-16) tests.Methods The Sniffin’Sticks test was used to assess the olfactory function of 68 PD patients and 76 healthy volunteers , and the relationship between smell and age, disease duration, Unified Parkinson’ s Disease Rating Scale score, Hoehn-Yahr (H-Y) rating, and cognitive function level (Montreal Cognitive Assessment) was analyzed.Results (1)The prevalence of olfactory dysfunction in PD group (83.3%) was significantly higher than that in control group (21.2%).The Sniffin’ Sticks test showed that the odor threshold score (6.6 ±3.2, P=0.000), odor discrimination score (6.6 ±3.3, P=0.000), 16 kinds of odor identification score (6.8 ±2.4, P=0.000) in PD group were significantly lower than those in control group.( 2 ) When comparing the PD cases and healthy controls in recognition , the sensitivity and the specificity of the Sniffin ’ Sticks test were 0.897 and 0.737, respectively, similar to the SS-16 test.However, the Sniffin’ Sticks test showed advantage compared with odor threshold and odor discrimination.( 3 ) The olfactory score in PD group was positively correlated with cognitive function (r=0.243, P=0.046), and was unrelated with age, gender, disease duration, and disease severity.The olfactory score in control group was negatively correlated with age (r=-0.270, P=0.018), but positively correlated with cognitive function (r=0.281, P=0.014).Conclusions There is a higher incidence of olfactory dysfunction in PD patients than in control group.Sniffin’ Sticks test is superior to SS-16 test in quantitative and qualitative analysis of olfactory function in PD patients.Two tests both have high sensitivity and specificity in the recognition of PD .

Objective To investigate the diagnostic correlation and sensitivity of amplitude integrated electroencephalogram (aEEG),brainstem auditory evoked potential (BAEP) and cranial magnetic resonance imaging (MRI) for acute bilirubin encephalopathy (ABE) in the newborn.Method Term and near-term neonates (gestational age ≥ 35 weeks) with hyperbilirubinemia (the level of bilirubin over than 95th percentile) of high and intermediate risk group admitted in the neonatal ward of Guangxi Maternal and Child Health Care Hospital from Jan 2014 to Dec 2015 were recruited retrospectively.The infants were assigned to ABE group and non-ABE group according to the diagnostic criteria of ABE.The clinical data of the newborns were collected and the diagnostic correlation between clinical diagnosis and aEEG,BAEP and cranial MRI were analyzed.The receiver operating characteristic (ROC) curve was adopted to assess the diagnostic efficiency of the peak level of serum bilirubin,aEEG,BAEP and cranial MRI on the early diagnosis of ABE.Result A total of 152 newborns with hyperbilirubinemia were recruited,including 33 cases in the ABE group and 119 cases in non-ABE group.(1) The results of aEEG and MRI were marginally positively correlated with clinical diagnosis of ABE (aEEG:r =0.487,P ＜ 0.001;MRI:r =0.220,P=0.018),while the results of BAEP were closely related to the clinical diagnosis of ABE (r =0.593,P ＜ 0.001);(2) The results of BAEP and MRI on the diagnosis of ABE were positively correlated with those of aEEG (BAEP:r =0.424,P ＜ 0.001;MRI:r =0.307,P ＜ 0.001).(3) The area under the ROC curves for predicting the onset of ABE were 0.899 for the peak level of serum bilirubin,0.767 for BAEP,0.738 for aEEG and 0.590 for MRI.Conclusion There was the correlation on the diagnosis of ABE among the methods of aEEG,BAEP and MRI.The combined diagnosis of the three methods could play a complementary role.The aEEG contributed to the early diagnosis of ABE with high sensitivity.

BACKGROUNDTissue inhibitor of metalloproteinase (TIMP)-1 is a multifunctional protein. The aim of the study was to examine the feasibility of using a combination of adenovirus-mediated gene delivery of TIMP-1 plus endostatin and cell transplantation techniques to treat tumor growth and metastasis in mouse melanoma.

METHODSA enzyme-linked immunosorbent assay (ELISA) was used to detect the level of TIMP-1 and endostatin in vitro and in vivo. A tumor bearing mouse model and an experimental lung metastasis model in animal experiments were used to explore the therapeutic effect of in vivo production of human TIMP-1 and endostatin after the implantation of primary fibroblasts infected with the indicated adenovirus into tumor-bearing mice and a cytochemical method was used to observe histopathological changes of the tumor. An experimental lung metastasis model was established by injecting B16BL6 cells into the tail vein of mice and adenovirus-infected primary fibroblasts were subcutaneously implanted into the mice 24 hours later. Twenty-one days after tumor cell injection, mice were sacrificed to examine the effect on nodules visible as black forms on the surface of the lungs in B16BL6 cells.

RESULTSTIMP-1 and endostatin were secreted into the supernatants of cultures of Ad-TIMP-1 and Ad-End-infected mouse primary fibroblasts. We also observed that implantation of fibroblasts infected with Ad-TIMP-1 alone, Ad-End alone, or Ad-TIMP-1 plus Ad-End resulted in detectable blood levels which may clearly inhibit the tumor growth and metastasis in a murine melanoma model.

CONCLUSIONThese results suggest the high capacity of transfection for the delivery of TIMP-1 or endostatin gene constructs into primary fibroblasts, and demonstrate that the implantation of TIMP-1 and endostatin producing fibroblasts at a site in vivo where direct secretion of TIMP-1 and endostatin into the blood is possible represented a promising approach for the development of cancer therapy.

Adenoviridae ; genetics ; Animals ; Cell Line ; Cell Line, Tumor ; Endostatins ; blood ; genetics ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; cytology ; metabolism ; Humans ; Melanoma ; therapy ; Mice ; Mice, Inbred C57BL ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; genetics ; metabolism