Analysis of disulfidptosis- and cuproptosis-related LncRNAs in modulating the immune microenvironment and chemosensitivity in colon adenocarcinoma.

The main objective was to establish a prognostic model utilising long non-coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA-Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan-Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis-related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors' model, the high-risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.

High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression.

Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.

Reeducation of medical research ethics based on medical staff's cognition and practice of medical research ethics / 中华医学科研管理杂志

Objective:To investigate and analyze the cognition of medical staff on medical research ethics in a grade A tertiary hospital, combined with the current situation of practice, to provide a basis and ideas for exploring new educational models of medical research ethics.Methods:Medical staff in a grade A tertiary hospital were investigated through an anonymous questionnaire to collect and analyze their cognition of medical research ethics and the current situation of practice.Results:There were statistically significant differences ( P<0.05) in the cognition of medical research ethics among different educational backgrounds, majors, and professional titles. The survey results showed that doctors, medical staff with graduate degrees or above, and senior title personnel had better cognition of medical research ethics than nurses, medical staff with bachelor degrees or below, and intermediate or junior title personnel. Conclusions:The medical staff's cognition and practice of medical research ethics are still insufficient. Hospitals should pay attention to the education of medical research ethics and enrich the content and form of training to improve the ethical literacy of medical personnel.

MG53 is a double-edged sword for human diseases / 生理学报

Mitsugumin 53 (MG53), also named Trim72, is a multi-functional TRIM-family protein, which is abundantly expressed in cardiac and skeletal muscle. It has been shown that MG53 not only plays important physiological roles but also acts as a crucial pathogenic factor of various diseases. First, MG53 preserves cardiac and skeletal muscle integrity via facilitating plasma membrane repair. Second, MG53 is essentially involved in cardiac ischemic preconditioning and postconditioning by activating PI3K-Akt-GSK3β and ERK1/2 cell survival signaling pathways. Moreover, systemic delivery of recombinant MG53 is able to abolish mechanic or ischemia-reperfusion (I/R)-induced injury of multiple organs, including heart, skeletal muscle, lung, kidney and skin. Importantly, MG53 acts as an E3 ligase to mediate the degradation of insulin receptor and insulin receptor substrate-1, and subsequently induces insulin resistance and metabolic diseases such as type-2 diabetes and its cardiovascular complications. In addition, MG53 negatively regulates myogenesis. As a potential therapeutic target of human diseases, multiple facets of MG53 biological function and mechanisms of action should be taken into the consideration to maximize its beneficial effects and minimize potential side-effects. Here in this review, we intend to comprehensively summarize the current progresses on the biological functions of MG53, focusing on its clinical value as a therapeutic target.

Diagnostic Value of (18)F-FDG-PET/CT for Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the diagnostic value of (18)F-FDG-PET/CT in multiple myeloma (MM).</p><p><b>METHODS</b>A total of 66 patients, who were highly suspected of MM in our hospital from July 2012 to December 2014, were chosen as study objects. All patients were diagnosed or excluded by pathological examination. All patients were detected by (18)F-FDG-PET/CT, and its diagnostic value was analyzed. The number of focuses were counted.</p><p><b>RESULTS</b>Out of 66 patients 59 patients (89.39%) were diagnosed with multiple myeloma. The sensitivity of PET was 98.31%, the specificity of PET was 85.71%, the Youden index was 0.8402; the sensitivity of CT was 96.61%, the specificity of CT was 85.71%, the Youden index was 0.8232; the sensitivity of PET/CT was 100.00%, the specificity of PET/CT was 83.33%, the Youden index was 0.8333. In 59 MM patients, 635 focuses were detected, out of them 572 focuses (90.08%) were detected by CT, 593 focuses (93.39%) were detected by PET, 530 focuses (83.46%) were coincided on PET/CT.</p><p><b>CONCLUSION</b>(18)F-FDG-PET/CT has diagnostic value for multiple myeloma, and it can be used in locating and counting focuses, as well as in evaluating the treatment efficacy and guiding the clinical work.</p>

Transcription-replication collision increases recombination efficiency between plasmids.

It has been proposed that the stalling of the replication forks can induce homologous recombination in several organisms, and that arrested replication forks may offer nuclease targets, thereby providing a substrate for proteins involved in double-strand repair. In this article, we constructed a plasmid with the potential for transcription-replication collision (TRC), in which DNA replication and RNA transcription occur on the same DNA template simultaneously. Theoretically, transcription will impede DNA replication and increase homologous recombination. To validate this hypothesis, another plasmid was constructed that contained a homologous sequence with the exception of some mutated sites. Co-transfection of these two plasmids into 293T cells resulted in increased recombination frequency. The ratio of these two plasmids also affected the recombination frequency. Moreover, we found high expression levels of RAD51, which indicated that the increase in the recombination rate was probably via the homologous recombination pathway. These results indicate that mutant genes in plasmids can be repaired by TRC-induced recombination.

Mechanisms of icariin in regulating bone formation of osteoblasts and bone resorption of osteoclasts / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanisms of icariin (ICA) in regulating the bone formation of osteoblasts and the bone resorption of osteoclasts.</p><p><b>METHODS</b>Primary osteoblast cell cultures were obtained from newborn rat calvarial. Calcified nodules were stained by alizarin red. The mRNA levels of osterix (OSX), runt-related transcription factor 2 (Runx-2), alkaline phosphatase (ALP), Collagen1, osteoprotegerin (OPG), and receptor activator of nuclear factor-ΚB ligand (RANKL) were analyzed by quantitative real-time RT-PCR, the protein levels of OPG, RANKL, and Collagen1 were examined by Western blotting, and the intracellular Ca(2+) concentration of osteoblasts was measured on a flow cytometer using the Cellquest program.</p><p><b>RESULTS</b>Compared with control group, ICA markedly promoted bone formation by significant up-regulating the gene expressions of OSX, Runx-2,ALP, and Collagen1, the protein expression of Collagen1(all P<0.01), and the Ca(2+) concentration. Furthermore, ICA remarkably inhibited bone resorption by significant up-regulating the mRNA and protein expressions of OPG as well as the OPG/RANKL ratio.</p><p><b>CONCLUSIONS</b>ICA could promote bone formation of osteoblasts through inducting the gene expressions of OSX,Runx-2, ALP and Collagen1, and the protein expressions of Collagen1, and by increasing the Ca (2+) concentration. Moreover, ICA could inhibit bone resorption of osteoclasts through regulating OPG/RANKL signal pathway.</p>

Emergence of novel variants of gyrA, parC, qnrS genes in multi-drug resistant Klebsiella caused pneumonia / 中华流行病学杂志

Objective To investigate the resistant mechanism of quinolones on multi-drug resistant Klebsiella caused pneumonia(MDR-KPN).Methods From August 2008 to May 2010,47 strains of MDR-KPN were collected from 6 hospitals in Hangzhou and Huzhou in Zhejiang province in China.Drug target genes to quinolones (gyrA,parC) and quinolone-resistance genes mediated by mobile genetic elements [qnrA,qnrB,qnrS,aac (6')-Ⅰ b-cr,qepA] were analyzed by PCR and verified by DNA sequencing.Results Positive results were found in 47 strains of MDR-KPN,43 strains (91.5％) of gyrA mutation,40 strains(85.1％) ofparC mutation,3 strains (6.4％) of qnrB2,1 strain (2.1％) ofqnrB 4,8 strains (17.0％) ofqnrS 1,5 strains (10.6％) of qnrS 4,2 strains (4.3％)of aac (6')-Ⅰ b-cr respectively.Moreover,5 novel variants of gyrA (GenBank accession number:JN811952,JN811953,JN811954,JN811955,JN811956),5 novel variants of parC (GenBank accession number:JN817432,JN817433,JN817434,JN817435,JN817436)were also identified.In addition,qnrS4 (GenBank accession number:JN836269) appeared to be the novel variants of qnrS.Conclusion Quinolone-resistance-determining region played a key role on the resistance to quinolones in this group of MDR-KPN,and quinolone-resistance genes mediated by mobile genetic elements [qnrB2,qnrB4,qnrS1,qnrS4,aac (6')-Ⅰ b-cr] showed positive in some parts of the strains.This was the first report on emergence of qnrS4 in the world.

Comparative study on effect of 8-prenlynaringenin and narigenin on activity of osteoclasts cultured in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the effects of 8-prenylnaringenin (PNG) and naringenin (NG) on the activity and apoptosis of osteoclasts cultured in vitro, in order to study physiological activity of 8-prenyl perssad.</p><p><b>METHOD</b>Osteoclasts were separated from long-limb bones of newly born rabbits, cultured in alpha-MEM containing 10% FBS, and then added with PNG and NG with the concentration of 1 x 10(-5) mol x L(-1). They were stained with TRAP and determined for enzymatic activity with TRAP after 4 d, and analyzed by toluidine blue staining after 7 d. The apoptotic osteoclasts were analyzed by Annexin V-FITC staining after 2, 4, 8, 12, 24, 36, and 48 hours, to observe their apoptosis. Their total RNAs were extracted, and analyzed for TRAP and Cathepsin K expressions by Real-time RT-PCR.</p><p><b>RESULT</b>Compared with the control group, both of the PNG group and the NG group showed much less osteoclasts (TRAP positive cells), lower TRAP activity and TRAP and Cathepin K (CTSK) expression, and smaller number of bone resorption pits and areas. The PNG group show lower indexes than the NG group. Additionally, the PNG group reached the apoptotic peak of osteoclasts at 12 h after drug administration, whereas the NG group reached after 24 h. And the former had more apoptotic cells than the latter.</p><p><b>CONCLUSION</b>8-PNG is much more active than NG in inhibiting the resorption of osteoclasts and inducing apoptosis of osteoclasts. Their only difference lies in 8-prenyl perssad, which is proved to be able to enhance the anti-bone resorption activity of 8-prenylnarigenin.</p>

Study on content of two sesquiterpenes in Alpinia oxyphylla / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for determining oxyphyllenodiol A (1) and teuhetenone A (2) contained in Alpinia oxyphylla and to compare the contents of the two components contained in medicinal materials and prepared herbal medicines in pieces sold in the market and different fractions.</p><p><b>METHOD</b>HPLC and Waters sunfire C18 column (4. 6 mm x 250 mm, 5 microm) were adopted for gradient elute with the mobile phase of acetonitrile and water. The flow rate was 1.0 mL x min(-1) and the detection wavelength was 250 nm.</p><p><b>RESULT</b>1 and 2 showed a good linear relationship within the range of 0.1296 - 0.8640 microg and 0.1635 - 1.0900 microg respectively, with the average recoveries of 99.08% and 97.80%. Their content ranges were 0.0059% - 0.0149% and 0.0080% - 0.0164% in different samples. The mean value of 1 and 2 were 0.0085% and 0.0104% in the whole fruits, and 0.0137% and 0.0157% in the seeds. They were undetected in the nutshells.</p><p><b>CONCLUSION</b>The method is so precise, accurate and highly reproducible that it can be used to determine the contents of oxyphyllenodiol A and teuhetenone A in A. oxyphylla. The contents of the two components are mainly extracted from the seeds, with certain difference among different samples. There are a higher contents and no significant difference in the salted and raw seeds.</p>

NF-E2: a novel regulator of alpha-hemoglobin stabilizing protein gene expression.

OBJECTIVE: To investigate whether α-hemoglobin stabilizing protein (AHSP), the α-globin-specific molecular chaperone, is regulated by erythroid transcription factor NF-E2. METHODS: We established the stable cell line with NF-E2p45 (the larger subunit of NF-E2) short hairpin RNA to silence its expression. Western blot, real-time polymerase chain reaction, and chromatin immunoprecipitation (ChIP) analysis were performed to detect the expression of AHSP, the histone modifications at AHSP gene locus, and the binding of GATA-1 at the AHSP promoter with NF-E2p45 deficiency. ChIP was also carried out in dimethyl sulfoxide (DMSO)-induced DS19 cells and estrogen-induced G1E-ER4 cells to examine NF-E2 binding to the AHSP gene locus and its changes during cell erythroid differentiation. Finally, luciferase assay was applied in HeLa cells transfected with AHSP promoter fragments to examine AHSP promoter activity in the presence of exogenous NF-E2p45. RESULTS: We found that AHSP expression was highly dependent on NF-E2p45. NF-E2 bound to the regions across AHSP gene locus in vivo, and the transcription of AHSP was transactivated by exogenous NF-E2p45. In addition, we observed the decrease of H3K4 trimethylation and GATA-1 occupancy at the AHSP gene locus in NF-E2p45-deficient cells. Restoration of GATA-1 in G1E-ER4 cells in turn led to increased DNA binding of NF-E2p45. CONCLUSION: NF-E2 may play an important role in AHSP gene regulation, providing new insights into the molecular mechanisms underlying the erythroid-specific expression of AHSP as well as new possibilities for ß-thalassemia treatment.

Epigenetic repression of SATB1 by polycomb group protein EZH2 in epithelial cells.

OBJECTIVE: To study the regulatory mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1. METHODS: HeLa epithelial cells were treated with either histone deacetylase inhibitor (HDACi) trichostatin A (TSA) or DNA methylation inhibitor 5-Aza-C before detecting SATB1 expression. Luciferase reporter system was applied to measure effects of EZH2 on SATB1 promoter activity. Over-expression or knockdown of EZH2 and subsequent quantitative reverse transcription-polymerase chain reaction were performed to determine the effect of this Polycomb group protein on SATB1 transcription. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of EZH2 and trimethylated H3K27 (H3K27me3) at SATB1 promoter in HeLa cells. K562 cells and Jurkat cells, both having high-level expression of SATB1, were used in the ChIP experiment as controls. RESULTS: Both TSA and 5-Aza-C increased SATB1 expression in HeLa cells. Over-expression of EZH2 reduced promoter activity as well as the mRNA level of SATB1, while knockdown of EZH2 apparently enhanced SATB1 expression in HeLa cells but not in K562 cells and Jurkat cells. ChIP assay Results suggested that epigenetic silencing of SATB1 by EZH2 in HeLa cells was mediated by trimethylation modification of H3K27. In contrast, enrichment of EZH2 and H3K27me3 was not detected within proximal promoter region of SATB1 in either K562 or Jurkat cells. CONCLUSION: SATB1 is a bona fide EZH2 target gene in HeLa cells and the repression of SATB1 by EZH2 may be mediated by trimethylation modification on H3K27.

Susceptibility of Candida albicans to Fluconazole by Rapid Flow Cytometry / 中华医院感染学杂志

0.05) and the two methods had good correlation(r=0.822).CONCLUSIONS The method of FCST established by as in this study is simple,repeatable,with high accuracy and easy to determine MIC and has good application prospects in clinical antifungal susceptibility testing.

Isolation and Resistance of Acinetobacter calcoaceticus-baumannii in Hospital: A 7-Year Surveillance Study / 中华医院感染学杂志

OBJECTIVE To study the isolation and resistance tendency of Acinetobacter calcoaceticus-baumannii to antimicrobial agents from 1998 to 2004 to provide valuable data for infection prevention and therapy. METHODS We reviewed the isolation rates,distribution in clinical specimens and wards,and the resistance rates of(A.calcoaceticus-baumannii)to 14 kinds of antimicrobial agents from 1998 to 2004. RESULTS There was an increasing tendency of isolation rates of A.calcoaceticus-baumannii every year,which was 0.18% in 1998 but 1.48% in 2004.In the seven years,there was the highest isolation rate of 70.58% in specimens from respiratory tract,the next was from the urine(9.42%),and blood(4.63%).Concerning the wards distribution,ICU had the highest rate of 47.28%.In 1998,A.calcoaceticus-baumannii had resistance rates more than 50% only to one kind of antimicrobial agents(aztreonam),but in 2004,it had increased to thirteen kinds(except cefoperazone/sulbactam).About the fourteen kinds of antimicrobial agents we inspected,that were increased in their resistance rate.The highest increasing of resistance rate was ceftazidime from 11.1% in 1998 to 88.9% in 2004,the imipenem was second for 0.0% to 64.8%,and the third was sulfamethoxazole/trimethoprim form 0.0% to 64.0%,while there still was an increasing resistance tendency to them. CONCLUSIONS The clinical isolation rate of A.calcoaceticus-baumannii is increasing,and it has higher resistance rates to many antimicrobial agents as well as an increasing resistance tendency to relatively susceptive antimicrobial agents every year.So physicians should prescribe on the basis of antimicrobial agents susceptibility tests in vitro.

Effects of pamidronate on proliferation and differentiation of osteoblasts of rat / 中国康复理论与实践

@#ObjectiveTo investigate effects of pamidronate on the proliferation and differentiation of osteoblasts of rats in vitro.MethodsOsteoblasts isolated from newborn rat calvaria were treated with various concentrations of pamidronate, the proliferation of osteoblasts was evaluated with the method of methyl thiazole tetrazolium (MTT) and activity of alkaline phosphatase (ALP) in medium was measured with kit of ALP detecting.ResultsThe proliferation of osteoblasts increased under the stimulation of Pamidronate range 10-6-M-10-12 M(P<0.05), but was inhibited at the concentration of high level (10-4 M). The activity of ALP decreased in the experiment.ConclusionPamidronate can act on the osteoblasts directly and increase the proliferation of bone cells, but inhibit the differentiation of the same cells.