Abordagem de Bioinformática e Biologia de Sistemas para Identificar a Ligação Patogenética entre Insuficiência Cardíaca e Sarcopenia / Bioinformatics and Systems Biology Approach to Identify the Pathogenetic Link between Heart Failure and Sarcopenia

Resumo Fundamento Apesar das evidências crescentes de que pacientes com insuficiência cardíaca (IC) são suscetíveis à sarcopenia, o motivo da associação não é bem compreendido. Objetivo O objetivo deste estudo é explorar ainda mais o mecanismo molecular de ocorrência desta complicação. Métodos Conjuntos de dados de expressão gênica para HF (GSE57345) e Sarcopenia (GSE1428) foram obtidos do banco de dados Gene Expression Omnibus (GEO). Genes diferencialmente expressos (DEGs) foram identificados usando pacotes 'edgeR' e "limma" de R, e suas funções foram analisadas usando Gene Ontology (GO) e a Enciclopédia de Genes e Genomas de Kyoto (KEGG). Redes de interação proteína-proteína (PPI) foram construídas e visualizadas usando Search Tool for the Retrieval of Interacting Genes (STRING) e Cytoscape. Os genes hub foram selecionados usando o plugin cytoHubba e validados com GSE76701 para IC e GSE136344 para Sarcopenia. As vias relacionadas e os mecanismos moleculares dos genes hub foram realizados pela análise de enriquecimento de genes (GSEA). As análises estatísticas foram realizadas no software R. P < 0,05 foi considerado estatisticamente significativo. Resultados Foram encontrados 114 DEGs comuns. As vias relacionadas ao fator de crescimento, secreção de insulina e cGMP-PKG estavam enriquecidas tanto na IC quanto na sarcopenia. Descobriu-se que CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT e VCAM1 são genes hub significativos após validação com GSEA enfatizando a importância dos genes hub na regulação da resposta inflamatória. Conclusão Nosso estudo revela que a IC e a Sarcopenia compartilham vias e mecanismos patogênicos comuns. Estes achados podem sugerir novas direções para pesquisas futuras sobre a patogênese subjacente.

Abstract Background Despite increasing evidence that patients with heart failure (HF) are susceptible to sarcopenia, the reason for the association is not well understood. Objective The purpose of this study is to explore further the molecular mechanism of the occurrence of this complication. Methods Gene expression datasets for HF (GSE57345) and Sarcopenia (GSE1428) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using 'edgeR' and "limma" packages of R, and their functions were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks were constructed and visualized using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Hub genes were selected using the plugin cytoHubba and validation with GSE76701 for HF and GSE136344 for Sarcopenia. The related pathways and molecular mechanisms of the hub genes were performed by Gene set enrichment analysis (GSEA). The statistical analyses were performed using R software. P < 0.05 was considered statistically significant. Results A total of 114 common DEGs were found. Pathways related to growth factor, Insulin secretion and cGMP-PKG were enriched in both HF and Sarcopenia. CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT, and VCAM1 were found to be significant hub genes after validation, with GSEA emphasizing the importance of the hub genes in the regulation of the inflammatory response. Conclusion Our study reveals that HF and Sarcopenia share common pathways and pathogenic mechanisms. These findings may suggest new directions for future research into the underlying pathogenesis.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.

Circulating miRNA-1-3p as Biomarker of Accelerated Sarcopenia in Patients Diagnosed with Chronic Heart Failure

ABSTRACT Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusion: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia.

Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.

Clinical Efficacy of Tongxie Yaofang on Diarrhea-predominant Irritable Bowel Syndrome （IBS-D） Patients with Liver Depression and Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and mechanism of Tongxie Yaofang in treating diarrhea-predominant irritable bowel syndrome（IBS-D） patients with liver depression and spleen deficiency. MethodA total of 168 IBS-D patients with liver depression and spleen deficiency who were treated from August 2017 to June 2021 were divided into observation group and control group by random number table，84 in each group. The observation group was administrated with Tongxie Yaofang decoction-free granules orally，and the control group received oral treatment of pinaverium bromide，both for 4 weeks. The main symptoms of IBS were compared before and after treatment，such as the degree of abdominal pain，stool changes，traditional Chinese medicine pattern curative effect scoring system（TCM-PES），IBS quality of life questionnaire （IBS-QOL），IBS symptom severity scale（IBS-SSS），self-rating anxiety scale （SAS），and self-rating depression scale（SDS）. Nimodipine was used to evaluate the efficacy based on TCM syndrome score of liver depression and Qi stagnation. Enzyme-linked immunosorbent assay（ELISA） was conducted to detect the plasma interleukin-10（IL-10）and IL-12 before and after treatment. ResultAfter 4 weeks of treatment， the response rate of abdominal pain in observation group was 92.86% （78/84）， higher than that in control group （82.14%， 69/84）（χ2=6.254，P<0.05）. The response rates of diarrhea in observation group and control group were 91.67% （77/84）and 77.38% （65/84）， respectively（χ2=8.214，P<0.01）. TCM-PES and IBS-QOL scores of observation group after treatment were higher and IBS-SSS score was lower than those of control group （P<0.05）. The efficacy rate of TCM syndromes in observation group was higher than that of control group （P<0.05）. Additionally， after treatment， the observation group had lower SAS and SDS scores （P<0.05）and IL-12 level（P<0.05）and higher plasma IL-10 level than the control group （P<0.05）. ConclusionTongxie Yaofang can relieve abdominal pain and diarrhea in IBS-D patients with liver depression and spleen deficiency，reduce negative emotion，and improve the quality of life of patients，which may be related to alleviating the visceral hypersensitivity.

Efficacy and mechanism of acupuncture combined with for diarrhea-type irritable bowel syndrome of liver depression and spleen deficiency / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture at lower- acupoints and front- acupoints combined with (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism.@*METHODS@#A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared.@*RESULTS@#After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (<0.05).@*CONCLUSION@#The acupuncture at lower- acupoints and front- acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.

Clinical Efficacy and Mechanism of Tongxie Yaofang on Patients with IBS-D of Liver Depression and Spleen Deficiency / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Tongxie Yaofang on irritable bowel syndrome-D (IBS-D) of liver-stagnation and spleen-deficiency type, in order to explore its mechanism in regulating brain-intestine interaction by changing the intestinal flora before and after treatment. Method:Totally 116 patients with IBS-D with liver stagnation and spleen deficiency who were diagnosed from July 2016 to December 2018 were randomly divided into observation group and control group, with 58 patients in each group. Observation group was treated with Tongxie Yaofang orally. Control group was treated with pivalvonium orally. Both groups were treated for 4 weeks. Scores of traditional Chinese medicine pattern curative effect scoring system (TCM-PES), IBS quality of life questionnaire (IBS-QOL), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of two groups were compared before and after treatment. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were detected before and after treatment by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) was used to detect changes in Escherichia coli, Bifidobacteria, Lactobacillus acidophilus and Streptococcus faecalis and other intestinal flora before and after treatment. Result:TCM-PES and IBS-QOL scores of two groups were improved after treatment. TCM-PES and IBS-QOL scores of observation group were higher than those of control group (P<0.05). TCM syndromes of observation group were significantly higher than those of control group (P<0.05). SAS and SDS scores were significantly lower after treatment. SAS and SDS scores of observation group were lower than those of control group after treatment (P<0.05). Plasma CGRP and VIP decreased after treatment. Plasma CGRP and VIP in observation group were significantly lower than those in control group (P<0.05). There was no significant change in E. coli after treatment in two groups. After treatment, L. acidophilus, Bifidobacterium, and S. faecalis increased (P<0.05). In control group, intestinal L. acidophilus increased after treatment (P<0.05). The differences of intestinal L. acidophilus, Bifidobacterium, S. faecalis in two groups were statistically significant (P<0.05). Conclusion:TCM can alleviate clinical symptoms, such as abdominal pain and diarrhea in patients with IBS-D, improve patients' bad mood and improve their quality of life. This may be related to improvement of intestinal flora imbalance, regulation of brain intestinal peptide secretion and reduction of visceral hypersensitivity.

Association of bone mineral density with chronic obstructive pulmonary disease in postmenopausal women

Abstract Background Osteoporosis (OP) is common in patients with chronic obstructive pulmonary disease (COPD). The relationship between OP and COPD has been primarily studied in male patients, and few reports are available in postmenopausal women. Objective The purpose of this study was to investigate the association between bone mineral density (BMD) and COPD in postmenopausal women. Methods This cross-sectional study included 133 clinically stable female ex-smokers with confirmed COPD, and 31 age-matched “ex-smoker” female controls. We analyzed groups according to their airway obstruction category. BMD was measured on dual-energy X-ray absorptiometry images of the left femoral neck. Results Patients with COPD had lower T-scores and higher prevalence of osteopenia/OP than the control group. In the COPD group, the airway obstruction category was significantly associated with the T-score after adjustment for confounders. Multivariate logistic regression analysis showed COPD was an independent marker for increased risk of osteopenia/OP in postmenopausal women. Conclusions COPD and airway obstruction category were strongly related to BMD. Postmenopausal women with COPD, especially those with severe airway obstruction, had a higher prevalence rate and a higher risk of osteopenia and OP than female controls without COPD.

MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

Stroke-induced immunosuppression and T helper cells 17 / 中国脑血管病杂志

In the acute phase of stroke, the injured brain tissue releases inflammatory mediators to trigger the inflammatory cascade reaction. As a result, the Interleukin 17A, a major effector of T helper (Th) cells 17, increases after stroke,further contribute to the inflammatory response and aggravated the neurological deficits. Then the stroke induces immune suppression to suppress the inflammatory response, thus play a role in brain protection. The relevant pathways of post-stroke immunosuppression can regulate the Th cell subset and exert feedback effects on Thl7 cells.

Association of Severity of Coronary Lesions with Bone Mineral Density in Postmenopausal Women / Associação entre Gravidade das Lesões Coronarianas e Densidade Mineral Óssea em Mulheres Pós-Menopausa

Abstract Background: Coronary artery disease (CAD) and osteoporosis (OP) are common diseases in postmenopausal women. In both cross-sectional and longitudinal epidemiologic studies, low bone mass has been related to increased frequency of CAD. However, available data on the relationship between bone mineral density (BMD) and severity of coronary lesions is limited. Objective: To investigate association between the BMD and severity of coronary lesions assessed by Gensini score in postmenopausal women. Methods: This study included 122 postmenopausal women who were diagnosed with CAD. These patients were divided into two groups according to the severity of coronary lesions assessed by the Gensini score - patients with mild coronary lesions (Gensini score < 25) and patients with severe coronary lesions (Gensini score ≥ 25). Femoral neck mineral density was measured with dual energy X-ray absorptiometry (DXA). Results: The study included postmenopausal women aged 64.31 ± 4.71 years, 85 of whom (69.7%) exhibited severe coronary lesions. Participants with severe coronary lesions had a significantly higher T score than did those with mild coronary lesions at the femoral neck (p < 0.05). The mean T-score was −0.84 ± 1.01 in mild coronary lesions group, −1.42 ± 1.39 in severe coronary lesions group (p < 0.05). Multivariable logistic regression analysis showed that osteopenia-osteoporosis at the Femoral neck (odds ratio 2.73; 95% confidence interval 1.06 to 6.13) was associated with an increased risk of developing severe coronary lesions. The multiple regression model showed that T-scores (b = −0.407, SE = 0.151, p=0.007) were the independent predictors of Gensini score. Conclusion: The relationship between severity of coronary lesions and BMD was significant in postmenopausal women. BMD, a low-cost technique involving minimal radiation exposure, widely used for osteoporosis screening, is a promising marker of severity of coronary lesions.

Resumo Fundamento: A doença arterial coronariana (DAC) e a osteoporose são doenças comuns em mulheres pós-menopausa. Tanto em estudos transversais como em estudos epidemiológicos longitudinais, a massa óssea diminuída foi relacionada à frequência aumentada de DAC. No entanto, dados disponíveis sobre a relação entre densidade mineral óssea (DMO) e gravidade das lesões coronarianas são limitados. Objetivo: Investigar a associação entre DMO e gravidade das lesões coronarianas avaliadas pelo escore de Gensini em mulheres pós-menopausa. Métodos: Este estudo incluiu 122 mulheres pós-menopausa diagnosticadas com DAC. As pacientes foram divididas em dois grupos de acordo com a gravidade das lesões coronarianas avaliada pelo escore de Gensini - pacientes com lesões coronarianas leves (escore de Gensini < 25) e pacientes com lesões coronarianas graves (escore de Gensini ≥ 25). A densidade mineral do colo femoral foi medida por absorção de raios-X de dupla energia (DXA). Resultados: O estudo incluiu mulheres pós-menopausa com idade de 64,31 ± 4,71 anos, 85 delas (69,7%) com lesões coronarianas graves. Pacientes com lesões coronarianas graves apresentaram um escore T mais elevado que aquelas com lesões coronarianas leves no colo femoral (p < 0,05). O escore T médio foi -0,84 ± 1,01 no grupo com lesões leves, e -1,42 ± 1,39 no grupo com lesões graves (p < 0,05). A análise de regressão logística multivariada mostrou que a osteopenia-osteoporose no colo femoral (odds ratio 2,73; intervalo de confiança de 95% 1,06 - 6,13) esteve associada com um risco aumentado de se desenvolver lesões coronarianas graves. O modelo de regressão múltipla mostrou que os escores T (b = -0,407; EP= 0,151; p = 0,007) foram preditores independentes do escore de Gensini. Conclusão: Encontrou-se uma relação significativa entre a gravidade das lesões coronarianas e a DMO em mulheres pós-menopausa. DMO, uma técnica de baixo custo que envolve mínima exposição à radiação, e amplamente utilizada no rastreamento de osteoporose, é um marcador promissor da gravidade de lesões coronarianas graves.

Development of a novel compound microbial agent for degradation of kitchen waste

Abstract Large quantities of kitchen waste are produced in modern society and its disposal poses serious environmental and social problems. The aim of this study was to isolate degradative strains from kitchen waste and to develop a novel and effective microbial agent. One hundred and four strains were isolated from kitchen waste and the 84 dominant strains were used to inoculate protein-, starch-, fat- and cellulose-containing media for detecting their degradability. Twelve dominant strains of various species with high degradability (eight bacteria, one actinomycetes and three fungi) were selected to develop a compound microbial agent "YH" and five strains of these species including H7 (Brevibacterium epidermidis), A3 (Paenibacillus polymyxa), E3 (Aspergillus japonicus), F9 (Aspergillus versicolor) and A5 (Penicillium digitatum), were new for kitchen waste degradation. YH was compared with three commercial microbial agents-"Tiangeng" (TG), "Yilezai" (YLZ) and Effective Microorganisms (EM), by their effects on reduction, maturity and deodorization. The results showed that YH exerted the greatest efficacy on mass loss which decreased about 65.87% after 14 days. The agent inhibited NH3 and H2S emissions significantly during composting process. The concentration of NH3 decreased from 7.1 to 3.2 ppm and that of H2S reduced from 0.7 to 0.2 ppm. Moreover, E4/E6 (Extinction value460nm/Extinction value665nm) of YH decreased from 2.51 to 1.31, which meant YH had an obvious maturity effect. These results highlighted the potential application of YH in composting kitchen waste.

Effect of Modified Danggui Yinzi on Delayed Allergy in Model Mice with Qi-Blood Deficiency Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Danggui Yinzi (DY) on delayed allergy in model mice with qi-blood deficiency syndrome (QBDS).</p><p><b>METHODS</b>QBDS model was established in 48 Kuming mice of SPF grade by using reserpine and acetophenone hydrazine. Forty of them were then randomly divided into the model group, the loratadine group, the high dose DY group, the middle dose DY group, and the low dose DY group, 8 in each group. Another 8 in line with the same standard were recruited as a blank group. Mice in high, middle, and low dose DY groups were administered with DY concentrated solution at 60, 30, 15 g/kg by gastrogavage. Mice in the loratadine group were administered with loratadine solution at 1.66 mg/kg by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank group by gastrogavage. All medication was given once per day for 1 successive week. Except those in the blank group, the rest mice were evenly smeared with 1% DNCB solution on the abdomen. Five days after skin allergy, 1% DNCB solution was smeared to right ear of all mice to stimulate allergic reaction. Mice in the blank group were smeared in the same way without allergenic reaction. The auricle swelling and the inhibition ratio were determined at 24 h after attack. Blood was collected from orbit and serum IgE level detected using double-antibody sandwich ELISA.</p><p><b>RESULTS</b>Compared with the blank group, auricle swelling obviously increased and serum IgE level was obviously elevated in the model group (P < 0.01). Compared with the model group, auricle swelling obviously decreased and serum IgE level was obviously reduced in the 3 dose DY groups (P < 0.05, P < 0.01). Meanwhile, the auricle swelling degree was superior in high and middle dose DY groups to that in the loratadine group (P < 0.05). The inhibition ratio of auricle swelling was sequenced from high to low as 67.3% in the high dose DY group, 56.0% in the middle dose DY group, 48.1% in the low dose DY group, 47.3% in the loratadine group.</p><p><b>CONCLUSIONS</b>DY could inhibit auricle swelling and lower serum IgE level. It also could inhibit delayed allergic reaction in model mice with QBDS to some extent.</p>

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.</p><p><b>METHODS</b>Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker.</p><p><b>RESULTS</b>Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells.</p><p><b>CONCLUSION</b>Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.</p>

Increased red cell distribution width in patients with slow coronary flow syndrome

OBJECTIVE: An elevated red cell distribution width has been recognized as a predictor of various cardiovascular diseases. Slow coronary flow syndrome is an important angiographic clinical entity with an unknown etiology. This study aimed to examine the relationship between red cell distribution width and the presence of slow coronary flow syndrome. METHODS: In total, 185 patients with slow coronary flow syndrome and 183 age- and gender-matched subjects with normal coronary flow (controls) were prospectively enrolled in this study. Red cell distribution width and C-reactive protein were measured upon admission, and the results were compared between the patients with slow coronary flow syndrome and normal controls. RESULTS: Red cell distribution width levels were significantly higher in the patients with slow coronary flow syndrome than the normal controls. Moreover, the data showed that the plasma C-reactive protein levels were also higher in the patients with slow coronary flow syndrome than in the normal controls. In addition, a multivariate analysis indicated that C-reactive protein and red cell distribution width were the independent variables most strongly associated with slow coronary flow syndrome. Finally, the red cell distribution width was positively correlated with C-reactive protein and mean thrombosis in the myocardial infarction frame counts of the patients with slow coronary flow syndrome. CONCLUSION: The data demonstrated that red cell distribution width levels are significantly higher and strongly positively correlated with both C-reactive protein and thrombosis in the myocardial infarction frame counts of patients with slow coronary flow syndrome. These findings suggest that red cell distribution width may be a useful marker for patients with slow coronary flow syndrome. .

TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.

Changes of CCK-8, CGRP, SP, and VIP in the colon and the lung tissue of allergic asthma model rats: an experimental observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe changes of cholecystokinin octapeptide (CCK-8), calcitonin gene related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) in each tissue of the digestive system of allergic asthma (AA) model rats.</p><p><b>METHODS</b>The pulmonary disease (AA) rat model was duplicated by 1% ovalbumin. Its effect on the pathological morphology of the six main parts of the digestive system (stomach, duodenum, jejunum, ileum, colon and rectum) and related regulating factors such as CCK8, CGRP, SP, and VIP were observed.</p><p><b>RESULTS</b>The pathological morphology of the lung was synchronously changed as that of the colon of model rats. But there was no obvious change in the stomach, duodenum, jejunum, ileum, or rectum. Significant changes occurred in CCK8 (79 961.4 +/- 12 577.9, 48 519.5 +/- 12 240.7), CGRP (41 950.1 +/- 12 600.1, 38 059.8 +/- 11 942.4), and SP (88 243.9 +/- 32 177.2, 47 417.8 +/- 16 462.4), and VIP (20 711.4 +/- 7 334.6, 43 208.1 +/- 13 433.8) of the lung tissue and the colon tissue of model rats (P < 0. 05, P < 0.01). But there was no significant change in the aforesaid substances of the stomach, duodenum, jejunum, ileum and rectum (P > 0.05).</p><p><b>CONCLUSIONS</b>Pulmonary disease might affect the colon, inducing pathological changes of the colon tissue and changes of related regulating factors such as CCK8, CGRP, SP, and VIP. It showed no significant effect on the stomach, duodenum, jejunum, ileum and rectum.</p>

Active compression-decompression cardiopulmonary resuscitation (CPR) versus standard CPR for cardiac arrest patients: a meta-analysis / 世界急诊医学杂志（英文）

@#BACKGROUND: Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) has been popular in the treatment of patients with cardiac arrest (CA). However, the effect of ACD-CPR versus conventional standard CPR (S-CRP) is contriversial. This study was to analyze the efficacy and safety of ACD-CPR versus S-CRP in treating CA patients. METHODS: Randomized or quasi-randomized controlled trials published from January 1990 to March 2011 were searched with the phrase "active compression-decompression cardiopulmonary resuscitation and cardiac arrest" in PubMed, EmBASE, and China Biomedical Document Databases. The Cochrane Library was searched for papers of meta-analysis. Restoration of spontaneous circulation (ROSC) rate, survival rate to hospital admission, survival rate at 24 hours, and survival rate to hospital discharge were considered primary outcomes, and complications after CPR were viewed as secondary outcomes. Included studies were critically appraised and estimates of effects were calculated according to the model of fixed or random effects. Inconsistency across the studies was evaluated using the I2 statistic method. Sensitivity analysis was made to determine statistical heterogeneity. RESULTS: Thirteen studies met the criteria for this meta-analysis. The studies included 396 adult CA patients treated by ACD-CPR and 391 patients by S-CRP. Totally 234 CA patients were found out hospitals, while the other 333 CA patients were in hospitals. Two studies were evaluated with high-quality methodology and the rest 11 studies were of poor quality. ROSC rate, survival rate at 24 hours and survival rate to hospital discharge with favorable neurological function indicated that ACD-CPR is superior to S-CRP, with relative risk (RR) values of 1.39 (95% CI 0.99–1.97), 1.94 (95%CI 1.45–2.59) and 2.80 (95% CI 1.60–5.24). No significant differences were found in survival rate to hospital admission and survival rate to hospital discharge for ACD-CPR versus S-CRP with RR values of 1.06 (95% CI 0.76–1.60) and 1.00 (95% CI 0.73–1.38). CONCLUSION: Quality controlled studies confirmed the superiority of ACD-CPR to S-CRP in terms of ROSC rate and survival rate at 24 hours. Compared with S-CRP, ACD-CPR could not improve survival rate to hospital admission or survival rate to hospital discharge.

Effect of acute stress stimulation on the seizure induction in epileptic model rats / 生理学报

This study was undertaken to observe the effect of acute stress on seizure occurrence in chronic period of epileptic model rats. Lithium-pilocarpine (LiCl-PILO)-induced epileptic rat model was constructed. At the spontaneous recurrent seizure period, acute stress stimulations such as cat's urine and foot electrical shock were applied to observe the behavioral changes and seizure occurrence. The results showed that after the cat's urine stimulation, the self-directed behaviors of the epileptic model rats decreased significantly, while the risk assessment behaviors increased significantly. The seizure occurrence, however, was not observed during the 45 min after the stimulation. Applying electrical foot shocks also did not evoke seizures in epileptic model rats. On the contrast, intra-peritoneal injection of low dose of pentylenetetrazole (PTZ, 30 mg/kg) evoked seizure more efficiently, and the duration of seizure activity was extensively prolonged in epileptic model rats than that of control rats. Taken together, these results indicate that although applying stress stimulations such as cat's urine and electrical foot shock cause several behavioral changes, they are not severe enough to evoke seizure in epileptic model rats.

Saturated hydrogen saline protects rats from acute lung injury induced by paraquat / 世界急诊医学杂志（英文）

@#BACKGROUND: Paraquat (PQ) intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury (ALI) caused by paraquat poisoning. METHODS: Thirty PQ poisoned rats were randomly divided into a PQ intoxication group (intoxication group), a saturated hydrogen saline intervention group (intervention group), and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OhdG). Histological changes of the lungs were also observed. RESULTS: Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage (P<0.01 or P<0.05). However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage (P<0.01 or P<0.05). CONCLUSIONS: Saturated hydrogen saline is effective in preventing acute lung injury caused by PQ. Possibly, it can neutralize toxic oxygen radicals selectively and alleviate the oxidative stress injury induced by PQ.