Role of Ferroptosis-related Gene GLS2 in Pan-cancer Prognosis and Immunity / 肿瘤防治研究

Objective To assess the role of the ferroptosis-associated gene GLS2 in the prognosis of pan-cancer and immunity using bioinformatics methods. Methods GLS2 expression levels in pan-cancer were profiled using publicly available databases: The Cancer Genome Atlas, GTEx, Cancer Cell Line Encyclopedia and the International Cancer Genome Consortium. The aim was to explore the role of GLS2 gene expression, gene variation survival analysis, immune infiltration, immune checkpoint related genes, TMB, and MSI in different tumors. Results Difference in GLS2 expression levels between cancer and paraneoplastic tissues was statistically significant in most cancer types, and the expression level was correlated with survival in these cancer types. A positive correlation was found between GLS2 expression and immune cell infiltration in multiple cancer types, and GLS2 expression level was positively correlated with TMB, MSI, and methylation, and its expression is an indicator for potential therapeutic response. Conclusion Pan-cancer analysis shows that the ferroptosis-related gene GLS2 can be used as a diagnostic and prognostic marker of clear cell carcinoma of kidney, adrenocortical carcinoma, lung adenocarcinoma, and pancreatic cancer.

Effect of glutaminase 1 inhibitor on carbon tetrachloride-induced liver fibrosis in mice / 中国生物制品学杂志

@#Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-（5-phenylacetamido-1,3,4-thiadiazol-2-yl）ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10%CCl4(10 μL/g,model group)or 10% CCl4(10 μL/g)+ BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model. Collagen deposition in mouse liver tissue was observed by Sirius red staining. The expression levels of actin alpha 2(Acta2),collagen typeⅠalpha 1(Col1a1)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t = 2. 979,P < 0. 05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t = 7. 661,P < 0. 01),the relative expression levels of Acta2 and Col1a1 significantly increased(t = 4. 335 and 5. 319,respectively,each P < 0. 01),and the mRNA and protein levels of GLS1 significantly increased(t = 5. 319 and 9. 725,respectively,each P < 0. 01). However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t = 7. 427,P < 0. 01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t = 3. 713 and 2. 628,respectively,each P < 0. 05).Conclusion Inhibition of GLS1activity can significantly improve the degree of liver fibrosis induced by CCl4,providing a new idea for the treatment of liver fibrosis.

Strain echocardiography in predicting LV dysfunction in RV apical pacing

Right ventricular (RV) pacing is associated with a reduction in left ventricular (LV) systolic function, thought to be mediated by pacing-induced ventricular dyssynchrony. The prevalence of heart failure after RV pacing is reported to range from 31±3%. We studied 60 subjects with high-grade atrioventricular block and Complete Heart Block (CHB) scheduled to undergo right ventricular apical pacing. 2D echocardiography was done at baseline, 1 month and 12 months. Pacing-induced cardiomyopathy was defined as a reduction in LVEF to <45%. Strain was evaluated off-line from digitally stored images using all advanced software package (cardiac wall motion quantification (CMQ); Toshiba Medical Systems). Longitudinal strain for individual myocardial segments was measured from the apical four-chamber, two-chamber and long axis views (16 segment AHA/ASE model). None had LV dysfunction at baseline based on 2D and strain echo imaging. Subsequently 18 patients were detected to develop low GLS score (less than -14.5) at 1 month. On subsequent follow up at 1 year, all 18 patients developed LV dysfunction on 2D Echocardiography. Thus Strain imaging with GLS score helped in early detection of LV dysfunction in RV apical pacing subjects. Pacing-induced cardiomyopathy had significant association with high grade AV block with pacemaker dependency. It had no significant associations with other comorbidities like diabetes, hypertension, ischemic heart disease or with the type of medication intake. However there was a statistically significant association with heart failure

Cardiac and metabolic effects of Bariatric Surgery among obese patients in a Malaysian Tertiary Hospital: A 6-month prospective cohort study / Journal of the ASEAN Federation of Endocrine Societies

Objective@#Obesity is known to be associated with left ventricular diastolic dysfunction due to its effect on blood pressure and glucose tolerance. We aimed to investigate whether weight loss after bariatric surgery might improve diastolic dysfunction through in-depth echocardiographic examination.@*Methodology@#We recruited twenty-eight patients who were about to undergo bariatric surgery by purposive sampling. They underwent echocardiography at baseline and 6 months after surgery with a focus on diastolic function measurements and global longitudinal strain (GLS). They also had fasting serum lipid and glucose measurements pre- and post-surgery.@*Results@#The mean weight loss after surgery was 24.1 kg. Out of the 28 subjects, fifteen (54%) initially had diastolic dysfunction before surgery. Only two had persistent diastolic dysfunction 6 months after surgery. The mean indexed left atrial volume 6 months post-surgery was 27.1 from 32 ml/m2 prior to surgery. The average E/e’ is 11.78 post-surgery from 13.43 pre-surgery. The left ventricular GLS became (-)25.7% after surgery from (-)21.2% prior to surgery. Their post-surgery fasting serum lipid and glucose levels also showed significant improvement.@*Conclusion@#Our study reinforced the existing evidence that bariatric surgery significantly improved echocardiographic parameters of diastolic function and left ventricular global longitudinal strain, along with various metabolic profiles.

Estenosis aórtica: ¿Cuándo intervenir?

La estenosis aórtica es la valvulopatía más frecuente en los países desarrollados. La etiología degenerativa es la principal, esto está íntimamente relacionado con una tendencia exponencial en la longevidad de la población actual; por lo que sería correcto esperar un aumento en la casuística de esta patología. El reemplazo valvular aórtico, ya sea percutáneo o quirúrgico, es la estrategia casi única de manejo. Las guías de manejo de las distintas sociedades científicas, actualmente, norman la realización del reemplazo valvular como indicación principal en aquellos pacientes portadores de estenosis aórtica severa que, además, presenten síntomas o bien presenten datos de reducción en su fracción de eyección. Sin embargo, varios estudios han demostrado el beneficio de no retrasar la intervención de estos pacientes y por el contrario realizar la intervención valvular de forma temprana.

Aortic stenosis is currently the most common valve disease in developed countries. Degenerative ethology is the main one, this being intimately related to the exponential trend towards longevity in the current population. Aortic valve replacement, either percutaneous or open, is almost the only management strategy. The current management guidelines of the different scientific societies regulate the performance of valve replacement in patients with severe aortic stenosis who also present symptoms or data of reduced ejection fraction. However, several studies have shown the benefit of not delaying the management of these patients and, on the contrary, performing valve intervention early.

Left ventricular global longitudinal strain imaging in identifying subclinical myocardial dysfunction among covid-19 survivors

Background: Covid-19 is multi-system viral infection caused by SARS-CoV-2 virus. Apart from having acute severe respiratory illness causing high mortality, the disease also has a variety of cardiovascular manifestations contributing to morbidity as well as mortality. Cardiac dysfunction and myocarditis are well established complications of Covid-19 as evident in multiple studies after the Covid-19 pandemic. However it is not sufficiently studied in Indian patients either by Echocardiography or by any other imaging modalities like cardiac magnetic resonance imaging (MRI). Methodology: In this study, we analysed the severity of Left ventricular(LV) dysfunction in Covid-19 survivors. A total of 100 consecutive patients of Covid-19 after one month of discharge who had no underlying cardiovascular diseases underwent echocardiography and global longitudinal strain (GLS) imaging. This study cohort included patients with mild 42 (42%),moderate 46(46%) and severe 12(12%) Covid-19 disease as defined by computerised tomography (CT) severity score. Result: We observed that total 36(36%) patients had reduced ejection fraction(EF) which included 11 patients having EF <40% and remaining 25(25%) having EF 40e50% (p<0.002). Also 22 (22%) patients had abnormal global longitudinal strain (GLS) values with normal ejection fraction which is suggestive of subclinical myocarditis. We observed LV dysfunction in 7(19.5%) patients who had severe Covid-19 while mild to moderate LV dysfunction observed in 29(80.5%) non critical patients. Conclusion: In conclusion our study demonstrates that myocardial dysfunction is common in covid-19 regardless of disease severity. 2D-echocardiography with GLS is likely to detect early LV dysfunction among these patients.

Novas concepções para reatores anaeróbios de manta de lodo: uso de mistura mecânica ou hidráulica com decantação lamelar e sem separador trifásico / New concepts for anaerobic sludge blanket reactors: the use of mechanical or hydraulic mixing with high-rate settler and without three-phase separator

RESUMO Neste artigo, apresenta-se uma abordagem conceitual sobre propostas de alternativas para a concepção de sistemas com reator anaeróbio de manta de lodo. Em essência, propõem-se: i) a eliminação dos separadores de gás, líquido e sólido que constam em reatores upflow anaerobic sludge blanket reactors e sua substituição por unidade de sedimentação de alta taxa em setor incluso ou externo ao volume do reator biológico; ii) a recirculação de parcela do lodo retido no sedimentador, transformando o conjunto em um sistema semelhante ao de lodo ativado, porém preservando a manta de lodo no reator anaeróbio (activated anaerobic sludge blanket system) e, assim, viabilizando melhor controle do tempo de retenção celular; e iii) a simplificação (menor número de entradas) do sistema de distribuição do afluente junto ao fundo da zona de reação, mediante duas alternativas: agitação mecânica ou agitação hidráulica com jatos — em ambos os casos, intermitentes. As propostas, conforme apresentadas, constituem resumo de pesquisa baseada em reatores de bancada sucedida pela operação e testes em duas unidades-piloto paralelas (volume total: 20,8 m3, incluindo volumes de reação e de sedimentação). Constatou-se que é possível remover sólidos suspensos do efluente da região de reação sem a necessidade do separador trifásico e, também, que é possível manter-se a manta de lodo mesmo com a agitação na região de reação. Foram obtidos bons resultados na remoção de sólidos suspensos totais, demanda bioquímica de oxigênio e demanda química de oxigênio nos sedimentadores com valores de taxa de aplicação superficial de 34,0 até 81,6 m3m-2dia. Constatou-se, também, que valores bastante baixos de gradiente de velocidade (G £ 20s-1) são suficientes para promover a manutenção da manta de lodo e que a intermitência na agitação é favorável ao processo biológico. Os resultados relacionados com a remoção de demanda química de oxigênio, demanda bioquímica de oxigênio e sólidos suspensos totais foram comparados com os de outros estudos sobre reatores upflow anaerobic sludge blanket reactors convencionais. Contudo, aqueles relacionados com o tempo de reação celulat foram os mais significativos para as conclusões desta pesquisa. Quando o reator foi operado com tempo de detenção hidráulica de 8,2 h e velocidade ascensional no reator biológico de 0,69 mh-1, o tempo de reação celular do sistema resultou em 175 dias. Com velocidade ascensional menores, os valores de tempo de reação nuclear foram ainda maiores (por exemplo: velocidade ascensional = 0,39 mh-1; tempo de reação celular = 363 dias). Os resultados deste trabalho abrem perspectivas para novas pesquisas e novos horizontes para projeto de sistemas com reatores anaeróbios de manta de lodo e decantadores de alta taxa.

ABSTRACT This paper presented a conceptual approach toward alternatives for the design of anaerobic sludge blanket reactors. In essence, it is proposed: i) the elimination of gas-liquid-solid separators that integrate the upflow anaerobic sludge blanket reactors and their replacement by a high rate settlers placed inside or outside the volume of biological reactor; ii) the recirculation of a fraction of the of the sludge retained in the settler, converting the process into a solution that resembles the activated sludge system, however, preserving the sludge blanket (Activated Anaerobic Sludge Blanket System), and thus ensuring better control of the cell retention time; and iii) the simplification (lower inlet points) of the influent distribution system placed over the bottom of the reaction zone, upon the implementation of two alternatives: mechanical mixing or hydraulic agitation with jet discharges, intermittent, in both cases. The proposals, as presented, are a summary of researches based on bench scale tests succeeded by the operation and tests in two parallel pilot units (total volume: 20.8 m3, including reaction zone and settler). It was found that it is possible to remove suspended solids from the effluent of the reaction zone without the need for a three-phase separator, and also, that it is possible to maintain the sludge blanket even with mixing in the reaction zone. Good results regarding total suspended solids, biochemical oxygen demand and chemical oxygen demand removal in the settlers were obtained, with applied hydraulic loading rate from 34.0 to 81.6 m3m-2 day. It was also found that very low velocity gradient values (G £ 20 s-1) are required to promote the maintenance of the sludge blanket, and the intermittency in the agitation is favorable to the biological process. The results concerning, , and TSS removal were compared with those of other studies on conventional upflow anaerobic sludge blanket reactors. However, those related to sludge age were the most significant to the conclusions of this research. When the reactor was operated with a hydraulic retention time of 8.2 h and a upflow velocity upflow velocity of 0.69 mh-1 in the biological reactor, the average sludge age reached 175 days. When applying smaller values of upflow velocity, the sludge age values reached greater values (Example: upflow velocity = 0.39 mh-1; sludge age = 363 days). The results and conclusions of this research open new perspectives for future research and new horizons for designing systems consisting of anaerobic sludge blanket and high-rate settlers.

Nigeria's cocoa exports: a gravity model approach / Exportações de cacau da Nigéria: uma abordagem do modelo gravitacional

ABSTRACT: What are the major factors affecting Nigeria's cocoa export flows? In answering this question, the authors suggest a commodity-specific gravity model with three different analytical approaches, (the Heckman Sample Selection Model, the Generalised Least Square, and the Poisson Pseudo Maximum Likelihood), based on a period of 24 years of panel data for Nigeria and it's 36 importing partners to estimate the models. The results showed that GDP, exchange rate policy, WTO, EU, and colonial link are positively associated with the Nigerian cocoa export flows. Further, the negative impact of the GDP per capita, landlocked, distance, AU, and ECOWAS are observed. The need for the expansion of exports to the trading partners, especially the EU members (Netherlands, Germany, France, United Kingdom, Belgium, Spain, etc.), Canada, Malaysia, and the USA is particularly highlighted. These results are important for the formulation of future trade policy that could boost up the Nigerian cocoa exports. This would eventually contribute to the diversification of the Nigerian exports and also enhance the country's foreign earnings.

RESUMO: Quais são os principais fatores que afetam os fluxos de exportação de cacau da Nigéria? Ao responder a esta pergunta, os autores sugerem um modelo de gravidade específica de mercadoria com três abordagens analíticas diferentes (o Modelo de Seleção de Amostras de Heckman, o Mínimo Quadrado Generalizado e a Pseudo Máxima Verossimilhança de Poisson), com base em um período de 24 anos de dados em painel para a Nigéria e seus parceiros importadores para estimar os modelos. Os resultados mostram que o PIB, a política cambial, a OMC, a UE e a ligação colonial estão positivamente associados aos fluxos de exportação de cacau da Nigéria. Além disso, é observado o impacto negativo do PIB per capita, sem litoral, distância, UA e CEDEAO. Destaca-se a necessidade de ampliação das exportações para os parceiros comerciais, especialmente os membros da UE (Holanda, Alemanha, França, Reino Unido, Bélgica, Espanha, etc.), Canadá, Malásia e Estados Unidos. Esses resultados são importantes para a formulação de uma política comercial futura que possa impulsionar as exportações de cacau nigeriano. Isso acabaria por contribuir para a diversificação das exportações nigerianas e também aumentar as receitas externas do país.

The inhibition effect of GLS4JHS on the transcription activity of covalently closed circular DNA in HepAD38 cells / 中华传染病杂志

Objective The hepatitis B virus (HBV) core protein assembly inhibitors GLS4JHS could destroy HBV capsid assembly and the formation of non-capsid polymer structure.The aim of this study is to explore the mechanisms of GLS4JHS in inhibiting HBV replication.Methods HepAD38 cells was used as the study model.TaqMan real-time polymerase chain reaction (PCR) and quantitative real-time PCR with specific primers were used to measure the change in pregenomic RNA (pgRNA) and covalently closed circular DNA (cccDNA) levels under different concentrations.ChIP assay in HepAD38 cells was used to assess the recruitment of HBV core protein and histone modifications.Results The amount of cccDNA and pgRNA decreased with the increasing GLS4JHS concentrations.After the drug concentrations reached 400 nmol/L, cccDNA and pgRNA declined by 94% and 84%, respectively.Both HBV core protein occupancy on the cccDNA and cccDNA-bound H3 histone acetylation were reduced by GLS4JHS.Conclusions GLS4JHS decreases transcriptional activity of cccDNA and reduces pgRNA production by inhibiting cccDNA minichromosome bound to HBV core protein and acetylated histone H3, which results in HBV DNA formation.

The Effect of Radix Ranuncoli Ternati on the Expression of Granule Lytic Peptide and Bactericidal Ability of T Lymphocyte in Peripheral Blood Lymphocytes of Patients with Pulmonary Tuberculosis / 中国药学杂志

OBJECTIVE: To explore the effect of Radix Ranuncoli Ternati on the expression of granule lytic peptide and bactericidal ability of T lymphocyte in peripheral blood lymphocytes of patients with pulmonary tuberculosis. METHODS: Peripheral blood lymphocytes were treated with Ranunculus. MTT assay was used to detect cell proliferation. Real-time PCR was used to detect the mRNA level of GLS in patients. RESULTS: Radix Ranuncoli Ternati could enhance expression of Tubercle bacillus. The RESULTS of MTT assay indicated that the rate of peripheral blood lymphocytes apoptosis inducted by the Radix Ranuncoli Ternat. The Western blotting RESULTS showed that Radix Ranuncoli Ternati made the expression levels of GLS in peripheral blood lymphocyte increasing. When the concentration of the drug is 200 mg·L-1, it can effectively induce the activation of tuberculosis resting bacteria. The expression of GLS and the level of mRNA were increased in peripheral blood lymphocytes. CONCLUSION: Radix Ranuncoli Ternati may increase the expression of GLS and enhance the body's killing effect on pathogenic bacteria to achieve the therapeutic effect.

Application of CTI and 3G technology in modern 120 emergency command center / 医疗卫生装备

Multiple scientific technologies are used in modern 120 emergency command center. This paper introduces the frame of l20 emergency command center and the functions of CTI and 3G technology,and analyzes the practical application and effects of CTI and 3G in modern 120 emergency command center.