Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis / 器官移植

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Características clínico-oftalmológicas y evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social, Paraguay / Clinical-ophthalmological characteristics and evolution of patients with moderately severe active thyroid ophthalmopathy treated with methylprednisolone boluses who attended the Central Hospital of the Instituto de Previsión Social, Paraguay

Introducción: La oftalmopatía tiroidea (OT) es un trastorno debilitante en pacientes con enfermedad tiroidea autoinmune, principalmente enfermedad de Graves, que se desarrolla entre el 30 a 50% de los casos. Objetivos: Describir las características clínico-oftalmológicas y la evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social en el tiempo comprendido entre enero de 2018 y setiembre de 2021. Materiales y métodos: Investigación de diseño observacional, con estudio descriptivo, retrospectivo. Resultados: Se revisaron fichas de 34 pacientes con OT activa moderada severa que recibieron bolos de metilprednisolona basado en las guías EUGOGO 2016, de los cuáles se excluyeron 3 pacientes por tener fichas incompletas y otros 3 pacientes ya que requirieron tratamiento de segunda línea previo al término del esquema de 12 sesiones. De los 28 pacientes estudiados, la edad promedio fue de 43,6 ±13,1 años, el 89% de sexo femenino y el 28,5%, fumadores. En cuanto a la función tiroidea de la población previo al tratamiento, se constató hipertiroidismo en el 82%, hipotiroidismo en el 11% y eutiroidismo en el 7%; y posterior al tratamiento, se constató hipertiroidismo en el 78,6% (subclínico), eutiroidismo en el 17,9% e hipotiroidismo en el 3,5%. La mayoría (92.6%) contaba con anticuerpos contra el receptor de TSH positivo, con un promedio de 18 ± 9,9 mIU/Ml. Respecto a la actividad de la oftalmopatía según la escala CAS, se constató un promedio de 4,1 ±1,0 previo al tratamiento y posterior 1,2 ±1,4; de ellos el 46,4% presentó un estado leve según escala de gravedad, 39% sin criterios de gravedad y 14 % persistió en moderada -severa. Se constató mejoría de la agudeza visual tras el tratamiento (57,1%), el promedio de exoftalmía previo al tratamiento fue 22,2 mm y posterior 21,1 mm; se presentó diplopía en el 7,1% previo al tratamiento y en el 3,6% posterior al tratamiento. Conclusión: El tratamiento con glucocorticoides endovenosos en la oftalmopatía de Graves moderada-severa (esquema EUGOGO 2016) fue muy efectivo, revirtiendo la actividad y consecuentemente ayudando a disminuir la gravedad, en la gran mayoría de nuestros pacientes. Esto podría explicarse porque la oftalmopatía era incipiente y por el alto grado de adherencia de los pacientes en el contexto de un manejo multidisciplinar bien protocolizado.

Introduction: Graves' orbitopathy (GO) is a debilitating disorder in patients with autoimmune thyroid disease, mainly Graves' disease, which develops in 30 to 50% of cases. Objectives: To describe the clinical-ophthalmological characteristics and evolution of patients with moderate-to- severe active GO treated with methylprednisolone boluses who attended the Central Hospital of the Institute of Social Security between January 2018 and September 2021. Materials and methods: Observational design research, descriptive, retrospective study. Results: Records of 34 patients with active moderate-to-severe GO who received boluses of methylprednisolone based on the EUGOGO 2016 guidelines, were reviewed, of which 3 patients were excluded due to having incomplete records and another 3 patients since they required second-line treatment prior to end the 12-session scheme. Of the 28 patients studied, the average age was 43.6 ±13.1 years, 89% were female and 28.5% were smokers. Regarding the thyroid function of the population prior to treatment, hyperthyroidism was found in 82%, hypothyroidism in 11% and euthyroidism in 7%; and after treatment, hyperthyroidism was found in 78.6% (subclinical), euthyroidism in 17.9% and hypothyroidism in 3.5%. The majority (92.6%) had positive thyrotropin receptor antibodies, with an average of 18 ± 9.9 mIU/Ml. Regarding the activity of orbitopathy according to the CAS scale, an average of 4.1 ±1.0 was found before treatment and 1.2 ±1.4 after; Of them, 46.4% presented a mild condition according to the severity scale, 39% without severity criteria and 14% persisted in moderate-severe. Improvement in visual acuity was noted after treatment (57.1%), the average exophthalmia before treatment was 22.2 mm and after 21.1 mm; Diplopia occurred in 7.1% before treatment and in 3.6% after treatment. Conclusion: Treatment with intravenous glucocorticoids in moderate-severe Graves' orbitopathy (EUGOGO 2016 scheme) was very effective, reversing the activity and consequently helping to reduce the severity, in the vast majority of our patients. This could be explained because the orbitopathy was incipient and by the high degree of patient adherence in the context of well-protocolized multidisciplinary management.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Screening of key targets for diabetic cardiomyopathy based on transcriptomics and proteomics / 中国药理学通报

Aim To explore a potential new target for the prevention and treatment of diabetic cardiomyopathy ( DCM) in mice. Methods The myocardial proteomics of normal and diabetic mice was studied. The GEO database GSE161931 dataset was analyzed using R language with P < 0.05 and I log

Alteración de la microbiota intestinal y su relación con enfermedades gastrointestinales y hepatobiliares / Disruption of the intestinal microbiota and its relationship with gastrointestinal and hepatobiliary diseases

La interrupción de la simbiosis que existe entre el cuerpo humano y su microbioma puede resultar en una disbiosis, un desequilibrio en la interacción huésped-microbiota, que puede asociarse al desarrollo de diversas enfermedades como el síndrome de intestino irritable, hígado graso no alco-hólico, enfermedad hepática alcohólica y cirrosis, entre otras. En ciertas condiciones patológicas y por múltiples factores de riesgo, la capacidad de autorregulación del intestino se puede alterar, contribuyendo al incremento de la permeabilidad con inflamación intestinal crónica. El diagnóstico y el tratamiento, así como la relación entre la permeabilidad intestinal, la disbiosis y las patologías gastrointestinales y hepatobiliares, todavía no tienen estudios clínicos validados o con el soporte científico adecuado, por lo que se realiza una revisión de la literatura con la finalidad de aportar conceptos que puedan orientar con respecto a la importancia del estudio del microbioma humano en estas enfermedades.

Disruption of the symbiosis that exists between the human body and its microbiome can result in dys-biosis, an imbalance in the host-microbiota interaction, which may be associated with the develop-ment of various diseases such as irritable bowel syndrome, non-alcoholic fatty liver disease, alcoholic liver disease and cirrhosis, among others. In certain pathological conditions and due to multiple risk factors, the self-regulating capacity of the intestine may be lost, contributing to increased permeability with chronic intestinal inflammation. Its diagnosis and treatment as well as the relationship between intestinal permeability, dysbiosis and gastrointestinal and hepatobiliary pathologies have not been validated in clinical studies or have adequate scientific support, so a review of the literature is carried out in order to provide concepts that can guide with respect to the importance of the study of the human microbiome in these diseases

O Papel bidirecional da nicotina na tarefa Go/No-go: um ensaio clínico piloto / The bidirectional role of nicotine in a Go/No-go task: a pilot clinical trial / El papel bidireccional de la nicotina en la tarea Go/no-go: un ensayo clínico piloto

Estudos mostram que o tabagismo é responsável por afetar algumas funções cognitivas. No entanto, a nicotina é apenas um dos componentes existentes no cigarro e existem evidências de que pode servir como agente neuroprotetivo e causar melhoras em algumas funções cognitivas. O objetivo desta pesquisa foi investigar como a nicotina interage com algumas funções cognitivas. Um ensaio clínico piloto com administração de gomas de nicotina contendo 2-mg ou 4-mg, ou gomas placebo contendo a mesma textura, sabor e aparência, foi realizado. Quarenta e dois participantes participaram da pesquisa e os resultados indicaram que a relação entre nicotina e o desempenho na tarefa Go/No-Go podem ser bidirecionais. Os resultados indicaram que participantes do grupo que utilizaram 4-mg de nicotina apresentaram menor desempenho, enquanto os participantes que fizeram uso de 2-mg de nicotina tiveram melhor desempenho do que os demais. Esta pesquisa tem aplicações biopsicossociais e podem ajudar na compreensão da relação entre tabagismo e nicotina, além de contribuir para estratégias que possam ajudar no abandono do cigarro ou na melhora de condições que afetem a cognição (AU).

Past findings in the literature indicated that smoking could affect given cognitive functions. However, nicotine is only one of the components in cigarettes and there is evidence that it may act as a neuroprotective agent and improve some cognitive functions. The purpose of this research was to investigate how nicotine interacts with certain cognitive functions. We conducted a pilot clinical trial using nicotine gum containing 2-mg or 4-mg, or placebo gum with the same texture, flavor, and appearance. Forty-two healthy nonsmokers were enrolled in this research. Our findings indicated that the relationship between nicotine and performance on the Go/No-Go task might be opposite. The results showed that participants in the 4-mg group performed worse, while participants who used 2-mg of nicotine performed better than the others. This research supports biopsychosocial applications and can help interpret the relationship between smoking and nicotine, and contribute to strategies that may support smoking cessation, or improve conditions that affect cognition (AU).

Estudios demuestran que el tabaquismo es responsable de afectar a algunas funciones cognitivas. Sin embargo, la nicotina es solo uno de los componentes de los cigarrillos, y existen evidencias de que la nicotina puede actuar como un agente neuroprotector y mejorar algunas funciones cognitivas. El objetivo de este estudio fue investigar cómo la nicotina interactúa con algunas funciones cognitivas. Se realizó un ensayo clínico piloto con la administración de chicles de nicotina de 2 mg o 4 mg, o chicles de placebo con la misma textura, sabor y apariencia. Cuarenta y dos participantes participaron en la investigación y los resultados indicaron que la relación entre la nicotina y el rendimiento en la tarea Go/No-go puede ser bidireccional. Los resultados indicaron que los participantes del grupo de 4 mg obtuvieron un menor rendimiento en las variables del Go/No-Go, mientras que los participantes que utilizaron 2 mg de nicotina obtuvieron un mejor rendimiento que los demás. Esta investigación respalda las aplicaciones biopsicosociales y puede ayudar a interpretar la relación entre el tabaquismo y la nicotina, además de contribuir a las estrategias que pueden ayudar a dejar de fumar o mejorar las condiciones que afectan la cognición (AU).

Expression and significance of HERG protein in Cajal interstitial cells of gallbladder tissue in patients with gallbladder stones / 中华肝胆外科杂志

Objective:To investigate the expression and significance of human ether-a-go-go related gene (HERG) protein in interstitial cells of Cajal (ICC) in patients with gallbladder stones.Methods:The gallbladder tissues of 60 patients with gallbladder diseases who underwent cholecystectomy from January 2018 to December 2020 in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were collected, including 36 males and 24 females, aged (46.0±14.0) years. They were divided into two groups according to whether there were gallstones: gallstone group and control group (patients with gallbladder polyps and gallbladder adenomyosis), with 30 cases in each group. Color ultrasound was used to detect and calculate the gallbladder contraction rate. The neck, body and bottom tissues of the gallbladder were excised and sectioned. The expression of HERG protein and CD117 ( marker of ICC) was detected by immunofluorescence staining, immunohistochemistry and Western blot.Results:The gallbladder contraction rate in the gallstone group was (65.8±4.1)%, lower than that in the control group (73.8±5.3)%, with a statistically significant difference ( t=4.14, P<0.001). Immunohistochemistry showed that HERG protein was mainly distributed in the mucosal layer of gallbladder tissue, which was pale brown. The relative expression of HERG protein at the bottom of gallbladder in the gallstone group was (0.293±0.102), lower than that in the control group (0.694±0.059), with a statistically significant difference ( t=3.38, P=0.027). Immunofluorescence staining showed that HERG protein was mainly distributed in ICC of gallbladder epithelium. HERG protein expression in ICC at the bottom of gallbladder in gallstone group was lower than that in control group, while HERG protein expression at the neck and body of gallbladder had no significant difference. Conclusion:There are ICC and HERG protein in gallbladder tissue of patients with gallstone. The decrease of gallbladder contraction rate may be related to the decrease of HERG protein expression in ICC in gallbladder bottom tissue.

Effect of TRPV4-Nox2 complex on aortic vasodilatory function of obese mice / 中国药理学通报

Aim To investigate the effects of TRPV4-Nox2 complex on ROS production and aortic vasodilatory function in mice fed with high-fat diet.Methods Male C57 BL/6J mice and TRPV4 KO mice were randomly divided into seven groups, with 10 mice in each group: normal diet group(ND), high-fat diet group(HFD), TRPV4 KO mice fed with high-fat diet group(TRPV4 KO-HFD), HFD+AAV-Flt1-Vector/Nox2 ▵3 group, TRPV4 KO-HFD+AAV-Flt1 -Vector/Nox2 ▵3 group.Body weight and blood pressure were recorded.14 weeks later primary aortic endothelial cells were isolated for CM-H2DCFDA staining and immuno-FRET assay, and aortic rings were isolated for vascular tone assay.Results ① Obesity significantly increased ROS production, triggered vasodilatory dysfunction and increased the strength of physical coupling between TRPV4-Nox2 complex(P<0.05); ② Decreasing the physical association of TRPV4-Nox2 complex could help reduce obesity-induced increased ROS production and vasodilatory dysfunction(P<0.05); ③ Entrectinib had no effect on the expression and function of TRPV4 and Nox2, but only decreased the physical association of the TRPV4-Nox2, which in turn improved obesity-induced oxidative stress and restored vasodilatory function.Conclusions Reducing the physical association of TRPV4 and Nox2 through Entrectinib can help reduce obesity-induced increase in ROS production and improve vasodilatory function of obese mice.

The core traditional Chinese medicines and mechanism of traditional Chinese medicine enema treatment of chronic kidney disease based on data mining and network pharmacology / 西安交通大学学报(医学版)

【Objective】 To analyze and mine the prescription rules of traditional Chinese medicine enema treatment of chronic kidney disease （CKD） in CNKI platform journals based on data mining and network pharmacology so as to find high-frequency core Chinese medicines and predict the potential targets of core Chinese medicines and explore the mechanism of action of core Chinese medicines in the treatment of CKD. 【Methods】 Taking CNKI as the data source， we retrieved the clinical literature of traditional Chinese medicine enema in the treatment of CKD. SPSS modeler 18.0 statistical software was used for statistical processing and association rule analysis. IBM SPSS statistics 21 statistical software was used for cluster analysis. BATMAN-TCM and TCMSP were used to retrieve the effective components and related targets of drugs. Genecards， OMIN， Drugbank， DisGenet， TTD， and PharmGkb databases were used to retrieve disease-related targets， and Venny platform was used to screen disease and drug intersection targets. We used STRING database to obtain relevant documents， Cytoscape 3.8.2 software for visual analysis， Metascape database for enrichment analysis， Wechat website to draw bubble diagram， and AutoDockTools-1.5.6 software for molecular docking prediction. 【Results】 We selected 276 effective prescriptions involving 120 traditional Chinese medicines. The frequency of 19 traditional Chinese medicines was more than 10. Totally 18 core drug combinations were obtained. Cluster analysis could be divided into four categories. The visual net-work analysis shows that “rhubarb， dandelion， oyster， Salvia miltiorrhiza and aconite” are highly correlated and occupy the core position. Through the prediction of the potential targets of five core drugs， 659 “drug disease” intersection targets and 173 core targets were obtained， of which “MAPK1， AKT1 and STAT3” are the key targets， “progesterone， neocryptotanshinone Ⅱ and emodin”. It is predicted that it may play a role in “PI3K Akt signal pathway， MAPK signal pathway， JAK-STAT signal pathway”. Molecular docking showed that the key components have good binding activity with key targets. 【Conclusion】 Based on data mining and network pharmacology， traditional Chinese medicine enema treatment of CKD mainly uses rhubarb as the main drug， assisting warming yang to remove blood stasis and turbidity relief drugs. The key components of its core drug can act on PI3K-Akt by regulating key targets such as PIK3R1. Signal pathways and other pathways play a role in providing new ideas for the treatment of this disease with traditional Chinese medicine enema， medication strategies for clinical prescriptions， and a basis for follow-up further research.

Go tani and his influence on the kinesiology field in the brazilian scientific context / Go tani e sua influência no campo da cinesiologia no contexto científico brasileiro

ABSTRACT This study aimed to group some perspectives on Go Tani's epistemological activity in the context of Brazilian Physical Education (PE), establishing his contributions and reflections on Kinesiology for the structuring of undergraduate and graduate Physical Education in Brazil. This is a bibliographical and exploratory study, which prioritized Tani's production on the most varied platforms and the materials that circulated about Kinesiology in national and international literature. Finally, through the theoretical review, it was possible to identify that the PE field is a scenario full of disputes and that even with the transformations of paradigms that infer the legitimate alternatives in the scientific context, the relationships that are established between the different schools of PE thought have erupted in a process of mutual incomprehension that contributes to the circularity of perspectives and the maintenance of beliefs in the field.

RESUMO O presente estudo objetivou agrupar algumas perspectivas sobre a atividade epistemológica de Go Tani no contexto da Educação Física (EF) brasileira, estabelecendo suas contribuições e reflexões a partir da Cinesiologia para a estruturação da graduação e da pós-graduação em Educação Física no Brasil. Trata-se de um estudo bibliográfico e exploratório, o qual priorizou a produção de Tani nas mais variadas plataformas, bem como os materiais que circularam sobre a Cinesiologia na literatura nacional e internacional. Por fim, através da referida revisão teórica, foi possível identificar que o campo da EF é um cenário repleto de disputas e que mesmo com as transformações dos paradigmas que inferem nas alternativas legítimas no contexto científico, as relações que são estabelecidas entre as distintas escolas de pensamento da EF têm eclodido num processo de interincompreensão que contribui com a circularidade de perspectivas e a manutenção de crenças no campo.

Utilização de sensores inerciais no teste timed up and go: uma revisão narrativa / Use of inertial sensors in the timed up and go test: a narrative review

O teste funcional Timed Up and Go (TUG) é amplamente utilizado para avaliar o risco de queda, através do equilíbrio e mobilidade, por ser de fácil aplicação e boa reprodutibilidade na prática clínica. Porém, o TUG ainda possui algumas limitações, pois se concentra no tempo total em que o teste é realizado. Uma proposta de avaliação é através da utilização de sensores inerciais, baseados na tecnologia de sistemas microeletromecânicos, e vem sendo muito utilizados para análise do movimento humano. Logo, o objetivo desse estudo foi realizar uma revisão narrativa sobre o uso dos sensores inerciais nas medidas temporais e cinemáticas do TUG e suas subfases. Metodologia: Essa revisão narrativa foi realizada nas bases de dados PubMed, CENTRAL, BVS e PEDro, por meio do vocabulário MeSH entre o período de maio a junho de 2020. Os critérios de inclusão foram estudos que utilizaram sensores inerciais para avaliação de medidas temporais e cinemáticas do TUG e suas subfases. Resultados: Foram incluídos 11 artigos de um total de 2305 achados. Desses, 5 utilizaram os sensores de smartphones. Não houve padronização em relação à quantidade utilizada, nem à fixação e posicionamento. Os sensores conseguiram mostrar diferenças no TUG e suas subfases nas medidas temporais e cinemáticas nos diferentes grupos avaliados. Considerações Finais: Sensores inerciais são capazes de avaliar medidas temporais e cinemáticas do TUG e de suas subfases, mostrando serem ferramentas confiáveis. Entretanto, mesmo obtendo resultados satisfatórios, necessita-se de mais estudos abrangendo uma população maior.

The Timed Up and Go (TUG) functional test is widely used to assess the risk of falling through balance and mobility since it is easy to apply and presents good reproducibility in clinical practice. However, the TUG test still has some limitations, as it focuses on the total time the test is performed. A proposal for evaluation is the use of inertial sensors, based on the microelectromechanical system technology, which has been widely used for the analysis of human movement. Therefore, the objective of this study was to carry out a narrative review on the use of inertial sensors in the temporal and kinematic measurements of TUG and its subphases. Methodology: This narrative review was carried out in the PubMed, CENTRAL, BVS, and PEDro databases using the MeSH vocabulary between the period of May to June 2020. The inclusion criteria were studies using inertial sensors to evaluate temporal and kinematic measurements of the TUG and its subphases. Results: A total of 11 articles were selected from 2305 hits. From these, five (5) used smartphone sensors. There was no standardization regarding the quantity used, nor their fixation and positioning. The sensors were able to show differences in the TUG and its subphases in the temporal and kinematic measurements in the different groups evaluated. Final Considerations: Inertial sensors are capable of evaluating temporal and kinematic measurements of the TUG and its subphases, showing that they are reliable tools. Nevertheless, although satisfactory results were obtained, further studies are needed covering a larger population.

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

Effect of metformin on miRNA expression in type 2 diabetic patients and potential targets / 中华内分泌代谢杂志

Objective:To investigate the effect of metformin on the microRNA (miRNA) expression and screen potential target with network pharmacology analysis in patients with type 2 diabetes.Methods:Fifteen patients with new diagnosed type 2 diabetes admitted to our hospital were selected, who received metformin during hospitalization and after discharge. The expression of serum matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β1, and myocardial fibrosis related miRNAs were compared before and 6 month after metformin treatment. In addition, gene ontology (GO) and KEGG pathway enrichment analysis were applied to analyze differential expression miRNAs showing statistical significance. Meanwhile, the network figure was established to reflect the target gene messenger RNA (mRNA) corresponding to differentially expressed miRNA.Results:Compared with pre-medication, the serum level of MMP-9 was significantly decreased after treatment ( P<0.05). Besides, the expression of homo sapiens microRNA (hsa-miR)29a-3p, hsa-miR133a-5p, hsa-miR21-5p, hsa-miR30c-5p, and hsa-miR1-3p in patients with type 2 diabetes were dramatically down-regulated by metformin ( P<0.05 or P<0.01). Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in endoplasmic reticulum lumen, synapse, basement membrane and other cell components. The molecular functions such as Rho GTPase binding and participation in extracellular matrix structural constituent were exerted through biological processes such as collagen catabolic process, regulation of short-term neuronal synaptic plasticity, and axon extension, which were mainly enriched in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, tumor necrosis factor (TNF) signaling pathway, and Wnt signaling pathway, etc. The outcome of miRNA-mRNA network analysis demonstrated that there were 230 target genes mRNAs corresponding to differentially expressed miRNA. Conclusion:Metformin could play its role in the treatment of type 2 diabetes by down regulating the expression of miRNA, participating in the transduction of related cellular signaling pathways, regulating chromatin, nucleic acid binding, and enzyme activities.

Evaluation of Workshop for Recommending Advance Care Planning (ACP) for Medical and Health Care Professionals

Purpose: We held workshops (WSs) that recommend the use of advance care planning (ACP) for medical and health care professionals, and clarified whether or not these WSs motivated them to engage in their own ACP using two indicators: the proportion of professionals who wanted to conduct ACP and changes in the Death Attitude Inventory (DAI). Method: After the WS, we divided participants into two groups, depending on whether or not they wanted to have end-of-life discussions with their family and loved ones. The changes in the DAI brought about by the WSs and their impressions of the WS were compared between the groups. Results: A total of 91 participants were analyzed, of which 42 (46.2%) wanted to have end-of-life discussions with their family and loved ones. In both groups, “afterlife view” and “death anxiety and fear” in the DAI were significantly reduced after the WS when compared to attitudes from before the WS. In the group which wanted to have end-of-life discussions, “death avoidance” (effect size −0.42) and “sense of purpose in life” (effect size 0.51) changed significantly and positively. Conclusion: About half of the participants wanted to perform ACP after having attended the WSs, apparently due to an increased sense of purpose in life and a reduced death avoidance.

Mechanism of Shouhui Tongbian Capsules in treating constipation based on network pharmacology and molecular docking / 中国中药杂志

To explore the mechanism of Shouhui Tongbian Capsules in treating constipation by means of network pharmacology and molecular docking approach. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinfoematics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN) were applied to obtain chemical components and potential targets of eight herbs in Shouhui Tongbian Capsules according to the screening principles of oral availability(OB)≥30% and drug-like property(DL)≥0.18. Disease targets relating to constipation were screened out through GeneCards, PharmGkb and other databases, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Shouhui Tongbian Capsules for treating constipation; PPI network of potential targets was constructed using STRING platform, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) pathway data were obtained to conduct enrichment analysis and predict its mechanism of action. Cytoscape 3.6.1 was used to construct a network of "medicinal materials-chemical components-drug targets", and the network topology analysis was carried out on the PPI network to obtain its main components and key targets. Molecular docking between components and key targets of Shouhui Tongbian Capsules verified the accuracy of network pharmacological analysis results. The PPI network analysis showed 92 chemical components, including quercetin, stigmaste-rol, aloe-emodin, rhein, and key targets for instance AKT1, MAPK1, IL6, JUN, TNF and TP53. The enrichment analysis of KEGG screened out 157 signal pathways(P<0.01), mainly involving interleukin 17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, thyroid hormone signaling pathway. Quercetin, resveratrol and lysine with top degree value had a rational conformation in docking site of protein crystal complexes. This study preliminarily showed that various active ingredients in Shouhui Tongbian Capsules could regulate multiple signaling pathways, increase intestinal smoothness and peristalsis function, ensure smooth intestinal lumen, and play a role in treating constipation by acting on key targets, such as AKT1, MAPK1, IL6 and JUN.

G604S-HERG mutation in LQT2 leads to autophagy via the UPR-related pathway

Congenital long QT syndrome (LQTS) is a heart channel disease associated with fatal ventricular arrhythmiasor cardiac arrest. Human ether-a-go-go-related gene (HERG) mutation is one of the main causes in type 2LQTS since it may lead to abundant immature HERG channel protein accumulate in the endoplasmic reticulum(ER). In our study, we have successfully constructed the G604S-HERG mutation in HEK293 cells anddemonstrated that the immature HERG protein on ER via Western blot and immunofluorescence. Herein wefound that unfolded protein reaction (UPR) process has been activated in order to counter this endoplasmicreticulum stress (ERS) since the main sensors got upregulated. Meanwhile, autophagy was also observed inthis process and verified by Western blot and transmission electron microscopy. To explore the relationshipunderlying autophagy and UPR in the condition of ERS, we found that PERK-EIF2a-CHOP axis was activated. Our findings provides insight for G604S-HERG mutation in type 2 LQTS.

Timed Up And Go Performance In Older People With Diabetes Mellitus: Associations With Sensorimotor Function, Balance, Cognition, And Falls

Background: The Timed up and Go Test (TUG) is often used as a mobility measure in older people. However, it is unclear whether the TUG is useful for identifying fall risk in people with diabetes mellitus (DM) and which physical and cognitive/psychological factors influence the performance of this test. Objectives: To investigate whether slow TUG times (standard test and when performed with a secondary cognitive task (c-TUG)) are a risk factor for falls in older people with DM and to determine the relative contributions of a range of sensorimotor, balance and cognitive/psychological factors to TUG performance in this population. Methods: Community-dwelling people (n=103, mean age 61.57, SD=6.3) underwent the TUG and c-TUG tests as well as quantitative tests of vision, peripheral sensation, strength, reaction time, balance, cognition, and fear of falling. Participants were then followed up for falls for six months. Results: Negative binomial regression analyses revealed that each 1s increase in TUG and c-TUG times increased the risk of falling by 29% and 13%, respectively. Multiple regression analyses identified vibration sense (p<0.001), knee extension strength (p=0.001, r²=0.430), edge contrast sensitivity (p=0.002), neuropathy examination score (p=0.001, r²=0.498) and controlled leaning balance (p=0.033) as significant and independent explanatory predictors of TUG performance. The regression model for c-TUG was similar, vibration sense (p=0.042), knee extension strength (p=0.009, r²=0.256), neuropathy examination score (p=0.156, r²=0.272) and sway path-floor (p=0.042) except that the MOCA cognitive assessment (p=0.015) was included instead of edge contrast sensitivity. The combined explanatory variable models explained 43% and 26% of the variance in TUG and c-TUG times, respectively. Conclusions: Slow TUG and c-TUG times significantly increased the risk of falls in community-dwelling older people with DM. Poor TUG and c-TUG performances were related independently to decreased vibration sense, lower limb weakness, and poor balance, with the c-TUG additionally influenced by cognitive function.

A study of timed get up and go scores as falls risk assessment in elderly in a tertiary care centre

Background: Early detection of falls risk in the community dwelling elderly helps to take preventive measures to avoid falls and hence decrease morbidity associated with falls. Falls are a serious threat to independent living and self-confidence of the elderly. Using simple tools to determine risk of falls helps in early detection and prevention of falls. Aims and objectives of the study was to establish TUG data among patients attending the geriatric clinic at MGM hospital, Kamothe and to determine risk of falls in these patients with respect to their systemic involvement.Methods: A prospective observational study of 100 geriatric age group patients were studied for their TUG scores and classified based on systems involved. TUG was performed using standard protocol and scores were stratified based on gender, age and diagnosis. Participants were required to perform TUG and were instructed to rise from an armless chair walk 3 meters and turn around at the chalk mark, walk back, and sit. They were instructed to walk at a normal pace without walking aids and shoes. Time was recorded when participants’ buttocks were lifted off the chair to stand and stopped when the buttocks touched the seat when returning to sitting position.Results: The results showed that the average TUG score of this cohort of 100 patients attending our geriatric outpatient clinic was 13 sec. 60 Males and 40 females were analyzed of which  38 patients had less than 12 s  as TUG score and 62 patients  had more than or equal to 12 sec  as TUG score. Maximum number of patients undergoing the TUG test had musculoskeletal complaints. Yet patients with respiratory conditions had the highest mean TUG score of 14 sec and patients with abdominal and CNS conditions had lowest mean TUG scores.Conclusions: This study of TUG score of cohort of 100 patients showed that average TUG score was 13 sec which was higher than  12 second mark which indicates that these patients who did not have any previous fall had a  risk of future falls and hence a requirement of  an in depth  mobility assessment and early intervention.

Screening chronic periodontitis-related genes using whole-genome expression profiling / 中国组织工程研究

BACKGROUND: Whole-genome expression profiling is a technical method for gene expression research, with high sensitivity and specificity. This technique can be used to detect differential genes related to chronic periodontitis in the whole genome, therefore efficiently and quickly finding chronic periodontitis-related factors. OBJECTIVE: To screen genes related to chronic periodontitis by using the whole-genome expression profiling. METHODS: Normal periodontal ligament tissue of 15 patients with orthodontic extraction was selected as control group, and periodontal tissue of 21 patients with chronic periodontitis was selected as experimental group. To screen up-regulated and down-regulated genes. the genome-wide expression profile chips of four chronic periodontitis tissues and four healthy tissues were compared. The expression of the differential gene PI3K-Akt signal pathway was verified by real-time PCR (7 normal cases and 13 cases of chronic periodontitis) and western blot (4 normal cases and 4 cases of chronic periodontitis). The experimental protocol was approved by the Ethics Committee of the First Affiliated Hospital of Hainan Medical University (approval No. HNM20180034) and informed consent was obtained from each patient. RESULTS AND CONCLUSION: Analysis of the whole genome expression profile chip revealed that 1 565 up-regulated genes and 1 849 down-regulated genes were significantly differentially expressed in chronic periodontitis samples. The enrichment analysis revealed that the expression of PI3K-Akt signaling pathway was significantly different in chronic periodontitis (P < 0.001). Real-time PCR and western blot assay results indicated that PI3K and Akt expression was higher in the experimental group than in the control group (P < 0.05). All the findings indicate that the genome-wide expression profile chip is fast and highly sensitive to screen the changes in chronic periodontitis-related genes. Significantly differential expression of PI3K-Akt signal pathway in chronic periodontitis provides an experimental basis for the treatment of chronic periodontitis.