Destinos e distâncias da caminhada recreativa e utilitária: estudo empírico na cidade de Londrina-Paraná / Destinations and distances of recreational and utilitarian walking: empirical study in the city of Londrina-Paraná

Pesquisas indicam correlatos ambientais distintos para caminhada utilitária e recreativa. Este estudo teve como objetivo identificar locais, destinos e distância percorrida em caminhadas recreativas e uti-litárias, e comparar espacialmente a percepção sobre os locais caminhados. Para isso, foi realizado um estudo observacional transversal, conduzido em Londrina, Brasil. Os dados foram coletados através de questionário aplicado na plataforma Survey123, que contemplou pessoas maiores de 18 anos que reportassem ao menos uma rota de caminhada realizada no município de Londrina. A análise dos deslocamentos reportados foi feita pela estimativa de densidade de Kernele as distâncias de cami-nhada foram analisadas através do coeficiente de correlação ponto-bisserial ­ rpb. A espacialização dos dados perceptivos, obtidos através do questionário Neighborhood Environment Walkability Scale­ NEWS, foi realizada pela identificação de agrupamentos significativos através do indicador Gi*. A amostra totalizou 182 participantes e 305 deslocamentos a pé, dos quais, 61 classificados como ca-minhada recreativa e 244 como utilitária. Os locais de maior densidade de deslocamentos recreativos possuem ampla infraestrutura para pedestres, enquanto os de concentração de deslocamentos utili-tários são caracterizados pela diversidade de uso do solo. A caminhada recreativa registrou distância média de 3.955,3 ± 2.503,5m sendo que, para a caminhada utilitária, a média foi 1.247,0 ± 1.034,0m. A correlação ponto-bisserial obteve rpb = 0,611 e p<0,001, moderada a forte, indicando correlação po-sitiva entre a realização de viagens recreativas e uma maior distância média de caminhada. A pesquisa contribui para a investigação do comportamento de caminhada pela associação de variáveis objetivas e subjetivas e pela captura dos trajetos de deslocamento a pé.

Studies indicate distinct environmental correlates for utilitarian and recreational walking. This study aimed to identify the locations, destinations and the distance traveled in recreational and utilitarian walks, and to compare spatially the perception about the walked places. To achieve this, a cross-sectional observational study was conducted in Londrina, Brazil. Data was collected through a questionnaire applied on the Survey123 platform, including people aged 18 or over that reported at least one walking route performed in Londrina. The route analysis was made by Kernel density estimation and walking distances were analyzed through the point-bisserial correlation coefficient - rpb. The spatialization of perception data, obtained through the Neighborhood Environment Walkability Scale - NEWS form, was performed by identifying significant clus-ters through the Gi* indicator. The sample totaled 182 participants who reported 305 walk routes, of which 61 were classified as recreational walking and 244 as utilitarian. The places of higher recreational walking density have ample infrastructure for pedestrians, and the places with utilitarian walking concentration are characterized by the diversity of land use. Recreational walking recorded mean distance of 3.955.3 ± 2.503.5m, and for utilitarian walking, the average was 1.247.0 ± 1.034.0m. The point-bisserial correlation obtained rpb = 0.611 and p<0.001, moderate to strong, indicating a positive correlation between recreational trips and a greater average walking distance. This research contributes to the investigation of walking behav-ior through the association of objective and subjective variables and through the capture of walking routes.

Ciclismo recreacional e mobilidade urbana: análise das motivações dos ciclistas de Blumenau/SC / Urban mobility: an analysis of the motivations of cyclists in Blumenau/SC

A motivação é um fenômeno complexo que impulsiona as ações humanas. O diagnóstico de tais interesses oferece elementos de reflexão para a promoção de atividades e a implementação de políticas públicas. Neste contexto, o presente trabalho tem o objetivo de analisar as motivações dos praticantes de ciclismo recreacional de Blumenau/SC, município com uma população de 363 mil habitantes e uma malha cicloviária de 137 quilômetros. A coleta dos dados empíricos da pesquisa ocorreu por meio da aplicação de um questionário. Ao final, obteve-se uma amostra de 304 respondentes. Os resultados do estudo indicam a motivação para as atividades físicas ocupa papel central na relação com outros fatores de interesse, contribuindo para a superação de aspectos eventualmente desencorajadores. Em contrapartida, praticantes que têm outras motivações, como a interação social e o desenvolvimento pessoal, dependem mais de estímulos encorajadores, o que sugere que em tais casos existe a necessidade de maior incentivo para a prática do ciclismo recreacional. As conclusões deste estudo são relevantes para planejadores urbanos e gestores de comunicação. Ao mensurar a pertinência de causas motivadoras e desmotivadoras do ciclismo, os resultados da pesquisa indicam a importância de investir em infraestrutura adequada como a expansão da rede cicloviária e a criação de campanhas de divulgação, a fim de promover a bicicleta como meio de transporte e/ou recreação.

Motivation is a complex phenomenon that drives human actions. Diagnosing these interests provides elements for reflection in promoting activities and implementing public policies. In this context, the present study aims to analyze the motivations of recreational cyclists in Blumenau, SC (Brazil), a city with a population of 363,000 inhabitants and a cycling network of 137 kilometers. Empirical data for the research were collected through a questionnaire. Ultimately, a sample of 304 respondents was obtained. The study's results indicate that motivation for physical activities plays a central role in the relationship with other factors of interest, contributing to overcoming potentially discouraging aspects. Conversely, individuals motivated by other factors, such as social interaction and personal development, rely more on encouraging stimuli, suggesting that in such cases there's a need for greater incentives for recreational cycling. The conclusions of this study are relevant for urban planners and communication managers. By assessing the relevance of motivating and demotivating factors in cycling, the research results underscore the importance of investing in appropriate infrastructure, such as expanding the cycling network and launching promotional campaigns, to promote cycling as a means of transportation and/or recreation.

Socio-environmental factors contributing to the high incidence of COVID-19 in a border city in northern Uruguay / Factores socioambientales que contribuyen a alta incidencia de COVID-19 en ciudad fronteriza del norte de Uruguay / Fatores socioambientais que contribuem para alta incidência de COVID-19 em cidade fronteiriça no norte do Uruguai

Background and Objectives: the present study was conducted in the city of Rivera, situated in northern Uruguay on the border with Brazil. The disease initially progressed slowly in 2020, with subsequent outbreaks followed by a rapid increase in incidence. The objective was to explore the relationship between the spatial distribution of COVID-19 cases in a binational city and variables such as socioeconomic status, population density, and mobility patterns, with the aim of informing public policies. Methods: an exploratory study was conducted between August 2020 and January 2021 using data obtained from the Ministry of Health. The explanatory variables considered included population density, socioeconomic level, and mobility. Three distinct periods from 2020 to 2021 were identified. Spatial autocorrelation was analyzed using Moran's Index and the Gi* statistic (Getis & Ord). Hierarchical cluster analysis was employed to identify homogeneous groups of census segments. Results: a total of 1,846 cases were georeferenced. Through hierarchical cluster analysis, seven homogeneous groups were identified. Mobility was found to explain the incidence of cases among the high socioeconomic level group, while population density accounted for the differences observed in the low socioeconomic group. Conclusion: in this city, priority should be given to populations residing in areas with higher population density and greater mobility. This small-scale territorial analysis provides valuable information for developing localized policies aimed at addressing health crises.(AU)

Justificación y Objetivos: el estudio se realizó en la ciudad de Rivera, situada en el norte del país en la frontera con Brasil. La enfermedad progresó lentamente durante 2020, con brotes posteriores seguidos de un rápido aumento de la incidencia. El objetivo fue explorar la relación entre la distribución espacial de los casos de COVID-19 en una ciudad binacional y variables como nivel socioeconómico, densidad poblacional y patrones de movilidad, con el objetivo de informar políticas públicas. Métodos: se realizó un estudio exploratorio entre agosto 2020 y enero 2021 con datos del Ministerio de Salud, considerando semanas epidemiológicas. Las variables explicativas consideradas fueron densidad poblacional, nivel socioeconómico y movilidad. Se identificaron tres periodos temporales desde agosto 2020 hasta enero 2021. Se analizo la autocorrelación espacial empleando el Índice de Moran y estadística Gi* (Getis & Ord). Mediante el análisis de cluster jerárquico, fue posible identificar grupos homogéneos de segmentos censales. Resultados: se georreferenciaron un total de 1.846 casos. Mediante análisis de cluster jerárquico, se identificaron siete grupos homogéneos. Para el nivel alto socioeconómico, la movilidad es el factor explicativo de una mayor incidencia de casos. Mientras que, para para el grupo de nivel bajo, la densidad de la población fue el factor explicativo de las diferencias en la presentación de la enfermedad. Conclusión: la población a ser priorizada en esta ciudad corresponde a aquellas zonas con mayor densidad poblacional y donde se incrementa la movilidad. El análisis territorial a pequeña escala genera información para la construcción de política local, ante una crisis sanitaria, que la hace más eficaz.(AU)

Justificativa e Objetivos: o presente estudo foi realizado na cidade de Rivera, localizada no norte do Uruguai, na fronteira com o Brasil. A doença progrediu lentamente durante 2020, com surtos subsequentes seguidos por um rápido aumento na incidência. O objetivo foi explorar a relação entre a distribuição espacial dos casos de COVID-19 em uma cidade binacional e variáveis como nível socioeconômico, densidade populacional e padrões de mobilidade, com o objetivo de informar políticas públicas. Métodos: estudo exploratório foi realizado entre agosto de 2020 e janeiro de 2021 com dados do Ministério da Saúde. As variáveis explicativas incluíram densidade populacional, nível socioeconômico e mobilidade. Três períodos distintos de 2020 a 2021 foram identificados. Autocorrelação espacial foi analisada com o Índice de Moran e a estatística Gi* (Getis & Ord). Utilizando a análise de cluster hierárquico, foi possível identificar grupos homogêneos de segmentos censitários. Resultados: um total de 1.846 casos foi georreferenciado. Através da análise de cluster hierárquico, sete grupos homogêneos foram identificados. A mobilidade foi encontrada como explicativa para a incidência de casos no grupo de alto nível socioeconômico, enquanto a densidade populacional explicou as diferenças observadas no grupo de baixo nível socioeconômico. Conclusão: nessa cidade, as populações a serem priorizadas são aquelas que residem em áreas com maior densidade populacional e maior mobilidade. Essa análise territorial em pequena escala fornece informações valiosas para o desenvolvimento de políticas locais destinadas a lidar com crises de saúde.(AU)

HMGB1 gene knockout alleviates acute lung injury of sepsis mice via inhibiting TLR4/NF-κB pathway / 安徽医科大学学报

Objective To study the effect of high mobility group box B1(HMGB1)gene knockout on alleviating a-cute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway of sepsis mice.Methods Wild-type(WT)mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO)mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO2)was detected,oxy-genation index(OI)was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO2,OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1 β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P＜0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO2,OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P＜0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the re-lated molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.

Inhibitory effect of downregulating HMGB2 expression on epithelial-mesenchymal transition of liver cancer LM3 cells and its AKT/m TOR signaling pathway mechanism / 吉林大学学报(医学版)

Objective:To discuss the effect of downregulating of high mobility group box protein 2(HMGB2)expression on the biological behavior of the liver cancer cells and the epithelial-mesenchymal transition(EMT)process,and to clarify its mechanism.Methods:The human liver cancer LM3 cells at logarithmic growth phase were divided into negative control group and HMGB2 RNA interference group(HMGB2 siRNA group);the cells in two groups were transfected with RNA oligonucleotides(RNA oligos)with irrelevant sequences and RNA oligos designed to knock down HMGB2,and the Lipofectamine 2000 was regarded as the vector.The expression levels of HMGB2 mRNA and protein in the cells in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods;cell scratch assay and Transwell chamber assay were used to detect the migration and invasion abilities of the cells in two groups;the expression levels of E-cadherin,N-cadherin,and Vimentin proteins and protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway related proteins in the cells in two groups were detected by Western blotting method.Results:Compared with negative control group,the expression levels of HMGB2 mRNA and protein in the cells in HMGB2 siRNA group were significantly decreased(P<0.05),the cell scratch healing rate was significantly decreased(P<0.01),the number of invasion cells was significantly decreased(P<0.01),and the expression level of E-cadherin protein in the cells was significantly increased(P<0.01),while the expression levels of N-cadherin,Vimentin,mTOR,AKT,and phosphorylated AKT(p-AKT)proteins in the cells were significantly decreased(P<0.05 or P<0.01).Conclusion:Downregulating the expression of HMGB2 can reduce the migration and invasion abilities of the liver cancer LM3 cells and inhibit the EMT,and its mechanism may be related to regulating the expression of the AKT/mTOR pathway related proteins.

Structure Study of Proton Tautomers Based on Ion Mobility Mass Spectrometry and Ab Initio Molecular Dynamics Calculations / 分析化学

Investigating the structural characteristics of proton tautomers is of great significance for understanding organic reactions and biochemical processes.In this study,a method based on ion mobility mass spectrometry combined with ab initio molecular dynamics calculations was proposed.The structures of proton tautomers were determined by comparing the experimental and theoretical collision-induced dissociation(CID)mass spectrograms of different proton tautomers.Ion mobility mass spectrometry was used to separate proton tautomerism produced during ionization.The CID mass spectra of each isomer could be obtained after mobility separation.The quantum chemical mass spectrometry(QCXMS)program based on ab initio molecular dynamics calculations was used to calculate the fragmentation process and obtain the theoretical CID mass spectra.The results of experiment and calculation showed that this method effectively solved the issue of difficult identification of proton tautomers.This method was also of great significance for the study of ionization mechanism and organic reaction process using mass spectrometry.

miR-142-3p inhibits cerulein-induced apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1 / 基础医学与临床

Objective To investigate the effect of miR-142-3p on the apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1.Methods AR42J cells were divided into blank group(blank),acute pancreatitis model group(AP,100 nmol/L cerulein for 24 h),and then transfected with miR-142-3p mimics,mimics NC,miR-142-3p inhibitor and inhibitor NC,respectively.The cells in the model group were recorded as miR-142-3p mimics group,mimics NC group,miR-142-3p inhibitor group and inhibitor NC.The expression of miR-142-3p in cells was detected by RT-qPCR.The protein expressions of HMGB1,caspase-3,Bax and Bcl-2 were detected by Western blot.Hoechst staining was used to determine cell apoptosis.The apoptosis rate of cells was detected by flow cytometry.The targeting relationship between miR-142-3p and Hmgb1 was determined by dual luciferase reporter gene assay.Results Compared with blank control group,the expression level of miR-142-3p in the AP group was significantly down-regulated(P＜0.01),the expression level of HMGB1 and caspase-3 proteins was up-regulated(P＜0.05),the expression level of Bax protein was significantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was significantly decreased(P＜0.01)and the apoptosis rate increased significantly(P＜0.01).Compared with the mimics NC group,the level of miR-142-3p in the miR-142-3p mimics group was significantly up-regulated(P＜0.01),the expression of HMGB,caspase-3 and Bax proteins was significantly down-regulated(P＜0.01),the expression of Bcl-2 protein was up-regulated(P＜0.05),and the apoptosis rate decreased signifi-cantly(P＜0.01).Compared with inhibitor NC group,the expression level of miR-142-3p in miR-142-3p inhibitor group was down-regulated(P＜0.05),the expression levels of HMGB1,caspase-3 and Bax proteins were signifi-cantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was decreased(P＜0.05)and the apoptosis rate increased significantly(P＜0.01).The dual luciferase reporter gene assay showed that Hmgb1 was the target gene of miR-142-3p.Conclusions 1)The expression of miR-142-3p was low in the model group.2)miR-142-3p can inhibit the apoptosis of AR42J cells by inhibiting the expression of Hmgb1.

CT-guided pulsed radiofrequency combined with continuous nerve block for the treatment of refractory postherpetic neuralgia:a clinical study / 介入放射学杂志

Objective To investigate the clinical efficacy of CT-guided pulsed radiofrequency combined with continuous nerve block in the treatment of refractory postherpetic neuralgia(PHN).Methods A total of 208 patients with refractory PHN,who were admitted to the Hengshui Municipal People's Hospital of China between January 2021 and January 2023,were selected as the subjects of study.Using random number table method,the patients were divided into combination group and control group,with 104 patients in each group.The patients of control group received CT-guided pulsed radiofrequency therapy,and the patients of combination group received additional continuous nerve block therapy on the basis of the treatment of control group.The pain degree at different time point,clinical effective rate,number of analgesia remedy times,quality of sleep,and the levels of serum high mobility group box 1(HMGB1),interleukin-1 β(IL-1β)and interleukin-10(IL-10)were compared between the two groups.Results During the follow-up period,4 patients were lost in touch.Finally,103 patients were included in the combination group and 101 patients were included in the control group.The total treatment response rate in the combination group was 89.32％,which was significantly higher than 78.22％in the control group(P＜0.05).There were statistically significant differences in visual analogue scale(V AS)scores and Athens insomnia scale(AIS)scores including the time effect,inter-group effect and time-group interaction effect,between the two groups(P＜0.05).The postoperative one-week,2-week,4-week VAS scores and AIS scores in the combination group were remarkably lower than those in the control group(P＜0.05).The number of analgesia remedy times in the combination group was smaller than that in the control group,and the used dosage of tramadol in the combination group was lower than that in the control group(P＜0.05).Four weeks after treatment,the serum levels of HMGB1,IL-1β and IL-10 in the combination group were lower than those in the control group(P＜0.05).Conclusion For the treatment of refractory PHN,CT-guided pulsed radiofrequency combined with continuous nerve block can effectively alleviate neural inflammatory damage,and improve pain symptoms and sleep quality,besides,its analgesic effect and clinical efficacy are superior to CT-guided pulsed radiofrequency alone.(J Intervent Radiol,2024,33:264-268)

Prospective Clinical Study of Combined Treatment of Periodontal Orthodontics for Chronic Periodontitis / 昆明医科大学学报

Objective To investigate the effect of dynamic monitoring of occlusal force on the final therapeutic effect and the change of periodontal supporting tissue during combined periodontal orthodontic treatment.Methods The periodontal clinical index of 20 patients with traditional periodontal orthodontic treatment and 20 patients with combined periodontal orthodontic treatment assisted by T-Scan Ⅲ and Anycheck digital occlusion analysis system were compared before,during and after treatment,as well as the changes of bite force,bite time and tooth mobility in the experimental group.Results The depth of periodontal pocket(PD),loss of attachment(AL),bleeding index(BI)and tooth looseness were significantly reduced after combined periodontal orthodontic treatment in both groups.In the control group,the percentage of anterior and posterior biting force changed obviously,and the occlusion force balance was improved.Conclusion The combined treatment of periodontitis and orthodontics can improve the periodontal tissue of patients with periodontitis,and T-Scan system can observe and guide the adjustment of occlusal and better achieve occlusion force balance.

The expression of serum procalcitonin,pentraxin 3 and high mobility group protein B1 in children after open gastrointestinal surgery and its value in predicting early infection / 临床外科杂志

Objectiv To analyze the expression of serum procalcitonin(PCT),pentraxin 3(PTX3)and high mobility group protein B1(HMGB-1)in children after open gastrointestinal surgery and their application value in early infection prediction.Methods A retrospective analysis was performed on 206 children with open gastrointestinal surgery admitted to the hospital from January 2020 to January 2023.They were divided into infection group(27 case)and non-infection group(179 case)according to whether they had postoperative infection.The levels of serum PCT,PTX3 and HMGB-1 before operation,1 d and 3 d after operation were compared between the two groups.The predictive value of single and combined detection of serum indexes 1 d and 3 d after operation for postoperative infection in children with open gastrointestinal surgery was observed.The influencing factors of postoperative infection were analyzed by multivariate Logistic regression.Results The levels of serum PCT,PTX3 and HMGB-1 in the infection group were(2.42±0.39)μg/L,(3.74±0.53)pg/L,(2.07±0.66)p,g/L,(3.06±0.75)μg/L,(18.35±2.74)μg/L,and(26.09±4.16)μg/L at 1 d and 3 d after operation,which were higher than those in the non-infection group(1.71±0.35)pg/L,(2.29±0.36)μg/L,(1.48±0.52)μg/L,(1.73±0.59)pg/L,(13.04±2.26)μg/L,and(15.75±2.83)pg/L(P＜0.05).Receiver operating characteristic curve showed that the area under the curve(AUC)of combined detection of serum PCT,PTX3 and HMGB-1 in predicting postoperative infection in children with open gastrointestinal surgery was the largest(0.989)at 3 days after operation;Multivariate Logistic regression analysis showed that age was an independent protective factor for postoperative infection in children,and Intraoperative blood loss,operation time,serum PCT,PTX3 and HMGB-1 at 1 d and 3 d after operation were independent risk factors(P＜0.05);The levels of serum PCT,PTX3 and HMGB-1 in children with moderate to severe infection were(2.63±0.34)μg/L,(4.12±0.56)μg/L,(2.31±0.69)μg/L,(3.39±0.81)μg/L,(19.86 ±2.91)pg/L,and(28.84±4.40)μg/L at 1 d and 3 d after operation,which were higher than those in children with mild infection(2.11±0.28)μg/L,(3.19±0.49)μg/L,(1.72±0.60)μg/L,(2.58± 0.73)μg/L,(16.15±2.39)μg/L,and(22.09±3.96)pg/L(P＜0.05).Conclusion The expression of serum PCT,PTX3 and HMGB-1 in children after open gastrointestinal surgery was significantly increased,and its expression was related to early postoperative infection and the severity of infection,and the combined predictive value of the three was higher,which could provide reference for early infection prediction.

Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN-γ/IL-4 ratio in patients with severe pneumonia / 实用医学杂志

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End-Product(RAGE)and High-Mobility Group Protein B1(HMGB1)expression with the occurrence of acute respiratory distress syndrome(ARDS)and interferon-γ/interleukin-4(IFN-γ/IL-4)ratio in patients with severe pneumonia(SP).Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022,and the participants were classified into ARDS group(n = 56)and control group(n = 44)based on the occurrence of secondary ARDS.General informations werec-ollected.The expression of RAGE,HMGB1,IFN-γ and IL-4 in peripheral blood was measured using Enzyme-Linked Immunosorbent Assay(ELISA).Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children,and the correlation with IFN-γ/IL-4 ratio was verified by pearson correla-tion analysis,moreover,receiver operating characteristic(ROC)curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children.Results There were no statistical difference in gender,age,body temperature and onset season between the two SP groups.The ARDS group had more types of pathogenic bacteria,larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction(PaO2/FiO2),higher Acute Physiological Score(APS),and up-regulated expression of RAGE,HMGB1,IFN-γ and IL-4,as well as larger IFN-γ/IL-4 ratio than those of control group,with statistical difference(all P<0.05).Multivariate Logistic regression analysis revealed that pathogen type,PaO2/FiO2 ratio,RAGE,HMGB1,IFN-γ,IL-4 and IFN-γ/IL-4 were the influencing factors for the occurrence of ARDS in children with SP.Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN-γ,IL-4 and IFN-γ/IL-4 ratio(P<0.05).ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750,with a sensitivity of 73.2%and 64.3%,and a specificity of 68.2%and 77.3%.The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848,providing a sensitivity and specificity of 80.4%and 81.8%respectively.Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS,and the two are positively correlated with IFN-γ/IL-4 ratio.Therefore,monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.

Clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma and its impact on serological indicators and airway function of children / 新乡医学院学报

Objective To explore the clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma(CVA)and its impact on serological indicators,airway function of children.Methods A total of 124 children with CVA admitted to the Zigong First People's Hospital from March 2019 to April 2022 were selected as the research subjects.The children were divided into control group and observation group according to random number table method,with 62 cases in each group.The children in the control group were treated with procaterol hydrochloride,and the children in the observation group were treated with procaterol hydrochloride and Xiaokechuan capsule for two weeks.The clinical efficacy of children was compared between the two groups after treatment.The cough scores during the day and night of children were evaluated in the two groups before and 2 weeks after treatment.The serum high mobility group protein B1(HMGB1),Toll like receptor 4(TLR4),nuclear factor-κB(NF-κB),interleukin-4(IL-4),interferon-γ(INF-γ)levels of children in the two groups were measured by enzyme linked immunosorbent assay before and 2 weeks after treatment,and the ratio of INF-γ/IL-was calculated.The 25％maximal expiratory flow-volume(MEF25),50％maximal expiratory flow-volume(MEF50),75％maximal expiratory flow-volume(MEF75)of children in the two groups were measured by lung function detector before and 2 weeks after treatment.The adverse reactions of children in the two groups were recorded during treatment.Results The total effective rate of children in the control group and observation group was 82.26％(51/62)and 95.16％(59/62),respectively;the total effective rate of children in the observation group was significantly higher than that in the control group(P＜0.05).There was no significant difference in cough scores during the day and night of children between the two groups before treatment(P＞0.05);the cough scores during the day and night of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the cough scores during the day and night of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in serum HMGB1,TLR4,NF-κB levels of children between the two groups before treatment(P＞0.05);the serum HMGB1,TLR4,NF-κB levels of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the serum levels of HMGB1,TLR4,and NF-κB of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in MEF25,MEF50,and MEF75 of children between the two groups before treatment(P＞0.05);the MEF25,MEF50,and MEF75 of children after treatment were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the MEF25,MEF50,and MEF75 of children in the observation group were significantly higher than those in the control group(P＜0.05).There was no significant difference in serum IL-4,INF-γ levels and the ratio of INF-γ/IL-4 of children between the two groups before treatment(P＞0.05);the serum IL-4 level of children after treatment were significantly lower than those before treatment,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the serum IL-4 level of children in the observation group was significantly lower than that in the control group,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those in the control group(P＜0.05).All children had good drug tolerance during the treatment period,and no significant adverse drug reactions were observed.Conclusion The combination of Xiaokechuan capsules and procaterol hydrochloride has a significant therapeutic effect for pediatric CVA,and its mechanism of action may be related to the regulation of HMGB1-TLR4-NF-κB signal pathway.

Bushen Yugu Formula （补肾愈骨方） for Postoperative Functional Rehabilitation of Patients with Chronic Lateral Ankle Instability with Syndrome of Liver-Kidney Insufficiency and Sinews-Vessels Deprived of Nourishment：A Retrospective Cohort Study / 中医杂志

ObjectiveTo investigate the effectiveness and safety of Bushen Yugu Formula （补肾愈骨方） promoting postoperative functional rehabilitation of patients with chronic lateral ankle instability （CLAI） with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nourishment. MethodsClinical data were retrospectively collected from 40 patients with CLAI with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nou-rishment who underwent external ankle ligament repair surgery. They were divided into 20 cases each in the treatment group and control group according to whether or not they took Bushen Yugu Formula； patients in the control group underwent postoperative functional rehabilitation， while patients in the treatment group took Bushen Yugu Formula in the 3rd and 4th postoperative weeks combined with the rehabilitation. The American Orthopaedic Foot and Ankle Society （AOFAS） scores， the flexion/extension and internal/external rotation， the imaging scores of the ankle joint on the operated side and the traditional Chinese medicine （TCM） syndrome scores were recorded in the preoperative and 3-month postoperative， respectively. The patients' liver and kidney functions were tested in the preoperative and 4-month postoperative， and adverse events during treatment were recorded. ResultsCompared with the preoperative period， the AOFAS scores were higher and the TCM syndrome scores were lower in both groups 3 months after surgery （P＜0.01）， and the ankle internal and external rotation mobility and imaging scores were higher in the treatment group （P＜0.05 or P＜0.01）， and ankle flexion/extension mobility was lower in the control group （P＜0.05）. At 3 months after surgery， the AOFAS score was higher in the treatment group than in the control group， and the TCM syndrome score was lower than in the control group （P＜0.05 or P＜0.01）. Two cases of gastrointestinal reactions were reported in the treatment group， which relieved on their own after stopping the formula， and no abnormality was observed in liver and kidney function indexes. ConclusionBushen Yugu Formula can promote functional rehabilitation of ankle joint and improve clinical symptoms in CLAI patients with syndrome of liver-kidney insufficiency and sinews-vessels deprived of nourishment， and it shows a good safety.

Investigation of the hydromechanical threshold of high-mobility group box 1 release from synovial cells and chondrocytes / 口腔疾病防治

Objective@#To investigate the effect of fluid flow shear stress (FFSS) on the fluid mechanic threshold of high-mobility group box 1 (HMGB1) release by synovial cells and chondrocytes. Moreover, the mechanism of chondrocyte and synovial cell damage induced by abnormal mechanical force was investigated to provide an experimental basis for exploring the pathogenesis and pathology of temporomandibular joint osteoarthritis.@*Methods@#With the approval of the Ethics Committee for Animal Experiments of the hospital, synovial tissue and cartilage tissue blocks were obtained from the knee joints of Sprague-Dawley (SD) rats, and synovial cells and chondrocytes were cultured and digested for subsequent experiments. Synovial cells and chondrocytes of 3-4 generations were acquired, and FFSS was applied to synovial and cartilage cells using a fluid shear mechanical device. The cells were divided according to the FFSS values of different sizes. Synovial cells were stimulated for 1 h with 1, 3, 5, or 10 dyn/cm2 of FFSS, and chondrocytes were stimulated for 1 h with 4, 8, 12, or 16 dyn/cm2 of FFSS. Resting cultures (0 dyn/cm2) were used as the control group. Changes in the morphology of the cells were observed. The expression and distribution of HMGB1 and interleukin-1β (IL-1β) were observed by immunohistochemistry. The expression of HMGB1 and IL-1β in the supernatant was analyzed by ELISA. The protein expression levels of intracellular HMGB1 and IL-1β were detected by Western blot.@*Results@#With increasing FFSS, the synovial cells and chondrocytes gradually swelled and ruptured, and the number of cells decreased. With increasing FFSS, the localizationof HMGB1 and IL-1β gradually shifted from the nucleus to the cytoplasm. In synovial cells, compared with those in the control group, the expression levels of HMGB1 and IL-1β were increased both in the supernatant and cells in the 1, 3, 5 and 10 dyn/cm2 intervention groups (P<0.01). In chondrocytes, compared with those in the control group, the expression levels of HMGB1 in the supernatant were increased in the 4, 12 and 16 dyn/cm2 intervention groups (P<0.05), and the protein expression levels of HMGB1 were significantly increased (P<0.01). The expression levels of HMGB1 in the supernatant were significantly increased in the 8 dyn/cm2 intervention groups (P<0.01); however, the protein expression levels of HMGB1 were significantly decreased. Compared with those in the control group, the expression levels of IL-1β in the supernatant gradually increased in the 4, 8, 12 and 16 dyn/cm2 intervention groups (P<0.01). With the exception of those in the 4 dyn/cm2 group, the protein expression levels of IL-1β gradually increased with increasing FFSS (P<0.05).@*Conclusion@#With increasing FFSS, synovial cells and chondrocytes gradually swelled and burst, and the hydromechanical thresholds of HMGB1 release were 1 dyn/cm2 and 8 dyn/cm2, respectively. Therefore, upon stimulation with a mechanical force, synovial damage was damaged before chondrocytes.

Effect of miR-141-3p targeting HMGB1 on LPS-induced A549 cell injury / 安徽医科大学学报

Objective @#To investigate the effect of miR-141-3p on LPS induced A549 cell injury by targeting high mobility group protein 1 (HMGB1) ．@*Methods @#A549 cells derived from type Ⅱ alveolar epithelial cells were taken as the study object，miR-141-3p mimics，mimics NC，HMGB1 gene overexpression plasmid (pcDNA3. 1-HMGB1) and empty Vector were transfected into A549 cells respectively or co-transfected，then 10 μg / ml LPS was used for 24 h．Cell proliferation activity was detected by cell counting kit-8 ( CCK-8) ．The activity of lactate dehydrogenase ( LDH) in the supernatant of cell culture was detected by colorimetry．The apoptosis level of each group was detec- ted by flow cytometry．The levels of interleukin (IL) -1 β , IL-6 and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (Elisa) ．Dual luciferase reporter gene assay verified the targeted regulatory relationship between miR-141-3p and HMGB1 . @*Results @#After treatment with LPS ，the proliferative activity of A549 cells and the expression level of miR-141-3p decreased ( P ＜0. 05 ) ，the apoptosis rate increased ( P < 0. 05) ，the levels of IL-1 β , IL-6，TNF-α and the activity of LDH in supernatant increased (P＜0. 05) ．Overex- pression of miR-141-3p increased the proliferation activity of A549 cells treated with LPS (P ＜0. 05 ) ，and de- creased the apoptosis rate and the levels of IL-1 β , IL-6，TNF-α in cells and LDH activity in supernatant (P < 0. 05) ．However，overexpression of HMGB1 gene could reverse the ameliorative effect of miR-141-3p on LPS-in- duced A549 cell injury．Dual luciferase reporter gene experiment confirmed that HMGB1 was the downstream target gene of miR-141-3p．@*Conclusion @# miR-141-3p can inhibit LPS-induced apoptosis，reduce the expression level of inflammatory factors，and improve the damage of A549 cells，which may be related to the targeted regulation of HMGB1 expression.

Role of thrombomodulin-thrombin-high mobility group box 1 pathway in chronic subdural hematoma / 中华神经医学杂志

Chronic subdural hematoma (CSDH) is a collection of blood, blood clots and their degradation products, encapsulated by membrane and located within dural border cell layer. Pathophysiological processes such as inflammatory responses within hematoma cavity, coagulation abnormalities, and abnormalities in neovascularization play significant roles in CSDH development. High mobility group box 1 (HMGB1) can mediate processes such as inflammation, angiogenesis, and hemostasis, while thrombomodulin (TM) can bind with HMGB1 and rely on thrombin to degrade HMGB1. Current research has confirmed that the expressions of TM, HMGB1, and their downstream related factors are abnormally increased in the hematoma fluid of CSDH; however, the role of TM-thrombin-HMGB1 pathway in CSDH development is not fully clear. This article reviews the role of TM-thrombin-HMGB1 pathway in CSDH development, aiming to provide some references for pathogenesis and new therapeutic targets of CSDH.

Effect of oxymatrine on Cryptosporidium parvum infection in mice based on the HMGB1-TLR2/TLR4-NF-κB pathway / 中国血吸虫病防治杂志

Objective To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice. Methods Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay. Results HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05). Conclusions C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.

Clinical significance of changes in peripheral blood angiotensin-converting enzyme 2, high mobility group protein B1 and interleukin-33 levels in patients with primary lung cancer complicated by pulmonary infection after surgery / 中国医师进修杂志

Objective:To investigate the changes in peripheral blood angiotensin-converting enzyme 2 (ACE2), high mobility group protein B1 (HMGB1) and interleukin 33 (IL-33) levels and their clinical significance in patients with primary lung cancer complicated by lung infection after surgery.Methods:The clinical data of 92 primary lung cancer patients treated at Longchang People′s Hospital from August 2018 to February 2021 were retrospectively collected, they were underwent radical lung cancer surgery, and were divided into the pulmonary infection group(27 cases) and the non-pulmonary infection group(65 cases) according to whether the patients had postoperative complications of pulmonary infection. The clinical data, peripheral blood ACE2, HMGB1 and IL-33 levels before and after surgery between the two groups were compared. The risk factors associated with postoperative pulmonary infection were analyzed by Lasso regression and Logistic regression. The predictive value of pulmonary infection was analyzed by receiver operating characteristic (ROC) curve. The cut-off values of peripheral blood ACE2, HMGB1 and IL-33 in the ROC curve were used as the boundary to divide the high level group and low level group, and the Kaplan-Meier survival curve was drawn to compare the survival rates of patients with high levels and low levels of peripheral blood ACE2, HMGB1 and IL-33.Results:The incidence of chronic obstructive pulmonary disease in the pulmonary infection group was higher than that in the non-pulmonary infection group: 40.74%(11/27) vs. 15.38%(10/65), there was statistical difference ( χ2 = 6.96, P<0.05). The levels of postoperative peripheral blood ACE2, HMGB1 and IL-33 in the pulmonary infection group were higher than those in the non-pulmonary infection group: (36.87 ± 9.87) mg/L vs. (25.94 ± 8.69) mg/L, (24.49 ± 8.14) μg/L vs. (16.74 ± 5.07) μg/L, (51.48 ± 8.25) ng/L vs. (39.88 ± 6.85) ng/L, there were statistical differences ( P<0.05). The results of Lasso regression and Logistic regression showed that the chronic obstructive pulmonary disease, postoperative peripheral blood ACE2, HMGB1 and IL-33 levels were independent risk factors for postoperative complications of pulmonary infection in patients with primary lung cancer ( P<0.05). The results of ROC curve showed that the area under the curve(AUC) values for postoperative peripheral blood ACE2, HMGB1 and IL-33 levels predicting postoperative complications of lung infection were 0.705, 0.821 and 0.768, respectively, and the AUC for the combination was 0.935. The risk of death in patients with high levels of postoperative peripheral blood ACE2, HMGB1 and IL-3 were 7.500, 4.874 and 2.857 times than the patients with low levels. Conclusions:Postoperative peripheral blood ACE2, HMGB1 and IL-3 levels in patients with primary lung cancer are important factors for pulmonary infection, which can be used for early prediction and evaluation after operation.

Effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/HMGA1 axis regulation / 中国医科大学学报

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

Glycyrrhizic Acid Showed Therapeutic Effects on Severe Pulmonary Damages in Mice Induced by Pneumonia Virus of Mice Infection / 实验动物与比较医学

Objective In this study, inbred BALB/c mice infected with the pneumonia virus of mice (PVM) were used to establish an animal model of viral pneumonia, and the changes in the pro-inflammatory alarmin molecule, high mobility group box 1 protein (HMGB1), during PVM infection were observed, as well as the in vivo intervention effects of the HMGB1 inhibitor, glycyrrhizic acid (GA), on PVM-induced lung injury. Methods Three-week-old female BALB/c mice were randomly divided into three groups, each consisting of 6 mice. One group, uninfected by PVM, served as the control group (Control). The other two groups were inoculated intranasally with PVM at a dose of 1×104 50% tissue culture infective dose (TCID50)/25 μL, and subsequently treated with GA saline solution (GA group) or plain saline solution (normal saline, NS group) via gavage for 15 consecutive days. During this period, changes in body weight and appearance were monitored in each group. At the end of the experiment, lung tissue samples were collected from all groups. The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry. The expression levels of HMGB1 and its Toll-like receptor 4 (TLR-4), advanced glycosylation end-product-specific receptor (AGER), and inflammatory cytokines such as interleukin (IL)-1β, IL-2, and tumor necrosis factor-α (TNF-α) in lung tissues of mice were measured using real time fluorescence quantitative PCR. Results Compared with the Control group, the NS group showed a significant weight loss after 6 days (P<0.05). Histopathological tests revealed pronounced inflammatory lesions in their lungs. Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm, and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1, IL-1β, and IL-2 were significantly upregulated (P<0.05). In the GA group, there was no significant change in the clinical symptoms or body weight. However, compared with the NS group, the pathological damages of lung tissues in the GA group were significantly reduced, and the expression levels of HMGB1, IL-1β, IL-2, and interferon-γ (IFN-γ) in lung tissues were also significantly decreased (P<0.05), although the expression level of AGER was significantly increased (P<0.05).ConclusionPVM infection can cause significant inflammatory pathological lung damages in mice, and GA can effectively alleviate the damages. Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.