Dopamine Dynamics in the Amygdala Influence Emotional Changes in the Early Stage of Systemic Inflammatory Response Syndrome in Rats / La Dinámica de la Dopamina en la Amígdala Influye en los Cambios Emocionales en la Etapa Temprana del Síndrome de Respuesta Inflamatoria Sistémica en Ratas

SUMMARY: Systemic inflammatory response syndrome (SIRS) is a potentially fatal reaction to various forms of tissue damage and infections that cause damage to various organs. Furthermore, the brain is damaged earlier than other organs, resulting in diffuse brain dysfunction. The central clinical symptom of SIRS is delirium and emotional changes are involved in disease development. Although the amygdala is known to play a major role, the mechanisms underlying emotional changes in the early stages of SIRS have not been elucidated. Therefore, changes to dopamine levels in the amygdala were observed using an in vivo model of lipopolysaccharide (LPS)- induced SIRS to clarify the biochemical mechanisms activated in the early stages of SIRS. Extracellular dopamine was collected from the amygdala of free moving rats via microdialysis and then analyzed by high-performance liquid chromatography. In addition, emotional changes were assessed with the open field and sucrose preference tests. In the LPS group, dopamine release in the amygdala increased remarkably immediately after LPS administration, peaking at 120 min. Thereafter, dopamine release temporarily decreased, but then significantly increased again after 180 min. The present results suggest that diffuse brain dysfunction in the early stages of SIRS may involve altered dopamine levels in the amygdala.

El síndrome de respuesta inflamatoria sistémica (SRIS) es una reacción potencialmente fatal a diversas formas de daño tisular e infecciones que causan injuria a varios órganos. Además, el cerebro se daña antes que otros órganos, lo que provoca una disfunción cerebral difusa. El síntoma clínico central del SIRS es el delirio y los cambios emocionales están involucrados en el desarrollo de la enfermedad. Aunque se sabe que la amígdala desempeña un papel importante, no se han dilucidado los mecanismos que subyacen a los cambios emocionales en las primeras etapas del SRIS. Por lo tanto, en el estudio se provocaron cambios en los niveles de dopamina en la amígdala utilizando un modelo in vivo de SRIS inducido por lipopolisacáridos (LPS) para dilucidar los mecanismos bioquímicos activados en las primeras etapas del SRIS. La dopamina extracelular se recogió de la amígdala de ratas en movimiento libre mediante microdiálisis y luego se analizó mediante cromatografía líquida de alta resolución. Además, se evaluaron los cambios emocionales con las pruebas de campo abierto y de preferencia de sacarosa. En el grupo de LPS, la liberación de dopamina en la amígdala aumentó de manera notable inmediatamente después de la administración de LPS, alcanzando un máximo a los 120 minutos. A partir de entonces, la liberación de dopamina disminuyó temporalmente, pero luego volvió a aumentar significativamente después de 180 min. Los resultadosactuales sugieren que la disfunción cerebral difusa en las primeras etapas del SIRS puede implicar niveles alterados de dopamina en la amígdala.

Analysis of the metabolic profile and comorbidities in women with endometriosis before and after surgical treatment / Análise do perfil metabólico e comorbidades em mulheres com endometriose antes e depois do tratamento cirúrgico

Aim: this study aimed to evaluate the effects of surgical treatment for endometriosis on the metabolic profile of women diagnosed with deep endometriosis. Methods: we conducted a prospective observational study with a sample of 30 women in the menacme diagnosed with deep endometriosis who underwent videolaparoscopic surgery in a reference center in Brazil between October 2020 and December 2021. A total of 30 women performed clinical and laboratory tests regarding their metabolic profile on two occasions, during preoperative tests and six months after video-laparoscopy. Results: patients had lower average levels of Total Cholesterol (TC), Low-Density Cholesterol (LDL-c), Triglycerides (TGC), and Fasting Glycemia (FG) after the surgical procedure. The average TC level was 8.2% lower after surgery, LDL-c was 12.8% lower, TGC was 10.9% lower, and FG was 7.3% lower. The results showed a statistically significant difference for all these parameters (p < 0.001). Conclusions: video-laparoscopy was associated with a favorable lipid profile compared to the preoperative lipid profile, with a significant improvement in the average levels of LDL-c, HDL-c, TC, TGC, and FG. Long-term follow-up studies are needed to determine whether surgical treatment for endometriosis can improve the metabolic parameters of women with endometriosis and favor a lower predisposition to atherogenesis.

Objetivo: Aeste estudo teve como objetivo avaliar os efeitos do tratamento cirúrgico da endometriose no perfil metabólico de mulheres com diagnóstico de endometriose profunda. Métodos: foi realizado um estudo observacional prospectivo com uma amostra de 30 mulheres na menacme, com diagnóstico de endometriose profunda, que foram submetidas à videolaparoscopia em um centro de referência no Brasil, entre outubro de 2020 e dezembro de 2021. As mulheres realizaram exames clínicos e laboratoriais quanto ao seu perfil metabólico em duas ocasiões, durante exames pré-operatórios e seis meses após a videolaparoscopia. Resultados: as pacientes apresentaram níveis médios mais baixos de Colesterol Total (CT), Colesterol de Baixa Densidade (LDL-c), Triglicerídeos (TGC) e Glicemia de Jejum (GJ) após o procedimento cirúrgico. O nível médio de CT foi 8,2% menor após a cirurgia, o LDL-c foi 12,8% menor, o TGC foi 10,9% menor e a GJ foi 7,3% menor. Os resultados mostraram diferença estatisticamente significativa para todos esses parâmetros (p < 0,001). Conclusões: a videolaparoscopia foi associada a um perfil lipídico favorável em comparação ao perfil lipídico pré-operatório, com melhora significativa nos níveis médios de LDL-c, HDL-c, CT, TGC e GJ. Estudos de acompanhamento a longo prazo são necessários para determinar se o tratamento cirúrgico da endometriose pode melhorar os parâmetros metabólicos de mulheres com endometriose e favorecer uma menor predisposição à aterogênese.

Definition, epidemiology and characterization of sepsis

Sepsis is a condition that occurs when the body's response to infection becomes unbalanced and potentially life-threatening. In this study, there is a focus on understanding and addressing sepsis. This detailed review explores how sepsis is defined in its prevalence in populations and how it is present clinically. The development of sepsis involves a series of events triggered by infections resulting in inflammation and dysfunction in organs. The symptoms of sepsis can range from signs like fever and changes in state to more severe complications such as septic shock. Early recognition of these symptoms using criteria like Systemic inflammatory response syndrome (SIRS) is crucial for intervention, which can greatly impact patient outcomes. Various diagnostic markers, imaging techniques and a deeper understanding of the pathophysiology behind sepsis have contributed to identification and targeted treatment approaches. Managing sepsis involves a combination of therapy, support for blood circulation, respiratory interventions and careful use of agents that modulate the system. It's important to emphasize the efforts among healthcare professionals from disciplines when it comes to managing sepsis effectively. Providing follow up care is essential for survivors as they may experience long term consequences such as sepsis syndrome. Due to its impact on health ongoing research is necessary to explore therapeutic options and refine existing strategies for managing sepsis effectively. The field continues to evolve with advancements, in precision medicine host directed therapies and interdisciplinary collaboration playing roles. This review seeks to grasp the concept of sepsis, providing insights into its various aspects, including the difficulties, in diagnosis and the ever-evolving treatment strategies.

Protective Mechanism of Paeoniflorin on Mice with Ulcerative Colitis Based on AMPK/mTOR Autophagy Pathway / 中国实验方剂学杂志

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg-1）， paeoniflorin （50 mg·kg-1） + inhibitor （20 mg·kg-1） group， and high dose （50 mg·kg-1）， medium dose （25 mg·kg-1）， and low dose （12.5 mg·kg-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.

Chaihu Longgu Mulitang Relieves Generalized Anxiety Disorder in Rats via p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

The improving effect and mechanisms of Anshen Dingzhi Prescription on Alzheimer's disease-like behavior induced by D-galactose combined with AβO in mice / 药学学报

The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.

Molecular mechanism of adipose tissue inflammation induced by acute exposure to cooking oil fumes / 环境与职业医学

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON3 group), 7-day control group (CON7 group), 3-day oil fume exposure group (COF3 group), and 7-day oil fume exposure group (COF7 group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4+ and CD8+T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF3 group and the COF7 group were significantly increased (P<0.05) except IL-6 in the COF3 group, and the levels in the COF7 group were significantly higher than those in the COF3 group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF7 group after HE staining. The flow cytometry results showed that the proportions of CD4+ and CD8+T cells in adipocytes of the COF3 group and the COF7 group were increased compared to the corresponding control group, with a significant increase in the COF7 group (P<0.05), and the CD4+/CD8+T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF3 group and the COF7 group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF3 group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF7 group were significantly higher than those in the CON7 group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

Research progress of Notch1/Jagged1 signaling pathway in related pathogenesis of chronic heart failure immune inflammation / 重庆医学

Heart failure is a clinical syndrome caused by various causes of myocardial damage and cardi-ac function decrease that cannot meet the body's metabolic needs.The proinflammatory cytokines play an im-portant role in the process of occurrence and development of heart failure.The Notch1/Jagged1 signaling path-way is related to the proinflammatory cytokines,inflammatory responses and immune responses.This paper discusses the involvement of the Notch1/Jagged1 signaling pathway in the development and development of chronic heart failure by modulating immune inflammation.

Relationship between hsa_circ_401724 expression and inflammatory response and pancreatic islet cell function in type 2 diabetic patients / 国际检验医学杂志

Objective To analyze the relationship between the expression of hsa_circ_401724 and the in-flammatory response in type 2 diabetes mellitus(T2DM)patients and pancreatic islet cell function.Methods A total of 102 patients with T2DM treated in Linfen Central Hospital from April 2017 to December 2022 were selected as the observation group,and 100 healthy subjects with normal glucose tolerance were se-lected as the control group during the same period.The levels of tumor necrosis factor α(TNF-α),interleukin-6(IL-6)and intercellular adhesion molecule-1(ICAM-1)in the blood of the subjects were detected by en-zyme-linked immunosorbent assay to evaluate the levels of inflammatory factors in the subjects.The relative expression level of hsa_circ_401724/U6 was calculated according to the dissolution curve,and the pancreatic islet cell function of the subjects was assessed,including homeostasis model assessment of insulin resistance(HOMA-IR)and homeostatic model assessment beta cell function(HOMA-β)as assessed by homeostasis model.Pearson correlation was used to analyze the correlation between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function,and Logistics regression model was used to analyze the rela-tionship between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function.Results The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in observation group were significantly higher than those in control group,while the levels of HOMA-β in observation group were significantly lower than those in control group,with statistical significance(P＜0.05).The relative expression level of hsa_circ_401724 in observation group(0.75±0.13)was significantly higher than that in control group(0.24±0.06),and the difference was statistically significant(P＜0.05).The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in hsa_circ_401724 high expression group were significantly higher than those in hsa_circ_401724 low expres-sion group,and the levels of HOMA-β were significantly lower than those in hsa_circ_401724 low expression group.The difference was statistically significant(P＜0.05).The relative expression level of hsa_circ_401724 was positively correlated with the levels of HOMA-IR,TNF-α,IL-6 and ICAM-1(r=0.657,0.671,0.703,0.698,P＜0.05).hsa_circ_401724 expression level was negatively correlated with HOMA-β level(r=-0.611,P＜0.05).The high expression of hsa_circ_401724 was an independent risk factor affecting the levels of HOMA-IR,HOMA-β,TNF-α,IL-6 and ICAM-1 in T2DM patients(P＜0.05).Conclusion The high ex-pression of hsa_circ_401724 is related to the inflammatory response and the decline of pancreatic islet cell function in T2DM patients.

Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer / 国际肿瘤学杂志

Objective:To analyze the preoperative and postoperative serum cholinesterase (CHE) levels in patients with stage ⅠA-ⅢA breast cancer who underwent surgical treatment, and to explore the roles of them and peripheral blood inflammatory markers in the prognostic prediction of stage ⅠA-ⅢA breast cancer.Methods:The relevant blood indicators of 152 patients with stage ⅠA-ⅢA breast cancer who underwent surgery and postoperative adjuvant therapy from January 2012 to December 2017 at Affiliated Huai'an Hospital of Xuzhou Medical University were retrospectively studied. The optimal cut-off values of serum CHE levels and peripheral blood inflammatory markers [systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) ] were calculated using X-tile 3.6.1 software. Patients were categorized into low and high value groups based on the optimal cutoff values. Kaplan-Meier curves and Cox regression analysis were used to assess the correlation between CHE and peripheral blood inflammation indexes and disease-free survival (DFS). Spearman correlation coefficient and Wilcoxon test were used to assess the correlation and changes of CHE and inflammation indexes before and after treatment. In addition to this, a nomogram prediction model was conscturcted based on independent prognostic factors by R software, which was validated by Bootstrap method.Results:The CHE levels of patients before and after treatment was 8 645.0 (7 251.3, 10 229.3) and 9 309.0 (7 801.0, 10 835.3) U/L, respectively, with a statistically significant difference ( Z=2.73, P=0.006) .The optimal cut-off values for postoperative CHE (Post-CHE), postoperative SII (Post-SII), and postoperative SIRI (Post-SIRI) associated with patients' DFS, being 7 773 U/L, 741, and 0.9, respectively. Univariate analysis showed that tumor size (≤2 cm vs.>2 cm and ≤5 cm: HR=2.55, 95% CI: 1.30-4.99, P=0.006; ≤2 cm vs. >5 cm: HR=8.95, 95% CI: 4.15-19.32, P<0.001), number of positive lymph nodes ( HR=3.84, 95% CI: 2.24-6.58, P<0.001), clinical stage (stage Ⅰ vs. stage Ⅱ: HR=1.52, 95% CI: 0.68-3.39, P=0.309, stage Ⅰ vs. stage Ⅲ: HR=8.12, 95% CI: 3.76-17.55, P<0.001), Ki-67 expression ( HR=2.19, 95% CI: 1.24-3.84, P=0.007), whether radiotherapy ( HR=2.05, 95% CI: 1.19-3.53, P=0.010), Post-CHE ( HR=6.81, 95% CI: 3.94-11.76, P<0.001), Pre-neutrophil to lymphocyte ratio (NLR) ( HR=1.11, 95% CI: 1.02-1.21, P=0.014), Post-NLR ( HR=5.23, 95% CI: 2.78-9.85, P<0.001), Pre-platelet to lymphocyte ratio (PLR) ( HR=2.08, 95% CI: 1.01-4.26, P=0.046), Post-PLR ( HR=7.11, 95% CI: 3.78-13.37, P<0.001), Pre-lymphocyte to monocyte ratio (LMR) ( HR=0.37, 95% CI: 0.20-0.66, P<0.001), Post-LMR ( HR=0.23, 95% CI: 0.13-0.41, P<0.001), Pre-SII ( HR=1.81, 95% CI: 1.05-3.12, P=0.033), Post-SII ( HR=6.12, 95% CI: 3.48-10.76, P<0.001), Pre-SIRI ( HR=2.12, 95% CI: 1.24-3.63, P=0.006), and Post-SIRI ( HR=4.93, 95% CI: 2.87-8.48, P<0.001) were associated with DFS in patients with stage ⅠA-ⅢA breast cancer. Multivariate analysis showed that tumor size (≤2 cm vs. >2 cm and ≤5 cm: HR=2.86, 95% CI: 1.41-5.78, P=0.003; ≤2 cm vs. >5 cm: HR=3.72, 95% CI: 1.50-9.26, P=0.005), number of positive lymph nodes ( HR=4.66, 95% CI: 2.28-9.54, P<0.001), Ki-67 expression ( HR=2.13, 95% CI: 1.15-3.94, P=0.016), Post-CHE ( HR=0.18, 95% CI: 0.10-0.33, P<0.001), Post-SII ( HR=2.71, 95% CI: 1.39-5.29, P=0.004), and Post-SIRI ( HR=3.77, 95% CI: 1.93-7.36, P<0.001) were independent influencing factors for DFS in patients with stage ⅠA-ⅢA breast cancer. Kaplan-Meier survival curve analysis showed that the median DFS of patients in the Ki-67<30% group was not reached, and the median DFS of patients in the Ki-67≥30% group was 89.0 months, and the 3- and 5-year DFS rates were 84.9% vs. 75.9% and 80.8% vs. 64.3%, respectively, with a statistically significant difference ( χ2=7.65, P=0.006) ; the median DFS of patients in the tumor size≤2 cm group was not reached, the median DFS of the 2 cm<tumor size≤5 cm group was 93.5 months, and the median DFS of the tumor size>5 cm group was 26.3 months, and the 3- and 5-year DFS rates were 95.5% vs. 74.6% vs. 42.1%, 86.3% vs. 68.6% vs. 25.3%, with a statistically significant difference ( χ2=40.46, P<0.001) ; the median DFS of patients in the group with the number of positive lymph nodes<4 was not reached, and the median DFS of the group with the number of positive lymph nodes≥4 was 30.7 months, and the 3- and 5-year DFS rates were 87.9% vs. 46.4% and 81.4% vs. 28.6%, respectively, with a statistically significant difference ( χ2= 47.34, P<0.001) ; the median DFS of patients in the Post-CHE<7 773 U/L group was 47.3 months, and the median DFS of patients in the Post-CHE≥7 773 U/L group was not reached, and the 3- and 5-year DFS rates were 52.8 % vs. 88.6% and 27.8% vs. 81.2%, respectively, with a statistically significant difference ( χ2=62.17, P<0.001) ; the median DFS was not achieved in patients in the Post-SII<741 group, and the median DFS was 30.5 months in the Post-SII≥741 group, with 3- and 5-year DFS rates of 88.1% vs. 38.5% and 80.1% vs. 30.8%, respectively, with a statistically significant difference ( χ2=50.78, P<0.001) ; the median DFS of patients in Post-SIRI<0.9 group was not reached, the median DFS of Post-SIRI≥0.9 group was 33.3 months, and the 3- and 5-year DFS rates were 93.5% vs. 46.7% and 84.9% vs. 39.9%, respectively, with a statistically significant difference ( χ2=40.67, P<0.001). Spearman correlation analysis revealed that Post-CHE was not correlated with Post-SII ( r=-0.111, P=0.175), and Post-CHE was negatively correlated with Post-SIRI ( r=-0.228, P=0.005). Post-treatment CHE was elevated compared to preoperative and the median DFS was not reached in patients with elevated CHE group and 61.8 months in patients with reduced CHE group after treatment, with a statistically significant difference ( χ2=25.67, P<0.001). The nomogram based on independent prognostic factors had good predictive performance, with a C-index of 0.893. Conclusion:The serum CHE level exhibited a significant increase following treatment. Postoperative serum CHE combined with SII and SIRI can effectively predict DFS in patients with stage ⅠA-ⅢA breast cancer, and the prognosis of patients with elevated CHE after treatment is better. The nomogram constructed based on independent prognostic factors has good predictive performance for DFS in breast cancer patients.

Study on the Regulatory Mechanism of Xuanfei Tongluo Pingchuan Decoction on Immune Function and Inflammatory Response in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease / 广州中医药大学学报

Objective To investigate the clinical efficacy of Xuanfei Tongluo Pingchuan Decoction in treating patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to explore its regulatory mechanism on immune function and inflammatory response.Methods A retrospective study was conducted in 122 patients with AECOPD of phlegm-stasis obstructing lung type,and the patients were divided into an observation group and a control group according to the therapy,with 61 patients in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xuanfei Tongluo Pingchuan Decoction on the basis of treatment for the control group.The treatment lasted for 14 days.Before and after treatment,the patients of the two groups were observed in the changes of pulmonary function indicators,6-minute walking distance(6MWD),COPD Assessment Test(CAT)scores,immune function indicators,and serum inflammatory factors.After treatment,the clinical efficacy and the overall occurrence rate of the adverse reactions were compared between the two groups.Results(1)After 14 days of treatment,the total effective rate of the observation group was 95.08%(58/61),and that of the control group was 77.05%(47/61).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,pulmonary function indexes such as the forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and peak expiratory flow(PEF)of the two groups were significantly improved compared with those before treatment(P＜0.05),and the effect on improving all pulmonary function indexes in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the 6MWD of the two groups were significantly higher(P＜0.05)and the CAT scores were significantly lower than those before treatment(P＜0.05),and the observation group was significantly superior to the control group in terms of improving the 6MWD and decreasing CAT scores(P＜0.01).(4)After treatment,the levels of immune function indicators of T lymphocyte subsets CD4+ and CD4+/CD8+ in the two groups were significantly higher than those before treatment(P＜0.05),and CD8+ level was significantly lower than that before treatment(P＜0.05),and the observation group had stronger effect on increasing T lymphocyte subsets CD4+ and CD4+/CD8+ levels and on decreasing CD8+ level than the control group(P＜0.01).(5)After treatment,the serum levels of inflammatory factors C-reactive protein(CRP)and tumor necrosis factor alpha(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the levels of serum CRP and TNF-α in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the trial,the total incidence of adverse reactions in the observation group was 3.28%(2/61)and that in the control group was 6.56%(4/61),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P＞0.05).Conclusion Xuanfei Tongluo Pingchuan Decoction can effectively alleviate the symptoms of cough and expectoration in AECOPD patients,improve the lung function and immune function,and reduce the inflammatory response.During the treatment,no obvious adverse reactions occur and the therapy is safe and effective.

Basic Study on Inhibitory Effect of Sulforaphane on Inflammatory Response and Alleviation of Airway Remodeling in COPD Rats / 广州中医药大学学报

Objective To investigate the ameliorative effect of sulforaphane on inflammatory response and airway remodeling in rats with chronic obstructive pulmonary disease(COPD).Methods Seventy-five SD rats were randomly divided into the normal group,the model group,and the low-,medium-,and high-dose groups of sulforaphane,with 15 rats in each group.Except for the normal group,the COPD model was prepared in the remaining group using aroma smoke inhalation combined with intratracheal droplet lipopolysaccharide(LPS)method.After the successful modelling,the rats were administered the drug by gavage for 28 days.At the end of the administration,the general conditions of the rats in each group were observed,and the lung function[forced vital capacity(FVC),peak expiratory flow-rate(PEF),forceful expiratory volume in 1 second(FEV1)]was examined,and the pathological changes of the lung tissues were observed by hematoxylin-eosin(HE)staining method,and the indexes of airway remodeling(thickness of the bronchial wall,thickness of the smooth muscle)were measured;the enzyme-linked immunosorbent assay(ELISA)was used to examine the lung function of the rats.The levels of inflammatory factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)]were detected in lung tissue by enzyme-linked immunosorbent assay(ELISA),and changes in the protein expressions of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear transcription factor κB(NF-κB)were detected in lung tissue by Western Blot.Results(1)The rats in the model group had dry and lack of glossy fur,obvious coughing and nose scratching,shortness of breath,slow movement,and preferred to arch their backs and lie curled up;the rats in the low-,medium-and high-dose groups of sulforaphane showed significant improvement in shortness of breath,coughing,and other abnormal manifestations.(2)HE staining showed that the airway wall and smooth muscle of rats in the model group were thickened,the airway epithelium was damaged,and alveolar destruction,fusion,and massive infiltration of inflammatory cells were seen;the histopathological changes in the lungs of rats in the low-,medium-and high-dose groups of sulforaphane improved to varying degrees,with the airway wall becoming thinner,the degree of alveolar destruction being reduced,and the infiltration of inflammatory cells being reduced.(3)Compared with the normal group,FVC,PEF and FEV1 were significantly reduced in the model group(P＜0.05),and the levels of TNF-α and IL-1β,bronchial wall thickness,smooth muscle thickness,and the expression levels of TLR4,MyD88 and NF-κB were significantly increased in the model group(P＜0.05);and in comparison with the model group,the levels of FVC,PEF,and FEV1 were significantly increased in the rats in the sulforaphane low-,medium-,and high-dose groups(P＜0.05),and the levels of TNF-α,IL-1β,bronchial wall thickness,smooth muscle thickness,and the expression levels of TLR4,MyD88,and NF-κB were significantly decreased(P＜0.05)compared with the model group.Conclusion Sulforaphane helps to inhibit the inflammatory response,attenuate airway remodeling,and improve the pathological injury and lung function of lung tissue in rats with COPD,and its mechanism may be related to the inhibition of TLR4,MyD88,and NF-κB protein expressions.

Effect of Naringenin Inhibiting the Activation of cGAS-STING Pathway on the Lower Extremity Deep Venous Thrombosis in Rats / 广州中医药大学学报

Objective To investigate the mechanism of naringenin resisting lower extremity deep venous thrombosis(LEDVT)in rats.Methods Sixty rats were randomly divided into 6 groups,i.e.,sham-operation group,model group,naringenin low-,medium-,and high-dose groups,and naringenin high-dose + STING agonist 2.5 hexamethylene cacodylate(DMXAA)group,with 10 rats in each group.The coagulation indexes[D-dimer,thrombin time(TT),activated partial thromboplastin time(APTT),prothrombin time(PT)],inflammation indexes[interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)]and oxidative stress indexes[malondialdehyde(MDA),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)];Hematoxylin-eosin(HE)staining to detect thrombus formation in venous tissues;wet and dry mass of thrombus were detected;ultrastructure of venous thrombus was detected by transmission electron microscope(TEM);protein expressions of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)in venous thrombus tissue were detected by Western Blot.Results(1)Compared with the sham-operation group,rats in the model group showed an increase in D-dimer levels,IL-1β,IL-6,TNF-α levels,MDA content,thrombus wet and dry mass,and a decrease in TT,APTT,PT,SOD activity,and GSH-Px activity(all P＜0.05);and compared with the model group,rats in naringen's low-,medium-,and high-dose groups showed a decrease in D-dimer levels,IL-1β,IL-6,TNF-α levels,MDA content,thrombus wet and dry mass,TT,APTT and PT,SOD activity and GSH-Px activity were increased(P＜0.05)in a dose-dependent manner compared with the model group;compared with the naringenin high-dose group,rats in the naringenin high-dose + DMXAA group,D-dimer levels,IL-1β,IL-6,TNF-α levels,MDA content,thrombus wet and dry mass were elevated,TT,APTT and PT,SOD activity and GSH-Px activity were decreased(P＜0.05).(2)Compared with the sham-operation group,the expression levels of cGAS and STING proteins in the venous thrombus tissues of rats in the model group were elevated(P＜0.05);compared with the model group,the expression levels of cGAS and STING proteins in the venous thrombus tissues of rats in the naringeno low-,medium-and high-dose groups were significantly reduced(P＜0.05);cGAS and STING protein expression levels in the naringenin high-dose + DMXAA group were significantly higher than those in the naringenin high-dose group(P＜0.05).Conclusion Naringenin can inhibit the activation of cGAS/STING signalling pathway,thereby inhibiting the inflammatory response and resisting oxidative stress,and thus alleviating the LEDVT.

Clinical Study on Oral Use of Jiawei Puji Xiaodu Granules Combined with External Application of Xiaozhong Sanjie Ointment in the Treatment of Acute Tonsillitis in Children / 广州中医药大学学报

Objective To evaluate the clinical efficacy of oral use of Jiawei Puji Xiaodu Granules(mainly composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Taraxaci Herba,Violae Herba,Schizonepetae Herba,Arctii Fructus,Gleditsiae Spina,Paeoniae Radix Rubra,Moutan Cortex,and Phragmitis Rhizoma)combined with external application of Xiaozhong Sanjie Ointment(mainly composed of Scutellariae Radix,Coptidis Rhizoma,Phellodendri Chinensis Cortex,and Gleditsiae Spina,etc.)in the treatment of acute tonsillitis in children,and to observe their effects on the immune function and related inflammatory indexes of the patients.Methods A total of 116 children with acute tonsillitis of heat stagnation in the lung and stomach type were randomly divided into the control group and the observation group,with 58 cases in each group.The control group was treated with Cefixime Dispersible Tablets,while the observation group was treated with Jiawei Puji Xiaodu Granules for oral use and Xiaozhong Sanjie Ointment for external application.Both groups were treated for 14 days and then were followed-up for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,white blood cell(WBC)count,T lymphocyte subset CD3+,CD4+,CD8+ and CD4+/CD8+ levels,and serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6)and C-reactive protein(CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and time for the disappearance of clinical symptoms were compared between the two groups,and the occurrence of adverse reactions and the recurrence of tonsillitis in the two groups were monitored at the same time.Results(1)During the trial,there were 8 cases falling off in the control group but none case falling off in the observation group,and eventually 50 cases in the control group and 58 cases in the observation group completed the full course of treatment.(2)After 14 days of treatment,the total effective rate of the observation group was 98.28%(57/58),while that of the control group was 90.00%(45/50).The intergroup(tested by rank sum test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the time for the disappearance of sore throat,time for the disappearance of purulent spots,time for subsiding fever and time for the tonsils recovering to normal in the observation group were all significantly shorter than those in the control group(P＜0.05).(4)After treatment,the scores of primary and secondary symptoms and the overall symptom scores in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction of the scores in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the levels of T lymphocyte subset CD3+,CD4+ and CD4+/CD8+ in the two groups were significantly higher(P＜0.05)while the level of CD8 + was significantly lower(P＜0.05)than those before treatment,and the increase in the levels of CD3+,CD4+ and CD4+/CD8+ and the reduction of the CD8+ level of the observation group were significantly superior to those of the control group(P＜0.05).(6)After treatment,the levels of WBC,TNF-α,IL-1β,IL-6 and CRP in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the treatment period,no skin allergy,nausea,vomiting or other gastrointestinal adverse reactions occurred in the two groups,which showed a high degree of safety.(8)The 6-month follow-up showed that the recurrence rate of tonsillitis in the observation group was 5.17%(3/58),which was significantly lower than that of 24.00%(12/50)in the control group,and the difference was statistically significant(χ2 = 8.330,P＜0.05).Conclusion The efficacy of Jiawei Puji Xiaodu Granules combined with Xiaozhong Sanjie Ointment exert notable curative effect for children with acute tonsillitis of heat stagnation in the lung and stomach type.The combined therapy can significantly shorten the duration of the disease,improve the clinical symptoms of the children and effectively reduce the recurrence rate of tonsillitis.The therapeutic mechanism may be related to the enhancement of the immune function and the inhibition of inflammatory response.

Clinical Observation on Acupuncture Combined with Guanxinning Tablets in the Treatment of Heart Vessel Obstruction Type of Chest Obstruction Syndrome / 广州中医药大学学报

Objective To observe the clinical efficacy of acupuncture combined with Guanxinning Tablets in the treatment of heart vessel obstruction type of chest obstruction syndrome.Methods Eighty patients with heart vessel obstruction type of chest obstruction syndrome were randomly divided into the observation group and the control group,with 40 cases in each group,the control group was given conventional western medicine treatment,the observation group was given acupuncture combined with Guanxinning Tablets on the basis of the treatment in the control group,and the patients in the two groups were treated continuously for 30 days.The clinical efficacy of the two groups was evaluated after 1 month of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes in the traditional Chinese medicine(TCM)scores,including chest tightness,palpitations,stabbing pains in the chest,and dark complexion,as well as the frequency and duration of angina pectoris were observed before and after the treatment in the two groups.The changes of serum monocyte chemotactic factor 1(MPC-1),hs-CRP,tumor necrosis factor α(TNF-α),mitogen-activated protein kinase(MAPK),and Toll-like receptor 4(TLR4)were observed before and after treatment in the two groups.Results(1)The total effective rate was 95.00%(38/40)in the observation group and 75.00%(30/40)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups,including chest tightness and palpitations,chest tingling,and dark complexion,were significantly improved,and the observation group was significantly superior to the control group in improving the TCM syndrome scores of chest tightness and palpitations,chest tingling,and dark complexion,and the difference was statistically significant(P＜0.05).(3)After treatment,the frequency and duration of angina attacks in the two groups were significantly improved,and the observation group was significantly superior to the control group in improving the frequency and duration of angina attacks,and the difference was statistically significant(P＜0.05).(4)After treatment,the serum hs-CRP,MPC-1,and TNF-α levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum hs-CRP,MPC-1 and TNF-α levels,and the difference was statistically significant(P＜0.05).(5)After treatment,the serum MAPK and TLR4 levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum MAPK and TLR4 levels,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Guanxinning Tablets for the treatment of heart vessel obstruction type of chest obstruction syndrome can significantly improve the clinical symptoms of the patients,effectively alleviate the body's inflammatory response,reduce the level of serum MAPK and TLR4,and the clinical efficacy is remarkable.

C-X3-C motif chemokine ligand 1/C-X3-C motif chemokine receptor 1 pathway in the recovery of memory function in hemorrhagic shock/resuscitation rats / 解剖学报

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

Identification of Atrial Fibrillation-related Inflammatory Genes and Their Association with Immune Cell Infiltration Based on Comprehensive Bioinformatic Analysis / 昆明医科大学学报

Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.

Predictive value of inflammatory markers on the risk of stroke-associated pneumonia in acute ischemic stroke patients / 临床神经病学杂志

Objective To explore the predictive value of inflammatory markers for stroke-associated pneumonia(SAP)in patients with acute ischemic stroke(AIS)based on the nomogram model.Methods According to whether pneumonia occurred,259 AIS patients were divided into SAP group(81 cases)and non-SAP group(178 cases).The clinical data of the two groups were compared.The systemic inflammatory response index(SIRI),systemic immunoinflammatory index(SII)and neutrophil to lymphocyte ratio(NLR)were calculated according to the formula.The variables with statistically significant differences were included in the multivariate binary Logistic regression model to screen out the independent risk factors for SAP in AIS patients.The independent risk factors were used to construct a predictive model,and the predictive ability of the two models,which only included traditional factors and included inflammatory indicators at the same time,was further compared from the aspects of discrimination,calibration,clinical practicability and so on.Reclassification analysis was used to evaluate the extent to which the nomogram model improved the predictive value of SAP risk in AIS patients.Results Compared with those in the non-SAP group,the rates of smoking,diabetes,dysphagia,leukocytes,neutrophils,lymphocytes,triglyceride level,NIHSS score on admission,SIRI,SII and NLR were significantly increased in the SAP group,and the rate of hypertension was decreased(all P＜0.05).Diabetes mellitus(OR =2.505,95%CI:1.070-5.850,P =0.034),dysphagia(OR =3.492,95%CI:1.501-8.119,P =0.004),NIHSS score on admission(OR = 1.310,95%CI:1.188-1.446,P＜0.001),SIRI(OR =2.417,95%CI:1.327-4.401,P =0.008),NLR(OR =1.434,95%CI:1.101-1.860,P =0.007)were independent risk factors for SAP in AIS patients.The area under the curve was 0.788(95%CI:0.725-0.852,P＜0.001)for the prediction model without inflammatory factors and 0.884(95%CI:0.838-0.930,P＜0.001)for the prediction model with independent risk factors.The calibration curve showed a good consistency between the predicted risk and the observed results.The decision curve showed that the model had a significant net benefit for predicting SAP.In addition,by calculating the net reclassification index(NRI)and the comprehensive discriminant improvement index(IDI),it was found that the nomogram model had a significant improvement in predicting the risk of SAP in AIS patients.Internal verification also proves the reliability of the nomogram model.Conclusions SIRI and NLR are independent predictors of SAP in AIS patients on admission.Adding SIRI and NLR to the traditional model can significantly improve the ability to identify the risk of SAP occurrence in AIS patients.

Mechanism of Atractylodes macrocephala in Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Validation / 世界科学技术-中医药现代化

Objective To explore the molecular mechanism of Atractylodes macrocephala in the treatment of Ulcerative colitis(UC)based on network pharmacology,and verify it with animal experiments.Methods The active components of Atractylodes macrocephala was screened from the TCMSP database,the TCM-ID database,and in combination with relevant references,and the corresponding targets were obtained through Swiss database.The relevant targets of UC were obtained from GeneCards database,construct the"drug-component-target-disease"network diagram and"pathway-active ingredient-target"network diagram and draw PPI network diagram;GO function enrichment analysis and KEGG signal pathway annotation analysis were carried out.Autodock software is used for molecular docking of active components and targets.Then,the experimental validation of the network pharmacology prediction was carried out.The mouse UC model was induced by dextran sodium sulfate(DSS).The pathological changes of the colon tissue,the number of goblet cells,and the positive expression of inflammatory factorswere detected by HE staining,AB-PAS staining and immunohistochemistry in colon tissue of UC mice.Results The results have shown 30 active ingredients including atractylolactone I,II and III were screened,and 591 corresponding targets were obtained,of which the key target was IL-1β、TNF-α and so on.Molecular docking show that the core components had good binding affinity with the key targets.And the results of animal experiments showed that the alcohol extract of Atractylodes macrocephala could significantly increase the colon length,reduce the DAI score,improve the pathological changes of colon tissue of UC mice,increase the number of goblet cells,and inhibit the expression of IL-1β,TNF-α in colon tissue.Conclusion This study indicated that Atractylodes macrocephala could regulate the release of inflammatory factors through multiple components,multi-target and multi-channel,which could inhibit inflammatory reaction and play a role in improving UC.