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Objective: Recent reports have demonstrated that a wider pulse pressure upon admission is correlated with heightened in-hospital mortality following spontaneous supratentorial intracerebral hemorrhage (ssICH). However, the underlying mechanism remains ambiguous. We investigated whether a wider pulse pressure was associated with hematoma expansion (HE). Methods: Demographic information, clinical features, and functional outcomes of patients diagnosed with ssICH were retrospectively collected and analyzed. Multivariate logistic regression was conducted to identify independent predictors of HE. Weighted logistic regression, restricted cubic spline models, and propensity score matching (PSM) were employed to estimate the association between pulse pressure and HE. Results: We included 234 eligible adult ssICH patients aged 60 (51-71) years, and 55.56% were male. The mean pulse pressure was 80.94 ± 23.32 mmHg. Twenty-seven patients (11.54%) developed early HE events, and 116 (49.57%) experienced a poor outcome (modified Rankin scale 3-6). A wider mean pulse pressure as a continuous variable was a predictor of HE [odds ratios (OR) 1.026, 95% confidence interval (CI) 1.007-1.046, p = 0.008] in multivariate analysis. We transformed pulse pressure into a dichotomous variable based on its cutoff value. After adjusting for confounding of HE variables, the occurrence of HE in patients with ssICH with wider pulse pressure levels (≥98 mmHg) had 3.78 times (OR 95% CI 1.47-9.68, p = 0.006) compared to those with narrower pulse pressure levels (<98 mmHg). A linear association was observed between pulse pressure and increased HE risk (P for overall = 0.036, P for nonlinear = 0.759). After 1:1 PSM (pulse pressure ≥98 mmHg vs. pulse pressure <98 mmHg), the rates of HE events and poor outcome still had statistically significant in wider-pulse pressure group [HE, 12/51 (23.53%) vs. 4/51 [7.84%], p = 0.029; poor outcome, 34/51 (66.67%) vs. 19/51 (37.25%), p = 0.003]. Conclusion: Widened acute pulse pressure (≥98 mmHg) levels at admission are associated with increased risks of early HE and unfavorable outcomes in patients with ssICH.
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Amyloid-ß (Aß) accumulation is the main pathological change in Alzheimer's disease (AD), which results from the imbalance of production and clearance of Aß in the brain. Our previous study found that chronic sleep deprivation (CSD) led to the deposition of Aß in the brain by disrupting the balance of Aß production and clearance, but the specific mechanism was not clear. In the present study, we investigated the effects of oxidative stress on Aß accumulation in CSD rats. We found that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after CSD, while superoxide dismutase (SOD) decreased in the brain. Furthermore, the serum ROS was elevated and SOD declined after CSD. The levels of oxidative stress in the brain were significantly correlated with ß-site APP-cleaving enzyme 1 (BACE1), low-density lipoprotein receptor-related protein-1 (LRP1), and receptor of advanced glycation end products (RAGE) levels in hippocampus and prefrontal lobe, and the concentration of serum oxidative mediators were strongly correlated with plasma levels of soluble LRP1 (sLRP1) and soluble RAGE (sRAGE). These results suggested that the oxidative stress in the brain and serum may involved in the CSD-induced Aß accumulation. The underlying mechanism may be associated with disrupting the balance of Aß production and clearance.
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Enfermedad de Alzheimer , Privación de Sueño , Ratas , Animales , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Especies Reactivas de Oxígeno , Ácido Aspártico Endopeptidasas/metabolismo , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/patología , Estrés Oxidativo , Productos Finales de Glicación Avanzada/metabolismo , Superóxido DismutasaRESUMEN
The tumor microenvironment includes blood vessels, lymph, nerves, non-malignant cells, and their metabolites at and near the tumor lesion site, which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption, or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply, forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors, widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer, occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets, the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer, inhibit the proliferation, invasion, and metastasis of breast cancer cells in the hypoxia environment, induce apoptosis, reverse their drug resistance, intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment, and inhibit their angiogenesis, thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation, invasion, metastasis, drug resistance, immune function, metabolic reprogramming, non-coding RNA, iron death, and autophagy of breast cancer cells, which affected the occurrence and development of breast cancer, and it elaborated the mechanism behind it. Then, the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine, so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.
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Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7%of patients met the criteria of LLDAS,while 10.4%of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.
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ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 (AMPK/PGC-1α/SIRT3) signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling, they were randomly divided into high, medium, and low dose Tangbikang granule groups (2.5, 1.25, 0.625 g·kg-1·d-1) and lipoic acid group (0.026 8 g·kg-1·d-1), and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4, 8, 12 weeks after intervention. At the 12th week, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), nerve blood flow velocity, mechanical pain threshold, and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin (HE) staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in sciatic nerve were determined by enzyme-related immunosorbent assay (ELISA). The mRNA expressions of AMPKα, AMPKβ, PGC-1α, and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the normal group, fasting blood glucose in the model group was increased at each time point (P<0.01). The mechanical pain threshold was decreased (P<0.05), and the incubation time of the hot plate was extended (P<0.01). MNCV, SNCV, and nerve blood flow velocity decreased (P<0.05). The expression level of SOD was decreased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were increased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were decreased (P<0.01). The structure of sciatic nerve fibers in the model group was loose, and the arrangement was disordered. The demyelination change was obvious. Compared with the model group, the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks (P<0.01). The mechanical pain threshold increased (P<0.05). The incubation time of the hot plate was shortened (P<0.01). MNCV, SNCV, and Flux increased (P<0.05). The expression level of SOD was increased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were decreased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were increased (P<0.01). The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged, with only a few demyelinating changes. The high, medium, and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.
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Background Long-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM2.5 exposure. Objective To investigate the association between long-term exposure to PM2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM2.5 was (38.10±4.67) μg·m−3. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L−1 for each 1 μg·m−3 increase in PM2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L−1 in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM2.5 concentration showed that the risks of diabetes were increased in the low PM2.5 pollution-low vegetable intake frequency group and the high PM2.5 pollution-low vegetable intake frequency group compared with the low PM2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM2.5 pollution and low fruit intake frequency than in participants with low PM2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM2.5 on diabetes. Conclusion Long-term exposure to ambient PM2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM2.5.
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Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.
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Objective The aim of this study is to analyze the prevalence of depression and anxiety symptoms and its relationship with the socio-economic position(SEP)among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Methods A multi-stage stratified random sampling method was used to conduct a questionnaire survey among 1409 people aged 60 and over in Dai rural areas of Jinggu County,Yunnan Province.The individual SEP index was constructed using the principal component analysis.Results The prevalence of anxiety symptoms,depression symptoms,and mixed anxiety-depressive disorder symptoms was 4.8%,52.0%,and 4.2% among them,2.6%,49.4%,and 2.3% among the males,and 6.8%,54.5%,and 6.0% among the females respectively.Females had the higher prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than males(P<0.05).Elderly people with the higher level of education,annual per capita household income and SEP had the lower prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than their counterparts(both P<0.05).The prevalence of depression symptoms increased with age(P<0.01).The difference in the prevelence of depression symptoms among the elderly people with the different numbers of chronic conditions was statistically significant(P<0.01).The results of multivariate logistic regression analysis showed that the elderly people with lower SEP were more likely to suffer from the anxiety symptoms(OR=0.707,95% CI:0.566~0.883),depression symptoms(OR=0.492,95% CI:0.438~0.552),and mixed anxiety-depressive disorder symptoms(OR=0.602,95% CI:0.469~0.773).Conclusion There are significant socio-economic differences in the prevalence of anxiety symptoms and depression symptoms among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Future mental health interventions should more focus on females,elderly people with advanced age,multiple chronic diseases and low SEP,so as to reduce the occurrence of depression symptoms and anxiety symptoms.
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Objective To explore the feasibility of the multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)sequence in neck MRI,and to compare with traditional single-shot echo-planar imaging diffusion weighted imaging(SS-EPI-DWI)sequence.Methods Thirty healthy volunteers underwent MUSE-DWI and SS-EPI-DWI sequences scanning in neck.Two groups of images were independently scored by two radiologists for magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality.The noise,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the regions of interest(ROI)of the two groups of images were measured and compared on the nasopharyngeal fossa layer,parotid gland layer,glottic layer and thyroid layer.Results Qualitative analysis showed that the image quality scores of MUSE-DWI sequence were significantly better than those of SS-EPI-DWI sequence in terms of magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality(P<0.001).Quantitative analysis showed that the noise values of ROIs of MUSE-DWI sequence were significantly lower than those of SS-EPI-DWI sequence(P<0.001).The SNR and CNR of ROIs of MUSE-DWI sequence were higher than those of SS-EPI-DWI sequence(P<0.001).Conclusion MUSE-DWI sequence can significantly reduce geometric distortion,magnetic sensitivity artifact and chemical shift artifact,and SNR and CNR of images are significantly increased compared with SS-EPI-DWI sequence,which is more suitable for neck MRI scanning.
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BACKGROUND:Most scholars now believe that children with cerebral palsy who have severe spinal deformities in early childhood(<15 years of age)may have a higher risk of progression of spinal deformities,which may result from imbalances in movement due to pelvic tilt,pain,etc. OBJECTIVE:To investigate the relationship between lumbar spine development and hip joint development in children with spastic cerebral palsy. METHODS:A retrospective analysis was performed in 102 children with spastic cerebral palsy admitted at Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from January 2014 to December 2021.All admitted children had X-rays of the pelvic position and the lumbar lateral position.Anteroposterior X-ray of the pelvis was performed to measure femoral head migration percentage,central edge angle,neck-shaft angle,and acetabular index.The sagittal Cobb angle,sacral slope,arch-top distance,and lumbar lordosis index were measured by the lateral X-ray of the lumbar spine.Correlation of the two sets of indicators was further analyzed.All children were divided into normal group,risk group,hip subluxation group and total hip dislocation group according to their femoral head migration percentage,and the differences in lumbar spine indexes between groups were evaluated. RESULTS AND CONCLUSION:Pearson correlation analysis showed that the femoral head migration percentage was moderately positively correlated with sagittal Cobb angle and arch-top distance,and weakly positively correlated with lumbar lordosis index;the central edge angle was moderately negatively correlated with the arch-top distance and weakly negatively correlated with the sagittal Cobb angle;the neck-shaft angle was weakly positively correlated or not correlated with the sagittal Cobb angle and lumbar lordosis index;and the acetabular index was weakly positively correlated with the sagittal Cobb angle and arch-top distance.No statistically significant correlation was found between the remaining indicators.According to the femoral head migration percentage,the children were divided into four groups,including 25 cases in the normal group,41 cases in the risk group,27 cases in the hip subluxation group,and 9 cases in the total hip dislocation group.The sagittal Cobb angle was significantly increased in the risk group,the hip subluxation group and the total hip dislocation group compared with the normal group,showing an increasing trend group by group,and there were significant differences between groups(P<0.05).Compared with the normal group,the lumbar lordosis index in the risk group and the hip subluxation group increased significantly,and there were significant differences between groups(P<0.05).There was an increase trend in the lumbar lordosis index of the total hip dislocation group compared with the normal group.Compared with the normal group,the arch-top distance in the hip subluxation group and the total hip dislocation group increased significantly(P<0.05),and there was a stepwise increasing trend.There was no significant difference in sacral slope between groups.To conclude,the development of the lumbar spine in children with cerebral palsy is closely related to the development of the pelvic hip joint,and the most obvious relationship is between lumbar lordosis and hip dislocation.
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BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo. OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them. METHODS:The first author searched PubMed and Web of Science databases by using"cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells"as English search terms,and searched CNKI and Wanfang databases by using"myocardial patch,biological 3D printing,myocardial"as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis. RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial patches mainly include:making myocardial patches after co-cultivation of multiple cells,improving the ink formulation and scaffold composition in biological 3D printing technology,improving the therapeutic effect of myocardial patches,suppressing immune rejection after transplantation,and perfecting the differentiation and cultivation protocols of stem cells.(4)There is no optimal cell source or method for making myocardial patches,and myocardial patches obtained from a particular cell or technique alone often do not achieve the desired therapeutic effect.Therefore,researchers need to choose the appropriate strategy for making myocardial patches based on the desired therapeutic effect before making them.
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BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P<0.01 or P<0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P<0.01),the expression of interleukin 10 was decreased(P<0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P<0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P<0.01 or P<0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P<0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P<0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.
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BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P<0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P<0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P<0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P<0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P<0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P<0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P<0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.
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Objective To investigate the application value of tear inflammatory factors in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients.Methods A total of 150 eyes of 150 patients with angle-closure glaucoma who underwent trabeculectomy in Department of Ophthalmology of Zhangjiagang Hospital of Traditional Chinese Medicine were included.The clinical data of all patients were collected,and the levels of inflammatory factors(including G-CSF,GM-CSF,IFN-γ,MCP-1,TNF-α,IL-12,IL-13,IL-15,IL-1β,IL-4,IL-7,IL-10,IL-17,IL-5)in tears were detected before surgery.According to the occurrence of postoperative complications,the patients were divided into the complication group and the control group,and the clinical data of the two groups were compared.Logistic regression was used to analyze the related factors of the occurrence of complications after trabeculectomy in glaucoma patients.The predictive model of tear inflammatory factors was established by Logistic regression,and the receiver operating characteristic(ROC)curve was drawn to analyze the value of this model in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients.Results Complications occurred in 35(23.33%)of 150 glaucoma patients after trabeculectomy,including 24 cases of shallow anterior chamber,5 cases of ciliary body or choroid detachment,3 cases of iridocyclitis,2 cases of hyphema,and 1 case of retinal detachment.IFN-γ,GM-CSF and IL-5 levels of the patients in the complication group were lower than those in the control group(P<0.05).There was no significant difference in the levels of other inflammatory factors of patients between the two groups(P>0.05).Multivariate Logistic regression analysis showed that increased levels of IFN-γ(OR=0.999),GM-CSF(OR=0.988)and IL-5(OR=0.996)were independent protective factors for complications after trabeculectomy in glaucoma patients(P<0.05).ROC curve analysis showed that the sensitivity and specificity of the model were 94.29%and 83.84%in early evaluation of the occurrence of complications after trabeculectomy in glaucoma patients,and the AUC was 0.906,which was higher than that predicted by IFN-γ(AUC=0.642),GM-CSF(AUC=0.721)and IL-5(AUC=0.666)alone.Conclusion Preoperative analysis of tear inflammatory factors in glaucoma patients can early evaluate the occurrence of postoperative complications,especially the combined detection of IFN-γ,GM-CSF and IL-5 levels is of great significance for predicting the occurrence of complications.
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Objective:This article is to investigate NADPH oxidase 4(NOX4)expression,prog-nosis,signaling pathway and key immune cells infiltrating in tumor tissues in gastric cancer.Meth-ods:Data were downloaded from the Cancer Genome Atlas(TCGA)and the Integrated Gene Ex-pression Database(GEO).The expression of NOX4 in gastric cancer and normal tissues,the rela-tionship between NOX4 expression level and clinical characteristics of patients,gene enrichment analysis of signaling pathways and immune infiltration analysis have been analyzed.Results:In terms of NOX4 expression,tumor tissue is significantly higher than normal tissue,which has certain diagnostic value;NOX4 is an important prognostic factor with poor prognosis in patients with high NOX4 expression;NOX4 is associated with cell adhesion molecules(CAMs),transforming growth factor-β(TGF-β),and WNT signaling pathway.NOX4 high expression group was mainly related to M2 macrophages and plasma cell infiltration in tumor tissues.Conclusion:NOX4 plays an impor-tant role in the progression of gastric cancer(GC).
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Objective To explore the effect of nursing intervention based on the integrated theory of health behavior change(ITHBC)on the health behavior of patients with diabetes retinopathy(DR).Methods 157 patients with diabetes retinopathy admitted from July to December 2022 in a tertiary A hospital in Wuhan,Hubei Province,were selected as the experimental group by convenience sampling method,while 156 patients with diabetes retinopathy hospitalized from January to June 2022 were selected as the control group,and routine nursing was caried out.The disease cognition scale scores,self-management scale scores,and quality of life scale scores were compared between the 2 groups before and after 6 months of intervention.Results After 6 months of intervention,the disease cognition scale scores,self-management scale scores,and quality of life scale scores of both groups improved,and the results in the experimental group were better than these in the control group,and the difference is statistically significant(P<0.05).Conclusion Nursing interventions based on the ITHBC theory can help improve the disease cognition of DR patients,establish and maintain healthy behaviors,improve their self-management level,and improve their quality of life.
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BACKGROUND: Dysregulation of lipid metabolism is the most prominent metabolic alteration observed in obesity, cancer, and cardiovascular diseases. The present study aimed to explore the sex differences associated with lipid metabolism in urinary exosome proteins, and evaluate the correlation of urinary exosome proteins with serum lipid biomarkers. METHODS: The key enzymes regulating lipid metabolism in healthy adults were screened using urinary exosome data. Urinary exosomes were isolated from 120 healthy subjects and the expression of urinary proteins was assessed by Western blotting and ELISA. The correlation between urinary protein concentrations and the levels of serum lipid biomarkers was analyzed using correlation analysis. RESULTS: Three urinary exosome proteins, namely fatty acid synthase (FASN), phosphoenolpyruvate carboxykinase (PCK1), and ATP-citrate synthase (ACLY) were identified, and only FASN showed sex differences. Sex differences were also observed in the serum triglyceride (TG) levels. Healthy males had higher FASN levels than females, and a moderate positive correlation was found between FASN concentrations and serum TG levels in healthy males (r = 0.479, P < 0.05). FASN concentrations in different age groups were positively correlated with the level of serum TG (18 ~ 30 years, r = 0.502; 31 ~ 44 years, r = 0.587; 45 ~ 59 years, r = 0.654; all P < 0.05). In addition, FASN concentrations was positively related to the increase in serum TG levels (range:1.0 ~ 1.7 mmol/L; r = 0.574, P < 0.05). CONCLUSIONS: Sex differences were observed in urinary exosome FASN protein levels in healthy adults. FASN protein levels positively correlated with increased serum TG levels. FASN may serve as a novel biomarker to evaluate fatty acid synthesis in the human body.
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Exosomas , Caracteres Sexuales , Humanos , Masculino , Adulto , Femenino , Ácido Graso Sintasas , Biomarcadores , Lípidos , Triglicéridos , Acido Graso Sintasa Tipo I/genéticaRESUMEN
Shark variable domain of new antigen receptors (VNARs) are the smallest naturally occurring binding domains with properties of low complexity, small size, cytoplasmic expression, and ease of engineering. Green fluorescent protein (GFP) molecules have been analyzed in conventional microscopy, but their spectral characteristics preclude their use in techniques offering substantially higher resolution. Besides, the GFP molecules can be quenched in acidic environment, which makes it necessary to develop anti-GFP antibody to solve these problems. In view of the diverse applications of GFP and unique physicochemical features of VNAR, the present study aims to generate VNARs against GFP. Here, we identified 36 VNARs targeting eCGP123, an extremely stable GFP, by phage display from three immunized sharks. These VNARs bound to eCGP123 with affinity constant KD values ranging from 6.76 to 605 nM. Among them, two lead VNARs named aGFP-14 and aGFP-15 with nanomolar eCGP123-binding affinity were selected for in-depth characterization. aGFP-14 and aGFP-15 recognized similar epitopes on eCGP123. X-ray crystallography studies clarified the mechanism by which aGFP14 interacts with eCGP123. aGFP-14 also showed cross-reaction with EGFP, with KD values of 47.2 nM. Finally, immunostaining analyses demonstrated that aGFP-14 was able to bind effectively to the EGFP expressed in both cultured cells and mouse brain tissues, and can be used as a fluorescence amplifier for EGFP. Our research demonstrates a feasible idea for the screening and production of shark-derived VNARs. The two high-affinity VNARs developed in the study contribute to the diversity of GFP sdAbs and may enhance the applications of GFP.
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Tiburones , Anticuerpos de Dominio Único , Ratones , Animales , Proteínas Fluorescentes Verdes/genética , Epítopos , Proteínas PortadorasRESUMEN
The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: â For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). â¡ Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ⢠Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.
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Terapia por Acupuntura , Moxibustión , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metaanálisis en Red , Bases de Datos Factuales , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
PURPOSE: Obesity has become a serious public health problem with its alarmingly increasing prevalence worldwide, prompting researchers to create and develop several anti-obesity drugs. Here, we aimed to investigate the protective effects of perilla seed oil (PSO), sunflower oil (SFO), and tea seed oil (TSO) against obesity through the modulation of the gut microbiota composition and related metabolic changes in mice fed a high-fat diet (HFD). METHODS: Mice were divided into six equal groups: ND (normal diet); HFD; ORL (HFD supplemented with 20 mg/kg body weight of orlistat); PSO, SFO, and TSO (HFD supplemented with 2 g/kg body weight of PSO, SFO, and TSO, respectively). RESULTS: Our findings showed that PSO, SFO, and TSO supplementation significantly reduced body weight, organ weight, blood glucose, lipopolysaccharides (LPS), insulin resistance, and improved serum lipid levels (TG, TC, LDL-C, and HDL-C). Meanwhile, the three treatments alleviated oxidative stress and hepatic steatosis and reduced liver lipid accumulation. Relative mRNA expression levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and MCP-1) and lipid synthesis-related genes (PPAR-γ, FAS, and SREBP-1) were down-regulated, while ß-oxidation-related genes (PPAR-α, CPT1a, and CPT1b) were up-regulated in the liver tissue of treated mice. Besides, dietary oil supplementation alleviated HFD-induced gut microbiota dysbiosis by promoting gut microbiota richness and diversity, decreasing the Firmicutes-to-Bacteroidetes ratio, and boosting the abundance of some healthy bacteria, like Akkermansia. CONCLUSIONS: PSO, SFO, and TSO supplementation could alleviate inflammation, oxidative stress, and hepatic steatosis, likely by modulating the gut microbiota composition in HFD-fed mice.