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ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.
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Objective:To screen the endoplasmic reticulum stress (ERS) signature-related differentially expressed genes (DEG) in gastric cancer and to construct a prognostic risk model based on a bioinformatics.Methods:Transcriptome sequencing data (RNA-seq) of 375 gastric cancer and 32 paracancerous tissue samples downloaded from The Cancer Genome Atlas (TCGA) database and the corresponding clinical information were obtained as training set samples; data of 387 gastric cancer patients (GSE84437) from Gene Expression Omnibus (GEO) database were downloaded as validation set samples. All data were obtained on December 25, 2021. A total of 785 ERS signature-related genes (ERS-RG) were obtained from the GeneCards database. DEG between gastric cancer tissues and paracancerous tissues in the TCGA database was analyzed. The identified gastric cancer DEG were intersected with ERS-RG from the GeneCards database to obtain gastric cancer ERS signature-related DEG, which were analyzed for gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Univariate Cox proportional risk model was used to screen ERS signature-related DEG with prognostic value in gastric cancer, and LASSO regression analysis was performed to construct a polygenic prognostic risk model, and to calculate the prognostic risk score. The patients in training set and validation set were divided into high-risk group and low-risk group according to the median of the prognostic risk score (2.369); Kaplan-Meier survival analysis was used to compare the overall survival (OS) and to draw time-dependent receiver operating characteristic (ROC) curves of patients in the two groups; nomogram was drawn based on the prognostic independent influencing factors of gastric cancer. The characteristic immune cell infiltration abundance between the two groups was analyzed by using the inverse convolution-based CIBERSORT algorithm. Cytolytic activity scores were calculated by using the geometric mean of granzyme A and perforin 1 expression. According to the median prognostic risk score (2.369) and median tumor mutation burden (TMB) (3.000), all patients with gastric cancer were divided into high risk score-high TMB group, high risk score-low TMB group, low risk score-high TMB group and low risk score-low TMB group to compare the OS of patients in each group.Results:A total of 444 ERS signature-related DEG in gastric cancer including 168 down-regulated genes and 276 up-regulated genes were obtained, which were mainly enriched in biological processes such as protein processing in the endoplasmic reticulum, extracellular matrix (ECM) receptor interactions and unfolded protein responses (all P < 0.05). Univariate Cox regression analysis showed that 12 prognostic-related ERS signature-related DEG in gastric cancer were screened out. LASSO regression analysis was performed to obtain a prognostic risk score = 0.052×NOS3+0.137×PON1+0.067×CXCR4+0.131×MATN3+0.116×ANXA5+0.090×SERPINE1. The results of Kaplan-Meier analysis showed that the OS of the low-risk group in both the training and validation sets was better than that of the high-risk group (all P < 0.01). The results of the time-dependent ROC curve analysis showed that the AUC for the 3-year, 5-year, 8-year OS rates was 0.695, 0.786, 0.698, respectively in the training set, while the AUC for the 3-year 5-year, 8-year OS rates was 0.580, 0.625, 0.627, respectively in the validation set. Multivariate Cox regression analysis showed that prognostic risk score ( HR = 3.598, 95% CI 2.290-5.655, P < 0.001) and tumor stage ( HR = 1.344, 95% CI 1.057-1.709, P < 0.05) were independent factors influencing the prognosis of gastric cancer. Among 375 gastric cancer patients in the TCGA database, the expression levels of ATF6, HSPA5, XBP1 and ATF4 in the high-risk group were higher than those in the low-risk group (all P < 0.05); CIBERSORT results showed that the abundance of activated CD4 memory T cells in the high-risk group was lower than that in the low-risk group, and the abundance of both M0 and M2 macrophages in the high-risk group was higher than that in the low-risk group (all P < 0.05). The expression levels of common immune checkpoints (CD274, CTLA4, TNFRSF9, TIGIT, PDCD1, LAG3) in the high-risk group were all higher than those in the low-risk group (all P < 0.05). Cytolytic activity score in the high-risk group was higher than that in the low-risk group ( P < 0.05). The prognostic risk score was negatively correlated with TMB ( r = -0.20, P < 0.001). Patients in the low-risk score-high TMB group had the best OS and those in the high-risk score-low TMB group had the worst OS (both P < 0.001). Conclusions:The prognostic risk score model is established based on 6 ERS signature-related DEG in gastric cancer and its prognostic risk score may be effective as an independent prognostic factor to predict the prognosis of gastric cancer patients.
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Objective:To evaluate incision scars of transaxillary breast augmentation by different methods of scar assessment.Methods:A retrospective study was carried out on 30 patients (age range 20 to 50 years, with mean age of 32 years) who underwent endoscopic assisted transaxillary type Ⅰ dual plane breast implant augmentation by a same surgeon from August 2014 to November 2016. Scars were estimated by 3 methods which included Vancouver Scar Scale (VSS), Visual Assessment Scale (VAS) and patients' questionnaire.Results:VAS score for left side scars ranged from 0 to 8 and the median was 1. VAS score for right side scars ranged from 0 to 8.3 and the median was 1. A total of 48 scars were scored in the 0-2 point range, representing 80% of the 60 total. VSS score for left side scars ranged from 0 to 11.6 and the median was 0.8. VSS score for right side scars ranged from 0 to 11.3 and the median was 1.2. A total of 46 scars were scored in the 0-2 point range, representing 76.7% of the total 60 breats. The scores between VSS and VAS had significant statistical differences ( P<0.001). 80.0% of our patients regarded scars as unconspicuous or basically invisible in our questionnaire. Conclusions:The majority of transaxillary incision scars recover in favorable status with high patients satisfactory rate. VAS is a practical tool for evaluating transaxillary incision scars. The VSS score is not equivalent to the VAS score when grading scars only by photos.
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Objective:To analyze the trend, hotspots and frontiers of diabetic retinopathy (DR) therapy by bibliometric method.Methods:Data were taken from the Web of Science website of Science Citation Index. Articles from 2017 to 2021, which were related to the therapy of diabetic retinopathy (DR), were included. The bibliometric analysis softwares, VOSviewer and CiteSpace were used to generate and analyze visual representations of the complex data input, including high-frequency keywords, keywords with the strongest citation bursts and co-occurrence networks of keywords.Results:A total of 3,845 articles were included. The amounts of papers published from 2017 to 2021 is 633, 651, 708, 893, and 960 respectively, increasing over years. Chinese scholars published the most articles, followed by the United States. The number of articles funded by the National Natural Science Foundation of China ranks third. There were 47 high-frequency keywords clustered into DR treatment, pathogenesis of DR, diagnosis of DR, Oxidative stress, diabetic macular edema (DME), type 2 diabetes, optical coherence tomography and deep learning. Those keywords were research hotspots and new keywords were constantly emerging. Among the top 11 burst words, the burst values of "intravitreal bevacizumab", "vascular endothelial growth factor (VEGF)", "choroidal neovascularization", "inhibition", and "receptors" were all over 10. Highly cited references showed a significant clustering tendency, which were treatment of DME, review of DR, clinical research of anti-VEGF drug therapy.Conclusions:The amount of paper related to DR therapy is on the rise; the specific treatment methods for the pathogenesis of DR are constantly research hotspots. In addition, formulating treatment strategies to reduce macular edema and other complications of diabetes, applying optical coherence tomography, deep learning and other technologies to improve the efficiency of DR diagnosis and treatment, improve targeted drug delivery systems, and finding new target points were research frontiers.
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Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.
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Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.
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Objective:To study the teaching effect of traditional teaching combined with virtual simulation teaching in pharmaceutical content analysis using high performance liquid chromatography (HPLC).Methods:The students in two parallel classes of grade 2016 were divided into experimental group (44 students) and control group (38 students). Taking the content analysis and its related analytical methodology of Metronidazole by HPLC as an example, the experimental group adopted the traditional offline teaching combines with virtual simulation teaching, and the control group adopted the traditional offline teaching. The teaching effects of the two groups were compared. SPSS 22.0 was used to conduct independent-samples t-test. Results:According to the mid-term test results, the experimental group was superior to the control group in practical operation assessment [(17.98±6.75) vs. (14.03±5.92)], and the difference was statistically significant ( P < 0.05). But there were no differences between the two groups in the scores of theory, discussion report and presentation. There was no significant difference in the final exam scores between the two groups. Conclusion:The ability of practical training and the teaching effect can be improved by the teaching method of traditional offline teaching combined with virtual simulation. Through the training of this project, students have mastered the operation of HPLC, the content determination of pharmaceutical preparations, the verification of analytical methods, data processing, and the writing of analytical reports, and have certain practical analysis ability.
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Background Exposure to heavy metals has potential adverse impacts on human health, and the concentration of heavy metals in abandoned mining areas may still be higher than that in general areas, so the health risk assessment in such areas cannot be ignored. Objective To explore the health risk of heavy metal exposure and the spatial distribution characteristics of associated main metals in a typical abandoned mining area. Methods Environmental samples of irrigated soil, rice, and drinking water were collected from 13 natural villages under the jurisdiction of a township in Liuzhou, Guangxi from November to December 2019, where a typical abandoned mining was located. Finally, 13 irrigation soil samples, 11 rice samples, and 13 drinking water samples were collected. The concentrations of six metals and metalloid elements in each environmental sample were detected by inductively coupled-plasma mass spectrometry (ICP-MS), including cadmium (Cd), arsenic (As), lead (Pb), chromium (Cr), copper (Cu), and zinc (Zn). At the same time, 251 local residents were recruited for health risk assessment. Model parameters such as body weight, rice intake, and drinking water intake of local residents were obtained through field survey, and the median metal concentration of each environmental sample was taken as the risk assessment parameter of the region. The health risk of heavy metal exposure of local residents was assessed by using oral health risk assessment model of U.S. Environmental Protection Agency. The spatial distribution characteristics of health risks associated with heavy metals were evaluated by empirical Bayes interpolation method using Geographic Information System (GIS) technology. Results The positive rates of Cd, As, Pb, Cr, Cu, and Zn in the irrigated soil samples were 100.00%. The positive rate of Pb was 63.64% in the rice samples, while the rates of other metals were 100.00%. The positive rates of Cd, As, Pb, Cr, Cu, and Zn in the drinking water samples were 53.85%, 76.92%, 92.31%, 15.38%, 84.62%, and 100.00%, respectively. The results of non-carcinogenic risk assessment of oral exposure to heavy metals suggested that the contribution of heavy metals causing non-carcinogenic risk from high to low was As (70.52%) > Cd (18.03%) > Zn (6.63%) > Cu (4.12%) > Pb (0.64%) > Cr (0.06%), and the corresponding estimated non-carcinogenic risk values were 3.54 × 100, 9.05 × 10−1, 3.33 × 10−1, 2.07 × 10−1, 3.23 × 10−2, and 5.42 × 10−4, respectively. The results of carcinogenic risk assessment of oral exposure to heavy metals suggested that the contribution of studied metals from high to low was Cd (87.00%) > As (10.24%) > Cr (2.60%) > Pb (0.16%), and the estimated carcinogenic risks were 4.35× 10−3, 5.12 × 10−4, 1.30 × 10−4, and 3.08 × 10−7, respectively. Rice was the leading media associated with non-carcinogenic risk and carcinogenic risk (99.4% and 99.8% respectively). The spatial distribution characteristics of GIS showed no obvious regularity in the distribution of As in irrigated soil, rice, and drinking water. In rice and irrigated soil, the content of Cd in the villages adjacent to the mining area was obviously higher than that in the other villages, while in drinking water, the content in the villages far away from the mining area was higher. Conclusion As and Cd are the main heavy metals that increase the health risk of local residents in a typical abandoned mining area, and the distribution characteristics of the two heavy metals in different environmental media are not completely consistent.
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【Objective】 To explore the effects of periodontitis on the brains of Alzheimer’s disease (AD) mice and the effects of N-acetyl-L-cysteine (NAC) on the periodontium and the brain of AD mice with experimental chronic periodontitis (CP). 【Methods】 Ten wild-type C57 mice were in the blank control group (Group C57), and another 40 3-month-old APP/PS1 transgenic mice were randomly divided into four groups: AD+CP group, AD+CP+NAC group, AD+NAC group, and AD group. The periodontitis model was established in mice in AD+CP group and AD+CP+NAC group by silk ligation. At the same time, mice in AD+CP+NAC group and AD+NAC group were injected with NAC (200 mg/kg). The height of alveolar bone loss was detected after 3 weeks, and the cell morphology of the hippocampus was observed. We determined the expression levels of NLRP3 inflammasome and amyloid-β (Aβ) in the hippocampus as well as the expression levels of interleukin (IL)-1β and IL-18 in the hippocampus and gums by ELISA. 【Results】 Compared with AD group, the height of alveolar bone loss in AD+CP group was higher (P<0.05), and the expression levels of IL-18 in the gum and IL-1β and NLRP3 in the hippocampus were increased significantly (P<0.05). In addition, compared with AD+CP group, the height of alveolar bone loss in AD+CP+NAC group was reduced significantly (P<0.05), the expression levels of IL-1β and IL-18 in the gum were reduced significantly (P<0.05) as well as the expression levels of IL-1β and Aβ in the hippocampus were reduced significantly (P<0.05). Compared with C57 group, the neurons in the hippocampus of AD+CP group were more loose and disordered, and the activation of microglia was increased, while the disarrangement of cells in AD+CP+NAC group was less than that in AD+CP group. 【Conclusion】 Periodontitis can aggravate brain inflammation in AD mice. NAC can effectively reduce alveolar bone resorption in AD mice caused by periodontitis as well as reduce the levels of inflammatory factors in the gum and hippocampus. NAC can effectively reduce the alveolar bone absorption of AD mice caused by periodontitis, reduce the level of inflammatory factors in the gingiva and hippocampus, and reduce the damage of nerve cells in the hippocampus.
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Patient experience is an important window for modern hospital management and medical service quality, and also an important point for humanistic hospital construction. Improving patient experience is of great significance for constructing harmonious doctor-patient relationship and improving patients’ satisfaction and sense of gain. Based on the perspective of patient experience improvement, this paper analyzed the core value of "patient demand first" of Mayo Clinic and the operational experience of Cleveland Medical Center Patient Experience Office, and applied them to the cultivation of humanistic hospital culture in the First Affiliated Hospital of Xi’an Jiaotong University. Based on the concept of "strengthening patient demand orientation", with the goal of "building a high-quality patient service system and significantly improving patient satisfaction", through building education platforms for medical ethics and medical humanism, exploring the medical humanism dissemination mode for medical staff, and carrying out the humanism literacy cultivation practice in the training camp for improving hospital service efficiency, the humanistic cultural atmosphere of the hospital has been further enhanced, and the patient satisfaction has been steadily improved. It provides reference for the cultivation of humanistic literacy and the construction of new culture in public hospitals in the context of high-quality development.
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Atherosclerotic cardiovascular disease is a common disease with high incidence rate and mortality worldwide. Atherosclerosis is an important pathological basis for the formation of ischemic cardiovascular diseases such as cardiovascular disease， which is related to inflammation， oxidative stress， apoptosis， vascular endothelial damage， foam cell formation， platelet activation， and so on， involving mitogen-activated protein kinase （MAPK）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， cyclic adenosine monophosphate/protein kinase A （cAMP/PKA）， Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase （ROCK）， nuclear factor-kappa B （NF-κB）， and other signaling pathways. In the past few decades， high-intensity statins were mainly used to treat atherosclerosis by reducing blood lipid levels， which usually caused obvious side effects. Therefore， the development of safer and more effective drugs and treatment modes is the focus of research at this stage. In recent years， Chinese medicine has been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. There are many studies on the mechanism of Chinese medicine in the prevention and treatment of atherosclerosis， and it is found that a variety of single Chinese medicine regulate the formation process of atherosclerosis by regulating targeted signal molecules. This paper reviewed the research results of related signaling pathways involved in the pathological formation of atherosclerosis and the mechanism of Chinese medicine in the prevention and treatment of cardiovascular diseases， thereby providing references for the clinical treatment of cardiovascular diseases.
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Background Environmental pollutants can affect N6-methyladenosine (m6A) level in the body, but the change of m6A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m6A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg−1 cadmium chloride (CdCl2) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m6A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg−1 cadmium chloride group (P<0.05). The expression levels of m6A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m6A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m6A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m6A and miR-21 may be associated with Cd-induced renal fibrosis.
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Background Individual lead or cadmium exposure can cause abnormal blood glucose level and changes in telomere length, and the role of telomere length in the relationship between heavy metal joint exposure and blood glucose level is still unclear. Objective To explore the role of telomere length in the relationship between lead and cadmium coexposure and blood glucose. Methods A cross-sectional study was conducted. By convenient sampling method, 600 residents living in two communities in a city in North China were selected as participants from April to June 2016. Face-to-face interviews were performed to collect general demographics and lifestyles of the participants. The peripheral blood samples of the participants were collected for blood glucose and telomere length detection, the urine samples were collected for urinary cadmium, urinary lead, and urinary creatinine measurement, and both urinary cadmium and urinary lead were corrected by urinary creatinine. The included participants were divided into a control group, a high-cadmium and low-lead group, a high-lead and low-cadmium group, and a high-lead and high-cadmium group, according to the median levels of urinary cadmium and urinary lead. A restricted cubic spline model was constructed to analyze the relationship between urinary lead/cadmium levels and blood glucose concentrations in the four groups and the relationship between cadmium exposure and telomere length in the high-lead and high-cadmium group. Intermediary model test was conducted to analyze the effect of telomere length on the relationship between exposures to lead and cadmium and blood glucose. Results The included participants were divided into the control group (n=99), the high-cadmium and low-lead group (n=91), the high-lead and low-cadmium group (n=145), and the high-lead and high-cadmium group (n=265). The differences in age, education level, per capita monthly household income, smoking, blood glucose, and telomere length were statistically significant among the four groups (P＜0.05). The high-lead and high-cadmium group had the highest blood glucose concentration, (5.63±1.68) mmol·L−1, and the shortest telomere length, (2.63±1.05) Kb. The restricted cubic spline results showed that urinary cadmium level was correlated with blood glucose concentration in the high-lead and high-cadmium group (F=3.45, P=0.037), and there was a non-linear association (F=6.91, P=0.002); the association between urinary cadmium level and telomere length was also non-linear (F=5.93, P=0.043). The intermediary model test results showed that telomere length was a mediating variable between urinary cadmium level and blood glucose concentration, and the mediating effect size was 0.0192 (95%CI: 0.0007-0.0563), with a mediation ratio of 15.57%. Conclusion Correlations between urinary cadmium and blood glucose and between urinary cadmium and telomere length were observed in the high-lead and high-cadmium coexposure group, and telomere length may play a mediating role in the relationship between them.
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Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors leading to serious complications in the cardiovascular system. As somatostatin receptor (SSTR) is highly expressed in PPGL, SSTR-targeting imaging, particularly PET/CT based on 68Ga-labelled somatostatin analog represented by 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), becomes an important tool for location and assessment of systemic metastases. Treatments for metastatic PPGL are limited. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE provides a new therapeutic option for patients with inoperable PPGL and demonstrates satisfying efficacy. This article summarizes the advances of SSTR-targeting imaging and PRRT in the diagnosis and treatment of PPGL.
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Objective:To investigate the gaze characteristics of children with autism spectrum disorder (ASD) on dynamic threatening (fear, anger) and non-threatening emotional (sadness, happiness) faces, and to explore the correlation between their eye-tracking data and autism symptomatology scores to provide a basis for the treatment and rehabilitation of children with ASD.Methods:From November 2020 to June 2021, 26 children with ASD and 30 age-and sex-matched normally developing children (typical developmental, TD) who met the enrollment criteria were included, and children with ASD were assessed for symptoms by the childhood autism rating scale (CARS). The SMI-red portable eye-tracking recording system was used to record the eye-movement gaze characteristics of children in both groups during free viewing of dynamic threatening and non-threatening emotional face segments.Statistical processing was performed by SPSS 21.0 software.The independent sample t-test and chi square test were used for the data conforming to the normal distribution, and the non parametric test was used for the data not conforming to the normal distribution, and Pearson correlation analysis was used to analyze the correlation between eye-tracking data and symptomatology scores. Results:The total CARS score of the ASD group was (32.64±7.42). The eye tracking data for children with ASD showed gaze aversion characteristics.Children with ASD spent significantly less time gazing at the eye area of threatening emotional faces in fear (2.41(0.26, 10.65)s) and anger (2.17(0.13, 6.13)s) than children with TD (8.81(2.54, 12.11)s, 5.21(3.80, 12.49)s), with statistically significant differences (fear: Z=-2.252, P<0.05.anger: Z=-2.793, P<0.01). Children with ASD spent significantly less time gazing at the mouth area of all four emotional faces (sad: 3.56(0.44, 7.16)s, fear: 2.68(0.42, 4.78)s, anger: 2.13(0.35, 4.20)s, happiness: 2.93(0.46, 5.71)s) than children with TD (sad: 11.43(6.97, 14.22) s, fear: 6.73(3.65, 10.10)s, anger: 6.86(4.55, 12.33)s, happiness: 11.72(7.22, 14.39)s), with statistically significant differences (sad: Z=-4.502, P<0.01.fear: Z=-3.493, P<0.01.anger: Z=-4.025, P<0.01.happiness: Z=-4.699, P<0.01). Correlation analysis revealed that the time spent gazing at emotional faces in children with ASD was negatively correlated with the total CARS score ( r=-0.476, P<0.05), and further analysis of different emotional faces revealed that the time spent gazing at fearful faces in children with ASD was negatively correlated with the total CARS score ( r=-0.455, P<0.05). Conclusions:Eye tracking in children with ASD show a gaze profile with less gaze time to threatening emotional faces compared with TD children, and the more severe the symptoms in children with ASD, the less gaze time to fearful faces.
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Exosomes are extracellular vesicles secreted by cells with a variety of molecular components, which can play the role of substance transport and signal communication between cells through autocrine and paracrine. Exosomes exist widely in vivo and participate in many physiological and pathological processes, including force-related periodontal inflammation. There are stress receptor cells in the periodontium, which can sense force loading on the tooth. An appropriate amount of mechanical loading can maintain health of the periodontium, while excessive mechanical loading may cause destruction and absorption of the periodontium, leading to periodontal inflammation. This article reviews the role of exosomes in force-related inflammation response, especially in periodontal inflammation response.
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Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders.Impaired social functioning is a core characteristic of individuals with ASD.Social attention deficits are important manifestation of their impaired social functioning.And it mainly reflected in the gaze on faces and social interactions.Eye movement technology is an objective and sensitive non-invasive measurement tool.Its application makes the measurement of individual core characteristics of ASD more accurate and objective.A review of recent studies revealed that the type of eye-movement stimuli for social attention in patients with AD gradually shifted from face image processing to social interaction scenes, and developed from static presentation to dynamic presentation.Dimensional embodiment of the progress of eye-movement studies of social attention in individuals with ASD.These studies suggest that individuals with ASD are less likely to gaze at the face region and the eye region of the face.More studies are currently using eye-tracking technology, and the analysis of emotional face gaze reveals that, the reduction in eye gaze in individuals with ASD is due to the discomfort associated with threatening faces.These findings validate the " gaze aversion" hypothesis regarding impaired social attention in individuals with ASD.Related neural mechanism studies have found a general lack of attention to social cues in the environment in individuals with ASD.Brain regions such as the amygdala, cingulate gyrus, superior temporal sulcus and anterior insula are associated with social attention in individuals with ASD.Especially with the superior temporal sulcus, the dorsal and ventral sides of the anterior insula, and so on.Future research should explore the cognitive neural mechanisms of social attention deficits in ASD, and the application of advanced information technology, such as eye-tracking technology, in the rehabilitation of patients with ASD.
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Objective:To select nucleic acid extraction reagents and amplification reagents by comparing the minimum detection limit, amplification efficiency, specificity, accuracy, and matching analysis with 6 nucleic acid extraction reagents of 6 novel coronavirus (2019-nCoV) nucleic acid detection reagents and provide scientific basis for clinical diagnosis and treatment.Methods:The national-standard material of 2019-nCoV nuclear acids was diluted as ths six fradient concentrations. Then, the diluted samples were analyzed by using the six kinds of agents/kits, Guangzhou Daan (DA), Beijing Jinhao (JH), Wuhan Mingde (MD), Sichuan Mike (MK), Jiangsu Shuoshi (SS) and Shanghai Zhijiang (ZJ). The minimum detection limit, amplification efficiency, accuracy, specificity and other properties of these kits were examined. The positive control levels 1, 2 (low and medium concentration) were extracted by using the six nucleic acid extraction reagents (numbered a-f) with six 2019-nCoV detective kits to detect target genes of 2019-nCoV genome, and compared between different nucleic acid extraction reagents and different nucleic acid detection reagents. Match between the different nucleic acid extraction reagents detection reagents, using two-way analysis of variance.Results:The minimum detection limit of Nucleocapsid (N) gene of DA, JH, MD, SS reagent was 7.0×10 2 copies/ml.The minimum detection limit of open reading frame 1ab (ORF1ab) gene of JH, MD, SS, MK reagent was 9.39 ×10 2 copies/ml.The minimum detection limit of envelope (E) gene of MK, ZJ reagent was 5.03×10 2 copies/ml. SS reagent N gene amplification efficiency was 89%, ORF1ab gene amplification efficiency was 90%, was the highest among six reagents.a, b, c, d extraction reagents and 6 nucleic acid detection reagents match well, But a extraction reagent was more suitable for use with SS,MK and ZJ reagents ( P<0.05), d extraction reagent was more suitable for MD,SS,DA,JH and MK nucleic acid detection reagents( P<0.05); e extraction reagent was more suitable for SS nucleic acid detection reagents( P<0.05), f extraction reagent was most suitable for DA, JH Nucleic acid detection reagents ( P<0.05); e and f reagents were not suitable for use with MK and ZJ. Conclusion:The 6 detection reagents have good performance, and the appropriate extraction reagents and detection reagents should be used in conjunction with the actual conditions of the laboratory.
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Background Exposure to environmental lead can cause kidney damage and telomere wear. However, the relationship among lead, peripheral blood telomere length, and glomerular filtration rate (eGFR) are unclear. Objective This study is conducted to investigate the relationships of urinary lead level with peripheral blood telomere length and renal function index eGFR, and further explore whether peripheral blood telomere length plays an intermediary role in the relationship between urinary lead level and eGFR. Methods A case-control study was conducted to select 497 residents from two communities in a city, including 230 in the control group (eGFR≥80 mL·min−1) and 267 in the abnormal eGFR group (eGFR<80 mL·min−1). Basic information and health information of the subjects were collected through a face-to-face questionnaire survey. Fasting morning urine was collected, and urinary lead and urinary creatinine (UCr) were detected. Fasting peripheral venous blood was collected to detect telomere length and serum creatinine (SCr) in peripheral blood leukocytes. eGFR was estimated by the Levey formula. After further adjusting for age, gender, education level, family per capita monthly income, smoking, and drinking the relationship among urinary lead level, peripheral blood telomere length, and renal function index eGFR was evaluated by mediating effect analysis. Results The overall level of creatinine-adjusted urinary lead [M (P25, P75)] in the abnormal eGFR group was 3.85 (1.56, 7.34) μg·g−1 which was higher than that in the control group, 1.57 (0.60, 3.62) μg·g−1(P<0.001). In addition, the overall level of peripheral blood telomere length in the abnormal eGFR group was 2.42 (1.89, 3.10) Kb, lower than that in the control group, 2.69 (2.09, 3.64) Kb (P<0.001). The results of mediating effect analysis showed that the magnitude of mediating effect by peripheral blood telomere length was −0.276 (95%CI: −0.708-−0.001) and it contributed 3.35% to the relationship between urinary lead level and eGFR. In women, the magnitude of mediating effect by peripheral blood telomere length was −0.484 (95%CI: −1.160-−0.023) between urinary lead level and eGFR, and the proportion of the mediating effect was 5.34%. In men, no mediating role of peripheral blood telomere length was found between urinary lead and eGFR. Conclusion Urinary lead level is closely related to renal function index eGFR and telomere length in peripheral blood. Peripheral blood telomere length plays a mediating role in the relationship between female urinary lead and eGFR in women.
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Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.