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ObjectiveTo investigate the effect of Stemona tuberosa alkaloids （STA） on apoptosis and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups （100， 150， 200， 250， 300 mg⋅L-1）. Thiazole blue （MTT） assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining， flow cytometry， and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2， and the expression of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， JNK， p-JNK， p38 MAPK， and p-p38 MAPK. ResultCompared with the blank group， STA groups （150， 200， 250， 300 mg⋅L-1） demonstrated the increase in inhibition rate of cell proliferation （P<0.01） and cell clone inhibition rate， and decrease in cell clone formation rate （P<0.01）. In comparison with the blank group， STA groups showed typical characteristics of apoptosis， such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group （P<0.01）. Compared with the blank group， STA （150， 200， 250， 300 mg⋅L-1） significantly up-regulated the protein expression of Caspase-3 and Bax （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 protein （P<0.01）. Compared with the blank group， STA had no significant influence on the total protein expression of PI3K， Akt， JNK， and p38 MAPK. However， STA （150， 200， 250， 300 mg⋅L-1） significantly decreased the levels of p-PI3K and p-Akt （P<0.05， P<0.01） and increased the level of p-p38 MAPK （P<0.05， P<0.01）. Compared with the blank group， STA （200， 250， 300 mg⋅L-1） significantly raised the level of p-JNK （P<0.05， P<0.01）. ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.
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Objective:To systematically evaluate the qualitative studies on the decision dilemma of blood glucose management during pregnancy in patients with gestational diabetes mellitus, so as to provide reference for the subsequent formulation of intervention strategies.Methods:The qualitative studies on the decision dilemma of blood glucose management during pregnancy in patients with gestational diabetes mellitus in the Cochrane Library, CINAHL, EMbase, PubMed, PsycINFO, ProQuest, Web of Science, China National Knowledge Internet, Wanfang, VIP and Chinese Biomedical Database were searched from inception to May 2022. The JBI Critical Appraisal Tool for qualitative studies in Australia (2016) was used to evaluate the literature quality, and research results were summarized and integrated by integrating methods.Results:A total of 13 studies were included, 56 themes were extracted, and they were summarized into 9 categories, forming 3 integrated results as following, lack of personalized and professional information on blood glucose management, worring about the influence of blood glucose management on the health of mothers and children, conflict between daily life and blood glucose management plan.Conclusions:Health care workers should provide gestational diabetes mellitus patients with adequate personalized professional information support on blood glucose management to facilitate scientific decision-making during pregnancy, and also analyze the benefits and risks of different decisions for patients to help them make the best decision and strengthen their external support system to help them implement blood glucose management decisions.
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Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.
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ObjectiveTo summarize the characteristics of traditional Chinese medicine （TCM） syndrome in primary Sjögren's syndrome （pSS） patients with interstitial lung disease （ILD） and to explore associated factors. MethodA survey was conducted and pSS patients who were treated in TCM department of rheumatism at China-Japan Friendship Hospital from December 2018 to April 2022 were included. Tongue manifestations and syndromes of patients were recorded. pSS patients with ILD were classified into the pSS-ILD group and those without the ILD were included in the pSS-non-ILD group. The tongue manifestations， syndromes， and laboratory indexes were compared between the two groups， and logistic regression was used to explore the factors associated with pSS-ILD. ResultA total of 200 pSS patients were included， with 186 （93.0%） females， median age of 57 years， and median disease course of 60 months， of which 44 （22%） had pSS-ILD. In terms of tongue manifestations， pSS-ILD patients generally had dark/purple/stasis tongue， fissured tongue， and tongue with little fluid， thick coating， yellow coating， and greasy coating. The proportion patients with yellow coating was higher in pSS-ILD group than in the pSS-non-ILD group （χ2=4.799，P<0.05）. In terms of syndrome， more than 40% of pSS-ILD patients had Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. As for Yin deficiency， liver-kidney Yin deficiency syndrome ranked the first. For Qi deficiency， lung Qi deficiency syndrome was most commonly seen. The proportion of patients with lung Qi deficiency was higher in the pSS-ILD group than in the pSS-non-ILD group （χ2=18.667，P<0.01）. As to laboratory indexes， compared with the pSS-non-ILD group， pSS-ILD group had high proportion of anti-SSA-positive patients （P<0.05） and high levels of C-reactive protein （CRP） （P<0.01）， complement C3 （χ2=4.332，P<0.05）， and complement C4 （P<0.05）. Logistic regression analysis showed that pSS with ILD was positively associated with lung Qi deficiency ［odds ratio （OR）=6.079， 95% confidence interval （CI） 2.585-14.298， P<0.01）］ and yellow coating （OR=5.260， 95% CI 1.337-20.692， P<0.05） and negatively associated with low C4 （OR=0.199， 95% CI 0.070-0.564， P<0.01）. ConclusionAbout 22% of pSS patients had ILD， and patients with pSS-ILD generally have Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. Yellow coating， lung Qi deficiency and C4 level are factors associated with pSS combined with ILD.
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ObjectiveTo analyze the clinical characteristics of geographic tongue in patients with primary Sjögren's syndrome （pSS）. MethodPatients with pSS treated in the China-Japan Friendship Hospital from December 2018 to October 2021 were enrolled and divided into different groups according to the presence of geographic tongue or the severity. Phi correlation analysis，Chi-square test， and Mann-Whitney test were used to analyze the clinical characteristics of patients with geographic tongue. ResultA total of 182 pSS patients were included in this study，including 75 （41.2%） patients with geographic tongue and 107 （58.8%） without geographic tongue. Partial exfoliation was more common than total exfoliation， and the anterior part of the tongue was the most common exfoliation site. The number of patients with severe geographic tongue was more than those with mild-to-moderate geographic tongue. Compared with pSS patients without geographic tongue，those with geographic tongue were more common in fissured tongue （92.0%/41.1%，χ2=48.491，P<0.05），red or crimson tongue （48.0%/23.3%，χ2=12.009，P<0.05），Yin deficiency syndrome （100.0%/43.9%，χ2=62.739，P<0.05），and Qi deficiency syndrome （94.7%∶50.5%，χ2=40.046，P<0.05），less common in phlegm-dampness syndrome （33.3%/72.0%，χ2=26.709，P<0.05），and showed higher proportions in hyperglobulinemia （89.3%/65.4%，χ2=13.547，P<0.01），ANA ≥1∶160 （78.1%/57.3%，χ2=8.227，P<0.01），and positive RF （51.4%/36.5%，χ2=3.877，P<0.05）. Compared with pSS patients with mild geographic tongue，pSS patients with moderate-to-severe geographic tongue had higher proportions in hyperglobulinemia （98.1%/68.2%，χ2=14.617，P<0.01），positive anti-CENP-B （26.0%/4.8%，χ2=4.214，P<0.05），and reduced complement 3 （26.4%/4.5%，χ2=4.647，P<0.05）. The geographic tongue was positively associated with fissured tongue （φ=0.531），Yin deficiency syndrome （φ=0.587），and Qi deficiency syndrome （φ=0.469），negatively associated with phlegm-dampness syndrome （φ=-0.447），and weakly associated with tongue color （φ<0.4）. There was no statistical difference in the disease activity index between patients with or without geographic tongue and severity. ConclusionMore than 40% of pSS patients had geographic tongue accompanied by fissured tongue. Geographic tongue is positively associated with Yin deficiency syndrome and Qi deficiency syndrome，and negatively associated with phlegm-dampness syndrome， indicating that treatment should be based on tonifying Qi and nourishing Yin. Compared with pSS patients without geographic tongue， those with geographic tongue may have higher positive rate of some immune indicators，which deserves further exploration.
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ObjectiveTo explore the characteristics of tongue manifestations and traditional Chinese medicine （TCM） syndromes in patients with primary Sjogren's syndrome （pSS） of different time. MethodpSS patients who visited TCM Department of Rheumatism in China-Japan Friendship Hospital from December 2018 to October 2021 were included and grouped according to the disease courses （short<5 years， medium 5-10 years， long > 10 years）. Chi-square test was used for comparison between three groups and Bonferroni method for multiple comparisons. In the pairwise comparison， P<0.017 indicated significant difference. Chi-square test was performed on the syndrome and specific tongue manifestations with inter-group differences to analyze the trend of tongue manifestations and TCM syndromes over time （interval： two years）. ResultA total of 193 pSS patients were enrolled， with 85 （44.0%） of short disease course， 69 （35.8%） of medium disease course， and 39 （20.2%） of long disease course. The common tongue manifestations were crimson tongue， fissured tongue， thin tongue， lack of fluid， and dry coating， which showed no significant difference among the three groups. Higher proportion of patients with light red tongue was observed in the group with short disease course than in group with medium disease course （χ2=6.407， P<0.017）. Higher proportions of patients with thick coating （χ2=6.784， P<0.017） and phlegm-dampness syndrome （χ2=11.545， P<0.017） and lower proportion of patients with Qi deficiency syndrome （χ2=12.706， P<0.017） were found in the group with short disease course than in the group with long disease course. Patients with medium （χ2=6.358， P<0.017） and long （χ2=8.279， P<0.017） disease course tended to have exfoliated coating compared with those with short disease course， and the proportion of patients with exfoliated coating rose and the proportion of patients with thick greasy coating decreased over time （Ptrend<0.05）. In addition， the proportion of patients with phlegm-dampness syndrome decreased and that with Qi deficiency syndrome increased over time （Ptrend<0.05）. ConclusionIn the early stage， patients with pSS often show both dryness and dampness， as manifested by the thick greasy coating and phlegm-dampness syndrome. In the medium and late stage， patients often have Qi-Yin deficiency， as evidenced by exfoliated coating and Qi deficiency. In the clinical practice， medicines should be prescribed based on tongue manifestations and TCM syndrome of patients.
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ObjectiveTo observe the efficacy and safety of Huashi Runzao prescription for patients with primary Sjögren's syndrome （pSS） of combined dryness and dampness pattern. MethodA total of 105 eligible patients were randomized into the experimental group （65 cases） and control group （40 cases）， and they were respectively treated with Huashi Runzao prescription and hydroxychloroquine for 12 weeks. Visual Analogue Scale （VAS） was employed to assess the symptoms. The symptoms of dryness， fatigue， and pain， European League Against Rheumatism （EULAR） Sjögren's Syndrome Patient Reported Index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， and immune inflammatory indicators before and after treatment were compared between the two groups， and adverse reactions were observed. ResultAfter treatment， the ESSPRI score was lower than that before treatment in the experimental groups （P<0.01） and was lower in the experimental group than in the control group （P<0.05）. The VAS scores of dry mouth， dry eyes， overall dryness， fatigue， and pain in the experimental group decreased compared with those before treatment （P<0.01）， and the experimental group had lower VAS scores of dry mouth and overall dryness than the control group （P<0.01）. After treatment， the ESSDAI score of both groups decreased compared with that before treatment （P<0.05， P<0.01）， but there was no significant difference between the groups. After treatment， the level of immunoglobulin M （IgM） decreased （P<0.01） and the level of complement C3 increased （P<0.01） in the experimental group， while the level of complement C3 decreased in the control group （P<0.05）. There was no significant difference in the laboratory indexes between groups. During the treatment， stomachache occurred to one case in the experimental group， which was alleviated after the treatment， and no adverse reaction was observed in the control group. According to the chi-square test， the occurrence of adverse reactions was insignificantly different between the two groups. ConclusionHuashi Runzao prescription can alleviate the symptoms of dryness， fatigue， and pain， and reduce disease activity without associated side effects in pSS patients with combined dampness and dryness pattern.
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ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg-1·d-1），and hydroxychloroquine （HCQ） group （1.30 g·kg-1·d-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.
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Arrhythmia is a significant cardiovascular disease that poses a threat to human health, and its primary diagnosis relies on electrocardiogram (ECG). Implementing computer technology to achieve automatic classification of arrhythmia can effectively avoid human error, improve diagnostic efficiency, and reduce costs. However, most automatic arrhythmia classification algorithms focus on one-dimensional temporal signals, which lack robustness. Therefore, this study proposed an arrhythmia image classification method based on Gramian angular summation field (GASF) and an improved Inception-ResNet-v2 network. Firstly, the data was preprocessed using variational mode decomposition, and data augmentation was performed using a deep convolutional generative adversarial network. Then, GASF was used to transform one-dimensional ECG signals into two-dimensional images, and an improved Inception-ResNet-v2 network was utilized to implement the five arrhythmia classifications recommended by the AAMI (N, V, S, F, and Q). The experimental results on the MIT-BIH Arrhythmia Database showed that the proposed method achieved an overall classification accuracy of 99.52% and 95.48% under the intra-patient and inter-patient paradigms, respectively. The arrhythmia classification performance of the improved Inception-ResNet-v2 network in this study outperforms other methods, providing a new approach for deep learning-based automatic arrhythmia classification.
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Humans , Arrhythmias, Cardiac/diagnostic imaging , Cardiovascular Diseases , Algorithms , Databases, Factual , ElectrocardiographyABSTRACT
Diabetic kidney disease （DKD） is one of the most common microvascular complications in patients with diabetes. DKD is also the main cause of end-stage renal failure， with very complex pathogenesis. A large number of experiments have confirmed that epigenetic mechanisms， including histone chemical modifications and lipid metabolites 12/15-lipoxygenase （12/15-LO）， are involved in regulating the characteristic pathophysiological process of DKD， based on which， this review further explores the pathogenesis of DKD and provides the new research direction for DKD treatment.
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ObjectiveTo explore the effect of hip neuromuscular training on reducing the risk of anterior cruciate ligament (ACL) injury in female soccer players. MethodsFrom March to May, 2022, 39 female soccer players from Xi'an Physical Education University were randomly divided into control group (n = 19) and experimental group (n = 20). On the basis of daily training, the control group received sham intervention, and the experimental group received hip neuromuscular training, for six weeks. Before and after training, they were measured dynamic knee valgus (DKV) angle and assessed with Landing Error Score System (LESS); while they were also measured the maximal voluntary isometric contraction (MVIC) and root mean square (RMS) of electromyography as single leg landing of gluteus medius and gluteus maximus. ResultsAll the indexes varied little after training in the control group (|t| < 1.178, P > 0.05), while the indexes improved in the experimental group (|t| > 2.288, P < 0.05), except sagittal score of LESS; and all the indexes improved more in the experimental group than in the control group (|t| > 2.609, P < 0.05), except sagittal score of LESS and MVIC of gluteus maximus. ConclusionHip neuromuscular training can reduce the risk of ACL injury in female soccer players.
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Objective@#To explore the effectiveness of preventive treatment for latent tuberculosis infection (LTBI) patients, so as to provide reference for the management and preventive treatment of clustered epidemic in schools.@*Methods@#Data came from the school tuberculosis outbreak of a boarding high school in Kaizhou District, Chongqing, which occurred between June 2017 and March 2018 among 2016 grade high school teachers and students for investigation and analysis. The total incidence, LTBI patients, and the incidence after preventive treatment for 5 years were followed up.@*Results@#A total of 34 cases of pulmonary tuberculosis from June 2017 to March 2018. A total of 1 357 individuals were screened for 6 concentrated contact screenings, with a confirmed tuberculosis rate of 2.43%, a tuberculosis skin test (TST) positive rate of 27.41%, and a strong TST positive rate of 7.39%. Among them, the confirmed tuberculosis rate and TST positive rate in the first case class were much higher than those in other classes, with statistically significant differences ( χ 2=286.30, 98.59, P ＜0.01). 88 cases of LTBI were found, with 31 cases receiving preventive treatment (35.23%), of which 28 completed preventive treatment (90.32%). After five years of follow-up, 73 cases of pulmonary tuberculosis were diagnosed in 2016 by the school senior high school, with a incidence rate of 0.98/10 2 (person/person years). Fifteen of the 88 LTBI patients were diagnosed with pulmonary tuberculosis, and the incidence rate was 3.33/10 2 (person/person years). The incidence rate of the preventive treatment group was 0.7/10 2 (person/person years)lower than that of the medical observation group 4.5/10 2 (person/person years), with a statistically significant difference ( χ 2=4.31, P ＜0.05).@*Conclusion@#The classes with higher TST positive rate and strong positive rate have higher incidence rate. Improving the preventive treatment rate of LTBI patients can effectively reduce the incidence rate of tuberculosis.
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@#We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.
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Insulin resistance is one of the main contributors to the pathogenesis of type 2 diabetes mellitus, which reduces the sensitivity of target tissues to insulin and increases the compensatory secretion of islet cells, leading to chronic hyperinsulinemia and inducing vascular endothelial cell dysfunction. Insulin resistance is also the pathological basis of a series of cardiovascular diseases such as hypertension, coronary heart disease and heart failure secondary to type 2 diabetes mellitus. Analyzing the relationship between insulin resistance and cardiovascular disease in type 2 diabetes mellitus can provide new ideas for the prevention and treatment of type 2 diabetes mellitus complicated with cardiovascular disease.
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Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.
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Objective To investigate the role of P-I-R classification and Laennec grading in evaluating histological changes in patients with hepatitis B cirrhosis after receiving antiviral therapy, as well as the association of these two evaluation systems with clinical prognosis. Methods A total of 218 patients from 14 centers were consecutively screened from October 2013 to October 2014, and these patients were diagnosed with liver cirrhosis based on pathology (Ishak score ≥5), received antiviral therapy for 72 weeks, completed two liver biopsies, and met the P-I-R classification criteria. The 218 patients were divided into non-hepatocellular carcinoma (HCC) group with 186 patients and HCC group with 32 patients. The chi-square test and the Fisher's exact test were used for comparison of categorical data between groups. For the comparison of HCC after antiviral therapy, the non-parametric Mann-Whitney U test was used for continuous variables, and for the comparison of P-I-R classification and Laennec grading, the non-parametric Kruskal-Wallis H test was used for continuous variables. Univariate and multivariate Cox regression analyses were used to calculate hazard ratio ( HR ) and 95% confidence interval ( CI ), and the Kaplan-Meier method was used to calculate the cumulative incidence rate of HCC. Results After 72 weeks of antiviral therapy, there was a significant difference in P-I-R classification between the non-HCC group and the HCC group ( P < 0.001). There were significant differences in the distribution of Laennec grading and P-I-R classification before and after antiviral therapy ( P < 0.001). After antiviral therapy, the 218 patients were divided into 4A group with 33 patients, 4B group with 71 patients, and 4C group with 114 patients according to Laennec grading, and there were significant differences between these three groups in platelet count (PLT) ( H =36.429, P < 0.001), liver stiffness measurement (LSM) ( H =13.983, P =0.004), Ishak score ( χ 2 =23.060, P < 0.001), and HAI score ( P < 0.001). After antiviral therapy, the 218 patients were divided into R group with 70 patients, I group with 52 patients, and P group with 96 patients according to P-I-R classification, and there were significant differences between these three groups in PLT ( H =7.193, P =0.028), LSM ( H =6.238, P =0.045), Ishak score ( χ 2 =7.986, P < 0.001), HAI score ( P =0.002), and HCC ( P < 0.001). There was a significant difference in the incidence rate of HCC between the P and R groups based on P-I-R classification ( HR =24.21, 95% CI : 0.46-177.99, P =0.002). After adjustment for other confounding factors, P-I-R classification was an independent predictive factor for HCC ( HR =12.69, 95% CI : 4.63-34.80, P =0.002). Conclusion Both P-I-R classification and Laennec grading can reflect the features and changes of fibrosis before and after antiviral therapy, and P-I-R classification is more sensitive to fibrosis changes after antiviral therapy. P-I-R classification (after treatment) can be used to assess the risk of HCC in patients after antiviral therapy.
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Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.
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Objective:To investigate the level of peripheral blood regulatory T cells in rheumatoid arthritis (RA) patients with cardiovascular disease (CVD) and its clinical significance.Methods:A total of 191 patients with RA in the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Shanxi Medical University and 86 healthy controls (HCs) were enrolled from January 2019 to January 2021. All peripheral blood CD4 + T lymphocyte subsets of participants were assessed by flow cytometry. Patients were divided into RA-CVD group ( n=71) and RA only group ( n=120) and their clinical data were recorded. The differences between the groups were analyzed by Independent-Samples t test, Mann-Whitney U test or χ2 test, and risk factors that affected CVD were analyzed using Logistic regression. Results:① The age of patients and the proportion of male patients in the RA-CVD group were significantly higher than those in the RA only group [age: (64±10) years old vs (56±12) years old, t=-4.16, P<0.001; male patients: 35 cases vs 31 cases, χ2=10.86, P=0.001]. ② The level of Treg cells in the peripheral blood of patients with RA only and RA-CVD groups was significantly lower than that of HCs ( Z=-4.14, P<0.001; Z=-6.27, P<0.001), while the numbers of peripheral Th17 cells in the two groups of patients were not significantly different from those of HCs ( P>0.05). The ratios of Th17/Treg cells in the two group patients were higher than those of HCs, but only the difference between RA-CVD patients and HCs was significant ( Z=-5.49, P<0.001). ③ Compared with the RA only group, the absolute number of Treg cells in peripheral blood of RA-CVD group was significantly lower [19.00(13.62, 26.73) vs 24.94 (19.32, 34.12), Z=-3.19, P=0.001], the level of Th17 cells was significantly higher [absolute number: 7.77 (3.86, 13.64) cell/μl vs 5.59 (3.49, 8.91) cells/μl, Z=-2.14, P=0.033; percentage: 1.37%(0.78, 2.00)% vs 0.80%(0.56, 1.24)%, Z=-4.20, P<0.001], and the ratio of Th17/Treg cells was significantly higher [0.40(0.24, 0.62) vs 0.23(0.14, 0.35), Z=-4.46, P<0.001]. ④ Logistic regression analysis showed that Treg cell [ OR(95% CI)=0.934 (0.903, 0.967)] was a protective factor, while elder age [ OR(95% CI)=1.038(1.003, 1.074), male [ OR(95% CI)=2.450(1.005, 5.973)], hypertension [ OR(95% CI)=2.654 (1.219, 5.779)] and Th17 cell [ OR (95% CI)=1.066 (1.019, 1.116)] were risk factors of RA complicated with CVD. Conclusion:The level of Treg cells in peripheral blood of RA patients with CVD decreases significantly, and the immune imbalance of Th17/Treg is more singificant than that of RA patients without CVD. It is suggested that the immune imbalance and dysfunction caused by the number and/or functional deficiency of Treg cells may be involved in the occurrence and development of RA complicated with CVD.
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Objective:To explore the expression level of interleukin-1 receptor-associated kinase-1 (IRAK1) in the peripheral blood of rheumatoid arthritis (RA) patients and analyze its relevance between disease activity and CD4 + T cell subsets. Methods:① The concentration of IRAK1 in the peripheral blood of 77 RA patients and 24 healthy controls were detected by enzyme linked immunosorbent assay (ELISA). ② The demo-graphic and clinical data of the RA group including disease activity score with 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 + T cell subsets in peripheral blood. ③Independent sample t test or Mann-Whitney U test were used to compare the differences between the two groups. Spearman rank correlation test and multiple linear regression were used to analyze the correlation between IRAK1 expression level and clinical data. Results:① The IRAK1 level of the peripheral blood of RA patients was significantly higher than in the normal controls ( P<0.001). ② Compared to normal controls, the peripheral blood of the RA group, the absolute numbers and proportion of regulatory T (Treg) cells were decreased ( P<0.001), the absolute numbers and proportion of helper T (Th) 17 and the ratio of Th17/Treg were increased. Moreover, the ratio of Th17/Treg was also increased. ③ With the increase of disease activity in RA patients, the expression of IRAK1 also increased. The expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR, number of joints involved and DAS28, and had statistically significant difference between the two groups ( r=0.23, P<0.05; r=0.24, P<0.05; r=0.27, P<0.05). Meanwhile, it was sign-ificantly negatively correlated with the percentage of Treg ( r=-0.27, P<0.05), and was significantly positively correlated with the ratio of Th17/Treg ( r=0.23, P<0.05) . However, there was no significant correlation with the ratio of Th1/Th2( P>0.05). Furthermore, multiple stepwise regression analysis showed that the expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR and the number of joints involved ( β=0.34, P=0.019; β=0.27, P=0.004), and it was inversely correlated with percentage of Treg ( β=-0.23, P=0.047, R2=0.219). Conclusion:IRAK1 expression in the peripheral blood of RA patients is up-regulated and correlated with disease activity. The decrease of Treg and the imbalance of Th17/Treg caused by high expression of IRAK1 may be one of the main factors for the occurrence and development of RA. Interfering the expression of IRAK1 may be a potential new target for RA treatment.
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ObjectiveTo assess the anxiety and depression symptoms and sleep quality in patients with menstrual migraine， so as to provide references for the prevention and treatment of menstrual migraine and its comorbidity. MethodsAccording to the diagnostic criteria of the International Classification of Headache Disorder， third edition （ICHD-3）， 501 female migraine patients， including 112 patients with menstrual migraine and 389 patients with non-menstrual migraine， who attended the outpatient clinic of the Affiliated Hospital of North Sichuan Medical College from February 2019 to February 2020， were selected for the study. The general and clinical data of the patients were collected， meantime， patients were assessed using Hamilton Anxiety Scale （HAMA）， Hamilton Depression Scale-24 item （HAMD-24）， 6-item Headache Impact Test （HIT-6） and Pittsburgh Sleep Quality Index （PSQI）. ResultsThe detection rates of pure anxiety， pure depression， comorbid anxiety-depression and sleep disorders in patients with menstrual migraine were higher than those in patients with non-menstrual migraine （χ2=4.198， 4.355， 5.236， 8.624， P<0.05 or 0.01）. Patients with menstrual migraine had higher scores of HAMA、HAMD-17、PSQI and HIT-6 than those of non-menstrual migraine patients （Z=-3.550、-2.723、-2.482、-4.717，P<0.05 or 0.01）. Correlation analysis showed that PSQI score of menstrual migraine patients was positively correlated with HAMA score （r=0.338， P<0.01）， HAMD-24 score （r=0.372， P<0.01） and HIT-6 score （r=0.192， P<0.05）. ConclusionCompared with non-menstrual migraine patients， patients with menstrual migraine experience more severe anxiety and depression symptoms and sleep problems and suffer greater negative life impacts. In addition， the influence of anxiety and depression symptoms and headache on daily life is associated with sleep quality.