Knockdown of NR4A1 alleviates doxorubicin-induced cardiotoxicity through inhibiting the activation of the NLRP3 inflammasome.

Doxorubicin (DOX) is a widely used antitumor drug, but its clinical applicability is hampered by the unfortunate side effect of DOX-induced cardiotoxicity (DIC). In our current study, we retrieved three high-throughput sequencing datasets related to DIC from the Gene Expression Omnibus (GEO) datasets. We conducted differential analysis using R (DESeq2) to pinpoint differentially expressed genes (DEGs, and identified 11 genes that were consistently altered in both the control and DOX-treated groups. Notably, our Random Forest analysis of these three GEO datasets highlighted the significance of nuclear receptor subfamily 4 group A member 1 (NR4A1) in the context of DIC. The DOX-induced mouse model and cell model were used for the in vivo and in vitro studies to reveal the role of NR4A1 in DIC. We found that silencing NR4A1 by adeno-associated virus serotype 9 (AAV9) contained shRNA in vivo alleviated the DOX-induced cardiac dysfunction, cardiomyocyte injury and fibrosis. Mechanistically, we found NR4A1 silencing was able to inhibit DOX-induced the cleavage of NLRP3, IL-1ß and GSDMD in vivo. Further in vitro studies have shown that inhibition of NR4A1 suppressed DOX-induced cytotoxicity and oxidative stress through the same molecular mechanism. We prove that NR4A1 plays a critical role in DOX-induced cardiotoxicity by inducing pyroptosis via activation of the NLRP3 inflammasome, and it might be a promising therapeutic target for DIC.

The association between smoking exposure and endothelial function evaluated using flow-mediated dilation values: a meta-analysis.

BACKGROUND: Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. RESULTS: Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of - 3.15 was obtained with a 95% confidence interval of (- 3.84, - 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. CONCLUSIONS: We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. TRIAL REGISTRATION: The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).

Impairment of Autophagy Mediates the Uric-Acid-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells.

INTRODUCTION: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism. METHODS: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells. RESULTS: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4. CONCLUSION: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.

Influence of Local Vibration Therapy on the Mental State, Neurological Function, and Quality of Life of Convalescing Patients With Spinal Cord Injury.

Context: The clinical postoperative recovery of patients with a spinal cord injury (SCI) is relatively long. Good self-efficacy can help patients actively cooperate with treatment and rehabilitation and improve their functional recovery and QoL. Local vibration stimulation has emerged as a potential nondrug therapy for SCI patients. However, the use of local vibration therapy for SCI patients is still rare, and its efficacy isn't clear yet. Objective: The study intended to analyze the combined effects of local vibration therapy and self-efficacy training on the psychological state and neurological function of SCI patients during rehabilitation as well as the therapy's correlation with quality of life (QoL). Design: The research team conducted a retrospective study. Setting: The study took place at Zhejiang Hospital in Hangzhou, China. Participants: Participants were 82 SCI patients who received surgery and postoperative interventions in the rehabilitation department at the hospital between March and September 2021 for surgery and postoperative intervention. Interventions: Based on the use of different interventions, the research team divided participants into two groups, with 41 participants in each group: (1) the local vibration group and (2) a control group. Patients in both groups received spinal cord reduction and internal fixation surgery and self-efficacy training after surgery. The local vibration group also received local vibration therapy. Outcome Measures: At baseline and postintervention, the research team measured: (1) neurological function, using the National Institutes of Health Stroke Scale (NIHSS); (2) daily living ability, using the Activities of Daily Living (ADL) scale; (3) psychological state, using the self-rating anxiety (SAS) and self-rating depression (SDS) scales; and (4) QoL, using the Generic Quality of Life Inventory-74 (GQOLI-74) questionnaire. The team used the Pearson correlation coefficient to analyze the relationship between patients' neurological function, psychological state, and QoL. Results: Between baseline and postintervention, the local vibration group's: (1) mean NIHSS score decreased significantly (P < .001), (2) mean ADL score increased significantly(P < .001), (3) mean SAS (P < .001) and SDS (P < .001) scores decreased significantly; and (4) mean total GQOLI-74 score (P < .001) and scores for the dimensions physical function (P < .001), social function (P < .001), psychological function (P < .001), and material function (P < .001) increased significantly. Between baseline and postintervention, the control group's: (1) mean NIHSS score decreased significantly (P < .001), (2) mean ADL score increased significantly (P < .001), (3) mean SAS (P < .001) and SDS (P < .001) scores decreased significantly; and (4) mean total GQOLI-74 score (P < .001) and scores for the dimensions physical function (P < .001), social function (P < .001), psychological function (P < .001), and material function (P < .001) increased significantly. Compared to the control group postintervention, the local vibration group's: (1) mean NIHSS score was significantly lower (P < .001), (2) mean ADL score was significantly higher (P < .001), (3) mean SAS (P < .001) and SDS scores (P < .001) were significantly lower, and (4) mean total GQOLI-74 score (P < .001) and scores for the dimensions physical function (P < .001), social function (P < .001), psychological function (P < .001), and material function (P < .001) were significantly higher. The Pearson correlation coefficient analysis showed that the NIHSS, SAS, and SDS scores were significantly negatively correlated with the GQOLI-74 score (all P < .05). Conclusion: Local vibration therapy combined with self-efficacy training positively influenced the rapid recovery of neurological function and daily-living ability postoperatively for SCI patients. It also effectively improved patients' psychological states and overall QoL. These findings suggest the potential for further clinical use. Additionally, the close relationship between neurological function, psychological state, and QoL underscores the importance of incorporating interventions that target these areas in clinical nursing management for SCI patients.

Postpartum hemorrhage and postpartum depressive symptoms: A retrospective cohort study.

BACKGROUND: Many psychological and obstetrical factors contribute to the development of postpartum depression. However, little is known about how postpartum hemorrhage (PPH) influences postpartum depressive symptoms. This study explored the relationship between PPH and postpartum depressive symptoms in the Chinese population. METHODS: A retrospective cohort study was conducted at the Baoan Maternal and Child Health Hospital in Shenzhen, China, from January 2016 to June 2020. The Edinburgh Postnatal Depression Scale was used to assess postpartum depressive symptoms. A multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence intervals (95% CIs) between PPH and risk of postpartum depressive symptoms. RESULTS: Of the 7734 respondents, 293 (3.8%) and 7441 were in the PPH and control groups, respectively. Puerperal women with PPH were more likely to screen positive for postpartum depressive symptoms than those without PPH (16.4% vs. 11.7%, p = .016). Adjusting for other covariates, women with PPH still had higher risk of postpartum depressive symptoms (OR = 1.68, 95% CI: 1.16-2.42). Stratification analyses revealed no interaction between PPH and maternal age, prepregnancy body mass index, mode of delivery, and fetal sex in developing depressive symptoms (p for interaction > .05). CONCLUSIONS: PPH may increase the risk of postpartum depressive symptoms. Therefore, women with PPH should be actively screened for depressive symptoms in the immediate postpartum period.

[Evaluation of yogurt intake status of Chinese adults in 8 cities and its relationship with metabolic syndrome in 2016].

OBJECTIVE: To investigate the level of yogurt intake in the Chinese population and its relationship between the level of yogurt intake and metabolic syndrome. METHODS: Samples were taken from populations in 8 cities in China. Dietary surveys, physical examinations, and blood sample were collected. The level of yogurt intake of the population were calculated and evaluated. The relationship between yogurt intake and metabolic syndrome and its components was analyzed by multiple logistic regression. The yogurt intake was investigated using a diet frequency questionnaire to record the frequency and intake of yogurt in the past month. RESULTS: A total of 1508 respondents were included in this study, including 538 males and 970 females; the average age was 51.74 years; the distribution ratio in the North and South regions was 5∶4.The rate of Chinese population in 8 cities which eat yogurt was 50.1%. The intake of yogurt was 3.7 g/d. Yogurt accounts for 27.22% of dairy products. There were differences in the distribution of different yogurt intake groups in different genders, age groups, Body Mass Index(BMI)groups, regions, education levels, monthly income, and smoking. The differences in calcium, fruit, and total dairy product intake among different yogurt intake groups were statistically significant difference. Sample analysis found that yogurt intake was negatively correlated with metabolic syndrome and its components. We adjusted gender, age group, body mass index group, region, education grade, monthly income, smoking, total energy, protein, fat, Ca, fruit, total dairy products for multi-factor analysis and found that this negative correlation was weakened. But this negative correlation remained on abnormal blood glucose[OR=0.61(95%CI 0.42-0.89)]. CONCLUSION: The yoghurt intake of Chinese residents is low. The intake of yogurt has a negative correlation with abnormal blood glucose.

[Association between dietary energy and protein intake and sarcopenia among the elderly in 8 cities across China].

OBJECTIVE: To explore the association between energy and protein intake and sarcopenia among elder people from eight cities across China. METHODS: The current study is based on a previous research conducted in 2016 which was named "Chinese Urban Adults Diet and Health Study". A total of 427 participants aged 65 and older were enrolled. Questionnaire was conducted to obtain the socio-demographic characteristics of participants. 24 h dietary recall was used to assess the dietary intake and energy and protein intake was calculated according to China Food Composition. The subjects were then divided into four groups(Q1, Q2, Q3, Q4) according to their energy intake(<1197. 6 kcal/d, 1197. 6-1531. 4 kacl/d, 1531. 4-1984. 0 kcal/d, ≥1984. 1 kacl/d) and protein intake(<36. 8 g/d, 36. 8-50. 4 g/d, 50. 4-68. 6 g/d, ≥68. 6 g/d). Bioelectrical impedance analysis was used to measure the skeletal muscle mass, hand-held grip strength meter was used to measure the skeletal muscle strength, and four-meter gait speed test was used to measure the skeletal muscle performance. According to the criteria of Asian Working Group for Sarcopenia, the health status of the skeletal muscle was evaluated. RESULTS: Compared with the Q1 group, there was no significant difference in skeleton muscle mass, grip strength, walking speed and the detection rate of sarcopenia among the energy intake groups(Q2-Q4). Compared with the Q1 group, the Q2 protein intake group had greater grip strength(ß=0. 12, 95%CI 0. 03-0. 21, P=0. 009) and faster gait speed(ß=0. 20, 95%CI 0. 07-0. 34, P=0. 003). CONCLUSION: The level of protein intake is associated with the grip strength and gait speed of the elderly in China, but has no significant effect on the detection rate of sarcopenia.

Doxorubicin induces cardiomyocyte pyroptosis via the TINCR-mediated posttranscriptional stabilization of NLR family pyrin domain containing 3.

AIMS: Doxorubicin (DOX), a widely used powerful chemotherapeutic component for cancer treatment, can give rise to severe cardiotoxicity that limits its clinical use. Pyroptosis is characterized by proinflammation and has been defined as a new type of programmed cell death in recent years. However, whether the DOX-induced cardiotoxicity is related to pyroptosis, and if so, which genes are involved in this process is largely unknown. In this study, we sought to identify the effect of DOX on cardiomyocyte pyroptosis and further reveal the underlying regulatory mechanism. METHODS AND RESULTS: In vitro and in vivo experiments showed that DOX treatment induced cardiomyocyte pyroptosis as evidenced by increased cell death and upregulated expression levels of NLR family pyrin domain containing 3 (NLRP3), caspase-3, IL-1ß, IL-18 and GMDSD-N. Inhibition of NLRP3 rescued the DOX-induced pyroptosis. qRT-PCR showed that TINCR lncRNA was upregulated by DOX treatment and knockdown of TINCR reversed the DOX-induced pyroptosis both in vitro and in vivo. Mechanistic investigations revealed that TINCR increased NLRP3 level via recruiting IGF2BP1 to enhance NLRP3 mRNA. And the effect of TINCR on cardiomyocyte pyroptosis was attenuated by the inhibition of NLRP3 or IGF2BP1. Finally, TINCR was not involved in DOX-induced pyroptosis in cancer cells. CONCLUSION: TINCR mediates the DOX-induced cardiotoxicity and pyroptosis in an IGF2BP1-dependent manner. Therefore, TINCR may serve as a promising therapeutic target to overcome the cardiotoxicity of chemotherapy for cancer therapy.

Yellow Wine Polyphenolic Compounds prevents Doxorubicin-induced cardiotoxicity through activation of the Nrf2 signalling pathway.

Doxorubicin (DOX) is considered as the major culprit in chemotherapy-induced cardiotoxicity. Yellow wine polyphenolic compounds (YWPC), which are full of polyphenols, have beneficial effects on cardiovascular disease. However, their role in DOX-induced cardiotoxicity is poorly understood. Due to their antioxidant property, we have been suggested that YWPC could prevent DOX-induced cardiotoxicity. In this study, we found that YWPC treatment (30 mg/kg/day) significantly improved DOX-induced cardiac hypertrophy and cardiac dysfunction. YWPC alleviated DOX-induced increase in oxidative stress levels, reduction in endogenous antioxidant enzyme activities and inflammatory response. Besides, administration of YWPC could prevent DOX-induced mitochondria-mediated cardiac apoptosis. Mechanistically, we found that YWPC attenuated DOX-induced reactive oxygen species (ROS) and down-regulation of transforming growth factor beta 1 (TGF-ß1)/smad3 pathway by promoting nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nucleus translocation in cultured H9C2 cardiomyocytes. Additionally, YWPC against DOX-induced TGF-ß1 up-regulation were abolished by Nrf2 knockdown. Further studies revealed that YWPC could inhibit DOX-induced cardiac fibrosis through inhibiting TGF-ß/smad3-mediated ECM synthesis. Collectively, our results revealed that YWPC might be effective in mitigating DOX-induced cardiotoxicity by Nrf2-dependent down-regulation of the TGF-ß/smad3 pathway.

The Role of Tauroursodeoxycholic Acid on Dedifferentiation of Vascular Smooth Muscle Cells by Modulation of Endoplasmic Reticulum Stress and as an Oral Drug Inhibiting In-Stent Restenosis.

PURPOSE: The role of endoplasmic reticulum (ER) stress in cardiovascular disease is now recognized. Tauroursodeoxycholic acid (TUDCA) is known to have cardiovascular protective effects by decreasing ER stress. This study aimed to assess the ability of TUDCA to decrease ER stress, inhibit dedifferentiation of vascular smooth muscle cells (VSMCs), and reduce in-stent restenosis. METHODS: The effect of TUDCA on dedifferentiation of VSMCs and ER stress was investigated in vitro using wound-healing assays, MTT assays, and western blotting. For in vivo studies, 18 rabbits were fed an atherogenic diet to induce atheroma formation. Bare metal stents (BMS), BMS+TUDCA or Firebird stents were implanted in the left common carotid artery. Rabbits were euthanized after 28 days and processed for scanning electron microscope (SEM), histological examination (HE), and immunohistochemistry. RESULTS: In vitro TUDCA (10-1000 µmol/L) treatment significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration in VSMCs in a concentration-dependent manner and decreased ER stress markers (IRE1, XBP1, KLF4, and GRP78). In vivo, we confirmed no significant difference in neointimal coverage on three stents surfaces; neointimal was significantly lower with BMS+TUDCA (1.6 ± 0.2 mm2) compared with Firebird (1.90 ± 0.1 mm2) and BMS (2.3 ± 0.1 mm2). Percent stenosis was lowest for BMS+TUDCA, then Firebird, and was significantly higher with BMS (28 ± 4%, 35 ± 7%, 40 ± 1%; respectively; P < 0.001). TUDCA treatment decreased ER stress in the BMS+TUDCA group compared with BMS. CONCLUSIONS: TUDCA inhibited dedifferentiation of VSMCs by decreasing ER stress and reduced in-stent restenosis, possibly through downregulation of the IRE1/XBP1 signaling pathway.

[A clinical analysis of electrical status epilepticus during sleep in children and a follow-up study of methylprednisolone pulse therapy].

OBJECTIVE: To study the clinical features of electrical status epilepticus during sleep (ESES) in children, as well as the clinical effect of methylprednisolone pulse therapy in children with ESES. METHODS: A retrospective analysis was performed using the clinical data of 78 children with ESES. Among these children, 56 children who had had the failure of antiepileptic drugs were treated with methylprednisolone pulse therapy at a dose of 15-20 mg/(kg·d) for three courses. Each course of treatment was 3 days, followed by oral prednisone [1-2 mg/(kg·d)] for 3 days. The role of methylprednisolone pulse therapy in eliminating ESES, controlling clinical seizures, and improving intelligence and behaviors was analyzed. RESULTS: The mean age of onset of epilepsy in 78 children was 6.8±2.4 years, and the mean age for the first occurrence of ESES was 7.6±2.5 years. Compared with normal children, children with ESES had delayed intelligence development and higher scores of some behavior problems. Methylprednisolone pulse therapy had an overall response rate of 73% (41/56) on clinical seizures, and the overall response rate on electroencephalography (EEG)/spike-wave index was 70% (39/56) after treatment. There were significant improvements in verbal intelligence quotient, performance intelligence quotient and full intelligence quotient, and significant reductions in the scores of learning problems, impulse-hyperactivity and hyperactivity index after treatment (P<0.05). The overall recurrence rate after 1-year follow-up was 29% (11/38). CONCLUSIONS: ESES often presents around school age and impairs children's intelligence and behaviors. Methylprednisolone pulse therapy has a marked efficiency in reducing clinical seizures and EEG discharges in children with ESES and can improve intelligence and behavior development, but the recurrence rate remains high.

Folic acid delays development of atherosclerosis in low-density lipoprotein receptor-deficient mice.

Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and to elucidate the molecular processes underlying this effect. LDLR-/- mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α-actin (α-SMA) antibodies and anti-osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α-SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high-fat-fed LDLR-/- mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.

MicroRNA-384-mediated Herpud1 upregulation promotes angiotensin II-induced endothelial cell apoptosis.

BACKGROUND: Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of atherosclerosis. This study aimed to investigate the role of microRNA-384 (miR-384) in endothelial cell apoptosis. METHODS: The expression of five various miRNAs in Ang II-treated human umbilical vein endothelial cells (HUVECs) were detected by qPCR. The Ang II-induced apoptosis of HUVECs was determined by flow cytometry, TUNEL staining and western blot. Endoplasmic reticulum (ER) stress markers were detected by western blot analysis. The target gene of miR-384 was determined by bioinformatics analyses. qPCR, western blotting and immunofluorescence were performed to determine the expression level of homocysteine inducible ER protein with ubiquitin like domain 1 (Herpud1). RESULTS: miR-384 expression level was significantly decreased in Ang II-treated HUVECs. Ang II-induced HUVEC apoptosis was accompanied by the occurrence of ER stress. A decreased rate of HUVEC apoptosis and a decreased rate of ER stress were observed following restoration of miR-384 expression. Herpud1 expression level was increased in HUVECs treated with Ang II, and miR-384 mimics effectively inhibited Herpud1 expression. Mechanistically, miR-384 directly targets the 3'-untranslated region of Herpud1. Furthermore, effects of miR-384 on HUVECs apoptosis and ER stress were at least partly reversed by knockdown of Herpud1 expression. CONCLUSION: The results of the present study collectively indicated that miR-384 expression level was downregulated in Ang II-treated HUVECs and miR-384 overexpression protected HUVECs against Ang II-induced apoptosis by negatively regulating Herpud1. These findings point towards new strategies by which apoptosis of ECs can be suppressed.

Primary Culture of Rat Aortic Vascular Smooth Muscle Cells: A New Method.

BACKGROUND Developing a simple and efficient method of obtaining primary cultured VSMCs is necessary for basic cardiovascular research. MATERIAL AND METHODS The procedure of our new method mainly includes 6 steps: isolation of the aortic artery, removal of the fat tissue around the artery, separation of the media, cutting the media into small tissue blocks, transferring the tissue blocks to cell culture plates, and incubation until the cells reach confluence. The cells were identified as VSMCs by morphology and immunofluorescence. Then, VSMCs obtained by this new tissue explants method, the traditional tissue explants method, the enzyme digestion method, and A7r5 cell line were divided into 4 groups. The purity of cells was test by multiple fluorescent staining. Western blotting was used to investigate the phenotype of VSMCs obtained by different methods. RESULTS Cells began to grow out at about 8 days and became relatively confluent within 16 days. Compared with VSMCs from the traditional tissue explants method and enzyme digestion method or A7r5 cell line, VSMCs obtained by our method showed higher purity and manifested a more "contractile" phenotype characteristic. CONCLUSIONS We have conquered the disadvantages in the previous primary culture methods and established a simple and reliable way to isolate and culture rat aortic VSMCs with high purity and stability.

Efficacy and drug resistance of antibacterials in patients' with acute pancreatitis and stress ulcer bleeding.

This study was designed to discuss key points regarding the clinical observations and nursing of patients with acute pancreatitis and stress ulcer bleeding. Retrospective analysis of 280 cases admitted to our hospital between January 2010 and January 2015 with acute pancreatitis and stress ulcer bleeding. At the same time, we treated patients with antimicrobial agents based on the epidemiology of sever acute pancreatitis (SAP) infection. According to the results of bacterial culture and drug sensitivity, we analyzed the sequence of pathogenic bacteria and the rate of bacterial resistance. During hospitalization, patients were given omeprazole and other intravenous drip line. Within this group, there was one death. The rest were all cured and discharged. Cases of acute pancreatitis, especially cases combined with biliary stone obstruction, pancreatic abscess, or pancreatic pseudo cyst are likely to show stress ulcer hemorrhage. There is a high risk of bleeding within 7 weeks of onset. The key is good nursing assessment and dynamic observation. Timely and effective anti-shock treatment is crucial to nursing when cooperating in rescues.

The level of viral infection of antigen-presenting cells correlates with the level of development of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

UNLABELLED: Intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease in susceptible SJL/J mice but not in resistant C57BL/6 mice. Previous studies have indicated that the major histocompatibility complex (MHC) genes play the most prominent role in the development of TMEV-induced demyelinating disease. In this study, we used C57BL/6.S (B6.S) congenic mice, which carry H-2(s) MHC genes instead of H-2(b) MHC genes in conjunction with the C57BL/6 (B6) background genes. Our data show that virus-infected B6.S mice are free from disease and have significantly lower viral loads than susceptible SJL mice, particularly in the spinal cord. A strong protective Th1-type T helper response with virtually no pathogenic Th17 response was detected in B6.S mice, in contrast to the reduced Th1- and robust Th17-type responses in SJL mice. Notably, lower levels of viral infectivity in B6.S antigen-presenting cells (APCs) correlated with the disease resistance and T-cell-type response. In vitro studies using APCs from B6.S and SJL mice show that TLR2, -3, -4, and -7, but not TLR9, signaling can replace viral infection and augment the effect of viral infection in the differentiation of the pathogenic Th17 cell type. Taken together, these results strongly suggest that the viral replication levels in APCs critically affect the induction of protective versus pathogenic Th cell types via the signaling of pattern recognition receptors for innate immune responses. Our current findings further imply that the levels of viral infectivity/replication and TLR-mediated signaling play critical roles in the pathogenesis of chronic viral diseases. IMPORTANCE: This study indicates that innate immune cytokines produced in antigen-presenting cells stimulating the T cell immune responses during early viral infection play a critical role in determining the susceptibility of mice to the development of demyelinating disease. The level of innate immune cytokines reflects the level of initial viral infection in the antigen-presenting cells, and the level determines the development of T cell types, which are either protective or pathogenic. The level of initial viral infection to the cells is controlled by a gene or genes that are not associated with the major histocompatibility antigen complex genes. This finding has an important implication in controlling not only chronic viral infections but also infection-induced autoimmune-like diseases, which are closely associated with the pathogenic type of T cell responses.

Polyphenols and Polypeptides in Chinese Rice Wine Inhibit Homocysteine-induced Proliferation and Migration of Vascular Smooth Muscle Cells.

The beneficial effect of Chinese rice wine on atherosclerosis has been proved, but the exact components that have the cardiovascular protective effect are still unknown. This study aimed to explore the exact ingredients in Chinese rice wine that could inhibit homocysteine (Hcy)-induced vascular smooth muscle cell (VSMC) proliferation and migration. VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, and Hcy + Chinese rice wine. methyl thiazolyl tetrazolium (MTT) assay, Transwell chambers, and wound-healing assay were used to test the proliferation and migratory ability of the VSMCs. Western blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP-2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs. Polypeptides and polyphenols in the Chinese rice wine reduced the proliferation and migration ability of the VSMCs. Furthermore, they also decreased the expression and activity of MMP-2/9 but had no obvious impact on the expression of TIMP-2 in each group. This study further confirms that polypeptides and polyphenols in the Chinese rice wine could inhibit Hcy-induced proliferation and migration of VSMCs and maintain the balance between matrix metalloproteinases (MMPs) and TIMPs.

Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection.

The thymus contains a population of B cells that colocalize with dendritic cells and medullary thymic epithelial cells in the thymic medulla. The development and functional significance of these cells are largely unknown. Using recombination-activating gene 2 GFP reporter mice along with parabiosis experiments, we demonstrate that the vast majority of thymic B cells develop from progenitors within the thymus. Thymic B cells express unique phenotypic markers compared with peripheral B cells; particularly they express high levels of MHC class II, suggesting that they are poised to present self-antigens efficiently. Using Ig knock-in and T-cell receptor transgenic mice specific for the self-antigen glucose-6-phosphate isomerase, we show that autoreactive thymic B cells serve as efficient antigen-presenting cells for T cell negative selection even when they are present at low frequencies. Furthermore, the endogenous thymic B-cell repertoire also functions in this capacity. These results suggest that developing thymic B cells could efficiently capture a broad array of autoantigens through their B-cell receptors, presenting peptides derived from those autoantigens to developing thymocytes and eliminating cognate T cells.

Effects of Chinese yellow wine on nitric oxide synthase and intercellular adhesion molecule-1 expressions in rat vascular endothelial cells.

OBJECTIVE: The objective of this study was to determine similarities in the effect of yellow wine as compared to statin and the possibility that yellow wine inhibits tumour necrosis factor-α (TNF-α)-induced nitric oxide (NO) synthesis, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) in cultured rat vascular endothelial cells (VECs). METHODS: We isolated VECs, and cultivated and purified Sprague Dawley (SD) rat thoracic aortas in vitro. We selected the optimal wine concentration using clonogenic and MTT assays to measure cell survival. Next, we divided the cells into 9 groups: (1) control, (2) TNF-α, (3) TNF-α + rosuvastatin (10 µmol/L), (4) TNF-α + ethanol 0.5%, (5) TNF-α + yellow wine 0.5%, (6) TNF-α + ethanol 1.0%, (7) TNF-α + yellow wine 1.0%, (8) TNF-α + ethanol 1.5%, and (9) TNF-α + yellow wine 1.5% and they were given the corresponding treatment for 24 h. We determined NO production with nitrate reductase. We then measured eNOS activity, and detected eNOS, iNOS, and ICAM-1 protein levels by Western blotting. RESULTS: Compared with the TNF-α group, NO production, eNOS activity, and eNOS protein expression in the rosuvastatin, and yellow wine 1.0%, and 1.5% groups were significantly increased. Protein expression of iNOS and ICAM-1 in the rosuvastatin, yellow wine 1.0%, and 1.5% groups were significantly decreased. Compared with the rosuvastatin group, eNOS, iNOS, and ICAM-1 protein expression in the yellow wine (0.5% -1.5%) groups were significantly different. CONCLUSION: Treatment with yellow wine increased NO production, eNOS activity, and eNOS protein expression, which decreases iNOS and ICAM-1 protein expression. We conclude that yellow wine may have similar beneficial effects as rosuvastatin on the cardiovascular system. These effects may be attributed to their anti-atherosclerotic actions.

[Study on skeletal muscle mass of 1 836 check-up adults and its association with age in Qiqihar].

OBJECTIVE: To analyze the correlation between skeletal muscle mass and age among check-up adults. METHODS: The study objects were those who aged 18-87 years old and came to a city hospital of Qiqihar for health examination from December, 2013 to September, 2014, excepted those with coronary heart disease, infectious disease, endocrine system disease, hypertension, anemia, cancer, liver disease, kidney disease and those carrying with heart pacemaker. A total of 1 836 respondents were finally enrolled into analysis. Appendicular Skeletal Muscle (ASM) was measured by a Body Composition Analyzer, and relative skeletal muscle index (RSMI) was calculated. The relationship among ASM, RSMI and age was assessed by linear regression analysis. The difference of height, weight, BMI, waist-hip-ratio (WHR), total muscle mass and percentage of body fat between genders were tested by t-test. The difference of ASM and total skeletal muscle mass between genders and among age groups was tested by multi-factor variance analysis. The difference of the muscle decline between genders was compared by Chi-square test. RESULTS: The total muscle mass in males was (52.22 ± 6.65) kg, which was significantly higher than that in females ((38.05 ± 4.39) kg) (t=28.20, P<0.001). ASM in 18-29, 30-39, 40-49, 50-59, 60-69, 70-87 years was (24.64 ± 3.23), (24.00 ± 3.12), (24.35 ± 3.03), (23.33 ± 2.97), (22.54 ± 2.91) and (21.40 ± 3.36) kg (F=16.12, P<0.001) in males, respectively, and (16.48 ± 3.14), (16.72 ± 1.93), (16.75 ± 1.93), (16.84 ± 2.28), (16.52 ± 2.35) and(14.70 ± 2.37)kg (F=4.38, P=0.001) in females, respectively. ASM in males ((23.72 ± 3.16) kg) was higher than that in females ((16.65 ± 2.25) kg) (t=55.97, P<0.001). There was a negative correlation between age and ASM in males after 50 years old, the regression equation was y=28.31-0.09x (P<0.001). While a negative correlation between age and ASM in females occurred after 60 years old, the regression equation was y=27.69-0.18x (P<0.001). The prevalence of low ASM was 16.85% (124/736) in females, which was significantly higher than that in males (8.73%, 96/1 100) (χ(2)=27.57, P<0.001). CONCLUSION: A negative correlation was found between age and ASM in males after 50 years old and in females after 60 years old. The prevalence of low RSMI in females was significantly higher than that in males.