Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report.

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Feasibility and efficacy of endoscopic purse-string suture-assisted closure for mucosal defects induced by endoscopic manipulations.

BACKGROUND: Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close, although complete closure is recommended for better recovery. Endoscopic purse-string assisted suturing (EPSS) has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects. However, details regarding the efficacy of endoscopic pre-purse-string suture (P-EPSS) are unknown, especially that it offers several advantages over conventional EPSS (C-EPSS). AIM: To elucidate the outcomes of EPSS-assisted closure in different clinical situations, and evaluate the efficacy of P-EPSS. METHODS: This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS (n = 63) or C-EPSS (n = 117) between July 2014 and June 2020. The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size, location, and mor-phology, incidence of complete closure, intraoperative perforation, and delayed adverse events were evaluated. Data on the features and clinical course of cases with adverse events were collected for further analysis. RESULTS: Patients with lesion size larger than 3 cm, lesions located at the fundus of stomach, or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure. The P-EPSS group showed a sign-ificantly higher proportion of intraoperative perforation (56% vs 17%) and a much shorter procedure time (9.06 ± 6.14 min vs 14.84 ± 7.25 min). Among adverse events, the incidence of delayed perforation (5% vs 4%; P = 0.82) and delayed bleeding (3% vs 4%; P = 0.96) did not differ significantly between the groups. Multivariate analysis revealed that lesions with incomplete closure [odds ratio (OR) = 21.33; 95% confidence interval (CI): 5.45-83.45; P < 0.01] or size greater than 3 cm (OR = 3.14; 95%CI: 1.08-9.18; P = 0.039) showed a statistical tendency to result in an increase in delayed adverse events. CONCLUSION: The present study revealed that EPSS could achieve secure complete closure of mucosal defect. P-EPSS could shorten the procedure and yield complete closure of mucosal defects. Rather than closure-type selection, incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.

Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease.

BACKGROUND: Exosomes play an important role in metabolic-associated fatty liver disease (MAFLD), but the mechanism by which exosomes participate in MAFLD still remain unclear. AIM: To figure out the function of lipotoxic exosomal miR-1297 in MAFLD. METHODS: MicroRNA sequencing was used to detect differentially expressed miRNAs (DE-miR) in lipotoxic exosomes derived from primary hepatocytes. Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs. Quantitative real-time PCR (qPCR) was conducted for the verification of DE-miRs. qPCR, western blot, immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells (LX2 cells). A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN. RESULTS: MicroRNA sequencing revealed that there were 61 exosomal DE-miRs (P < 0.05) with a fold-change > 2 from palmitic acid treated primary hepatocytes compared with the vehicle control group. miR-1297 was the most highly upregulated according to the microRNA sequencing. Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis. miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR. Fibrosis promoting genes (α-SMA, PCNA) were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis. Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment. PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway. CONCLUSION: miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes. The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway, accelerating the progression of MAFLD.

Linc-SCRG1 accelerates progression of hepatocellular carcinoma as a ceRNA of miR26a to derepress SKP2.

BACKGROUND: Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear. METHODS: To explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models. RESULTS: LincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a. CONCLUSIONS: LincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.

[Extraintestinal manifestations and intestinal complications in children with Crohn's disease: an analysis of 54 cases].

OBJECTIVE: To summarize the extraintestinal manifestations and intestinal complications in children with Crohn's disease (CD). METHODS: The clinical data of 54 children who were diagnosed with CD in Peking Union Medical College Hospital from January 2008 to December 2018 were collected for retrospective analysis of extraintestinal manifestations and intestinal complications. According to the location of the lesion, the children were divided into ileocolonic group (30 cases), colonic group (6 cases), and ileal group (18 cases). RESULTS: In the 54 children, the mean age at diagnosis was 14.5±2.7 years, and the median duration from disease onset to definite diagnosis was 20 months (range: 1-36 months). Twenty-four patients (44%) had extraintestinal manifestations, with the two most common manifestations being growth retardation (11 cases, 20%) and oral mucosal ulcer (10 cases, 19%), followed by arthritis (2 cases, 4%), erythema nodosum (2 cases, 4%), and cholecystitis (2 cases, 4%). There were no significant differences in the incidence of extraintestinal manifestations among the three groups (P=0.792). The most common intestinal complications were anal fistula/perianal abscess (13 cases, 24%), followed by intestinal fistula (5 cases, 9%) and intestinal obstruction (4 cases, 7%). There was a significant difference in the incidence of intestinal complications among the three groups (P=0.0406). No intestinal complications were reported in the colonic group. CONCLUSIONS: Extraintestinal manifestations and intestinal complications are common in children with CD. Perianal examinations should be performed in children with suspected CD. Intestinal complications are less common in children with colonic CD, which may be associated with relatively mild disease condition.

Zinc-α2-glycoprotein 1 attenuates non-alcoholic fatty liver disease by negatively regulating tumour necrosis factor-α.

BACKGROUND: Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM: To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS: The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS: AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation; enhance steatogenesis, including promoting lipogenesis [sterol regulatory element-binding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid ß-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α]; accelerate proliferation; and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION: AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.

MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2.

BACKGROUND: Activation of hepatic stellate cells (HSCs) is a pivotal event in the onset and progression of liver fibrosis. Loss of microRNA-194 (miR-194) has been reported in activated HSCs, but the actual role of miR-194 in liver fibrosis remains uncertain. AIM: To explore the role and potential mechanism of miR-194-mediated regulation of liver fibrosis in vitro and in vivo. METHODS: The expression of miR-194 was examined in human fibrotic liver tissues, activated HSCs, and a carbon tetrachloride (CCl4) mouse model by qPCR. The effects of AKT2 regulation by miR-194 on the activation and proliferation of HSCs were assessed in vitro. For in vivo experiments, we reintroduced miR-194 in mice using a miR-194 agomir to investigate the functions of miR-194 in liver fibrosis. RESULTS: MiR-194 expression was notably lacking in activated HSCs from both humans and mice. Overexpression of miR-194 (OV-miR-194) inhibited α-smooth muscle actin (α-SMA) and type I collagen (Col I) expression and suppressed cell proliferation in HSCs by causing cell cycle arrest in G0/G1 phase. AKT2 was predicted to be a target of miR-194. Notably, the effects of miR-194 knockdown in HSCs were almost blocked by AKT2 deletion, indicating that miR-194 plays a role in HSCs via regulation of AKT2. Finally, miR-194 agomir treatment dramatically ameliorated liver fibrosis in CCl4-treated mice. CONCLUSION: We revealed that miR-194 plays a protective role by inhibiting the activation and proliferation of HSCs via AKT2 suppression. Our results further propose miR-194 as a potential therapeutic target for liver fibrosis.

[Establishment of STO Cell Lines Expressing Green Fluorescent Protein and Mouse Leukemia Inhibitory Factor].

OBJECTIVE: To establish the STO cell lines expressing green fluorescent protein (GFP) and mouse leukemia inhibitory factor (LIF) , and try to culture the mouse embryonic stem cells (mESCs) by using the established STO-GFP-mLIF cells as the feeder layer. METHODS: The lentiviral particles containing GFP and mLIF and puromycin-resistance gene were constructed and transduced into STO cell lines. The cell lines stably expressing GFP and mLIF genes were screened out. The expression level of the inserted exogenous LIF gene was tested by Western blot and ELISA. The STO-GFP-mLIF cells were treated with different concentrations of mitomycin C (5, 10, 15, 20 µg/ml) for different time (1.5, 2.5, 3, 3.5 hours) to prepare feeder layers and the cell proliferation level on feeder layer was observed. Mouse embryonic stem cells were cultured on mitomycin C-treated feeder layer and the growth of cell colonies was observed. RESULTS: The expression level of LIF protein in STO-GFP-mLIF cells was up-regulated, as compared with STO cells (P＜0.05). It was confirmed that the optimal concentration and time for inhibiting the proliferetion of STO-GFP-mLIF cells by mitomycin C were 10 µg/ml and 3 hours respectively. The observation also found that the embryonic stem cells could develop into typic "birdnest" shaped stem cell colony on mitomycin C-treated feeder layer. CONCLUSION: The stable STO cell lines effectively expressing green fluorescent protein and mouse leukemia inhibitory factor have been established successfully, which can maintain the undifferentiated state of mouse embryonic stem cells.

Effects of endomorphin-1 postconditioning on myocardial ischemia/reperfusion injury and myocardial cell apoptosis in a rat model.

Endomorphins (EMs) have important roles in the body with regards to analgesia, feeding behavior, gastrointestinal movement and inflammatory reaction. Recent studies have reported that EMs may also participate in chronic hypoxia in the protection of rat myocardial ischemia/reperfusion; however, the mediator and underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of EM­1 postconditioning on myocardial ischemia/reperfusion injury (MIRI) and myocardial cell apoptosis in a rat model, and to assess its likely mechanisms. A total of 48 male Sprague Dawley rats were randomly divided into four groups: Sham group, ischemia/reperfusion group (IR group), ischemic postconditioning group (IPO group) and EM­1 postconditioning group (EM50 group). A MIRI model was established via occlusion of the left anterior descending branch of the coronary artery for 30 min, followed by reperfusion for 120 min in vivo. Hemodynamic indexes were recorded and analyzed. Following reperfusion, plasma lactate dehydrogenase (LDH), creatine kinase­MB (CK­MB), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) contents or activities were measured, infarct size was determined, and the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA and cleaved caspase­3 protein were assessed. In the IR group, mean arterial pressure (MAP) and heart rate (HR) were decreased compared with in the sham group. In addition, LDH and CK­MB levels were increased; IL­6, TNF­α and MDA content was increased; SOD activity was decreased; the Bcl­2/Bax ratio was decreased; and cleaved caspase­3 protein expression levels were increased in the IR group. Compared with in the IR group, in the IPO and EM50 groups, MAP and heart rate (HR) were recovered to various extents post­reperfusion; LDH and CK­MB levels were decreased; IL­6, TNF­α and MDA content was decreased; SOD activity was increased; infarct size was reduced; the Bcl­2/Bax ratio was increased; and cleaved caspase­3 protein expression levels were decreased. In conclusion, EM­1 postconditioning was revealed to reduce I/R injury and inhibit myocardial cell apoptosis, which may be associated with reductions in oxidative stress and inflammatory reactions.

Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report.

Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage).There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered.

[Protective effect of hydrogen sulfide on kidneys of type 1 diabetic rats].

OBJECTIVE: To explore the protective effects of hydrogen sulfide (H2S) on kidneys of type 1 diabetic rats and its underlying mechanism. METHODS: Thirty-two male SD rats were randomly divided into four groups:normal control (NC) group, diabetes mellitus (DM) group, DM treatment (NaHS+DM) group and NaHS control (NaHS) group. The rats from DM group and NaHS+DM group were injected intraperitoneally with Streptozotocin 55 mg/kg to induce type 1 diabetes mellitus (n=8). After modeling, rats in NaHS+DM group and NaHS group were intraperitoneally injected with NaHS solution at the dosage of 56 µmol/kg. After 8 weeks, urinary protein content was detected in urine samples collected for 24 h. and the ratio of kidney weight/body weight (renal index) was determined in isolated kidneys. Besides, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured biochemically. The morphological changes of renal tissue were observed by HE staining. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and Caspase-3 in renal tissue were determined by spectrophotometry. The protein expression levels of Bcl-2 and Bax in renal tissue were detected using Western blot. RESULTS: There was no significant difference in the respective measured indexes in rats between NC group and NaHS group. However, in DM group, the levels of 24 h urinary protein, FBG, BUN, Scr and renal index were increased significantly; HE staining showed that the basement membrane was thickened and the amount of glomerular mesangial matrix was increased; MDA content, Caspase-3 activity and Bax expression levels were increased, while SOD activity and Bcl-2 expression were decreased. Compared with those in DM group, the morphological changes of renal tissue and its function were improved; MDA content, Caspase-3 activity and Bax expression were decreased significantly, while SOD activity and Bcl-2 expression were increased obviously in NaHS+DM group. CONCLUSIONS: H2S can protect the kidneys of type 1 diabetic rats, which is related to suppressing oxidative stress and cell apoptosis.

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: a meta-analysis.

AIM: To investigate the efficacy and safety of gemcitabine (Gem)-based combination chemotherapies for the treatment of advanced biliary tract cancer. METHODS: Clinical trials were identified by searching scientific literature databases (PubMed, EMBASE and the Cochrane Library) for studies published between 1975 and 2013. Two reviewers independently evaluated the relevant studies and manually searched references from these reports to locate additional eligible studies. The disease response and control rates, progression-free and overall survivals, and the grade 3-4 toxicities were evaluated by a meta-analysis. Odds-ratios (ORs) of the disease response and control rates and grade 3-4 toxicities, and the mean difference (MD) of both progression-free and overall survivals were calculated and used for statistical analysis. RESULTS: Seven randomized trials with a total of 858 patients were selected and included in the final analysis. The studies were divided into subgroups based on the chemotherapy regimens, including Gem-based and non-Gem-based chemotherapies. The overall analyses revealed that the patients treated with Gem-based combination chemotherapy had significantly higher disease response rates [OR = 1.69, 95% confidence interval (CI): 1.17-2.43; P = 0.01], a longer progression-free survival (MD = 1.95, 95%CI: 0.90-3.00; P = 0.00) and a longer overall survival (MD = 1.85, 95%CI: 0.26-3.44; P = 0.02). A higher incidence of grade 3-4 hematological toxicities, including leukopenia (OR = 2.98, 95%CI: 1.44-6.20; P = 0.00), anemia (OR = 2.96, 95%CI: 1.79-4.92; P = 0.00) and neutropenia (OR = 2.80, 95%CI: 1.39-5.64; P = 0.00) was found in the Gem-based combination chemotherapy group compared with the Gem monotherapy and non-Gem-based chemotherapy groups. CONCLUSION: Gem-based combination chemotherapy is a potential first-line treatment for advanced biliary tract cancer as a result of improved survival, though with additional toxicity.

Changes in cardiac mitochondrial aldehyde dehydrogenase 2 activity in relation to oxidative stress and inflammatory injury in diabetic rats.

The aim of the present study was to determine the changes in mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity in relation to oxidative stress and inflammatory injury in different stages of diabetes mellitus (DM) in rats and to investigate the related mechanisms. DM in Sprague-Dawley (SD) rats was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ). The rats were randomly allocated into a control group, as well as into DM4w, DM8w and DM12w groups containing DM rats 4, 8 and 12 weeks after DM induction, respectively. Ventricular hemodynamic parameters were recorded; fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were determined using an automatic biochemistry analyzer; plasma interleukin (IL)-1, IL-4 and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined using enzyme-linked immunosorbent assay (ELISA), and cardiac ALDH2 activity was measured. The mRNA expression levels of Bax and Bcl-2 of the left anterior myocardium were detected by reverse transcriptase­polymerase chain reaction (RT-PCR). FBG and HbA1c levels were increased in the DM groups compared to the control group. FBG levels were not significantly different among the DM4w, DM8w and DM12w groups, while HbA1c levels were increased with the progression of diabetes. The left ventricular developed pressure (LVDP), heart rate (HR) and rate-pressure product (RPP) were decreased, plasma IL-1 levels were increased, while IL-4 levels were decreased in the DM groups compared to the control group. Additionally, cardiac 4-HNE levels were increased, and ALDH2 activity was decreased in the DM groups compared to the control group. Bax mRNA levels were increased, Bcl-2 mRNA levels were decreased, and Bcl-2/Bax mRNA ratios were decreased in the DM groups compared to the control group. Moreover, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA ratios were further reduced, while 4-HNE and IL-1 levels were increased with the progression of diabetes. In conclusion, our results indicated that cardiac ALDH2 activity was further decreased with the progression of diabetes, which might be related to the increase of oxidative stress, inflammatory injury and the occurrence of apoptosis.

Inducible expression of functional mu opioid receptors in murine dendritic cells.

Opioids are known to exert direct effects on the immune system, and the expression of functional opioid receptors has been reported on several immune cell types. Dendritic cells (DCs) are important inducers and regulators of immune responses. In this study, we investigated whether murine dendritic cells express functional mu opioid receptors (MOR). RT-PCR analysis and double immunofluorescence staining revealed the expression of MOR in activated murine dendritic cells. We also studied the dynamic expression of MOR messenger RNA in murine dendritic cells in response to different Toll-like receptor ligands. Functionally, treatment of DCs with endomorphin 1 (EM1), a specific agonist of MOR, can inhibit the forskolin-induced formation of cyclic adenosine monophosphate level in activated DCs. Moreover, EM1 treatment resulted in less activation of p38 MAPK and more activation of ERK signaling in lipopolysaccharide-stimulated DCs. Consistently, treatment of DCs with EM1 altered cytokine production by increasing IL-10 and decreasing IL-12 and IL-23. Our results suggest that MOR is inducibly expressed on activated DCs and functionally mediates EM1-induced effects on DCs. Thus, dendritic cells might be involved in crosstalk between the neuroendocrine and the immune system.

[Clinical characteristics of 41 children with cyclic vomiting syndrome].

OBJECTIVE: To analyze the clinical characteristics of children with cyclic vomiting syndrome (CVS), summarize the experience for twelve years, and improve awareness, diagnosis and treatment level of CVS. METHODS: The clinical data and results of long-term follow-up of the children with CVS seen from 1994 to 2007 in our department were analyzed. RESULTS: Forty-one children were enrolled in the study, 21 were male, and 20 female, mean age was 8 years, mean age of onset was 4 years, mean interval from onset to proper diagnosis was 4 years; 13/41 and 20/41 patients had family history of migraine and motion sickness, 20/41 patients had triggers, such as upper respiratory tract infection, diet, and mental/emotional factor. Vomiting lasted for days, during the periods between the episodes of vomiting the children were completely healthy. The intervals of most patients were 2 to 8 weeks, and in 12/41 patients the episodes started at early morning. The peak number of emesis per hour exceeded six in 23/41 children. The episodes were characterized by a pattern of sudden onset and sudden ending. All patients showed depressed, social withdrawal, intractable nausea and anorexia. Associated symptoms and signs include pallor, excess salivation, hypertension, headache, photophobia, and abdominal pain. Electroencephalogram of 13/33 patients were slightly abnormal. Electrogastrogram showed dysrhythmia and gastrointestinal motility were abnormal during the period of onset and normal during complete remission. Eleven of the 41 of patients were treated as epilepsy, and 9 patients were diagnosed as esophageal hiatal hernia and 4 superior mesenteric artery compression syndrome and had surgery before the diagnosis was made. Eight patients diagnosed from 1994 to 2000 were followed up for ten years in average, 3 patients were treated with doxepin and alprazolanic, and were cured after 2.2 (1.0 - 4.0) years; and five patients who did not use any medicine recovered 7.7 (4 - 10) years later. Fourteen children diagnosed from 2001 to 2007 were followed up for longer than one year, 9 patients were treated with valproate, doxepin, cyproheptadine, and recovered 2.3 (1 - 4) years later; 5 patients without treatment recovered 1.9 (1 - 3) years later. CONCLUSIONS: The diagnosis must be based on the special manifestation of CVS, including intervals during which the patients are completely healthy, and the systemic diseases which can cause CV should be excluded. Most patients get better as they grow up. Therapeutic strategies may include combined use of neuroleptics, thymoleptics and anti-migraine when the episodes occur frequently and when there is growth retardation. Supportive care includes intravenous fluids and symptomatic treatment during an episode.