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ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） patterns as well as factors related to acute exacerbation in group E of chronic obstructive pulmonary disease （COPD）. MethodsThe general data of 161 COPD patients， including gender， age， body mass index （BMI）， disease course， smoking history， and past history， were collected. In terms of the four examinations of TCM， the differentiated patterns included phlegm-heat obstructing the lung， turbid phlegm obstructing the lung， phlegm stasis obstructing the lung， lung-spleen qi deficiency， and lung-kidney deficiency. The modified British Medical Research Council （mMRC） scale and COPD assessment test （CAT）， the pulmonary function indicators including forced expiratory volume in the first second （FEV1） and ratio of forced expiratory volume to forced vital capacity at second 1 （FEV1/FVC）， GOLD grade， and the patient's acute exacerbations in the previous year were recorded. Multivariate regression analysis was performed using logistic regression model to determine the relevant factors of patients in COPD group E. The distribution of acute exacerbations in different TCM symptom patients in group E was analyzed. ResultsThere were 80 patients （49.69%） in group E and 81 patients （50.31%） in non-group E. In group E， 23 （28.75%） patients had a history of two acute exacerbations， while 35 （43.75%） had three acute exacerbations， and 22 （27.5%） had more than three acute exacerbations. There were 13 （16.25%） cases of phlegm-heat obstructing the lung pattern， 6 （7.5%） cases of turbid phlegm obstructing the lung pattern， 8 （10%） cases of phlegm stasis obstructing the lung pattern， 22 cases （27.5%） of lung-spleen qi deficiency pattern， and 31 （38.75%） cases of lung-kidney deficiency pattern. There were significant differences in smoking history， disease course， TCM pattern， TCM syndrome score， mMRC score， and CAT score between groups （P＜0.05）. A total of 107 of the 161 patients completed pulmonary function tests， and the differences in FEV1， FEV1/FVC and GOLD grades between groups were statistically significant （P＜0.05）. Multivariate regression analysis showed that TCM pattern， TCM syndrome score and CAT score were statistically significant factors for COPD patients in group E （P＜0.05）. There were statistically significant differences in the number of acute exacerbations in different TCM patterns in group E （P＜0.05）. The patients with two acute exacerbations in the past year were mainly phlegm-heat obstructing the lung and lung-spleen qi deficiency patterns， while the three acute exacerbations were mainly seen in lung-spleen qi deficiency and lung-kidney deficiency patterns， and more than three exacerbations were more common with lung -kidney deficiency pattern. ConclusionsPatients in COPD group E were mainly the lung-spleen qi deficiency and lung-kidney deficiency patterns. Deficiency of healthy qi is the main reason for the increase in the number of acute exacerbations， and TCM patterns and CAT score were the main related factors.
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Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.
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Animals , Rats , Astrocytes/metabolism , DNA Demethylation , Epigenesis, Genetic , GATA1 Transcription Factor/metabolism , Inflammation/metabolism , Oligodeoxyribonucleotides/metabolism , Rats, Sprague-Dawley , Receptors, Purinergic P2X7/metabolism , Visceral Pain/metabolismABSTRACT
Eosinophil extracellular traps (EETs), an important pathway of eosinophil to exert its effects, are composed of DNA fibers, histone and eosinophil granule proteins. Recently, many researches have shown that EETs play an important role in the genesis and development of respiratory diseases including asthma, allergic bronchopulmonary aspergillosis and chronic obstructive pulmonary disease. EETs can directly damage airway epithelial cells, promote airway inflammation and airway hypersecretion, increase the stickiness of secretions and induce the generation of autoantibody, helping eosinophils and their products participate in a cascade of events leading to inflammation and disease. Researches on EETs can also be helpful in investigating new targets for the treatment of chronic airway diseases.
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Objective:To investigate the diagnostic and prognostic value of the growth differentiation factor 15 (GDF15) and the procalcitonin (PCT) in sepsis.Methods:A total number of 137 patients with sepsis (considered as the sepsis group) and 59 patients with inflammatory infection but not diagnosed as sepsis (the non-sepsis group) received treatment in intensive care unit of Renming Hospital of Wuhan University were collected from July 2020 to January 2021, and 62 cases of healthy physical examination (control group) were simultaneously chosen as control. Sepsis patients were divided into two groups (death group [ n=48] and survival group [ n=89]) according to their 28-day′s survival. The serum levels of GDF15, PCT, C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) were examined, and the levels of each index, was dynamically monitored on the 1st, 3rd and 7th day after admission. The differences of the two indicators between different groups were compared by non-parametric test. The correlation between GDF15 and PCT was analyzed by Spearman correlation test. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of the two indicators for sepsis. Results:The levels of GDF15 in the sepsis group, non-sepsis group and control group were 3.22 (1.39, 6.31) μg/L, 0.84 (0.21, 1.66) μg/L and 0.11 (0.09, 0.13) μg/L, respectively. The levels of PCT were 13.10 (1.99, 50.25) μg/L, 0.24 (0.13, 0.68) μg/L and 0.05 (0.03, 0.10) μg/L, respectively. The levels of CRP were 115.80 (26.40, 184.07) mg/L, 24.20 (11.30, 53.20) mg/L and 0.50 (0.50, 2.76) mg/L, respectively. The levels of IL-6 were 68.26 (21.59, 255.46) ng/L, 33.20 (10.81, 89.27) ng/L and 8.82 (7.33, 11.23) ng/L, respectively. The levels of IL-10 were 11.30 (5.88, 25.50) ng/L, 9.34 (5.65, 16.90) ng/L and 4.94 (4.31, 5.31) ng/L, respectively. The GDF15, PCT, CRP and IL-6 of the sepsis group were significantly higher than those of the non-sepsis group (The U values were 67.681, 86.034, 44.164 and 38.934, respectively, with P values less than 0.05) and the control group (The U values were 136.475, 138.667, 120.701 and 100.886, respectively, with P values less than 0.001). There was no significant difference in IL-10 between sepsis group and nonsepsis group, but it was higher than that of control group ( U=80.221, P<0.001). There was a positive correlation between GDF15 and PCT in patients with sepsis, and the spearman correlation coefficient was 0.234 ( P=0.006). The GDF15 of the death group and the survival group were 5.49 (3.60, 8.25) μg/L and 2.03 (1.06, 3.69) μg/L, and the PCT levels were 26.45 (11.23, 94.25) μg/L and 9.08 (1.33, 22.75) μg/L, respectively. GDF15 and PCT in the death group were significantly higher than those in the survival group ( U values were 3 305.500 and 3 060.000, respectively, and P values were both less than 0.001). The GDF15 and PCT levels in the death group were higher than those in the survival group on the 1st, 3rd and 7th day of dynamic monitoring ( P<0.05), however, the level of CRP and IL-10 were not significantly different ( P>0.05). The level of IL-6 in the death group was not significantly different from that of the death group on 1st day, but was higher than that of the survival group on the 3rd and 7th day ( P<0.05). The area under the curve (AUC) of GDF15, PCT, CRP, IL-6 and IL-10 alone and in the combined diagnosis of sepsis were 0.899, 0.938, 0.874, 0.789, 0.698 and 0.962, respectively. The combined detection of AUC was better than a single index; the GDF15, PCT, CRP, IL-6 and IL-10 alone and combined detection of sepsis prognosis AUC were 0.774, 0.716, 0.522, 0.623, 0.520 and 0.839, respectively, the combined detection of AUC is also better than single index. Conclusions:GDF15 and PCT have good clinical reference value in the differential diagnosis and prognosis of sepsis. The combination of indicators has a higher clinical value. GDF15 may become a biomarker for the diagnosis and prognosis of sepsis.
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Objective To investigate the clinical value of alpha-fetoprotein (AFP) combined with gamma-glutamyl transpeptidase (GGT)/aspartate aminotransferase (AST) ratio in the diagnosis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods A total of 352 subjects who received treatment or underwent physical examination in Renmin Hospital of Wuhan University from January 15 to June 15, 2020, were enrolled, among whom there were 86 healthy controls (HC group), 68 patients with chronic hepatitis B (CHB group), 69 patients with liver cirrhosis (LC group), and 129 patients with HCC (HCC group), and a retrospective analysis was performed for the serological test results of all subjects. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups, and the Nemenyi method was used for further comparison between two groups. A binary logistic regression analysis was used to calculate predictor variables; a receiver operating characteristic (ROC) curve was plotted for AFP, GGT/AST, and the predictor variables used alone or in combination, and the area under the ROC curve (AUC), sensitivity, and specificity were calculated; the Z test was used for comparison of AUC. Results The HCC group had significantly higher GGT/AST ratio and AFP than the other groups (all P < 0.05). The ROC curve analysis showed that AFP combined with GGT/AST ratio had a significantly higher AUC than AFP alone in the HCC group vs the LC group, the HCC group vs the HC+CHB+LC groups, and the HCC group vs the CHB+LC groups ( Z =2.684, 2.241, and 2.415, P =0.007, 0.025, and 0.016). Conclusion AFP combined with GGT/AST ratio can improve the clinical diagnostic performance of HBV-related HCC and thus has a certain diagnostic value.
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Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment.
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In December, the outbreak of a novel coronavirus (2019-nCoV) in Wuhan, China, has attracted extensive global attention. On January 20, 2020, the Chinese health authorities upgraded the coronavirus to a Class B infectious disease in the Law of the People′s Republic of China on the Prevention and Treatment of Infectious Diseases, and considered it as Class A infectious diseases in disease control and prevention. On January 18, 2020, the 2019-nCoV nucleic acid detection test was listed as the diagnostic criteria in the "guidelines for diagnosis and treatment of pneumonia due to 2019-nCoV (Trial Version 2)" . Therefore, standardizing the operation process of the 2019-nCoV nucleic acid detection in clinical laboratories has become a top priority. It is of paramount importance to establish standard protocols for detection of the 2019-nCoV nucleic acids in clinical laboratories to improve the reliability of the results and ensure the biosafety of laboratory personnel.
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Objective:To investigate the diagnostic value of immunoglobulin M (IgM) and immunoglobulin G(IgG) antibodies to 2019 Novel Coronavirus (2019-nCoV) in 2019-nCoV infection.Methods:This is a retrospective study. Serum samples were collected from 284 patients including outpatients and inpatients in the Renmin Hospital of Wuhan University from January 20 to February 17 in 2020. Among them 205 cases were 2019-nCoV infected patients, including 186 cases confirmed with nucleic acid test and 19 cases diagnosed by clinical symptoms and CT characteristics according to "the New Coronavirus Pneumonia Control Protocol (5th edition)" . A total of 79 subjects with other diseases but negative to 2019-nCoV infection were recruited as control group. Serum IgM and IgG antibodies to 2019-nCoV were measured with fully automated immunoassay technology for all subjects. Statistical significance between 2019-nCoV antibodies test and 2019-nCoV nucleic acid test was determined using the χ 2 tests. Results:The sensitivity of serum IgM and IgG antibodies to 2019-nCoV were 70.24%(144/205) and 96.10%(197/205) respectively and the specificity were 96.20%(76/79) and 92.41%(73/79) respectively. The positive and negative predictive values of 2019-nCoV antibodies were 95.63%(197/206) and 91.03% (71/78) respectively, and the positive and negative predictive values of 2019-nCoV nucleic acid test were 100%(186/186) and 80.61%(79/98) respectively. The total coincidence rate of diagnosing 2019-nCoV infection between antibody tests and nucleic acid test for 2019-nCoV were 88.03%(250/284).Conclusion:Joint detection of serum IgM and IgG antibodies to 2019-nCoV is an effective screening and diagnostic indicators for 2019-nCoV infection, and an effective complement to the false negative results to nucleic acid test.
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Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.
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The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Subject(s)
Animals , Male , Adrenergic Agents , Pharmacology , Ganglia, Spinal , Hyperalgesia , Drug Therapy , Hypersensitivity , Drug Therapy , Maternal Deprivation , Neurons , Patch-Clamp Techniques , Methods , Rats, Sprague-Dawley , Signal Transduction , Stress, Physiological , Physiology , Visceral Pain , MetabolismABSTRACT
Acute infection with hepatitis C virus is generally asymptomatic. Most patients can not clear the virus and are easy to develop into chronic infection, while a small number of patients even develop into cirrhosis, or liver cancer. The traditional treatment is combined pegylated interferon with ribavirin, but the antiviral effect is poor and the adverse reactions are large, which may be related to the ability of HCV to escape the host′s immune response through various mechanisms. The innate immune response is the first line of defense against pathogenic microorganisms. Retinoic acid inducible geneⅠ(RIG-Ⅰ) plays an important role in identifying HCV virus and initiating immune response as a pattern recognition receptor.
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Objective To detect mRNA expression of stimulator of interferon genes(STING)and type Ⅰ interferons(IFN-α and IFN-β)in peripheral blood mononuclear cells(PBMCs)of patients with chronic hepatitis B(CHB), and evaluate its correlation with hepatitis B virus load.Methods 88 untreated CHB patients(CHB group)and 74 healthy persons(control group)who performed physical examination were chosen from Renmin Hospital of Wuhan University during the same period between February 2016 and February 2017.Expressions of mRNA of STING, IFN-α, and IFN-βwere detected by quantitative real-time polymerase chain reaction(PCR), their relative expression values were obtained by 2-ΔΔCT method, results were statistically analyzed.Results The expression of STING, IFN-α, and IFN-βmRNA in peripheral blood of CHB patients were 2.95, 3.14, and2.01folds of healthy controls respectively, differences were statistically significant(t=-4.72, -3.41, -2.31, respectively, all P＜0.05).STING relative expression in patients with HBV DNA load≤104 IU/mL was 2.98, 3.76, and 3.97 folds of patients with HBV DNA load 104-105 IU/mL, 105-106 IU/mL, and＞106 IU/mL, respectively(P＜0.05).mRNA expressions of STING in CHB patients were positively correlated with that of IFN-αand IFN-βmRNA (r=0.475, 0.503, respectively, both P＜0.05).Conclusion The expression of STING increased in patients with CHB, high expression of STING impacted the replication of HBV.
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Objective To explore the implementing process and application effect of risk management in blood transfusion compatibility testing.Methods 16 957 patients receiving transfusion therapy along with blood transfusion compatibility testing at our hospital between July,2013 and June,2015 were selected as the control group,without any risk control in place.19 011 patients receiving such therapy yet with blood transfusion compatibility testing between July, 2015 and June, 2017 were selected as the observation group,and managed by the risk management procedure.The risk incidence and satisfactory rate of doctors,nurses and patients were analyzed between the two groups.Results The risk incidence was zero in the observation group, and 0.09% in the control group, indicating the risk incidence rate in the observation group significantly lower than the control group(P<0.05).The satisfactory rate of doctors, nurses and patients in the observation group(98.33%)was significantly higher than the control group (71.25%)(P <0.05).Conclusions Implementing risk management procedure in blood transfusion compatibility testing may effectively prevent and reduce the risk incidence, enhance the satisfactory rate of doctors,nurses and patients,and ensure the clinical transfusion safety.
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Objective To comparatively analyze the difference and characteristics of high mobility group box-1 protein(HMGB1) level with the levels in the patients with different severities of acute biliary tract infection (ABTI) to provide reference for its clinical diagnosis and treatment .Methods One hundred cases of ABTI in our hospital were divided into the mild group (48 cases) ,moder-ate group (29 cases) and severe group (23 cases) according to the severity of the disease .The HMGB1 detection results were com-pared among 3 groups and the differences in different disease types ,sex and age were analyzed .Results (1)The HMGB1 level had statistically significant difference among 3 groups (P0 .05) ,but in the severe group ,the HMGB1 level in males was significantly higher than that in females (P 0 .05) ,while in the moderate group and severe group ,the HMGB1 level in the patients aged > 60 years old was significantly higher than that in the patients aged ≤60 years old(P<0 .05);(4) in the above 3 groups ,the HMGB1 level in the patients with acute cholecystitis was signifi-cantly higher than that in the patients with acute cholangitis (P<0 .05) .Conclusion The study results analysis indicates that the severe the ABTI disease condition ,the serum HMGB1 level is also accordingly and relatively increased ,in the patients with different severity degrees of ABTI ,the serum HMGB1 level has significant differences in age ,sex and disease type ,which prompts that the HMGB1 level can be used as the laboratory index for predicting and reflecting the ABTI severity and can be paid attention to .
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Objective To explore the dynamic change of high mobility group box-1(HMGB1) expression in sepsis shock patients and its relationship with prognosis.Methods A total of 98 patients with septic shock in ICU from March 2014 to March 2016 were collected as the research subjects and divided into the shock group (48 cases) and control group(50 cases) according to whether de-veloping shock at admission.The HMGB1 levels and APACHE Ⅱ scores change within 28 d after admission were compared be-tween the two groups ;the shock group was divided into the group A (HMGB1≤35 pg/mL ,30 cases) ,B(HMGB1>35 pg/mL ,18 cases) according to the HMGB1 level before treatment ,the two groups were observed for 3 months from the day admitted to hospi-tal.The APACHEⅡ score ,ScvO2 ,lactic acid concentration and lactic acid clearance rate after 7 d treatment ,ICU mechanical venti-lation use rate and survival rate within 3 months were compared between the two groups.Results The HMGB1 level and A-PACHEⅡ scores before admission had no statistical difference between the shock group and control group (P>0.05);the HMGB1 and APACHEⅡ scores on 7 ,14 ,21 ,28 d after admission in the shock group were significantly higher than those in the control group ,the difference was statistically significant(P<0.05);the APACHEⅡ score ,mean lactic acid clearance rate and ScvO2 after 7 d treatment in the group A were significantly higher than those in the group B ,the difference was statistically significant (P<0.05) ,the survival rate within 3 months after admission in the group A was also significantly higher than that in the group B ,the difference was statistically significant (P<0.05) ,while the lactic acid concentration and ICU mechanical ventilation use rate after 7 d treatment in the group A were significantly lower than those in the group B with statistical difference (P<0.05).Conclusion The HMGB1 level change has a strong correlation with the prognosis ,the higher the HMGB1 level ,the worse the prognosis of patients with septic shock ,HMGB1 can be used as an important indicator of monitoring disease condition changes in sepsis ,which is worthy of attention in clinical laboratory.
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BACKGROUND/AIMS: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. METHODS: DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. RESULTS: Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. CONCLUSIONS: Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.
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Animals , Humans , Rats , Abdominal Pain , Action Potentials , Corticosterone , Cyclic AMP-Dependent Protein Kinases , Diagnosis-Related Groups , Dyspepsia , Ganglia , Ganglia, Spinal , Hypersensitivity , Injections, Intraperitoneal , Neck Muscles , Neurons , Protein Kinase C , Protein Kinases , Sodium , Sodium Channels , Spinal Nerve Roots , Stomach , Visceral PainABSTRACT
<p><b>OBJECTIVE</b>To explore the mRNA expression level of Notch1 and ASB2 in bone marrow mononuclear cells of patients with P210(+) chronic myeloid leukemia and the correlation between Notch signaling pathway and ubiquitination in chronic myeloid leukemia, so as to provide the valuable information for investigating the pathogenesis of chronic myeloid leukemia and clinical treatment.</p><p><b>METHODS</b>Bone marrow was collected from 32 patients with newly diagnosed chronic myeloid leukemia and 34 non-hematopathic and healthy individuals (control group), respectively. The mRNA expression levels of Notch1 and ASB2 were detected by real-time quantitative PCR.</p><p><b>RESULTS</b>The expression of Notch1 mRNA in CML patients were significantly different from that of healthy individuals group (t=36.3, P<0.01), which was 337.8 times of the healthy individuals. Moreover, the expression level of ASB2 mRNA in CML group was significantly higher than that in healthy individuals (t=19.4, P<0.01). The mRNA expression of Notch1 and ASB2 gene was positive correlation (r=0.504, P<0.01).</p><p><b>CONCLUSION</b>The aberrant expression of Notch1 and Asb2 exists in patients with P210 positive CML, which may be involved in incidence and development of CML.</p>
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Humans , Bone Marrow , Metabolism , Case-Control Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Receptor, Notch1 , Genetics , Metabolism , Signal Transduction , Suppressor of Cytokine Signaling Proteins , Genetics , MetabolismABSTRACT
Objective To explore the expression of ankyrin-repeat SOCS box containing protein 2 (ASB2)and Janus kinase 3 (Jak3)mRNA in bone marrow plasma mononuclear cells of patients with acute lymphoblastic leukemia (ALL)and discuss the correlation of them.Methods Bone marrow plasma was collected from 48 patients of newly diagnosed ALL (37 cases B-ALL and 11 cases T-ALL)and 34 non leukemia patients (control group),respectively.Expression levels of ASB2 and Jak3 mRNA were detected by real-time quantitative PCR.Results The expression of ASB2 mRNA in B-ALL and T-ALL were significantly different compared to control group (t =14.2,P <0.01;t =15.2,P <0.01),which were 68.5,32.7 folded more than control group,respectively.Moreover,the expression level of Jak3 mRNA in B-ALL group and T-ALL group were 2 336.1 and 7 131.5 folded more than control group (t =37.3,P <0.01;t =37.6,P <0.01). At last,the expression of ASB2 and Jak3 gene was positive correlation (r =0.523,P <0.001).Conclusion ASB2 and Jak3 are expressed abnormally in ALL patients and the correlation of them is positive.ASB2 and Jak3 may be related to the proliferation and differentiation in leukemia cells.
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Objective To investigate mRNA expressions of Toll-like receptors (TLR3 and TLR7)and type Ⅰ interferons (IFN-α and IFN-β) in peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis C (CHC).Methods Thirty patients with CHC and 30 healthy controls were collected from Renmin Hospital of Wuhan University during September 2013 and May 2014.Liver function was detected using enzyme-linked immunosorbent assay (ELISA).mRNA expressions of TLR3,TLR7,IFN-α and IFN-β were detected by real-time quantitative PCR,and their relative expression values were obtained by 2-△△Ctmethod.The t test was performed for the comparison of mean differences between CHC patients and healthy controls,and Pearson analysis was used to analyze the correlations between TLR mRNA and IFN mRNA,liver function,HCV RNA load.Results Taking mRNA expressions in healthy control group as 1,the relative mRNA expressions of TLR3,TLR7,IFN-α and IFN-β in CHC group were 0.086,0.633,0.145 and 0.423 respectively (t =4.25,2.39,2.37 and 2.80,all P ＜ 0.01).Pearson correlation analysis showed that mRNA expressions of TLR3 and TLR7 were positively correlated with that of IFN-β (r =0.381 and 0.487,all P ＜ 0.05),but not correlated with IFN-α mRNA expression,HCV RNA load,ALT and AST (all P ＞ 0.05).Conclusion The mRNA expressions of TLR3,TLR7 and IFN-α,IFN-β decrease in CHC patients,and the mRNA expressions of TLR3 and TLR7 are positively correlated with that of IFN-β,indicating that increasing the expression of TLRs might be a new strategy in CHC treatment.
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PURPOSE: To analyze the correlation of polymorphisms of toll-like receptor 7 (TLR7) (rs179009) and toll-like receptor 9 (TLR9) (rs187084) in hepatitis C virus (HCV) infections in the Han population. MATERIALS AND METHODS: The genotypes of TLR7IVS2-151 in HCV infection were detected by Sanger sequencing using polymerase chain reaction-restriction fragment length polymorphism to determine the TLR9 T-1486C single nucleotide polymorphisms (SNP) for all enrolled patients. RESULTS: We found no significant difference between males with spontaneous clearance of HCV versus those chronically infected [chi2=2.71, p=0.10, odd ratios (OR)=0.58, 95% confidence interval (CI) 0.31-1.11]. However, significant differences were found for the distribution of TLR7 (rs179009) in females (chi2=9.46, p=0.01). In females, a significant difference was also found between chronic hepatitis C and those with spontaneous clearance of HCV in terms of TLR7 IVS2-151G/A allele frequencies (chi2=9.50, p=0.00, OR=0.46, 95% CI 0.28-0.75). In HCV-infected patients, no significant association was found between the frequency of TLR9 genotypes and alleles. CONCLUSION: The site of TLR7 IVS2-151 (rs179009) G/A may be a factor for susceptibility of chronic HCV in the female Han population. TLR9T-1486C (rs18084) SNP may not play a major role in HCV infection. However, individual risk profiles for HCV infection did vary by sex and this relationship should be further investigated.