目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患...目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患者的病理标本。采用Western blot法检测甲状腺正常组织和PTC组织中AKR1B10蛋白的表达;采用免疫组织化学法检测不同甲状腺组织AKR1B10蛋白的表达。结果 Western blot结果显示,AKR1B10蛋白在PTC组织中的表达水平明显高于甲状腺正常组织(0.82±0.10 vs 0.22±0.07,t=2.702,P=0.011)。免疫组织化学法结果显示,AKR1B10在PTC组织中呈高表达,且在不同甲状腺组织中其阳性表达率最高(79.5%)。AKR1B10表达与甲状腺癌组织周围淋巴结转移有关(P=0.007)。结论 AKR1B10在甲状腺乳头状癌组织中呈高表达,且与周围淋巴结转移有关。展开更多
AIM: TO define the potential role of programmed death-i/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen spe...AIM: TO define the potential role of programmed death-i/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen specific CD8+T cells in peripheral blood of patients with chronic hepatitis B (CriB) and acute exacerbation of hepatitis B (AEHB) infection. METHODS: The PD-1 level on CD8+ T lymphocytes and the number of HBV specific CD8+ T lymphocytes in patients and healthy controls (HCs) were analyzed by staining with pentameric peptide-human leukocyte antigen2 (HLA2) complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction (PCR) was used to measure the serum HBV- DNA levels. RESULTS: The level of PD-1 expression on total CD8+ T cells in CHB patients (13.86% ± 3.38%) was significantly higher than that in AEHB patients (6.80%± 2.19%, P 〈 0.01) and healthy individuals (4.63% ± 1.23%, P 〈 0.01). Compared to AEHB patients (0.81% ± 0.73%), lower frequency of HBV-specific CD8+ T cells was detected in chronic hepatitis B patients (0.37% ± 0.43%, P 〈 0.05). There was an inverse correlation between the strength of HBV-specific CD8+ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8+ T cells in CriB and AEHB subjects (R = 0.541, P 〈 0.01). However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase (ALT) levels (R = 0.066, P 〉 0.05). CONCLUSION: Our results confirm previous reports that HBV specific CD8+T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8+ T cell response.展开更多
Objective: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods...Objective: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods: A total of 288 rats were used for SAP- (n= 108) and O J-associated (n= 180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=lS). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA:) in blood, and pathological changes of the hearts were investigated. Results: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P〉0.05). The contents ofendotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P〈0.01 and P〈0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion: In this study, we found that Salvia rniltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.展开更多
AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHOD...AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.展开更多
OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was establish...OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was established through the tail-clamping stimulation method. The rat model of FD was assessed by the state of rats, their weight, sucrose preference rate, and intestinal propulsion rate. The DNA was extracted from stool samples after treatment with SMT. Amplified polymerase chain reaction(PCR) products of the 16S r DNA were sequenced using Novase Q6000 after construction of libraries. Composition of gut microbial community in the stool samples was determined and analyzed by cluster analysis, bioinformatic analysis, and analysis of α-diversity and β-diversity.RESULTS: The rat model of FD was successfully established using the tail-clamping stimulation method. The statistical results of cluster analysis of operational taxonomic units(OTUs) showed that the relative abundance of OTUs in the FD group was the lowest, while it was the highest in the normal(N) group. The composition of microbiome in the four groups was similar at phyla level. Compared with the FD group, the abundance of Firmicutes was downregulated, and the abundance of Proteobacteria and Bacteroidetes was upregulated in the Simo Tang(SMT) and high-dose Simo Tang(SMT.G) groups. The ratio of Bacteroidetes/Firmicutes was also elevated. According to the analysis of α-diversity and β-diversity, the abundance of flora in FD rats was significantly reduced. The treatment using SMT appeared beneficial to improve the diversity of flora. SMT could improve the intestinal flora in FD rats. The results showed that FD rats had intestinal flora imbalance, and species diversity increased. The results suggested that SMT could regulate the disorders of intestinal flora caused by FD. CONCLUDIONS: SMT could restore gut homeostasis and maintain gut flora diversity by modulating the gut microbiota and its associated metabolites in rats, thereby treating gastrointestinal diseases.展开更多
文摘目的探讨醛酮还原酶1B10(aldo-keto reductase family 1B10,AKR1B10)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中的表达及其临床意义。方法收集2013年1月至2015年7月于郴州市第一人民医院经超声诊断的237例甲状腺结节患者的病理标本。采用Western blot法检测甲状腺正常组织和PTC组织中AKR1B10蛋白的表达;采用免疫组织化学法检测不同甲状腺组织AKR1B10蛋白的表达。结果 Western blot结果显示,AKR1B10蛋白在PTC组织中的表达水平明显高于甲状腺正常组织(0.82±0.10 vs 0.22±0.07,t=2.702,P=0.011)。免疫组织化学法结果显示,AKR1B10在PTC组织中呈高表达,且在不同甲状腺组织中其阳性表达率最高(79.5%)。AKR1B10表达与甲状腺癌组织周围淋巴结转移有关(P=0.007)。结论 AKR1B10在甲状腺乳头状癌组织中呈高表达,且与周围淋巴结转移有关。
文摘AIM: TO define the potential role of programmed death-i/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen specific CD8+T cells in peripheral blood of patients with chronic hepatitis B (CriB) and acute exacerbation of hepatitis B (AEHB) infection. METHODS: The PD-1 level on CD8+ T lymphocytes and the number of HBV specific CD8+ T lymphocytes in patients and healthy controls (HCs) were analyzed by staining with pentameric peptide-human leukocyte antigen2 (HLA2) complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction (PCR) was used to measure the serum HBV- DNA levels. RESULTS: The level of PD-1 expression on total CD8+ T cells in CHB patients (13.86% ± 3.38%) was significantly higher than that in AEHB patients (6.80%± 2.19%, P 〈 0.01) and healthy individuals (4.63% ± 1.23%, P 〈 0.01). Compared to AEHB patients (0.81% ± 0.73%), lower frequency of HBV-specific CD8+ T cells was detected in chronic hepatitis B patients (0.37% ± 0.43%, P 〈 0.05). There was an inverse correlation between the strength of HBV-specific CD8+ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8+ T cells in CriB and AEHB subjects (R = 0.541, P 〈 0.01). However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase (ALT) levels (R = 0.066, P 〉 0.05). CONCLUSION: Our results confirm previous reports that HBV specific CD8+T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8+ T cell response.
基金supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province (Nos. 2003C130 and 2004C142)the Grave Foundation Project for Technological and Development of Hangzhou City (No. 2003123B19)the Intensive Foundation Project for Technology of Hangzhou City (No. 2004Z006), China
文摘Objective: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods: A total of 288 rats were used for SAP- (n= 108) and O J-associated (n= 180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=lS). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA:) in blood, and pathological changes of the hearts were investigated. Results: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P〉0.05). The contents ofendotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P〈0.01 and P〈0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion: In this study, we found that Salvia rniltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.
基金The National Natural Science Foundation of China, No. 30800382the Youth Science Foundation of Dalian to Professor Hui-Shu Guo, No. 2006B3NS218
文摘AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.
基金National Natural Science Foundation of China:Changes of Ras Homolog Gene Family Member A/Rho-associated Coiled-coil Kinase Signaling Pathway in Liver-Stomach Disharmony Functional Dyspepsia Rats and Intervention Mechanism of Simo Tang (No. 81803896)the Role of Gut Microbiota-diaminopimelic Acid Nucleotide-binding and Oligomerization Domain1-receptorinteracting Protein 2 Signal Pathway in Severe Process of Acute Pancreatitis and the Intervention Mechanism of Qingxia Therapy (No. 81873156)Research Project of Liaoning Provincial Department of Education:the Role of Mitochondria-Derived Reactive Oxygen Species Mediated Autophagy Activation in Myocardial Injury in Sepsis (No. LZ2020036)。
文摘OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was established through the tail-clamping stimulation method. The rat model of FD was assessed by the state of rats, their weight, sucrose preference rate, and intestinal propulsion rate. The DNA was extracted from stool samples after treatment with SMT. Amplified polymerase chain reaction(PCR) products of the 16S r DNA were sequenced using Novase Q6000 after construction of libraries. Composition of gut microbial community in the stool samples was determined and analyzed by cluster analysis, bioinformatic analysis, and analysis of α-diversity and β-diversity.RESULTS: The rat model of FD was successfully established using the tail-clamping stimulation method. The statistical results of cluster analysis of operational taxonomic units(OTUs) showed that the relative abundance of OTUs in the FD group was the lowest, while it was the highest in the normal(N) group. The composition of microbiome in the four groups was similar at phyla level. Compared with the FD group, the abundance of Firmicutes was downregulated, and the abundance of Proteobacteria and Bacteroidetes was upregulated in the Simo Tang(SMT) and high-dose Simo Tang(SMT.G) groups. The ratio of Bacteroidetes/Firmicutes was also elevated. According to the analysis of α-diversity and β-diversity, the abundance of flora in FD rats was significantly reduced. The treatment using SMT appeared beneficial to improve the diversity of flora. SMT could improve the intestinal flora in FD rats. The results showed that FD rats had intestinal flora imbalance, and species diversity increased. The results suggested that SMT could regulate the disorders of intestinal flora caused by FD. CONCLUDIONS: SMT could restore gut homeostasis and maintain gut flora diversity by modulating the gut microbiota and its associated metabolites in rats, thereby treating gastrointestinal diseases.