ABSTRACT
Objective:To explore the potential mechanisms of anterior cingulate cortex (ACC) in modulating pain behavior and anxiety-like behavior of rats with chronic non-specific low back pain induced by nerve growth factor (NGF).Methods:Ninety-six male SPF grade SD rats aged 8 weeks were randomly divided into four groups according the random number table method: control group, model group, control+ D-2-amino-5-phosphonopentanoate (D-AP5) group (control+ D-AP5 group) and model+ D-AP5 group, with 24 rats in each group.Low back pain model of rat was established by injection of NGF into multifidus muscle (left side) of the low backs of rats(two times with a five-day interval). Five days after modeling, rats in model+ D-AP5 group and control+ D-AP5 group were injected with the N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5(2 μg, 0.3 μL) at the right side of the ACC once a day for consecutive 3 days, and rats in control group and model group were injected with the same amount of 0.9% sodium chloride solution. Seven days after modeling, the pain threshold of rats was evaluated by mechanical stimulation test and hot and cold plate test.The anxiety-like behavior was tested by open field test.The density of glial fibrillary acidic protein (GFAP) positive cells and c-Fos(a kind of immediate early gene) positive cells of the spinal cord were observed by immunofluorescence. The expression of GFAP, c-Fos, phosphorylated-c-Jun N-terminal kinases (p-JNK), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL-1) proteins in the L2 segment of the spinal cord were detected by Western blot. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used to analyze normal distribution measurement data for comparison among multiple groups, and Tukey test was used for further pairwise comparisons. The Kruakal-Wallis H test was used for non-normal distribution measurement data, and Mann-Whitney U test was used for further pairwise comparisons with Bonferroni-corrected P-values. Results:In the experiments measuring pressure pain threshold (PPT) and paw withdrawal threshold (PWT), there were statistically significant differences in the PPT and PWT of rats among the four groups ( F=53.498, 41.939, both P<0.001). Seven days after modeling, PPT ((418.5±46.9) g) and PWT ( (55.6±7.1) g) in the ipsilateral side of the rats in model+ D-AP5 group were higher than those in model group ((290.0±32.0) g, (30.5±7.5) g) (both P<0.001). In the open field test, there were statistically significant differences in percentage of the inner zone distance ( H=11.922, P<0.01) and the percentage of inner zone time ( H=21.614, P<0.001) of rats among the four groups. The percentage of inner zone time in model+ D-AP5 group was higher than that in model group (5.6(4.3, 7.9) %, 3.1(2.1, 3.8) %) ( P<0.01). The results of immunofluorescence showed that there were statistically significant differences in the density of GFAP positive cells and c-Fos positive cells at the ipsilateral side of the superficial laminae of rats among the four groups ( H=49.085, F=18.120, both P<0.001). The density of GFAP positive cells (34.3(21.1, 47.5) cells/mm 2) and c-Fos positive cells ((52.7±39.4) cells/mm 2) at the ipsilateral side of the superficial laminae in model+ D-AP5 group were less than those in model group (76.5(68.6, 94.9) cells/mm 2, (112.4±63.7) cells/mm 2) (both P<0.001). The Western blot results showed that there were statistically significant differences in the protein expression of GFAP, c-Fos, p-JNK, MCP-1 and CXCL-1 in the L2 segment of rats among the four groups ( F=49.413, 38.437, 41.867, 36.735, 130.951, all P<0.001). The protein expression of GFAP (1.7±0.5), c-Fos (1.1±0.1), p-JNK (1.7±0.3), MCP-1 (1.0±0.4) and CXCL-1 (0.8±0.1) in the L2 segment in model+ D-AP5 group were lower than those in model group ((4.3±0.7), (2.6±0.5), (2.8±0.4), (2.9±0.4), (3.5±0.4)) (all P<0.01). Conclusion:ACC modulates mechanical hyperalgesia and anxiety-like behavior in chronic non-specific low back pain rats, which might be associated with the involvement of spinal astrocytes, p-JNK signal pathway and chemokines such as MCP-1 and CXCL-1.
ABSTRACT
BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.
Subject(s)
Humans , Quality of Life , China , Arthritis, Rheumatoid/drug therapy , Piperidines/therapeutic use , Treatment Outcome , Antirheumatic Agents/therapeutic use , Pyrroles/therapeutic useABSTRACT
Objective:To explore the predictive efficacy of prothrombin time (PT) with regarding for the severity and prognosis of septic patients, along with comparing with other routine coagulation parameters.Methods:A retrospective analysis was conducted. The clinical data of 302 septic patients who were admitted to the intensive care unit (ICU) of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 1 to December 31 in 2019 were enrolled. Demographic and basic clinical data were collected. Laboratory data, including PT, activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer, fibrin (fibrinogen) degradation product (FDP), antithrombin (AT), platelet count (PLT) at ICU admission were recorded, and sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours of admission to ICU were also collected. What's more, some major clinical events, such as septic shock, disseminated intravascular coagulation (DIC), etc. during ICU stay were also monitored. A follow-up 28 days observation of prognosis was performed. The patients were divided into the septic shock group and the non-septic shock group according to the occurrence of septic shock, and they were divided into the survival group and the non-survival group according to the 28-day prognosis. The differences in terms of above parameters between each two groups were compared. Spearman correlation method was used to analyze the correlation between routine coagulation parameters and SOFA score or APACHEⅡ score. Receiver operator characteristic curve (ROC curve) was plotted to determine the predictive efficacy of each routine coagulation parameter with regarding to predict septic shock and 28-day mortality. Based on the cut-off value of PT, the septic patients were divided into two risk stratifications, and then the major clinical and end point outcome were compared. Kaplan-Meier survival curve analysis was applied to investigate the difference of the 28-day cumulated survival rate based on the different risk stratifications of PT level. Finally, multivariate Logistic regression analysis was used to explore whether prolonged PT level was an independent risk factor for septic shock and 28-day mortality.Results:The 302 patients were all enrolled, including 120 patients with septic shock and 182 patients without. Seventy-five patients died within 28 days, while 227 survived. Comparing with the non-septic shock group or the survival group, the septic shock group or the non-survival group patients both had longer PT, APTT and TT, higher D-dimer, FDP and lower PLT, FIB and AT. Correlation analysis revealed that PT and PLT were better correlated with SOFA score ( r values were 0.503 and -0.524, both P < 0.01), and PT was better correlated with APACHEⅡ score ( r = 0.407, P < 0.01). ROC curve analysis showed that PT had the most powerful predictive efficacy for septic shock and 28-day mortality. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were 0.831 (0.783-0.879) and 0.739 (0.674-0.805), respectively. The cut-off value were 16.8 s and 16.3 s, respectively, with the sensitivity of 64.2%, 72.0% and the specificity of 89.0%, 70.9%, respectively. Risk stratification based on PT level revealed that the patients with PT > 16.5 s ( n = 103) had higher rate of 28-day mortality, incidence of septic shock and DIC, and score of SOFA and APACHEⅡ comparing to those with PT ≤ 16.5 s ( n = 199). Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate was significantly lower in the patients with PT > 16.5 s than those with PT ≤ 16.5 s (52.43% vs. 86.93%; Log-Rank test: χ 2 = 49.428, P < 0.001). Multivariate Logistic regression analysis revealed that PT > 16.5 s was an independent risk factor both for septic shock and 28-day mortality [model 1 (enrolled SOFA score): odds ratio ( OR) and 95% CI were 6.003 (3.040-11.855), 4.842 (2.114-11.089); model 2 (enrolled APACHEⅡ score): OR and 95% CI were 7.675 (4.007-14.702), 5.160 (2.258-11.793)]. Conclusions:Compared with other routine coagulation parameters, PT has the potential best predictive value for evaluating the severity of sepsis and the prognosis. When a patient is diagnosed with sepsis and has a result of PT longer than 16.5 s at ICU admission, the patient may have a higher risk of progression to septic shock and short-term death.
ABSTRACT
OBJECTIVE@#To explore the IgG levels of newly diagnosed IgG-type multiple myeloma (MM) patients and analyze the relationship between the IgG levels and clinical efficacy and prognosis.@*METHODS@#The clinical data of 66 newly diagnosed IgG-type MM patients in our hospital from September 2012 to October 2018 were collected. These 66 patients were divided into group A (IgG≤64 g/L, n=41), and group B (IgG ＞64 g/L, n=25), then the MM patients in 2 groups were divided into 2 subgroups thalidomide (TM)-treated group (n=35) and bortezomib (BTZ)-treated group (n=25) according to therapeutic regimens. The climical efficacy, PFS and OS time as well as the factors affecting prognosis of patients were compared and analyzed.@*RESULTS@#The overall response rate (ORR) and CR+VGPR rate in group A were better than those in group B (P=0.008, P=0.036), the ORR of BTZ-treated group in group B was significantly better than that of TM-treated group (P=0.028), while the ORR of TM-treated group in group A was better than that of TM-treated group in group B (P=0.048), the CR+VGPR rate was better than that of TM-treated group in group B (P＜0.05). The number of patients with high risk cytogenetics (HRC) in group B was much more than that in group A (P=0.022). Spearman correlation analysis showed that serum IgG levels negatively correlated with albumin (r=-0.449，P=0.000) and hemoglobin (r=-0.608，P=0.000), and positively correlated with bone marrow plasma cells (r=0.328，P=0.007). Survival analysis showed that the PFS in group A was significantly better than that in group B (P=0.015), and the OS in group A was better than that in group B (P=0.049), but there was no significant difference in PFS and OS between TM group and BTZ group (PFS: P=0.695, OS: P=0.3250). Cox multivariate regression analysis showed that the ≥VGPR and standard-risk cytogenetics were independent prognostic factors for PFS and OS.@*CONCLUSION@#IgG＞64g/L in patients with newly diagnosed IgG-type MM is a poor prognostic factor affecting PFS and OS. The higher level of serum IgG at the initial diagnosis, the higher the risk of HRCs, and the worse clinical efficacy and prognosis of patients.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Immunoglobulin G , Multiple Myeloma , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE To investigate the effect of quercetin on primary cultured newborn rat cortex neuron cell which is estrogen depletion, and discuss the possible mechanism, to provide new ideas and strategies for developing a drug of neurodegenerative disease. METHODS Rat cortex neurons were isolated from one day old Sprague Dawley rats and treated with estrogen, quercetin and estrogen receptor antagonists (ICI182,780). Cell viability was determined by MTT assay, neurite outgrowth was measured by fluorescent microsope and estrogen receptors were determine by Western blot. RESULTS Quercetin functions like estrogen to increase cortex neuronal cell viability, the Que (50, 100 μmol·L-1) group compared with the control group could significantly improve the activity of the cortical neurons(P<0.05). It can also increase neurite out growth, the Que (50,100 μmol·L-1) group significantly promoted the formation of synapse, most of the neurons were full, and the synapses of neurons became thick, growth, and connect to a dense neural network. And in the Western blot experiments, Que (50, 100 μmol·L-1) group could obviously increase the expression of estrogen receptor alpha protein, in addition, the neural protective effect of quercetin can be inhibited by ICI182,780. CONCLUSION Quercetin like estrogen can protected cortex neuronal and the effect of quercetin on cortex neuronal cells was mediated by estrogen receptor alpha.
ABSTRACT
OBJECTIVE To explore the estrogen- like neuroprotective effects and the related mechanism of quercetin by using PC12 cells induced with Aβ25-35, provided thought and strategy for the drug therapy of AD. METHODS Cells were cultured with Aβ25- 35 for 24 h, 17β-estradiol (0.1 μmol·L- 1), genistein(50 μmol·L-1) and three different concentrations of quercetin (200 μmol·L-1, 300 μmol·L-1 and 400 μmol·L-1) were respectively added after 24h. The effects of quercetin on activity of AD model were tested by MTT. Immunohistochemical stain and Western blot were used to detect the expression of estrogen receptors alpha and beta, p-ERK1/2 and apoptosis related proteins.The mechanism of quercetin estrogen-like neuroprotective effects was detected using estrogen receptor antagonist ICI182,780 and MAPKK inhibitor U0126. RESULTS The results revealed thatthe toxic effects showed in a dose-dependent increase of Aβ25- 35 on PC12 cells.Comparing with the control group,cells injury was observed after cultured with 10 μmol·L-1 Aβ25-35 for 24 h(P<0.01). The MTT results showed that 17β-estradiol, genistein and three different concentrations of quercetin could significantly enhance the cell survival rate compared with the model group (P<0.05). Compared with model group,Immunofluorescence and Western blot results show that quercetin could improve the estrogen receptor alpha and p- ERK1/2 protein expression (P<0.05), and the expression of estrogen receptor beta protein is increased without significant difference. And in the Western blot experiments, the ratio of Bcl- 2 and Bax was increased and the expression of Caspase 3 was decreased( P<0.05).When estrogen receptor inhibition ICI182,780 were reduced,the expression of p- ERK1/2 was decreased (P<0.05) and the ratio of Bcl- 2 and Bax was decreased, Caspase 3 protein expression was increased (P<0.05). In addition,pretreatment of cells with U0126 would reduce Bcl-2/Bax ratio and increase Caspase 3 protein expression increased (P<0.05). CONCLUSION Quercetin protected PC12 cells, which suffered from Aβ25- 35-induced cytotoxicity and exert neuroprotective effects. The estrogen-like neuroprotective effect can reduce the apoptosis in the classic estrogen receptor pathway and MAPK pathway. And quercetin can also active MAPK signaling pathways by the mediation of estrogen receptor alpha.
ABSTRACT
AIM:To investigate the neuroprotective effect of progesterone against adenosine triphosphate (ATP)-injured human neuroblastoma SH-SY5Y cells.METHODS:The SH-SY5Y cells in the logarithmic phase were divided into different groups according to the progesterone and ATP concentrations.The cell viability was measured by CCK-8 assay.The membrane permeability was detected using fluorescent dye YO-PRO-1.Cytosolic Ca2+ concentration was measured with fluorescent dye Fluo-3/AM.The expression of purinergic P2X7 receptor was assessed by Western blot.RESULTS:The viability of the SH-SY5Y cells was significantly decreased (P ＜ 0.05) and YO-PRO-1 uptake was obviously increased (P ＜ 0.05) in a concentration-dependent manner compared with control group when SH-SY5Y cells were treated with ATP at 1,3,5 and 7 mmol/L for 2 h.The viability reduction of the SH-SY5Y cells induced by ATP was obviously counteracted by treatment with progesterone at 3,10 and 30 nmol/L for 30 min (P ＜ 0.05) as compared with ATP group.YO-PRO-1 fluorescence enhancement induced by ATP in SH-SY5Y cells was significantly reduced (P ＜ 0.05) by progesterone (30 nmol/L) or P2X7 receptor antagonist KN-62 (500 nmol/L) pretreatment for 30 min,and no obvious difference between treatments with progesterone and KN-62 was observed.Cytosolic Ca2+ fluorescence intensity in normal group was a little,but that in ATP group was increased (P ＜ 0.05).Progesterone or KN-62 pretreatment significantly decreased the cytosolic fluorescence intensity of Ca2+ induced by ATP (P ＜ 0.05).However,no obvious difference between treatments with progesterone and KN-62 was found.The expression of P2X7 receptor in ATP group was significantly higher than that in control group (P ＜ 0.05),and progesterone inhibited ATP-induced P2X7 receptor expression (P ＜ 0.05).CONCLUSION:Progesterone inhibits P2X7 receptor expression,membrane pore formation,intracellular Ca2+ increase and cell death induced by ATP,so progesterone may protect SH-SY5Y cells against ATP-induced injuries.
ABSTRACT
AIM:To investigate the neuroprotective effect of progesterone against adenosine triphosphate (ATP)-injured human neuroblastoma SH-SY5Y cells.METHODS:The SH-SY5Y cells in the logarithmic phase were divided into different groups according to the progesterone and ATP concentrations.The cell viability was measured by CCK-8 assay.The membrane permeability was detected using fluorescent dye YO-PRO-1.Cytosolic Ca2+ concentration was measured with fluorescent dye Fluo-3/AM.The expression of purinergic P2X7 receptor was assessed by Western blot.RESULTS:The viability of the SH-SY5Y cells was significantly decreased (P ＜ 0.05) and YO-PRO-1 uptake was obviously increased (P ＜ 0.05) in a concentration-dependent manner compared with control group when SH-SY5Y cells were treated with ATP at 1,3,5 and 7 mmol/L for 2 h.The viability reduction of the SH-SY5Y cells induced by ATP was obviously counteracted by treatment with progesterone at 3,10 and 30 nmol/L for 30 min (P ＜ 0.05) as compared with ATP group.YO-PRO-1 fluorescence enhancement induced by ATP in SH-SY5Y cells was significantly reduced (P ＜ 0.05) by progesterone (30 nmol/L) or P2X7 receptor antagonist KN-62 (500 nmol/L) pretreatment for 30 min,and no obvious difference between treatments with progesterone and KN-62 was observed.Cytosolic Ca2+ fluorescence intensity in normal group was a little,but that in ATP group was increased (P ＜ 0.05).Progesterone or KN-62 pretreatment significantly decreased the cytosolic fluorescence intensity of Ca2+ induced by ATP (P ＜ 0.05).However,no obvious difference between treatments with progesterone and KN-62 was found.The expression of P2X7 receptor in ATP group was significantly higher than that in control group (P ＜ 0.05),and progesterone inhibited ATP-induced P2X7 receptor expression (P ＜ 0.05).CONCLUSION:Progesterone inhibits P2X7 receptor expression,membrane pore formation,intracellular Ca2+ increase and cell death induced by ATP,so progesterone may protect SH-SY5Y cells against ATP-induced injuries.
ABSTRACT
<p><b>OBJECTIVE</b>To establish a multiple myeloma specimen bank applied for molecular biological researches and to explore the methods of specimen collection, transportation, storage, quality control and the management of specimen bank.</p><p><b>METHODS</b>Bone marrow and blood samples were collected from multiple myeloma patients, plasma cell sorting were operated after the separation of mononuclear cells from bone marrow specimens. The plasma cells were divided into 2 parts, one was added with proper amount of TRIzol and then kept in -80 °C refrigerator for subsequent RNA extraction, the other was added with proper amount of calf serum cell frozen liquid and then kept in -80 °C refrigerator for subsequent cryopreservation of DNA extraction after numbered respectively. Serum and plasma were separated from peripheral blood, specimens of serum and plasma were then stored at -80 °C refrigerator after registration. Meantime, the myeloma specimen information management system was established, managed and maintained by specially-assigned persons and continuous modification and improvement in the process of use as to facilitate the rapid collection, management, query of the effective samples and clinical data.</p><p><b>RESULTS</b>A total of 244 portions plasma cells, 564 portions of serum, and 1005 portions of plasma were collected, clinical characters were documented.</p><p><b>CONCLUSION</b>A multiple myeloma specimen bank have been established initially, which can provide quality samples and related clinical information for molecular biological research on multiple myeloma.</p>
ABSTRACT
Objective@#To investigate the association between interleukin-6 -572 gene polymorphism and aggressive periodontitis. @*Methods @#A case-control study involved 83 patients with aggressive periodontitis (AgP) and 69 health controls was held, and the genotype and allele distributions of interleukin-6 -572 gene polymorphism were analyzed by PCR-RFLP. @* Results @#There was statistically significant differences in the genotype distribution by the chi-square test in the two groups (χ2 = 13.710, P=0.001). The distribution of allele frequencies in AgP group was statistically different (χ2=13.213, P < 0.001) from the healthy control group, and the OR for the G allele is 2.988 (95%CI: 1.634-5.465) when compared with the C allele.@*Conclusion@#IL-6 -572 gene polymorphism is associated with the susceptibility to AgP in Chinese Han population of Guangdong, and the IL-6 -572 G allele might be a risk factor of the genetic susceptibility to AgP.
ABSTRACT
Objective To evaluate the effects of fluid restriction in combination with small dose of norepinephrine on cerebral oxygen metabolism in elderly patients undergoing gastrointestinal surgery.Methods Forty elderly patients of both sexes,aged 65-80 yr,with body mass index of 18-24 kg/m2,of ASA physical status Ⅰ or Ⅱ (NYHA Ⅰ or Ⅱ),with left ventricular ejection fraction≥50％,undergoing elective gastrointestinal surgery,were randomly divided into 2 groups (n =20 each) using a random number table:routine fluid administration group (group S) and restricted fluid administration + small dose of norepinephrine group (group RN).In group S,lactated Ringer's solution was given routinely,ephedrine 5 mg (per time) was injected intravenously,and MAP was maintained ≥ 65 mmHg during operation.In group RN,lactated Ringer's solution was infused intravenously at 5 ml · kg-1 · h-1 starting from 30 min before anesthesia,norepinephrine was infused intravenously at 0.01-0.03 μg · kg-1 · min-1 after induction of anesthesia,and MAP was maintained ≥ 65 mmHg.Intraoperative blood loss was replaced with the equal volume of 6％ hydroxyethyl starch 130/0.4 sodium chloride injection in both groups.At 5 min before skin incision,1 and 2 h after skin incision and postanesthesia care unit discharge time,arterial and jugular bulb venous blood samples were obtained for blood gas analysis,and arterial oxygen content,jugular bulb venous oxygen content,arteriovenous oxygen content difference,cerebral oxygen extraction rate,and the ratio of cerebral blood flow to cerebral oxygen metabolic rate were calculated.Results There were no significant differences between the two groups in arterial oxygen content,jugular bulb venous oxygen content,arteriovenous oxygen content difference,cerebral oxygen extraction rate,and the ratio of cerebral blood flow to cerebral oxygen metabolic rate.Conclusion Fluid restriction combined with small dose of norepinephrine produces no effects on cerebral oxygen metabolism in elderly patients undergoing gastrointestinal surgery.
ABSTRACT
Although previous reports showed drug-eluting stent (DES) could effectively inhibit neointima formation, in-stent restenosis (ISR) remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1-S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.
Subject(s)
Animals , Rats , Blotting, Western , Cell Cycle , Cell Cycle Proteins , Metabolism , Cell Proliferation , Cells, Cultured , Cyclin B1 , Metabolism , Cyclin D1 , Metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Cyclin-Dependent Kinase Inhibitor p27 , Metabolism , Endothelial Cells , Metabolism , Flow Cytometry , G1 Phase Cell Cycle Checkpoints , Immunohistochemistry , Microscopy, Fluorescence , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Metabolism , Paclitaxel , Pharmacology , Proliferating Cell Nuclear Antigen , Metabolism , Tubulin Modulators , PharmacologyABSTRACT
Objective To study absorption of shegan heji marker components in blood and their excretion in urine and feces of rats, after intragastric administration of shegan heji. Methods LC-MS/MS was used for determination of marker compounds. Rat metabolic cage technology was employed. Results Excretion of marker components were completed 24 hours after administration. Conclusion Ephedrine can be excreted from rats within 24 hours. The possibility of mutual transformation of flavonoids exists in the body. Taking shegan heji will not cause accumulation of ephedrine and flavonoids in the body.
ABSTRACT
Objective To evaluate the effects of ethyl gallate (EG ) on sepsis-induced acute lung injury (ALI) in rats .Methods Forty-eight healthy male Wistar rats ,aged 10-12 weeks ,weighing 150-250 g ,were randomly divided into 3 groups (n=16 each) using a random number table :control group (group C) ,group ALI , and group EG .The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg .Sepsis was induced by cecal ligation and puncture (CLP) .EG 1 ml/h (50 mg·kg-1 ·h-1 ) was infused intravenously via the femoral vein for 4 h starting from 6 h after CLP in group EG .The equal volume of normal saline was given instead in group ALI . The rats were sacrificed at 10 and 24 h after CLP (T1 ,2 ) , and the lungs were removed for determination of wet/dry lung weight ratio (W/D ratio ) , superoxide dismutase (SOD ) activity , contents of malondialdehyde (MDA ) and glutathione (GSH ) , and 3-NT expression (by immuno-histochemistry ) in lung tissues .The pathological changes of the lung were examined with light microscope .Results Compared with group C ,the W/D ratio ,MDA content and 3-NT expression were significantly increased and GSH content was decreased at T1 ,2 ,the SOD activity was significantly decreased at T2 in group ALI ,and the MDA content and 3-NT expression were increased at T1 ,and the W/D ratio ,MDA content and 3-NT expression were increased and GSH content was decreased at T2 in group EG ( P<0.05) .Compared with group ALI ,the MDA content was significantly decreased at T1 ,and the W/D ratio ,MDA content and 3-NT expression were decreased ,and GSH content and SOD activity were increased at T2 in group EG ( P<0.05) .The pathological changes of the lung were obvious in group ALI , and significantly attenuated in group EG .Conclusion EG can attenuate sepsis-induced ALI by antioxidative effects in rats .
ABSTRACT
Although previous reports showed drug-eluting stent (DES) could effectively inhibit neointima formation, in-stent restenosis (ISR) remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1-S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.
ABSTRACT
Objective To investigate the effect of one-lung ventilation (OLV) on the occurrence of subcutanous emphysema during retroperitoneal laparoscopic urologic surgery (RPLUS).Methods Twenty-seven ASA Ⅰor Ⅱ patients,aged 29-64 yr,with body mass index 19-25 kg/m2,scheduled for elective RPLUS,were randomly divided into 2 groups:two-lung ventilation (TLV) group (group Ⅰ,n =15) and OLV group (group Ⅱ,n =12).In group Ⅰ,the patients were tracheal intubated and TLV was performed.In group Ⅱ,the left-sided double lumen endobronchial tube was inserted and TLV was performed,OLV on the non-operated side was performed starting from 10-15 min before pneumoperitoneum and TLV resumed at the end of pneumoperitoneum.The end-tidal CO2 partial pressure and minute ventilation volume were measured before pneumoperitoneum (T1),at 30 and 60 min of pneumoperitoneum (T2,3),and at 30 min after the end of pneumoperitoneum (T4).The CO2 absorption capacity was calculated.The degree of pneumoderma was assessed and the occurance of pneumoderma was recorded at the end of pneumoperitoneum.Results Compared with group Ⅰ,the CO2 absorption capacity was significantly reduced,and the degree and incidence of pneumoderma were significantly decreased in group Ⅱ (P ＜ 0.05).Conclusion OLV on the non-operated side can reduce the CO2 absorption capacity,decrease the degree of subcutaneous emphysema and reduce the occurrence of subcutanous emphysema during pneumoperitoneum in patients undergoing RPLUS.
ABSTRACT
Objective To investigate the role of protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification in glutamine-induced improvement in the vascular hyporeactivity in rats with septic shock.Methods Thirty-two adult male Sprague-Dawley rats,aged 2-3 months,weighing 250-300 g,were randomly divided into 4 groups (n =8 each):sham operation group (S group); septic shock group (C group); glutamine group (G group) ; alloxan group (A group).Septic shock was induced by cecal ligation and puncture (CLP).In G and A groups,glutamine 0.75 g/kg was infused intravenously over 30 min at 1 h before CLP,and in addition alloxan 90 mg/kg was infused intraperitoneally in A group.Phenylephrine (PE) 0.5,1.0,2.0,and 2.5 μg/kg was injected intravenously at 20 min intervals at 6 h after CLP and the percentage increase in mean arterial pressure (MAP) was calculated.The thoracic aorta rings were isolated to perform the isolated vascular tension experiment.The concentration-response curve of PE was obtained in tension experiments,and the PE maximum efficacy (Emas) and median effective dose ( EC50 ) were calculated.The expression of O-GlcNAc modification and iNOS content in the thoracic aorta were detected in all groups.Blood samples were taken to determine the serum concentration of NO.Results Compared with S group,the percentage increase in MAP and Emax were significantly decreased,while the EC50,serum concentration of NO,and expression of O-GlcNAc modification and iNOS content in thoracic aorta were significantly increased in C,G and A groups ( P ＜ 0.05).Compared with C group,the expression of O-GlcNAc modification in the thoracic aorta was significantly increased,and EC50 was significantly decreased in G group,and the percentage increase in MAP and Emax were significantly increased,while the serum concentration of NO,and content of iNOS in the thoracic aorta were significantly decreased in G and A groups ( P ＜ 0.05).Compared with G group,the EC50,serum concentration of NO,and content of iNOS in the thoracic aorta were significantly increased,while the percentage increase in MAP,Emax and expression of O-GlcNAc modification in the thoracic aorta were significantly decreased ( P ＜ 0.05 ).Conclusion Glutamine improves the vascular hyporeactivity through increasing the level of protein O-GlcNAc modification in rats with septic shock.
ABSTRACT
ObjectiveTo investigate the effects of norepinephrine on oxygen metabolism and postoperative outcomes in the elderly patients undergoing fluid-restored abdominal surgery.MethodsAfter hospital ethics committee approval,and written informed consent was obtained from all patients,40 elderly patients,aged ＞ 64 yr,with a body mass index of 18-24 kg/m2,undergoing elective colorectal surgery,were randomly divided into 2 groups (n =20 each):routine fluid administration group (group A) and restricted fluid administration group (group B).In group A,lactated Ringer's solution was given routinely.Lactated Ringer's solution was given at a rate of 5 ml· kg- 1 · h- 1 and small dose of norepinephrine was infused intravenously at 0.01-0.03 μg· kg- 1 · h - 1 simultaneously during the surgery,and MAP was maintained ≥65 mm Hg in group B.Intraoperative blood loss was replaced with the equal volume of 6％ hydroxyethyl starch 130/0.4.Before the surgery ( baseline),1 and 2 h after beginning of the surgery,and while leaving postanesthesia care unit,mean arterial pressure (MAP),heart rate (HR),cardiac index (CI) and central venous pressure (CVP) were recorded,and arterial and central venous blood samples were drawn for blood gas analysis.Oxygen delivery index (DO2 I ),oxygen consumption index (YO2I) and oxygen extraction ratio (ERO2) were calculated.The gastric mucosal pH was determined before the surgery and 1 h after beginning of the surgery.Blood samples were taken form the peripheral vein to determine the concentration of Hb,serum albumin,blood urea nitrogen (BUN) and creatinine (Cr) concentrations before the surgery and 1 day after the surgery.The extubation time,duration of stay in hospital,the time when the patients passed the flatus,pulmonary complications,gastrointestinal complications,and wound infections were recorded.ResultsCompared with group A,CI,Hb,ScvO2 and DO2I were significantly increased,CVP and ERO2 were decreased during the surgery,the concentrations of Hb and serum albumin were significantly increased,1 day after the surgery,and the incidence of pulmonary complications and wound infections was significantly decreased after the surgery in group B (P ＜ 0.05 ).There were no significant differences in gastric muscosal pH,the indexes of renal function,extubatiotn time,the time when the patients passed the flatus,duration of stay in hospital and the incidence of gastrointestinal complications between the two groups ( P ＞ 0.05).ConclusionWhen small dose of norepinephrine is used to treat perioperative hypotension induced by fluid restriction,it can increase oxygen delivery,and reduce the incidence of postoperative complications,and has no adverse effects on gastrointestinal microcirculation and oxygen consumption in the elderly patients undergoing colorectal surgery.
ABSTRACT
Objective To evaluate the role of O-GlcNAc protein modification in attenuation of brain damage by glutamine in septic rats.Methods Sixty male SD rata weighing 180-240 g were randomly divided into 4 groups:sham operation group(group S,n =12),sepsis group(group CLP,n =16),glutamine group(group G,n =16),an inhibitor of O-linked-N-acetyl glucosamine transferase Alloxan + glutamine group(group G + A,n =16).Rats were submitted to sepsis by cecal ligation and perforation(CLP).Glutamine(Gln)0.75 g/kg was injected iv after CLP in group G.Gln 0.75 g/kg was injected iv and Alloxan 90 mg/kg was injected ip after CLP in group G + A.Equal volume of normal saline was given in group S and group CLP.A1 24 h afler CLP,the neural reflex score was evaluated,then rat was sacrificed.The brain was removed for measurement of brain water content,observation of histopathology and determination of O-GlcNAc-modified protein expression.Results Compared with group S,neural reflex score and brain water content were significantly increased in groups CLP,G and G + A(P ＜ 0.05).Compared with group CLP,neural reflex score and brain water content were significantly decreased in groups G and G + A(P ＜ 0.05),and the expression of O-GlcNAc-modified protein was upregulated in group G(P ＜ 0.05),Compared with groups G,neural reflex score and brain water content were significantly increased,and the expression of O-GlcNAc-modified protein downregulated in group G + A(P ＜ 0.05).There was no significant difference in O-GlcNAc-modified protein expression among groups S,CLP and G + A.Conclusion Glutamine attenuates brain damage through O-GlcNAc protein modification in septic rats.
ABSTRACT
Hookworm infection is a relatively common cause of anemia in endemic areas. The most common hookworm species are Ancylostoma duodenale and Necator americanus. In this report we present a case of overt gastrointestinal bleeding because of hookworm infection. Capsule endoscopy revealed many hookworms in the lumen of proximal jejunum where active bleeding was seen. The patient was successfully treated with Albendazole.