Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflamm...BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflammation and tissue repair.However,their role in systemic inflammatory response syndrome(SIRS) has been less well studied.This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS.We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group(n=50) and non-SIRS group(/7=35).The SIRS group was divided into MODS group(n=26) and non-MODS group(n=24) by their severity,and survival group(n=35) and non-survival group(n=15) by their prognosis.Another 30 healthy adults served as normal controls.uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay(ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls(P<0.001 and P<0.001).It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients(all P<0.05).However,there was no difference in uPA level between survivors and non-survivors(P>0.05).The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls(P<0.001 and P<0.001).There was a significant elevation of uPAR in sepsis patients,MODS patients and non-survivors as compared with non-sepsis patients,non-MODS patients and survivors respectively(all P<0.05).Plasma uPAR levels were positively correlated with APACHE Ⅱ score(r=0.575,P<0.001) and SOFA score(r=0.349,P=0.013).AUCs for the prediction of SIRS mortality were 0.67 and 0.51,respectively,for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS.展开更多
Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illne...Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally;VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls;2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;3) corrected estradiol, testosterone and 25-OH Vitamin D;4) returned pulmonary artery systolic pressure (PASP) during exercise to normal;and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.展开更多
Inflammation and coagulation constantly influence each other and are constantly in balance.Emerging evidence supports this statement in acute inflammatory diseases,such as sepsis,but it also seems to be very important...Inflammation and coagulation constantly influence each other and are constantly in balance.Emerging evidence supports this statement in acute inflammatory diseases,such as sepsis,but it also seems to be very important in chronic inflammatory settings,such as inflammatory bowel disease(IBD).Patients with Crohn's disease and ulcerative colitis have an increased risk of thromboembolic events,and several abnormalities concerning coagulation components occur in the endothelial cells of intestinal vessels,where most severe inflammatory abnormalities occur.The aims of this review are to update and classify the type of coagulation system abnormalities in IBD,and analyze the strict and delicate balance between coagulation and inflammation at the mucosal level.Recent studies on possible therapeutic applications arising from investigations on coagulation abnormalities associated with IBD pathogenesis will also be briefly presented and critically reviewed.展开更多
目的探索CX3CR1对创伤性骨髓炎大鼠骨骼肌微纤维、ERK/MAPK信号通路及炎症反应的影响。方法选取30只SPF级SD雄性大鼠,依据随机数字表法分为健康组、模型组、CX3CR1抑制组,每组10只。除健康组外,其余各组均建立创伤性骨髓炎模型。其中健...目的探索CX3CR1对创伤性骨髓炎大鼠骨骼肌微纤维、ERK/MAPK信号通路及炎症反应的影响。方法选取30只SPF级SD雄性大鼠,依据随机数字表法分为健康组、模型组、CX3CR1抑制组,每组10只。除健康组外,其余各组均建立创伤性骨髓炎模型。其中健康组、模型组大鼠均每日常规腹腔注射生理盐水,CX3CR1干预组向残腔内注射CX3CR1中和抗体进行处理。采用ELISA法检测血清中IL-6、IL-10、IL-1β、TGF-β水平,应用改良X线Norden评分检测骨骼肌微纤维,HE染色观察病理变化,免疫印迹及PCR检测股骨组织中细胞外信号调节蛋白激酶(Extracellular regulated protein kinase,ERK1/2)、丝裂原活化蛋白激酶(Mitogen activated protein kinase,MAPK)蛋白及mRNA表达。结果与健康组比较,模型组TGF-β、IL-1β、IL-10、IL-6等炎症因子含量均升高(P<0.05);与模型组比较,CX3CR1抑制组炎症因子含量降低(P<0.05)。与健康组比较,模型组随时间推移X线Norden评分升高(P<0.05);与模型组比较,CX3CR1抑制组X线Norden评分降低(P<0.05)。HE染色显示,健康组骨质完好;模型组可见大量炎性细胞浸润、灶性脓肿及坏死灶;CX3CR1抑制组大鼠的骨质明显改善,炎症反应降低。与健康组比较,模型组ERK1/2、MAPK蛋白及mRNA表达升高(P<0.05);与模型组比较,CX3CR1抑制组ERK1/2、MAPK蛋白及mRNA表达降低(P<0.05)。结论抑制CX3CR1可改善创伤性骨髓炎大鼠的疾病反应,可能与降低炎症反应、ERK/MAPK信号通路以及改善骨骼肌微纤维相关。展开更多
Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who we...Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.展开更多
In a recent article on World J Clin Cases 2019;7:3859-3865,Sun et al reported a case of 36-year-old female with macrophage activity syndrome as an onset of systemic lupus erythematosus.Although this is a very interest...In a recent article on World J Clin Cases 2019;7:3859-3865,Sun et al reported a case of 36-year-old female with macrophage activity syndrome as an onset of systemic lupus erythematosus.Although this is a very interesting case,some concerns still need to be addressed.First,the patient had an extremely elevated serum ferritin but a normal C-reactive protein level,which was unparallel with the inflammatory condition before she received any treatments.Second,the diagnosis of systemic lupus erythematosus seemed to be insufficient according to the patient’s medical information presented,most of which were not specific to lupus but could be explained by macrophage activity syndrome.Hence,more medical information on the patient should be provided,and a profound discussion needs to be addressed.展开更多
Cardiovascular diseases (CVD) are the leading cause of mortality necessitating its early detection. The emergence of newer subclinical biomarkers in addition to the known cardiometabolic risk factors may play an impor...Cardiovascular diseases (CVD) are the leading cause of mortality necessitating its early detection. The emergence of newer subclinical biomarkers in addition to the known cardiometabolic risk factors may play an important role in early detection of CVD risk. In the present study, 74 adult females (30 -?75 y) with metabolic syndrome (MS) were selected and additional biochemical parameters such as C-reactive protein (CRP) and Homocysteine (Hcy) levels were analyzed. The average body mass index (BMI) and waist circumference of subjects were found to be 30 kg/m2 and99 cmrespectively. Mean LDL levels were found to be much higher than normal (139 mg/dl) while the HDL levels were low (41.5 mg/dl). The average fasting blood sugar and insulin levels were within the normal range. However, 40.5% females had serum Hcy levels >13.2 μmol/l and 59.5% women had CRP levels >3 mg/L indicating increased risk of CVD. Higher Hcy levels were associated with hyperinsulinemia (p < 0.01) and hyperglycemia (p < 0.05), indicating predilection for glucose intolerance. CRP levels showed significant negative correlation with HDL (p < 0.05), indicating a predilection for glucose intolerance. The present study reports overall more than 40% MS women are classified as high risk group using the Western standards. Limited data on normal levels of inflammatory biomarkers are available for Asian Indians. The study results indicate the importance of Hcy and CRP values among females having metabolic syndrome, known to be at a high risk of CVD.展开更多
Background: Presence of metabolic syndrome (MS) in people with diabetes confers increased cardiovascular and diabetes-specific micro- and macrovascular complications. The pathogenic pathways for metabolic syndrome are...Background: Presence of metabolic syndrome (MS) in people with diabetes confers increased cardiovascular and diabetes-specific micro- and macrovascular complications. The pathogenic pathways for metabolic syndrome are still issues for discussion especially in some special groups like those with type 2 diabetes mellitus (T2DM). Recent evidences suggest that inflammation may play a key role in MS. This study assessed the relationship between MS (and its component risks) and markers of inflammation (high-sensitivity C-reactive protein {hs-CRP} and white blood cells {WBC}). Methods: A cross-sectional study involving 108 patients with T2DM. Anthropometric measurements and clinical examination were conducted. Blood sample was collected for hs-CRP, WBC, glycated haemoglobin etc. Metabolic syndrome was defined using the International Diabetes Federation criteria. Ethical approval was granted and informed consent was obtained from participants. Results: Mean age of male and female participants were 58.00 ± 7.01 years and 55.48 ± 8.35 years respectively (p = 0.092). Eighty-two (75.9%) participants had metabolic syndrome. Median values of hs-CRP and total WBC were 0.89mg/L and 5.73 x103/mm3 respectively. On correlation, hs-CRP showed statistically significant association with waist circumference (r = 0.194;p = 0.044), fasting plasma glucose (r = 0.191;p = 0.048) and serum triglycerides (p = 0.226;r = 0.019). There was no statistically significant association between WBC and the metabolic components. Conclusion: Prevalence of metabolic syndrome is high, and C-reactive protein was associated with waist circumference, fasting plasma glucose and serum triglycerides.展开更多
AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response...AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.展开更多
目的探讨血清降钙素原(procalcitonin,PCT)联合前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)对脓毒症病情严重程度及预后的评估价值。方法选择2021年1月—2022年1月莆田学院附属医院重症医学科收治...目的探讨血清降钙素原(procalcitonin,PCT)联合前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)对脓毒症病情严重程度及预后的评估价值。方法选择2021年1月—2022年1月莆田学院附属医院重症医学科收治的99例脓毒症患者为脓毒症组,另选取莆田学院附属医院重症医学科同时期收治的40例全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)患者为SIRS组,以及莆田学院附属医院体检中心40例健康者为对照组。抽取三组的静脉血样测定血清PCT水平,同时采用ELISA方法检测血清中PCSK9水平,比较三组指标的差异。根据不同病情严重程度将脓毒症组患者分为轻度组、中度组、重度组,比较三组指标的差异。根据不同预后将脓毒症组患者分为预后良好组和预后不良组,比较两组指标的差异。采用Logistic回归分析脓毒症患者病情存在的风险因素,利用受试者工作特征曲线(area under curve,ROC)分析患者各指标,对脓毒症预后进行评估。结果与对照组比较,SIRS组和脓毒症组PCT水平明显高(P<0.05)。与SIRS组比较,脓毒症组PCT水平呈现明显高(P<0.05)。与对照组比较,SIRS组和脓毒症组PCSK9水平均明显高(P<0.05);与SIRS组比较,脓毒症组PCSK9水平明显高(P<0.05)。脓毒症患者血清中PCT联合PCSK9的阳性率分别在不同程度组中呈现逐步升高的态势。与预后良好组对比,预后不良组PCT、PCSK9水平呈现明显升高的趋势。Logistic回归分析结果表明,PCT、PCSK9是脓毒症患者预后独立影响的因素(P<0.05)。脓毒症患者预后风险与血清PCT联合PCSK9水平呈显著性正相关(P<0.05)。PCT与PCSK9预测预后不良的曲线下面积(area under curve,AUC)为0.8288和0.7950,其中PCSK9的特异度、敏感度明显高于90.0%。结论PCT联合PCSK9与脓毒症风险评估之间具有协同性,二者联合用于脓毒症预后的评估具备提高预测的价值。展开更多
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
文摘BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflammation and tissue repair.However,their role in systemic inflammatory response syndrome(SIRS) has been less well studied.This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS.We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group(n=50) and non-SIRS group(/7=35).The SIRS group was divided into MODS group(n=26) and non-MODS group(n=24) by their severity,and survival group(n=35) and non-survival group(n=15) by their prognosis.Another 30 healthy adults served as normal controls.uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay(ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls(P<0.001 and P<0.001).It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients(all P<0.05).However,there was no difference in uPA level between survivors and non-survivors(P>0.05).The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls(P<0.001 and P<0.001).There was a significant elevation of uPAR in sepsis patients,MODS patients and non-survivors as compared with non-sepsis patients,non-MODS patients and survivors respectively(all P<0.05).Plasma uPAR levels were positively correlated with APACHE Ⅱ score(r=0.575,P<0.001) and SOFA score(r=0.349,P=0.013).AUCs for the prediction of SIRS mortality were 0.67 and 0.51,respectively,for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS.
文摘Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes;and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally;VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls;2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;3) corrected estradiol, testosterone and 25-OH Vitamin D;4) returned pulmonary artery systolic pressure (PASP) during exercise to normal;and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.
基金Supported by Italian Ministry of University,No. PRIN-2007Catholic University School of Medicine,No. Linea D1-2009
文摘Inflammation and coagulation constantly influence each other and are constantly in balance.Emerging evidence supports this statement in acute inflammatory diseases,such as sepsis,but it also seems to be very important in chronic inflammatory settings,such as inflammatory bowel disease(IBD).Patients with Crohn's disease and ulcerative colitis have an increased risk of thromboembolic events,and several abnormalities concerning coagulation components occur in the endothelial cells of intestinal vessels,where most severe inflammatory abnormalities occur.The aims of this review are to update and classify the type of coagulation system abnormalities in IBD,and analyze the strict and delicate balance between coagulation and inflammation at the mucosal level.Recent studies on possible therapeutic applications arising from investigations on coagulation abnormalities associated with IBD pathogenesis will also be briefly presented and critically reviewed.
文摘目的探索CX3CR1对创伤性骨髓炎大鼠骨骼肌微纤维、ERK/MAPK信号通路及炎症反应的影响。方法选取30只SPF级SD雄性大鼠,依据随机数字表法分为健康组、模型组、CX3CR1抑制组,每组10只。除健康组外,其余各组均建立创伤性骨髓炎模型。其中健康组、模型组大鼠均每日常规腹腔注射生理盐水,CX3CR1干预组向残腔内注射CX3CR1中和抗体进行处理。采用ELISA法检测血清中IL-6、IL-10、IL-1β、TGF-β水平,应用改良X线Norden评分检测骨骼肌微纤维,HE染色观察病理变化,免疫印迹及PCR检测股骨组织中细胞外信号调节蛋白激酶(Extracellular regulated protein kinase,ERK1/2)、丝裂原活化蛋白激酶(Mitogen activated protein kinase,MAPK)蛋白及mRNA表达。结果与健康组比较,模型组TGF-β、IL-1β、IL-10、IL-6等炎症因子含量均升高(P<0.05);与模型组比较,CX3CR1抑制组炎症因子含量降低(P<0.05)。与健康组比较,模型组随时间推移X线Norden评分升高(P<0.05);与模型组比较,CX3CR1抑制组X线Norden评分降低(P<0.05)。HE染色显示,健康组骨质完好;模型组可见大量炎性细胞浸润、灶性脓肿及坏死灶;CX3CR1抑制组大鼠的骨质明显改善,炎症反应降低。与健康组比较,模型组ERK1/2、MAPK蛋白及mRNA表达升高(P<0.05);与模型组比较,CX3CR1抑制组ERK1/2、MAPK蛋白及mRNA表达降低(P<0.05)。结论抑制CX3CR1可改善创伤性骨髓炎大鼠的疾病反应,可能与降低炎症反应、ERK/MAPK信号通路以及改善骨骼肌微纤维相关。
文摘Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.
文摘In a recent article on World J Clin Cases 2019;7:3859-3865,Sun et al reported a case of 36-year-old female with macrophage activity syndrome as an onset of systemic lupus erythematosus.Although this is a very interesting case,some concerns still need to be addressed.First,the patient had an extremely elevated serum ferritin but a normal C-reactive protein level,which was unparallel with the inflammatory condition before she received any treatments.Second,the diagnosis of systemic lupus erythematosus seemed to be insufficient according to the patient’s medical information presented,most of which were not specific to lupus but could be explained by macrophage activity syndrome.Hence,more medical information on the patient should be provided,and a profound discussion needs to be addressed.
文摘Cardiovascular diseases (CVD) are the leading cause of mortality necessitating its early detection. The emergence of newer subclinical biomarkers in addition to the known cardiometabolic risk factors may play an important role in early detection of CVD risk. In the present study, 74 adult females (30 -?75 y) with metabolic syndrome (MS) were selected and additional biochemical parameters such as C-reactive protein (CRP) and Homocysteine (Hcy) levels were analyzed. The average body mass index (BMI) and waist circumference of subjects were found to be 30 kg/m2 and99 cmrespectively. Mean LDL levels were found to be much higher than normal (139 mg/dl) while the HDL levels were low (41.5 mg/dl). The average fasting blood sugar and insulin levels were within the normal range. However, 40.5% females had serum Hcy levels >13.2 μmol/l and 59.5% women had CRP levels >3 mg/L indicating increased risk of CVD. Higher Hcy levels were associated with hyperinsulinemia (p < 0.01) and hyperglycemia (p < 0.05), indicating predilection for glucose intolerance. CRP levels showed significant negative correlation with HDL (p < 0.05), indicating a predilection for glucose intolerance. The present study reports overall more than 40% MS women are classified as high risk group using the Western standards. Limited data on normal levels of inflammatory biomarkers are available for Asian Indians. The study results indicate the importance of Hcy and CRP values among females having metabolic syndrome, known to be at a high risk of CVD.
文摘Background: Presence of metabolic syndrome (MS) in people with diabetes confers increased cardiovascular and diabetes-specific micro- and macrovascular complications. The pathogenic pathways for metabolic syndrome are still issues for discussion especially in some special groups like those with type 2 diabetes mellitus (T2DM). Recent evidences suggest that inflammation may play a key role in MS. This study assessed the relationship between MS (and its component risks) and markers of inflammation (high-sensitivity C-reactive protein {hs-CRP} and white blood cells {WBC}). Methods: A cross-sectional study involving 108 patients with T2DM. Anthropometric measurements and clinical examination were conducted. Blood sample was collected for hs-CRP, WBC, glycated haemoglobin etc. Metabolic syndrome was defined using the International Diabetes Federation criteria. Ethical approval was granted and informed consent was obtained from participants. Results: Mean age of male and female participants were 58.00 ± 7.01 years and 55.48 ± 8.35 years respectively (p = 0.092). Eighty-two (75.9%) participants had metabolic syndrome. Median values of hs-CRP and total WBC were 0.89mg/L and 5.73 x103/mm3 respectively. On correlation, hs-CRP showed statistically significant association with waist circumference (r = 0.194;p = 0.044), fasting plasma glucose (r = 0.191;p = 0.048) and serum triglycerides (p = 0.226;r = 0.019). There was no statistically significant association between WBC and the metabolic components. Conclusion: Prevalence of metabolic syndrome is high, and C-reactive protein was associated with waist circumference, fasting plasma glucose and serum triglycerides.
基金Supported by National Natural Science Foundation of China,No.81273843 and No.81674073National Key Basic Research Program of China(973 Program)+1 种基金No.2015CB554501Project of Shanghai Municipal Commission of Health and Family Planning,No.20144Y0153 and No.2017BR047
文摘AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.
文摘目的探讨血清降钙素原(procalcitonin,PCT)联合前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)对脓毒症病情严重程度及预后的评估价值。方法选择2021年1月—2022年1月莆田学院附属医院重症医学科收治的99例脓毒症患者为脓毒症组,另选取莆田学院附属医院重症医学科同时期收治的40例全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)患者为SIRS组,以及莆田学院附属医院体检中心40例健康者为对照组。抽取三组的静脉血样测定血清PCT水平,同时采用ELISA方法检测血清中PCSK9水平,比较三组指标的差异。根据不同病情严重程度将脓毒症组患者分为轻度组、中度组、重度组,比较三组指标的差异。根据不同预后将脓毒症组患者分为预后良好组和预后不良组,比较两组指标的差异。采用Logistic回归分析脓毒症患者病情存在的风险因素,利用受试者工作特征曲线(area under curve,ROC)分析患者各指标,对脓毒症预后进行评估。结果与对照组比较,SIRS组和脓毒症组PCT水平明显高(P<0.05)。与SIRS组比较,脓毒症组PCT水平呈现明显高(P<0.05)。与对照组比较,SIRS组和脓毒症组PCSK9水平均明显高(P<0.05);与SIRS组比较,脓毒症组PCSK9水平明显高(P<0.05)。脓毒症患者血清中PCT联合PCSK9的阳性率分别在不同程度组中呈现逐步升高的态势。与预后良好组对比,预后不良组PCT、PCSK9水平呈现明显升高的趋势。Logistic回归分析结果表明,PCT、PCSK9是脓毒症患者预后独立影响的因素(P<0.05)。脓毒症患者预后风险与血清PCT联合PCSK9水平呈显著性正相关(P<0.05)。PCT与PCSK9预测预后不良的曲线下面积(area under curve,AUC)为0.8288和0.7950,其中PCSK9的特异度、敏感度明显高于90.0%。结论PCT联合PCSK9与脓毒症风险评估之间具有协同性,二者联合用于脓毒症预后的评估具备提高预测的价值。
