Evaluation of nitric oxide and homocysteine levels in primary dysmenorrheal women in Taiwan

In this study, we investigated the possible pathophysiological mechanisms in primary dysmenorrhea. The study was undertaken to determine the effect of homocysteine on the nitric oxide (NO) pathway in primary dysmenorrheal women. A total of 94 students from a local nursing college participated. Group 1 consisted of 51 normal subjects with no dysmenorrhea. Group 2 had 43 subjects with dysmenorrheal symptoms. Our results show that serum NO levels in group 2 are higher than those in group 1. However, the serum homocysteine level was lower in group 2. These observations indicate that the NO pathway is involved in the pathophysiological mechanism responsible for the damaging effects of homocysteine on dysmenorrheal women.     

Circulating proinflammatory cytokines and N-terminal pro-brain natriuretic peptide significantly decrease with recovery of left ventricular function in patients with dilated cardiomyopathy

Background Increased levels of TNF-α, IL-6, their soluble receptors, and NT-proBNP have been observed in patients with dilated cardiomyopathy (DCM). In the present study, we assessed the possible involvement of proinflammatory cytokines and their soluble receptors with and without recovery of LV function in DCM patients. Methods and results Forty patients with DCM were enrolled and divided into two groups: Group I consisted of DCM patients (n = 30) whose left ventricular ejection fraction (LVEF) had not recovered on follow up and Group II comprised DCM patients (n = 10) whose LVEF had recovered. Ten healthy subjects were included as controls (Group III). TNF-α, IL-6,TNFR1, TNFRII, gp130, and NT-proBNP levels were significantly increased in Group I and were significantly lower in patients with LVEF recovery as compared to those without recovery of LVEF (P < 0.05). Conclusion Circulating TNF-α, IL-6, and NT-proBNP appear to correlate with the LV function recovery of patients with DCM and could be used as prognostic biomarkers.     

血清vaspin、IL-6水平对急性心肌梗死后左室重构的评估价值

目的:观察冠脉介入治疗的急性心肌梗死(AMI)患者的左室重构与血清脂肪特异性丝氨酸蛋白酶抑制剂(vaspin)和白介素-6(IL-6)水平的相关性。方法:入选的研究对象(50例)均来自于2018年9月～2019年6月就诊于同济大学附属普陀人民医院且被诊断为AMI的住院患者,患者均经早期经皮冠脉介入(PCI)治疗,术后规范药物治疗。采用酶联免疫吸附实验(ELISA)测定50例患者发病后1天、7天、30天的血清vaspin和IL-6水平并行超声心动图检查。同时以50例健康体健者作为对照组。比较两组间血清vaspin、IL-6水平的差异,观察AMI后血清vaspin、IL-6水平的变化趋势及其与左室重构的指标包括左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)的相关性。结果:(1)对照组血清vaspin水平为6.03±1.18 ng/mL,AMI组血清vaspin水平4.22±1.37 ng/mL,AMI组血清vaspin水平明显低于对照组(P0.05),且AMI后1月内血清vaspin水平逐渐降低(P0.05);对照组血清IL-6水平为12.04±3.97 ng/mL,AMI组血清IL-6水平为26.72±10.06 ng/mL,AMI组患者血清IL-6水平明显高于对照组(P0.05),且AMI后1月内血清IL-6水平逐渐升高(P0.05);(2)经相关性分析显示:AMI后1天、7天、30天血清vaspin水平与LVEDD、LVESD均呈负相关(P0.05),血清IL-6水平与LVEDD、LVESD均呈正相关(P0.05),血清vaspin水平与IL-6水平均呈负相关(P0.001)。结论:急性心肌梗死后早期,左室重构的进展伴随着血清vaspin的降低与IL-6的升高,临床上应监测两种指标的变化,对左室重构早期干预,预防心力衰竭的发生。     

经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清MMP-3、TIMP-1、IL-6及疗效的影响

目的:探讨经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶抑制因子-1(TIMP-1)、白细胞介素-6(IL-6)及疗效的影响。方法:选择60例2016年10月到2017年3月我院接诊的老年骨质疏松性胸腰椎压缩骨折患者,依照随机数表法分为实验组和对照组,每组30例,在都给予常规药物治疗的基础上,对照组给予复位枕垫和康复训练治疗,实验组采用经皮椎体成形术治疗。结果:治疗前,两组血清MMP-3、TIMP-1、IL-6水平无差异(P0.05);治疗后,两组血清MMP-3、IL-6水平均降低,实验组下降幅度更大,两组血清TIMP-1水平均升高,实验组上升幅度更大(P0.05);治疗前,两组患者VAS评分无差异(P0.05),治疗1周及治疗后,实验组患者VAS评分均低于对照组(P0.05);治疗前,两组患者Cobb角无差异(P0.05),治疗后,两组患者Cobb均明显下降,实验组较对照组下降更大(P0.05);治疗前,两组患者伤椎高度比无差异(P0.05),治疗后,两组伤椎高度比明显下降,实验组低于对照组(P0.05);治疗后,实验组有效率96.67%大于对照组的76.67%,差异显著(P0.05)。结论:经皮椎体成形术能有效降低患者血清MMP-3、IL-6水平,恢复TIMP-1水平,能显著提高治疗老年骨质疏松性胸腰椎压缩骨折的疗效     

Decreased Interleukin-10 Responses in Children with Severe Mycoplasma pneumoniae Pneumonia

Several cytokines may play roles in the immunological pathogenesis of mycoplasmal pneumonia caused by Mycoplasma pneumoniae. In this study, we investigated serum cytokine profiles in children with mycoplasmal pneumonia. The serum levels of interleukin (IL)-8, IL-10, and IL-18 were examined using ELISA kits in 34 patients with M. pneumoniae infection (Group 1, 11 with severe mycoplasmal pneumonia; Group 2, 13 with mild mycoplasmal pneumonia; Group 3, 10 with asthma) and 32 age-matched, non-infected controls. The serum levels of IL-8, IL-10, and IL-18 increased significantly in patients with mycoplasmal pneumonia compared with those in controls (P<0.01). The serum levels of IL-10 decreased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-18 increased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-10 and IL-18 decreased significantly in 10 M. pneumoniae-infected patients with asthma compared with those in 24 M. pneumoniae-infected patients without asthma (P<0.01). We examined the level of interleukins (IL-8, IL-10 and IL-18) after the patients started therapy. The data showed that IL-18 were lower after therapy (P<0.01). Collectively, our data suggested that these cytokines may be involved in the pathogenesis of mycoplasmal pneumonia.     

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy

Objective

Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.

Methods

Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).

Results

Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).

Conclusion

These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.     

脐带间充质干细胞对内毒素血症诱发的大鼠急性肝功能损伤的影响

目的评价脐带间充质干细胞（hUC-MSCs）对内毒素血症诱发的大鼠急性肝功能损伤的影响及其与凋亡机制的关系。 方法6周龄雄性SD大鼠18只,随机分为3组,分别是对照组（C组）、内毒素血症组（M组）和内毒素血症+hUC-MSCs治疗组（M+cells组）,每组6只。大鼠腹腔注射5 mg/kg脂多糖（LPS）诱导内毒素血症模型,并经尾静脉注射含20×10⁶个hUC- MSCs。4 h时检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）,ELISA方法检测肿瘤坏死因子（TNF-α）、白细胞介素6（IL-6）,HE常规染色鉴定肝脏组织病理,Western Blot法检测肝脏组织抗凋亡蛋白Bcl-2、促凋亡蛋白Bax、凋亡信号调节激酶1（ASK1）、应激活化蛋白激酶即JUN氨基末端激酶（JNK）蛋白的表达。多组间比较采用单因素方差分析,相关分析选用pearson。 结果（1）C组AST、ALT、TNF-α和IL-6浓度分别为（74.66±6.39）U/ L、（40.07±6.07）U/ L、（37.74±3.08）ng/L和（0.42±0.07）ng/L;与M组比较（310.75±9.13）U/L、（107.04±10.04）U/ L、（160.32±4.88）ng/L和（0.90±0.09）ng/L,差异具有统计学意义（P均 < 0.05）,M组AST、ALT、TNF-α、IL-6浓度分别为（310.75±9.13）U/L、（107.04±10.04）U/ L、（160.32±4.88）ng/ L和（0.90±0.09）ng/L,与M+cells组比较（204.49±15.36）U/L、（71.24± 7.34）U/ L、（117.61±9.37）ng/ L和（0.60±0.10）ng/L,差异具有统计学意义（P均 < 0.05）。（2）C组大鼠肝细胞形态正常,可见肝小叶结构清晰,肝汇管区无炎性细胞浸润,M组大鼠肝小叶散在点状坏死肝细胞伴炎性浸润,肝细胞间隙散布增生的Kuffer细胞,M+cells组大鼠肝小叶炎性细胞浸润及肝细胞间隙Kuffer细胞浸润改善。（3）与C组比较,M组大鼠肝脏组织JUN、ASK1和Bax蛋白表达均增高（P均 < 0.05）,Bcl-2蛋白表达降低（P < 0.05）;与M组比较,M+cells组大鼠肝脏组织JUN、ASK1和Bax蛋白表达降低（P均 < 0.05）,Bcl-2蛋白增加（P < 0.05）。（4）单因素相关分析显示大鼠血清ALT、AST与TNF-a指数呈正相关（r值分别为0.9580、0.9865,P均< 0.05）,大鼠血清ALT、AST与IL-6指数呈正相关（r值分别为0.9892、0.9630,P均 < 0.05）,大鼠血清ALT、AST分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9993、0.9851、0.7901、0.9864、0.9557、0.7128,P均 < 0.05）,大鼠血清ALT、AST分别与BCL-2指数均呈负相关（r值分别为-0.8824、-0.9338,P均 < 0.05）,大鼠血清TNF-α分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9466、0.8958、0.6025,P均< 0.05）,大鼠血清TNF-α与BCL-2指数呈负相关（r = -0.6025,P均 < 0.05）,大鼠血清IL-6分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9941、0.9997、0.8679,P均< 0.05）,大鼠血清IL-6与BCL-2指数呈负相关（r = -0.8078,P均 < 0.05）。 结论hUC-MSCs具有减轻内毒素血症大鼠急性肝功能损伤的作用,其机制与抑制肝脏细胞凋亡相关。     

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.     

Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6

Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.     

The involvement of IL-6 and IL-8 in acute invasive gastroenteritis of children

The involvement of the proinflammatory cytokines, interleukin 8 (IL-8) and 6 (IL-6), was studied during the first 72 h of acute invasive gastroenteritis. Study population included 33 infants and young children aged six months to six years and seven age-matched controls. As a group, patients with acute invasive gastroenteritis had an increased serum level of IL-8 and IL-6 as compared with healthy controls (p < 0.002 and p < 0.001, respectively). Subjects were then divided into two groups based on stool cultures (proven and non-proven bacterial cultures). Patients with bacterial-proven acute invasive gastroenteritis tended to have increased IL-8 serum concentrations (p < 0.07) as compared with those with non-proven bacterial etiologies and IL-6 levels were only detected in subjects with positive bacterial cultures (p < 0.05). When dividing each sub-group into early and late blood drawing with respect to disease onset, no statistical differences were found in each group but subjects with bacterial-proven etiologies had significant higher IL-6 levels as compared with non-proven etiologies at the two time points (p < 0.019 and p < 0.015, respectively).In conclusion, the proinflammatory cytokines, IL-6 and IL-8, are involved in acute invasive gastroenteritis. The difference in IL-6, and to a lesser degree IL-8, between proven and non-proven bacterial etiologies, needs further investigation.     

人羊膜上皮干细胞联合富血小板血浆对宫腔粘连大鼠纤维化因子、炎症因子的作用

摘要 目的：探究人羊膜上皮干细胞（hAECs）联合富血小板血浆（PRP）对宫腔粘连大鼠的治疗效果,为临床中优化宫腔粘连治疗方法理论基础。方法：选用SPF级雌性SD大鼠共40只,依照随机数字表法随机分为空白组（A组）、假手术组（B组）、hAECs组（C组）、PRP组（D组）、hAECs+PRP组（E组）,每组各8只。A组不做任何处理,B组仅做麻醉、开关腹腔处理,C组、D组、E组使用搔刮法制备宫腔粘连模型。随后C组进行hAECs治疗,D组注射等量生理盐水。D组进行PRP治疗,C组注射等量生理盐水。E组进行hAECs联合PRP治疗。观察比较两组大鼠子宫内膜组织基质金属蛋白酶-9（MMP-9）、盘状结构域受体2（DDR2）蛋白表达水平、PI3K/Akt/mTOR通路相关mRNA表达量、血清白细胞介素-6（IL-6）、白细胞介素-8（IL-8）水平以及各组大鼠妊娠孕囊数量比较。结果：与A组相比,B组的子宫内膜组织MMP-9、DDR2蛋白表达水平、p-mTOR mRNA、p-Akt mRNA水平以及血清IL-6、IL-8水平比较无差异（P＞0.05）;C组、D组、E组大鼠的子宫内膜组织MMP-9、DDR2蛋白表达水平明显下降,IL-6、IL-8水平、p-mTOR mRNA、p-Akt mRNA表达升高（P＜0.05）。其中,E组大鼠MMP-9、DDR2蛋白表达水平明显高于C组、D组,IL-6、IL-8水平及p-mTOR mRNA、p-Akt mRNA表达低于C组、D组（P＜0.05）。C组、D组大鼠MMP-9、DDR2蛋白表达水平、血清IL-6、IL-8水平及p-mTOR mRNA、p-Akt mRNA表达比较（P＞0.05）。妊娠孕囊数量方面,与A组比较,B组大鼠妊娠孕囊数量。结论：hAECs联合PRP治疗可能通过上调宫腔粘连大鼠子宫内膜组织MMP-9、DDR2蛋白表达水平并下调p-mTOR mRNA、p-Akt mRNA表达,同时降低炎性因子IL-6、IL-8水平,进而提高妊娠孕囊数量,起到治疗作用。     

In situ profiling of adipokines in subcutaneous microdialysates from lean and obese individuals

Adipose tissue (AT) had emerged as an endocrine organ and a key regulator of the metabolically triggered inflammation. The aims of this study were 1) to investigate the usefulness of a multiplexed bioassay in characterizing a panel of adipokines in subcutaneous (sc) microdialysate samples and 2) to determine whether lean and obese individuals differ in their interstitial adipokines levels following microdialysis (MD) probe insertion. Ultrafiltrating MD membranes were inserted in opposite sites of the sc abdominal AT of six lean (L) and six obese (OB) males at the beginning (M1) and during the last 120 min (M2) of the study. Interstitial and serum concentrations of adipokines were quantified using the Luminex technique and ELISA at 60-min intervals for 5 h. In comparison with L subjects, OB subjects exhibited elevated interstitial leptin (P < 0.001), IL-8 (P < 0.05), and IL-18 levels (P = 0.05), as well as higher serum concentrations of leptin (P < 0.0001), IL-6 (P < 0.0001), tumor necrosis factor-alpha (P < 0.001), IL-8 (P = 0.01) and interferon-gamma-inducible protein 10 (P < 0.05). In samples from the M1 membranes, leptin decreased and IL-1alpha, IL-18, and RANTES (regulated on activation, normal T-cell expressed and secreted) remained relatively stable, whereas IL-6, IL-8, and monocyte chemoattractant protein-1 significantly increased after the first hour (P < 0.0001 vs. baseline). Notably, either the magnitude of increase from the initial values or the time pattern of all the adipokines in M1 and M2 dialysates were similar between the groups. In conclusion, the current work provides valuable information on the optimal time frame to collect in situ AT microdialysate samples. Further studies are needed, however, to unravel the intricate interplay of cytokines in AT interstitial fluid.     

血清IL-6、miR-17-5p水平与卵巢癌患者化疗后生存期的相关性分析

目的:分析血清白细胞介素-6(IL-6)、微小RNA-17-5p(miR-17-5p)水平与卵巢癌患者化疗后生存期的相关性。方法:选取行手术治疗联合术后化疗的65例卵巢癌患者作为病例组,选取50名健康体检者作为对照组,选取50例良性卵巢疾病患者作为良性疾病组,对病例组患者术前及术后14d的血清IL-6、miR-17-5p水平进行检测和比较,对良性疾病组和对照组研究对象的血清IL-6、miR-17-5p水平进行检测和比较,对病例组患者进行随访,对其总生存期(OS)和无疾病进展生存期(PFS)进行观察和比较。结果:病例组患者血清IL-6、miR-17-5p表达水平显著高于良性疾病组,良性疾病组患者的血清IL-6、miR-17-5p表达水平显著高于对照组,各组之间的差异均有统计学意义(P0.05)。病例组患者术后14d血清IL-6、miR-17-5p表达水平较手术前显著下降,差异均有统计学意义(P0.05)。血清IL-6、miR-17-5p高表达的卵巢癌患者中TNM分期为Ⅲ~Ⅳ期的比例较高,差异均有统计学意义(P0.05)。血清IL-6、miR-17-5p高表达卵巢癌患者的OS和PFS明显短于血清IL-6、miR-17-5p低表达患者,差异均有统计学意义(P0.05)。血清IL-6和miR-17-5p同时呈现低表达的卵巢癌患者的OS和PFS水平最高,血清IL-6或miR-17-5p其中之一呈现高表达卵巢癌患者的OS和PFS水平居中,而血清IL-6和miR-17-5p同时呈现高表达的OS和PFS水平最低,差异均有统计学意义(P0.05)。结论:卵巢癌患者可表现为血清IL-6、miR-17-5p水平的显著升高,在手术治疗后,其水平会出现下降,术前较高的血清IL-6、miR-17-5p表达水平与较短的生存期和不良预后具有关联性,可作为预测患者预后的辅助指标。     

后路椎体间融合术与经椎间孔入路腰椎融合术治疗退行性腰椎滑脱症的疗效对比及对AGEs、IL-6的影响

摘要 目的：探讨后路椎体间融合术与经椎间孔入路腰椎融合术治疗退行性腰椎滑脱症的疗效对比及对晚期糖基化终末产物（AGEs）、白细胞介素6（IL-6）的影响。方法：选择2019年1月-2019年12月在我院接受治疗的100例退行性腰椎滑脱症患者,根据手术选择方式分为观察组（n=51）和对照组（n=49）。对照组给予后路椎体间融合术(PLIF)治疗,观察组给予经椎间孔入路腰椎融合术(TLIF)治疗。比较两组患者的临床优良率、血清AGEs、IL-6、手术情况、视觉模拟评分（AVS）、Oswestry功能障碍指数（ODI）评分变化情况及并发症发生情况。结果：治疗后,两组总优良率分别为90.20%,71.43%,差异显著（P<0.05）;观察组手术时间、术中出血量、术后引流量及卧床时间均显著低于对照组,差异显著（P<0.05）;治疗前,两组血清AGEs、IL-6水平无明显差异;治疗后,两组血清AGEs水平均显著降低,且观察组低于对照组,IL-6水平显著上升,观察组低于对照组（P<0.05）;治疗前,两组AVS、ODI评分水平无明显差异;治疗后,两组AVS、ODI评分水平均显著降低,且观察组低于对照组（P<0.05）;两组并发症总发生率为3.92%、18.37%,差异具有统计学意义（P<0.05）。结论：在退行性腰椎滑脱症患者中应用经椎间孔入路腰椎融合术临床效果更好,术后AGEs、IL-6水平更低,且并发症较少。     

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.     

Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications

Background

Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF).

Methods

A total of 197 subjects (64 normal glucose tolerance (NGT) subjects, 97 T1DM subjects without MVC and 36 with MVC) were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.

Results

Compared to NGT, T1DM subjects (both with and without MVC) had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05). No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC.

Conclusions

Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.     

Associations of galectin-3 expression and LGALS-3 (rs4652) gene variant with coronary artery disease risk in diabetics

BackgroundGalectin-3 protein encoded by lectin galactoside-binding soluble-3 (LGALS-3) gene is an important genetic factor in type 2 diabetes mellitus (T2DM) and its cardiovascular obstacles in various populations. We aimed to elicit the pro-inflammatory effect of galectin-3 as determined by interleukin-6 (IL-6) serum levels and to explore the relationship between galectin-3 (LGALS-3 rs4652) gene variant and its expression levels with coronary artery disease (CAD) risk among T2DM Egyptian patients.Methods112 lean subjects were compared to 100 T2DM without CAD and 84 T2DM with CAD. A tetra-primer amplification refractory mutation system polymerase chain reaction was used to test LGALS-3 (rs4652), and galectin3 expression was tested with a quantitative real-time polymerase chain reaction. Serum IL-6 was measured using an enzyme-linked immunosorbent assay.ResultsWe found that the prevalence of LGALS-3 (rs4652) AC genotype and galectin-3 gene expression levels in T2DM with CAD were significantly higher than the additional 2 groups and were correlated positively to IL-6 circulating levels. Also, the C allele carriers (AC+CC) had significantly higher relative Galectin-3 expression levels compared to the A allele carriers (AA).ConclusionsWe concluded that galectin-3 expression levels and LGALS-3 (rs4652) AC genotype were coronary artery disease risk factors in people with type two diabetes among an Egyptian sample.     

贺斯-平衡液为稀释剂的急性等容血液稀释对家兔IL-1、TNF-α等细胞因子的影响

目的：评价贺斯-平衡液为稀释剂的急性等容血液稀释（ANH）对家兔血清IL-1、IL-2、IL-6和TNF-α等细胞因子含量的影响,为临床应用提供理论依据。方法：选择20只健康成年家兔,随机分为两组（n=10）：C组为对照组、H组为贺斯组;实验家兔麻醉后行气管切开、高频喷射通气,游离股动脉、股静脉;C组不进行血液稀释;H组在股动脉放血的同时经股静脉输入2倍放血量的稀释液：6％贺斯＋复方乳酸钠溶液,晶／胶为2：1,放血量V=TBV×（HoHf）／Hav,所放血液于放血后60～120min回输。分别在放血前（T0）,放血后30min（T1）、60min（t2）、120min（T3）和24h（T4）取静脉血检测Hb、Hct和血清IL-1、IL-2、IL-6和TNF-α的浓度。结果：H组在ANH后从一时点开始血清IL-1、IL-2、IL-6和TNF-α均有增加,T3达高峰,T4开始回落;T1、T2、T3和T4时点与C组间比较差别显著（P〈0．01）;与ANH前自身对照差别显著（P〈0．01）;C组在各时间点的血清IL-1、IL-2、IL-6和TNF-α含量变化差别不显著。结论：贺斯-平衡液为稀释剂的急性等容血液稀释（ANH）对家兔血清IL-1、IL-2、IL-6和TNF-α等免疫性细胞因子浓度有上调作用;可引起机体强度不大、作用时间较短的良性应激反应,对机体免疫功能有增强作用。     

戊酸雌二醇联合甲羟孕酮治疗子宫内膜异位症的疗效及对血清CA125、CA199、VEGF水平的影响

目的:探讨戊酸雌二醇联合甲羟孕酮治疗子宫内膜异位症的疗效及对血清糖类抗原125(CA125)、糖类抗原199(CA199)、血管内皮生长因子(VEGF)水平的影响。方法:选择本院2016年6月～2018年1月收治的134例子宫内膜异位症患者,按随机数字表法分为对照组(n=76)和观察组(n=58),对照组采用甲羟孕酮治疗,观察组在对照组基础上联合戊酸雌二醇治疗,比较两组临床疗效,治疗前后血清CA125、CA199、VEGF水平,囊肿直径、月经不调评分、痛经评分和不良反应发生情况。结果:观察组总有效率高于对照组,差异有统计学意义(P0.05)。治疗前,两组血清CA125、CA199、VEGF水平,囊肿直径、月经不调评分、痛经评分比较差异无统计学意义(P0.05);治疗后,两组血清CA125、CA199、VEGF水平、囊肿直径、月经不调评分及痛经评分均下降,观察组低于对照组,差异有统计学意义(P0.05)。两组均有乏力、失眠及潮热发生,组间总副反应发生率差异无统计学意义(P0.05)。结论:戊酸雌二醇联合甲羟孕酮能够提高子宫内膜异位症的疗效,有效降低血清CA125、CA199及VEGF水平,安全性较高。