大鼠烧伤后库普弗细胞在促炎细胞因子产生中的作用

目的　观察大鼠严重烧伤后早期 ,库普弗细胞在肿瘤坏死因子α(TNFα)、白细胞介素(IL) 1β、IL 6产生中的作用。方法　观察 (1)烧伤血清对体外培养的大鼠库普弗细胞分泌TNFα、IL 1β、IL 6的刺激作用 ;(2 )烧伤后大鼠库普弗细胞的细胞因子mRNA表达变化 ;(3)应用库普弗细胞特异性抑制剂三氯化钆后 ,烧伤大鼠血浆内细胞因子含量变化。　结果　烧伤血清能刺激库普弗细胞释放TNFα、IL 1β、IL 6 ;大鼠烧伤后库普弗细胞TNFα、IL 1β、IL 6mRNA表达量显著升高 ;预先抑制库普弗细胞的活性 ,烧伤后血浆TNFα、IL 1β、IL 6水平均显著降低 ,分别为烧伤组的 34.71%、36 99%、33.70 %。结论　库普弗细胞是大鼠烧伤后血浆中TNFα、IL 1β、IL 6的主要来源     

结直肠癌患者手术前后血清中IL-6和NO水平的临床意义

目的探讨结直肠癌患者手术治疗前后血清中IL-6和NO水平变化及其临床意义。方法对40例结直肠癌患者分别采用酶联免疫分析法和化学比色法测定手术前后血清中的IL-6和NO水平,并与10名正常健康人作比较。结果结直肠癌患者手术前血清中IL-6水平高于正常人（P〈0.05）,NO水平明显低于正常人（P〈0.01）;经手术治疗2周后,患者血清IL-6水平较治疗前降低（P〈0.05）,而NO水平明显升高（P〈0.05）。结论结直肠癌患者血清中IL-6和NO水平的变化,对病情和预后判断具有重要的临床意义。     

Glucose intolerance and hepatocellular carcinoma: recent findings for old diseases

In the last years, an increasing number of evidences on the influence of metabolic syndrome on the occurrence of hepatocellular carcinoma (HCC) have been developed. Type 2 mellitus diabetes (T2MD) has been found to increase the occurrence of primary liver tumors and to define a more aggressive carcinogenetic process. Furthermore, several preclinical and observational studies and a recent meta-analysis have shown that anti-diabetic drugs can modify the risk of HCC development in patients with T2DM. However, despite these evidences, underlying molecular mechanisms linking both pathological conditions have to be completely cleared yet. The study published by Gao et al. has found a possible molecular link between the two conditions, describing the predisposition to T2DM and HCC given by the haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) in murine models. The authors have generated Ncoa5+/– (haploinsufficient) male mice and shown that 94% of male mutant mice developed HCC within 18 months of age, this in contrast with Ncoa5+/+ and Ncoa5+/– female mice. These results suggest that NCOA5 haploinsufficiency is linked to HCC development in male mice. Moreover, mutant male mice showed significantly elevated levels of fasting blood glucose and markedly decreased glucose tolerance and insulin sensitivity compared to Ncoa5+/+ littermates. This well-constructed work sheds light on the molecular link between T2DM and HCC and opens the way to further biological and clinical studies in the field of liver tumor prevention and treatment.     

Fibrin Plugging as a Cause of Microcirculatory Occlusion During Photodynamic Therapy

An experimental system that allows the white light observation of rapid changes in vessels without disturbance by red laser light was used. Mice were injected with mono-l-aspartyl chlorin-e-6 (Npe-6) i.v. via the tail vein and were immediately exposed to laser light. White emboli were observed forming on the inside of the vessel walls within seconds after commencement of light exposure. Emboli adhered to vessel walls and caused vascular obstruction. Light microscopy of the exposed material using fibrin staining was performed. Electron microscopy on the same material was also carried out. The embolisation time was influenced by both drug dose and laser power. With low laser power, it took a long time to stop the blood flow. Fibrin staining revealed the white emboli to be composed of fibrin. Electron microscopy findings revealed damage to endothelial cells and platelet aggregation. This study suggests that two main mechanisms (direct cellular damage and vascular shut-down ) might actually be complementary and synergistic in the production of vascular lesions using photodynamic therapy. Paper received 28 February 1998; accepted after revision 8 October 1998.     

C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (C_Cr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus C_Cr r = ?0.40 p < 0.001; IL-6 versus C_Cr r = ?0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a C_Cr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a C_Cr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0.5 g/dL). CRP and serum albumin were not significantly related (r = 0.17). CRP and IL-6 correlated positively with ESR (r = 0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation – even in the predialysis phase of renal failure – of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

急性胰腺炎合并肝损伤时IL-6、氧自由基变化及IL-2、川芎嗪干预的实验研究

目的：探讨IL－6、氧自由基在急性胰腺炎（acute pancreatitis，AP）合并肝损伤中的作用，及重组人白介素－2（IL－2）、川芎嗪的治疗价值。方法：SD大鼠112只，随机分为14只，每组8只，5％牛磺胆酸钠逆行胰胆管内注射诱发大鼠AP动物模型，检测血浆IL－6、SOD、MDA、ALT、AST、LDH、LIP、AMY，并观察肝、胰病理变化。结果；①AP组血浆AMY、LIP、ALT、AST、LDH明显升高（P＜0．05或0．01），镜下可见胰腺水肿、炎细胞浸润、坏死1肝脏肝窦充血、细胞浊肝及坏死，且损伤程度随时限延长而加重；②AP各组血浆IL－6明显升同（P＜0．01）；③AP各组MDA明显高（P＜0．01）、SOD明显降低（P＜0．01）。④IL－2治疗组、川芎嗪治疗组有IL－2、川芎嗪联合且与NS组比较血浆IL－6、MDA水平明显下降（P＜0．05），SOD明显升高（P＜0．05），胰、肝病理损害程度减轻，并且AMY、LIP、ALT、AST、LDH均明显降低（P＜0．05），平均存活时间明显延长（P＜0．05）；联合应用组降低IL－6、MDSA水平和减轻胰腺坏死优于单药组。结论：①IL－6、氧自由基在急性胰腺炎合并肝损伤程度和明显升同，起损伤作用，而SOD明显降低，其保护作用减弱。检测血浆IL－6、MDA、SOD可作为判断AP合并肝脏损伤程度和预后的指标；②大鼠急性胰腺合并肝损伤过程中应用IL－2、川芎嗪显示出良好的效果，联合应用于亿于这两药的单独应用。     

Effect of interleukin 6 on basal and FSH-stimulated secretion of estradiol and progesterone by human granulosa cells in vitro

Aim: To determine the effects of interleukin-6 (IL-6) on the secretion ofestradiol and progesterone by human granulosa cells in vitro. Methods:Granulosa cells were obtained from infertile patients undergoing IVF ETtreatment and cultured with serum-free supplemented HAM's F10 medium.In the absence or presence of FSH, granulosa cells were treated with differ-ent concentrations of gene recombinant human iterlukin-6 (rhIL-6). Themedia were collected after 24, 48, 72 and 96 h and assayed for estradiol andprogesterone. IL-6 and R mRNA was determined by means of RNA slotblot. Results: IL-6 had a significant inhibitory effect on estradiol secre-tion, especially in the presence of FSH. IL-6 inhibited the FSH-stimulatedprogesterone secretion, but not the basal progesterone release. The inhibi-tion shows certain degrees of dose- and time-dependency. Conclusion:IL-6 participates in the regulation of ovarian function through its inhibitoryeffect on FSH-stimulated steroidogenesis by granulosa cells.     

m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor

BackgroundN6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT.MethodsWe collected TGCT patients’ information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles ({"type":"entrez-geo","attrs":{"text":"GSE3218","term_id":"3218"}}GSE3218 and {"type":"entrez-geo","attrs":{"text":"GSE10783","term_id":"10783"}}GSE10783) as an independent external validation cohort.ResultsDistinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles ({"type":"entrez-geo","attrs":{"text":"GSE3218","term_id":"3218"}}GSE3218 and {"type":"entrez-geo","attrs":{"text":"GSE10783","term_id":"10783"}}GSE10783).ConclusionsBased on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.     

The prevalence of voiding difficulty after TVT,its impact on quality of life,and related risk factors

Objective: To determine the prevalence of voiding difficulty (VD), quality of life, and related risk factors after tension-free vaginal tape (TVT). Design: Prospective cohort study in 703 women with a TVT procedure for stress urinary incontinence. Main outcome measures: VD stated by women, Urogenital Distress Inventory (UDI-6) question 5 (difficulty in emptying the bladder), maximum flow rate, postvoid residual urine, necessity of postoperative catheterization, tape division, and impact on quality of life (Incontinence Impact Questionnaire, IIQ-7). Results: Postoperative catheterization (>24 h) was necessary in 11% and tape division in 1.3% of patients. There were 26% of women who stated VD and 25% reported moderate to great impairment on the UDI-6 after 36 months. While the negative impact on the outcome of TVT in women with abnormal voiding compared to women without is higher, the impact decreased significantly after TVT, implying a considerable improvement in quality of life. Pre-operative existing voiding difficulty and concomitant prolapse surgery were independent risk factors. Conclusions: Symptoms of VD occurred after TVT and caused lesser improvement in quality of life.     

Kelfiprim,a new sulpha-trimethoprim combination,versus cotrimoxazole,in the treatment of urinary tract infections: A multicentre,double-blind trial

Summary A new combination of trimethoprim with a sulphonamide, named Kelfiprim, differs from cotrimoxazole in that: a) the sulpha drug is sulphamethopyrazine instead of sulphamethoxazole; b) the trimethoprim to sulpha ratio is 5:4 instead of 1:5;c) the presence of a long-acting sulphonamide allows the administration of a daily dose of one capsule, following an initial loading dose of two capsules; d) a reduced amount of trimethoprim is given, as compared to cotrimoxazole, without any decrease of efficacy. Kelfiprim [KP] was compared to contrimoxazole [Co] in a multicentre double blind trial. Sixty four patients suffering from acute and chronic infections of the upper and lower urinary tract entered the study. Urine sterilisation and clinical improvement without relapses showed no differences from the two treatment groups. Tolerance was excellent except in two patients, one treated with KP and the other treated with Co, who showed a transient exanthema.     

Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice

Background

Perioperative neurocognitive disorders (PND) result in long-term morbidity and mortality with no effective interventions available. Because interleukin-6 (IL-6), a pro-inflammatory cytokine, is consistently up-regulated by trauma, including after surgery, we determined whether IL-6 is a putative therapeutic target for PND in a mouse model.

Novel mutations in response to vitamin B6 in primary hyperoxaluria type 1 after only kidney transplantation: a case report

Recently, the mainstream curative treatment for primary hyperoxaluria type 1 (PH1) is combined liver and kidney transplantation, and only kidney transplantation is considered ineffective for most PH1 patients. Furthermore, vitamin B6 (B6) is the only permitted drug available for treatment. However, except for specific mutations such as G170R and F152I in gene AGXT, data of B6 effect on other mutations are lacking. Insufficient research has evaluated the efficacy of the combination of kidney transplantation and B6 treatment in the therapeutic strategy in PH1 patients. Here, we report a case of a 52-year-old male with frequent stone events and end-stage renal diseases (ESRD), and subsequently undergone kidney transplantation. Sudden rising of serum creatinine within two months after the transplantation. After gene sequencing, the mutations of A186V, R197Q, and I340M were presented in gene AGXT. Therefore, the patient was diagnosed with PH1. B6 administration was attempted during the period of waiting for liver transplantation. Four-week oral B6 therapy (50 mg tid) reduced the serum creatinine of the patient from 194 to 145 µmol/L, which revealed that the patient probably responded to B6 treatment. At the almost three-year follow-up, the patient’s serum creatinine remained reduced (130 µmol/L), without urinary oxalate excretion. In this case, we established a positive effect, even a beneficial result, of the use of B6 as a retrospective therapeutic choice in PH1 treatment after kidney transplantation.     

IL-6对人精子顶体反应影响机制的初步探讨

目的:探讨IL-6对人精子顶体反应(AR)的影响机制。方法:采用BAEE/ADH法测定精子顶体酶的活性,以及通过FITC-PSA法检测精子顶体反应。结果:IL-6可诱导精子顶体酶及超氧化物歧化酶(SOD)的活性,促进精子顶体反应;胞外Ca2+单独不能诱导精子顶体反应,且没有胞外Ca2+的参与,IL-6也不能诱导精子顶体反应;蛋白激酶C(PKC)抑制剂calphC能逆转IL-6诱导的精子顶体反应。结论:IL-6对精子顶体反应有一定的促进作用,可能通过诱导精子的顶体酶和SOD活性等途径来实现,在此作用中,也涉及了PKC的激活,且还需要外源性Ca2+的参与。