甲状腺良性结节L-T4抑制性治疗的研究

目的评价L-T4抑制性治疗良性甲状腺结节的疗效、量效关系、疗效影响因素及不良反应等。方法以2007.1-2009.9上海交通大学医学院附属第一人民医院住院患者完成甲状腺细针穿刺细胞学检查诊断为良性结节的450例患者为研究对象,分为L-T4抑制性治疗组和对照组。分别于治疗后3、6、9、12月时随诊甲状腺功能和超声结节大小的变化、计算有效率(最大结节容积缩小≥50%)、不良反应发生率。将随访至12月份时治疗组患者分为有效组、无效组,比较两组相关参数差异。结果治疗组在治疗3、6、9、12月时治疗有效率分别为9.9%、28.8%、46.5%、48.3%,而对照组除3月时有3例(4.3%)患者出现最大结节容积缩小≥50%。有效组与无效组比较显示TSH被抑制水平较低(<0.43mIU/L)、结节含大量胶质、基线结节容积较小(<0.53 ml)患者治疗效果较好,而病理上皮细胞为主,B超提示结节钙化者治疗效果欠佳。以上指标两组差异有统计学意义(P<0.05)。结论L-T4抑制性治疗良性甲状腺结节是可选择的有效的方法,但年龄较大患者易发生心悸、失眠等不良反应。TSH抑制值、基线结节容积大小、结节有无钙化、是否含大量胶质、病理是否以上皮细胞为主影响L-T4抑制性治疗的有效性。

L-T_4对良性甲状腺结节的抑制性治疗

良性甲状腺结节是临床常见的内分泌疾病,临床上对甲状腺良性结节的主要治疗方法是左旋甲状腺素(L-T4)抑制性治疗,但目前对于L-T4抑制性治疗还存在着很多争议,如L-T4抑制性治疗的疗效,L-T4的应用指征和促甲状腺激素的抑制程度与L-T4治疗效果等.近年来的临床研究结果显示,L-T4抑制性治疗能显著抑制良性甲状腺结节的生长,将促甲状腺激素水平维持在0.1～0.3 IU/L疗程维持在12个月左右即能达到理想的治疗效果,且长期应用可能对心血管和骨骼系统产生影响.

左旋甲状腺素抑制性治疗对良性甲状腺结节的影响

目的:探讨左旋甲状腺素抑制性治疗对良性甲状腺结节患者结节直径与疗效的影响。方法:随机选取河源市源城区上城社区卫生服务中心2015年5月至2017年5月收治治疗的良性甲状腺结节患者共80例,按治疗方式不同,将患者分为观察组和对照组两组,每组患者40例。观察组患者主要使用左旋甲状腺素片(L–T4)药物加以治疗,对照组患者在治疗的时候,不服用药物,对两组患者随访观察,对比两组患者的甲状腺体积及结节变化情况。结果:治疗前两组甲状腺结节体积和直径比较差异无统计学意义;治疗后6个月、12个月、24个月观察组甲状腺结节体积和直径均低于对照组,差异具有统计学意义(P <0.05)。结论:左旋甲状激素抑制疗法在对甲状腺单结节良性疾病患者加以治疗的时候,其治疗效果更加显著,对患者的结节直径具有减小的作用,同时也能够有效提升患者治疗依从性,这一治疗方式值得临床应用。

左旋甲状腺素对良性多发性甲状腺结节的抑制性治疗

本研究对121例良性、多发性甲状腺结节患者进行为期6个月的左旋甲状腺素(L-T4)抑制性治疗。结果显示,L-T4抑制性治疗能有效和安全地抑制良性、多发性甲状腺结节的生长。

分化型甲状腺癌术后促甲状腺激素抑制性治疗进展

甲状腺切除是治疗各种甲状腺良、恶性疾病的主要外科手段。左旋甲状腺素（1evothyroxine，L—T4）作为一种激素治疗的药物对于甲状腺疾病特别是分化型甲状腺癌（DTC）术后所致的功能减退及降低疾病复发率至关重要。然而，药物的吸收模式、正确的药物治疗剂量及个体化的治疗方案设定仍存在很大争议。如何合理制定促甲状腺激素的抑制治疗已成为目前DTC术后讨论的焦点。

采用0.75%甲硝唑阴道凝胶抑制性抗菌疗法预防复发性细菌性阴道病

Objective: Efficacy study of suppressive vaginal metronidazolein reducing recurrent symptomatic episodes of bacterial vaginosis.Study design: Multicenter prospective study with initial 10- day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Results: Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2% ) responded clinically and were randomly assigned.During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5% ) receiving metronidazole and 26 (59.1% ) receiving placebo (MITT analysis, relative risk [RR]- 0.43, 95% CI = 0.25- 0.73, P = .001). During the entire 28- week follow- up, recurrence occurred in 26 (51.0% ) on treatment compared with 33 (75% ) on placebo (RR 0.68, 95% CI = 0.49- 0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18% , respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Conclusion: Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

白血病化疗及造血干细胞移植对卵巢功能的影响

目的研究造血干细胞移植对卵巢功能的影响。方法观察45例因急性非淋巴细胞白血病分别接受同种异体造血干细胞移植(Allogeneicstemcelltransplantation,Allo-SCT)和自体造血干细胞移植(Autologousstemcelltransplantation,Auto-SCT)患者的月经恢复情况和性激素变化,同时抽取45名同年龄段健康妇女作为对照。结果Allo-SCT组有2例患者月经恢复,Auto-SCT组有4例恢复;移植时年龄越小,卵巢功能越易恢复。Allo-SCT和Au-to-SCT后促性腺激素较对照组显著升高,而雌激素显著降低,Allo-SCT患者雄激素也显著降低。结论造血干细胞移植后引起的卵巢功能降低主要是因为移植前化疗对卵巢的损害,但Allo-SCT引起的免疫调节障碍可进一步使卵巢功能减退。

Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.

Inhibitory effect of Patrinia scabiosaefolia on acute pancreatitis

AIM： To investigate the effect of Patrinia scabiosaefolia （PS） on the cholecystokinin （CCK） octapeptide-induced acute pancreatitis （AP） in rats.METHODS： Wistar rats weighing 240-260 g were divided into three groups： （1） Normal saline-treated group; （2） treatment with PS at 100 mg/kg group, in which PS was administered orally, followed by subcutaneous administration of 75μg/kg CCK octapeptide three times after 1, 3 and 5 h, and this whole procedure was repeated for 5 d; （3） treatment with saline group, in which the protocols were the same as in treatment group with PS. We determined the pancreatic weight/ body weight ratio, the levels of pancreatic HSP60, HSP72 and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in the typical laboratory findings of experimentally induced pancreatitis.RESULTS： PS reduced the pancreatic weight/body weight ratio, the levels of serum amylase and lipase, and inhibited expressions of pro-inflammatory cytokines in the CCK octapeptide-induced AP. Furthermore, PS pretreatment increased the pancreatic levels of HSP60 and HSP72.CONCLUSION： Pretreatment with PS has an antiiinflammatory effect on CCK octapeptide-induced AP.

Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance

AIM： To study the expression of suppressor of cytokine signaling-1 （SOCS-1） in the liver tissues of chronic hepatitis 13 （CHB） and the clinical significance of this expression. METHODS： The expression of SOCS-1 in liver tissues of 45 cases of CHB was investigated by immunohistochemical staining, and its correlations with inflammation grades and fibrosis stage were analyzed by SPSS statistics software. RESULTS： The result showed SOCS-1 expressing could be observed in the liver tissue of CriB. The expression of SOCS-1 was mainly distributed near the portal area in the liver tissue of mild inflammation CriB group, and was diffusely distributed in the liver tissue of moderate and severe inflammation groups. SOCS-1 positive stains mainly appear in the hepatocytes, only a few of liver interstitial cells were involved. Inside the hepatocyte, SOCS-1 positive stains are mainly distributed in the plasma. Some of the staining was observed on the membrane. The inclusion bodies in the plasma of hepatocytes were observed occasionally. There were both obvious correlations between the expression of SOCS-1 and the inflammatory grade, and that between the expression of SOCS-1 and the fibrosis stage, CONCLUSION： The distribution of SOCS-1 in the liver tissue of CriB is variable. This expression was correlated with the inflammation grade and fibrosis stage.

Historical reflections on autoimmune hepatitis

Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease

Inflammatory bowel disease (IBD), in particular Crohn's disease refractory to conventional therapy, fistulizing Crohn's disease and chronic active ulcerative colitis, generally respond well to anti-tumor necrosis factor (TNF) therapy. However, serious side effects do occur, necessitating careful monitoring of therapy. Potential side effects of anti-TNF therapy include opportunistic infections, which show a higher incidence when concomitant immunosuppression is used. Furthermore, antibody formation against anti-TNF is associated with decreased efficacy and an increased frequency of infusion reactions. The hypothesis of a slightly increased risk of lymphomas in IBD patients treated with anti TNF-therapy is debatable, since most studies lack the specific design to properly address this issue. Alarmingly, the occurrence of hepatosplenic T-cell lymphomas coincides with combined immunosuppressive therapy. Despite the potential serious side effects, anti-TNF therapy is an effective and relatively safe treatment option for refractory IBD. Future research is needed to answer important questions, such as the long-term risk of malignancies, safety during pregnancy, when to discontinue and when to switch anti-TNF therapy, as well as to determine the balance between therapeutic and toxic effects.

Structural basis of immunosuppression by the therapeutic antibody daclizumab

Interleukin-2 （IL）-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody （mAb） daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ra. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by dacllzumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ra ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL- 2Ra ectodomain. The antigen-binding site of daclizumab is mainly composed of live complementarity determining regions （CDRs） that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ru ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ra would prevent the IL-2 binding to IL-2Ra and the subsequent formation of the IL-2fIL-2Ra[~/c complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ra.

Proteasome inhibitor treatment in alcoholic liver disease

Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements （glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC） were upregulated when rats fed alcohol were treated with a low dose of PS-34Z （Bortezomib, Velcade）. This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.

Proton pump inhibitor-induced hypomagnesemia: A new challenge

Proton pump inhibitors （PPIs） are commonly used in clinical practice for the prevention and treatment of peptic ulcer, gastritis, esophagitis and gastroesophageal refux. Hypomagnesemia has recently been recognized as a side effect of PPIs. Low magnesium levels may cause symptoms from several systems, some of which being potentially serious, such as tetany, seizures and arrhythmias. It seems that PPIs affect the gastrointesti-nal absorption of magnesium. Clinicians should be vigi-lant in order to timely consider and prevent or reverse hypomagnesemia in patients who take PPIs, especially if they are prone to this electrolyte disorder.

Head-to-head comparison of H_2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

原发性血小板增多症转急性白血病M2a一例

1病例介绍患者，女，78岁，于8年前在本市某医院经相关检查确诊为原发性血小板增多症（ET）。长期使用羟基脲进行治疗，依据血常规结果调整剂量，维持在0．5～1．5g／d至今。2009-02-02因“发热”来我院就诊，查血常规：白细胞19．22×10^9／L，血红蛋白100g／L，血小板478×10^9／L，涂片镜检，中性粒细胞0．82、淋巴细胞0．16、单核细胞0．02，红细胞形态未见异常，门诊给予抗感染治疗，后痊愈。

Double layered self-expanding metal stents for malignant esophageal obstruction, especially across the gastroesophageal junction

AIM: To evaluate the clinical outcomes of double-layered self-expanding metal stents (SEMS) for treatment of malignant esophageal obstruction according to whether SEMS crosses the gastroesophageal junction (GEJ). METHODS: Forty eight patients who underwent the SEMS insertion for malignant esophageal obstruction were enrolled. Patients were classified as GEJ group (SEMS across GEJ, 18 patients) and non-GEJ group (SEMS above GEJ, 30 patients) according to SEMS position. Double layered (outer uncovered and inner covered stent) esophageal stents were placed. RESULTS: The SEMS insertion and the clinical improvement were achieved in all patients in both groups. Stent malfunction occurred in seven patients in the GEJ group and nine patients in the non-GEJ group. Tumor overgrowth occurred in five and eight patients, respectively, food impaction occurred in one patient in each group, and stent migration occurred in one and no patient, respectively. There were no significant differences between the two groups. Reflux esophagitis occurred more frequently in the GEJ group (eight vs five patients, P = 0.036) and was controlled by proton pump inhibitor. Aspiration pneumonia occurred in zero and five patients, respectively, and tracheoesophageal fistula occurred in zero and two patients, respectively. CONCLUSION: Double-layered SEMS are a feasible and effective treatment when placed across the GEJ for malignant esophageal obstruction. Double-layered SEMS provide acceptable complications, especially migration, although reflux esophagitis is more common in the GEJ group.