耐多药结核病耐药分子机制的研究

目的 研究耐多药结核分支杆菌耐药的分子机理，建立快速检测耐药基因的分子药敏试验方法。方法 通过ＰＣＲ和ＰＣＲ－ＳＳＣＰ分析结构分支杆菌耐多药临床分离株的ｒｐｏＢ、ｒｐｓＬ、ｋａｔＧ基因和ｉｎｈＡ调节序列。结果 ＰＣＲ分析耐药基因的敏感性为１－０ｐｇＤＮＡ；除ｒｐｏＢ基因引物ＰＣＲ扩增为属特异性外，余耐药基因引物ＰＣＲ扩增都具有较高的的特异性。２０株耐多药分离株中，９０％有２种以上耐药遗传标志改变，     

腹泻型肠易激综合征患者食物不耐受、症状指数及回盲部肥大细胞变化的相关性

目的:比较食物不耐受(food intolerance,FI)在腹泻型肠易激综合征患者(diarrhea-dominant irritable bowel syndrome,D-IBS)及健康人群中的存在情况,分析D-IBS患者食物不耐受严重程度、症状指数与回盲部肥大细胞数量变化之间的关系,以探讨食物不耐受在D-IBS发病中的意义及可能机制.方法:选取符合罗马Ⅲ诊断标准的D-IBS患者22例为病例组,无消化系症状的健康体检者21例为对照组,分别接受结肠镜检查.应用食物不耐受状况评价问卷对2组进行食物不耐受状况评分;用功能性肠病症状严重指数(functional bowel disorder severity index,FBDSI)和IBS病情尺度调查表(IBS symptomseverity scale,IBS-SSS)对病例组进行IBS症状严重程度评分.所有研究对象均接受结肠镜检查,在距回盲瓣4cm处取活检组织2块,采用甲苯胺蓝染色法计数黏膜肥大细胞数量,并与食物不耐受严重程度指数、IBS症状严重程度评分进行相关性分析.结果:D-IBS患者回盲部肠黏膜肥大细胞计数(4.68±0.55)个/高倍镜视野,健康对照组为(1.33±0.54)个/高倍镜视野,P<0.001,差异具有统计学意义;病例组食物不耐受存在情况明显高于对照组(P<0.05);食物不耐受严重程度与IBS症状严重程度指数间呈正相关(FBDSI:r=0.992,P<0.001;IBS-SSS:r=0.970,P<0.001);回盲部肥大细胞计数与I B S症状严重程度指数间呈正相关(FBDSI:r=0.957,P<0.001;IBS-SSS:r=0.985,P<0.001);食物不耐受严重程度与IBS患者回盲部肥大细胞计数间呈正相关(r=0.964,P<0.001),健康对照组中食物不耐受者回盲部肥大细胞计数明显高于无食物不耐受者(P<0.05).结论:D-IBS临床症状与肠道肥大细胞数量增多密切相关,食物抗原的刺激作用可能是D-IBS患者回盲部肥大细胞数目增多的原因之一;D-IBS患者食物不耐受存在情况普遍,食物不耐受可加重D-IBS患者肠道症状.     

核苷(酸)类似物抗病毒治疗对慢性乙型肝炎患者细胞免疫功能的影响

我国是乙型肝炎病毒(hepatitis B virus,HBV)感染的高流行区,大样本的调查显示我国慢性HBV感染者高达1.2亿人之多.由于持续HBV感染及复制激发的免疫应答失调是慢性乙型肝炎(chronic hepatitis B,CHB)患者病情进展的根本原因,要阻止疾病进展,应进行有效的抗病毒治疗.核苷(酸)类似物是目前公认有效的抗HBV的药物之一,被广泛应用于临床,主要通过抑制DNA聚合酶的复制从而发挥抗HBV作用.其在有效抗病毒治疗的同时对机体细胞免疫功能有何影响.本文就近年来此方面的研究进展进行综述.     

Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%). The overall actuarial survival from relapse was 36% at 6 years, with a significantly higher proportion of survivors among female patients (53% v 30%; P < .002). In univariate analysis, the 6-year probability of survival was 52% for patients with cytogenetic relapse and 30% for patients relapsing in chronic phase (CP), while no patient who relapsed in advanced phase (AP or BC) survived more than 3.5 years from relapse (P < .0001). The actuarial survival of patients relapsing before 6 months, between 6 and 12 months, and later than 12 months after transplant was 27%, 26%, and 45%, respectively (P < .002). Among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with interferon (IFN). However, IFN therapy significantly delayed progression toward hematologic disease. Cytogenetic responses were observed in 25% of patients who received IFN for relapse into CP, while only one minor cytogenetic response was reported in patients on conventional chemotherapy. For patients presenting with cytogenetic relapse as well as for those in hematologic relapse, IFN therapy significantly improved the 2-year probability of survival. However, long-term survival for IFN-treated patients in either group was not different from long-term survival in comparable patients not receiving IFN therapy. Twenty-nine patients of this series underwent a second bone marrow transplant (BMT) and the projected survival at 4 years after the second transplant is 28%. In multivariate Cox regression analysis, four factors remained significantly associated with survival: disease phase at relapse (P < .0001), duration of time interval from BMT to relapse (P = .0001), interferon therapy at relapse (P = .0024), and patient sex (P = .0032). This retrospective study provides evidence that some patients who relapse after BMT may benefit from treatment with IFN; a second BMT may offer the chance of cure. Data from this analysis may be useful in designing future prospective trials on posttransplant CML relapse.     

基本消灭班氏丝虫病后的远期监测

本文报道采用海群生对象治疗加流行村全民服药和对象治疗加食用海群生药盐基本消灭班氏丝虫病后的纵向和横向监测结果。两种不同措施基本消灭丝虫病后已监测9－11年，人群微丝蚴率均在逐年下降，前6年仍可检出残存微丝蚴血症者，以后连续5年未再发现微丝蚴阳性，蚊媒调查亦未发现幼丝虫自然感染，IFAT检测人群丝虫抗体阳性率为1．4－5．5％，降至非丝虫病流行区抗体水平，证明丝虫病的传播已被阻断。认为基本消灭班氏丝虫病后监测年限以10年左右为宜，并需连续3年以上未检出微丝蚴血症者和感染蚊，人群丝虫抗体阳性率降至当地非流行区水平，可以确认丝虫病已达到消除。     

骨髓间充质干细胞治疗早期骨性关节炎软骨T2值及相关因子的表达

背景：血清肿瘤坏死因子α和白细胞介素1β作为炎症递质,其水平与骨性关节炎病情相关。而骨髓间充质干细胞治疗骨性关节炎报道较少。目的：川骨髓间充质干细胞治疗兔早期骨性关节炎,观察关节软骨T2值及血清肿瘤坏死闪子α和白细胞介素1β水平并进行分析。方法：将36只新西兰大白兔随机均分成对照组、模型组和治疗组。模型组兔仅建立骨性关节炎模型,治疗组在造模后笫4周左膝关节腔内注射骨髓间充质干细胞;对照组膝关节腔内注射等量生理盐水。分别在治疗后第2周,1,2,3个月行左后膝关节核磁共振及血消肿瘤坏死因子α和白细胞介素1β水平检查。结果与结论：与模型组比较,治疗组T2值降低,无关节腔积液;血清肿瘤坏死因了α和白细胞介素1β水平降低：软骨T2值变化与二者呈正相关。MRI能够反映早期关节软骨的生物学改变,可用于评价骨性关节炎治疗前后的改变：骨髓间充质干细胞在关节腔内可向软骨分化,为早期骨性关节炎患者提供了一种新的有效疗法。     

A Comprehensive Study of the Mechanical and Durability Properties of High-Performance Concrete Materials for Grouting Underwater Foundations of Offshore Wind Turbines

With the increasing importance of offshore wind turbines, a critical issue in their construction is the high-performance concrete (HPC) used for grouting underwater foundations, as such materials must be better able to withstand the extremes of the surrounding natural environment. This study produced and tested 12 concrete sample types by varying the water/binder ratio (0.28 and 0.30), the replacement ratios for fly ash (0%, 10%, and 20%) and silica fume (0% and 10%), as substitutes for cement, with ground granulated blast-furnace slag at a fixed proportion of 30%. The workability of fresh HPC is discussed with setting time, slump, and V-funnel flow properties. The hardened mechanical properties of the samples were tested at 1, 7, 28, 56, and 91 days, and durability tests were performed at 28, 56, and 91 days. Our results show that both fly ash (at 20%) and silica fume (at 10%) are required for effective filling of interstices and better pozzolanic reactions over time to produce HPC that is durable enough to withstand acid sulfate and chloride ion attacks, and we recommend this admixture for the best proportioning of HPC suitable for constructing offshore wind turbine foundations under the harsh underwater conditions of the Taiwan Bank. We established a model to predict a durability parameter (i.e., chloride permeability) of a sample using another mechanical property (i.e., compressive strength), or vice versa, using the observable relationship between them. This concept can be generalized to other pairs of parameters and across different parametric categories, and the regression model will make future experiments less laborious and time-consuming.     

Identification and Characterization of a Novel Epitope of ASFV-Encoded dUTPase by Monoclonal Antibodies

Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) of African swine fever virus (ASFV) is an essential enzyme required for efficient virus replication. Previous crystallography data have indicated that dUTPase (E165R) may serve as a therapeutic target for inhibiting ASFV replication; however, the specificity of the targeting site(s) in ASFV dUTPase remains unclear. In this study, 19 mouse monoclonal antibodies (mAbs) were produced, in which four mAbs showed inhibitory reactivity against E165R recombinant protein. Epitope mapping studies indicated that E165R has three major antigenic regions: 100–120 aa, 120–140 aa, and 140–165 aa. Three mAbs inhibited the dUTPase activity of E165R by binding to the highly conserved 149–RGEGRFGSTG–158 amino acid sequence. Interestingly, 8F6 mAb specifically recognized ASFV dUTPase but not Sus scrofa dUTPase, which may be due to structural differences in the amino acids of F151, R153, and F154 in the motif V region. In summary, we developed anti-E165R-specific mAbs, and identified an important antibody-binding antigenic epitope in the motif V of ASFV dUTPase. Our study provides a comprehensive analysis of mAbs that target the antigenic epitope of ASFV dUTPase, which may contribute to the development of novel antibody-based ASFV therapeutics.     

GnRHa as a treatment for letrozole-resistant recurrent adult granulosa cell tumors: A case report

Introduction:The optimal management of recurrent ovarian granulosa cell tumors is still unknown, and hormone therapy may be an alternative for chemotherapy-resistant cases.Patient concerns:A 46-year-old woman presented with a third recurrence after primary treatment of granulosa cell tumors. She developed tumor progression and drug-induced nephritis after 6 cycles of combined treatment with cisplatin and paclitaxel for the second recurrence and failed to benefit from chemotherapy, after the third optimal cytoreduction and tumor progression after 6 months of letrozole treatment.Diagnosis:Letrozole-resistant recurrent ovarian granulosa cell tumorsInterventions:Intramuscular Diphereline 3.75 mg q28d.Outcomes:Computed tomography showed the metastatic neoplasm resolved. Progression-free survival is 20 months.Conclusion:Hormone therapy may be an alternative to treat recurrent granulosa cell tumors, and gonadotropin-releasing hormone agonists may be a rescue treatment for aromatase inhibitor-resistant cases.