胶原诱导性关节炎的评定与T细胞受体-热休克蛋白70DNA疫苗的保护作用

目的:纯化制备含有编码T细胞受体(TCR)Vβ5.2/8.2基因片段与结核杆菌热休克蛋白(HSP)70的一段保守序列P111-125的嵌合DNA疫苗,观察其对胶原诱导性关节炎的保护性作用。方法:实验于2006-07/2007-02在首都医科大学免疫学系实验室完成。①实验分组:36只Lewis大鼠随机分为6组,即正常对照组、胶原诱导性关节炎对照组、空质粒组、pTARGET-TCRVβ5.2-HSP70重组质粒治疗组、pTARGET-TCRVβ8.2-HSP70重组质粒治疗组及pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70重组质粒联合治疗组,每组6只。②实验方法:大量纯化制备重组DNA疫苗pTARGET-TCRVβ5.2-HSP70、pTARGET-TCRVβ8.2-HSP70和空质粒pTARGET,观察重组DNA疫苗对胶原诱导性关节炎的保护效果,包括关节炎指数评分、Eli-spot法测定脾细胞分泌的干扰素γ和白细胞介素4的水平、ELISA法测定血清中抗Ⅱ型胶原抗体的水平;光镜下观察大鼠后肢足关节的病理学变化。结果:36只Lewis大鼠均进入结果分析。重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70对胶原诱导性关节炎有较好的保护性作用,与胶原诱导性关节炎对照组相比,关节炎指数(P<0.05)下降,炎性细胞因子干扰素γ水平(P<0.05)和抗Ⅱ型胶原抗体水平(P<0.01)降低,抑制性细胞因子白细胞介素4水平(P<0.05)升高,病理学改变较轻。且两种重组质粒联合治疗的效果要比单种质粒好。结论:重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70能明显减轻胶原诱导性关节炎大鼠的关节炎症状和病理改变,二者联合应用效果更佳。     

Lack of evidence of hepatitis C infection in 290 blood component recipients, demonstrated by several single-antigen research immunoassays

BACKGROUND: A group of 290 transfusion recipients enrolled in a prospective study of posttransfusion hepatitis was studied to determine the possibility of previously unrecognized hepatitis C virus (HCV) transmission. STUDY DESIGN AND METHODS: Before and after transfusion, blood specimens that were negative in first-generation enzyme immunoassay (EIA) were tested by current commercial EIAs, several single-antigen research EIAs, and supplemental tests. RESULTS: Current second- and third-generation EIAs identified five subjects (1.7% of total) who had chronic hepatitis C before transfusion. Twenty additional sera had some reactivity with research EIAs. However, those results were the same before and after transfusion (n = 7), had reverted to partially reactive or nonreactive (n = 8), or could not be confirmed by serologic tests or polymerase chain reaction in follow-up specimens (n = 5). CONCLUSIONS: Transient or restricted reactivity to HCV antigens measured by more sensitive research EIAs does not seem to correspond to recent HCV transmission by transfusion. Whether such reactivity could reflect remote HCV infection, with the potential for chronic or intermittent viremia, remains to be determined.     

Recombinant immunoblot assay reaction patterns and hepatitis C virus RNA in blood donors and non-A, non-B hepatitis patients

To establish the value of the second-generation recombinant immunoblot assay (RIBA-2) and cDNA polymerase chain reaction (cDNA PCR) for confirmation of hepatitis C virus (HCV) infection, anti-HCV reaction patterns and the presence of HCV RNA were examined in 610 blood donors and 255 non-A, non-B hepatitis patients who were positive or indeterminate in RIBA-2. Of RIBA-2-positive donors (n = 191) and patients (n = 224), 75.4 and 89.7 percent, respectively, were HCV RNA positive. The most frequently observed anti-HCV recognition patterns in HCV RNA-positive donors and patients were c22, c33c, and c100 and/or 5- 1-1 (67.3%, 57.7%) and c22, c33c (24.8%, 29.3%). Among subjects with a RIBA-2-indeterminate result, HCV RNA was detected more often in patients (n = 31) than in donors (n = 419): 67.7 and 2.1 percent, respectively. In viremic persons with single-band reactivity in RIBA-2, this reactivity was always directed against either c22 or c33c. HCV RNA was detected by cDNA PCR in none of 162 persons with only anti-c100 and/or anti-5-1-1 reactivity. Therefore, RIBA-2 reactivity against c100 in combination with 5-1-1 should not be considered positive but indeterminate. In RIBA-2-indeterminate persons, HCV RNA detection is necessary for reliable confirmation of HCV infection.     

慢性胃病脾虚患者胃窦粘膜胃泌素细胞和分泌生长抑素细胞的变化及其意义

目的：观察以慢性胃病为主的脾虚患者胃窦粘膜分泌胃泌家(Gas)细胞(G细胞)、生长抑素(SS)细胞(D细胞)与脾虚证发生的关系。方法：将84例脾虚患者分为脾胃虚寒组、脾虚夹热组、胃阴不足组、脾胃湿热组、肝胃不和组，应用免疫组化技术标记胃窦粘膜G、D细胞，并定量分析。结果：以慢性胃病为主的脾虚证患者G、D细胞数均减少，D细胞面积缩小，G/D细胞数和细胞面积比值均增高(P＜0．05)。结论：G、D细胞的变化可能是慢性胃病脾虚证胃肠功能障碍的一个重要病理机制。     

斑蝥素毒性及其药（毒）动力学研究

目的 研究斑蝥素对小鼠肝、肾毒性及其在小鼠体内的动态行为。方法 用小鼠半数致死量（LD50）及生化指标的变化来表征斑蝥素的毒性,用小鼠急性死亡率法测定斑螫素药物动力学参数。结果和结论 斑蝥素对小鼠肝、肾有明显的毒性作用,该药在小鼠体内动态变化符合一级动力学,呈二室开放模型,其表观药动学参数为:A=10.1mg/kg;α=1.56 h-1;t1/2α=0.44h;B=1.19mg/kg;β=0.123h-1;t1/2=5.63h;K21=0.274h-1;K10=0.700h-1;K12=0.709h-1;CL=0.071kg/kg·h-1;AUC=16.15 mg·h/kg;Vc=0.102kg/kg;Vp=0.264 kg/kg。     

新疆喀什1499名中小学生舌象调查分析

对西域古城喀什1499名中小学生做舌象调查,舌体适中约2/3,胖大略高于1/3,齿痕合约1/4,舌裂15.8%;舌质以淡红为主(86.9％),舌苔以白薄苔为常见(94.2％,82.5％)。资料分析表明舌体、齿痕舌与体重相关;同时舌体、花剥舌与性别有关;舌胖、舌裂与花剥苔还随年龄增大而增多。但关系最密切的还是舌象与民族有关,即维吾尔族舌裂、绛红舌质、花剥苔、齿痕舌均高于汉族,而后者的厚苔、黄苔和舌边尖瘀点则高于维吾尔族。     

Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.     

Temporomandibular joint: comparison of single- and double-contrast arthrography

Lower-space, single-contrast arthrography and dual-space, double-contrast arthrotomography were sequentially applied to 58 fresh temporomandibular joint (TMJ) autopsy specimens, and the findings were compared with observations in corresponding cryosections. Both modalities had high accuracy rates (greater than or equal to 84%) and no statistically significant differences between the two techniques were found. A side-by-side comparison of the two types of arthrograms, however, revealed that video tape recording of lower-space, single-contrast arthrography was superior in demonstrating joint dynamics and that dual-space, double-contrast arthrotomography was superior in demonstrating the soft-tissue anatomic features of the joint. It appears that lower-space, single-contrast arthrography can be recommended for examination of patients with clicking, catching, and intermittent locking, and that dual-space, double-contrast arthrotomography is preferable when information about morphologic alterations is clinically more important than information about joint dynamics.     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.