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。     

Impact of low back pain on functional limitations, depressed mood and quality of life in patients with rheumatoid arthritis

Low back pain (LBP) and rheumatoid arthritis (RA) are common orthopedic problems, but there is little information on the importance of LBP in RA patients. The aim of this study was to investigate how LBP affects functional limitations, depressed mood, and quality of life in patients with RA. A complex questionnaire was answered by 281 RA patients, including questions about their RA and their experience of LBP. Functional limitations were assessed using the Hannover Activities of Daily Living questionnaire (ADL), depressed mood using the Center for Epidemiological Studies Depression Scale (CES-D) and health-related quality of life using the Short Form 12 health questionnaire (SF-12). The prevalence of LBP in RA patients was 53.4%. RA patients with LBP displayed a significantly higher degree of disability and depression than RA patients without LBP. There were no differences between the two groups with regard to the duration of RA, the number of operations or medication. LBP is an important factor for the physical and psychological behavior of RA patients. Therefore, the onset of LBP should not be overlooked or underestimated.     

云南红豆杉中四个新紫杉烷类四环二萜成分的分离和鉴定

从云南红豆杉(Taxus yunnanensis ChengetL.K.Fu)树皮的二氯甲烷部分又分离得到四个新紫杉烷类四环二萜化合物,分别命名为taxayuntin A,B,C和D。应用¹HNMR,¹³CNMR,¹H-¹HCOSY,¹³C-¹HCOSY及¹³C-¹HCOLOC等方法进行结构测定,证明它们都有5/7/6三环稠合的基本骨架,并在C₄和C₅上连有环氧丙烷。     

健骨冲剂对去势大鼠骨质疏松作用的研究

目的:研究健骨冲剂防治骨质疏松的作用。方法:观察去势大鼠骨密度、生物力学和血雌二醇、甲状旁腺素、降钙素、血钙、骨钙素的变化。结果:健骨冲剂能明显升高去势大鼠全身、腰椎和股骨骨密度;能增加股骨三点弯曲试验的屈服强度、最大载荷和断裂载荷;但不能提高去势大鼠血雌二醇的水平。结论:表明健骨冲剂能防治因雌二醇下降所致的骨质疏松症,但其作用机制不一定通过提高卵巢功能来实现。     

云南红豆杉化学成分的研究IV：二个新紫杉烷类三环二萜成分的分离和鉴定

在继续从云南红豆杉（ＴａｓｕｓｙｕｎｎａｎｅｎｓｉｓＣｈｅｎｇｅｔＬ．Ｋ．Ｆｕ）树皮中寻找抗肿瘤活性成分的研究中，又分离出７个紫杉烷类二萜化合物，经光谱解析（ＭＳ，１ＨＮＭＲ，１Ｈ－１ＨＣＯＳＹ，１３ＣＮＭＲ，１３Ｃ－１ＨＣＯＳＹａｎｄ１３Ｃ－１ＨＣＯＬＯＣ），鉴定其中５个为已知化合物：７－ｅｐｉ－１０－ｄｅａｃｅｔｙｌｔａｘｏｌ（Ｉ），７－ｅｐｉ－１０－ｄｅａｃｅｔｙｌｃｅｐｈａｌｏｍａｎｎｉｎｅ（ＩＩ），１０－ｄｅａｃｅｔｙｌｔａｘｏｌ（ＩＩＩ），１０－ｄｅａｃｅｔｙｌｃｅｐｈａｌｏｍａｎｎｉｎｅ（ＩＶ）和１０－ｄｅａｃｅｔｙｌｂａｃｃａｔｉｎＩＩＩ（ＶＩＩ）；２个新化合物是１３（２′，３′－ｄｉｈｙｄｒｏｘｙ－３′－ｐｈｅｎｙｌ）－ｐｒｏｐｉｏｎｙｌｂａｃｃａｔｉｎ，ＩＩＩ（Ｖ）和９－ｄｅｏｘｏ－９α－ｈｙｄｒｏｘｙｔａｘｏｌ（ＶＩ），分别命名为云南红豆杉醇（ｙｕｎｎａｎｘｏｌ）和云南红豆杉胺（ｙｕｎｎａｎｘａｍｉｎｅ）。     

东北红豆杉枝叶化学成分的研究

东北红豆杉(Taxus cuspidata SibeetZucc)枝叶乙醇提取物的二氯甲烷溶部分显示有较强的抗肿瘤活性,从这部分中已分离出十二个紫杉烷类二萜化合物,经理化常数测定和光谱解析证明其中十个为已知化合物taxinine(I),taxinineA(II),taxinineB(III),taxacin(V),taxagifine(VI),taxol(VII),cephalomannine(VIII),taxinineM(IX),10-deacetyl baccatinIII(X)和taxayuntin(XI),另二个化合物为新成分,分别命名为10-deacetyl taxinineB(IV)和taxacustin(XII),其中化合物VII,VIII,IX,X和XI均为首次从该植物枝叶中分离得到。     

Follow-up care of 12 months of patients with bladder cancer in Spain: A multicenter prospective cohort study

The therapeutic approach of bladder cancer strongly determines its prognosis. We describe the treatments and outcomes for a Spanish cohort of patients with bladder cancer for the first 12 months after diagnosis and identify the factors that influenced the decision to undergo the treatment received. We conducted a multicenter, prospective, cohort study including primary bladder cancer patients during the first 12 months after diagnosis. The clinical outcomes were performance status (ECOG), adverse events and any cause of mortality. We stratified the analysis by factors that might influence the treatments received. We conducted univariate and multivariable logistic regression models to assess which patient and tumor characteristics were associated with receiving adjuvant treatment in the subgroup of noninvasive bladder cancer patients. In total, 314 patients were included (85% men; 53.8% >70 years) in 7 tertiary Spanish hospitals; 82.2% had a noninvasive urothelial bladder cancer (NMIBC). Patients received mostly surgery plus adjuvant therapy (67.7%). BCG (32.8% patients) was the most frequently administered adjuvant therapy, followed by intravesical chemotherapy (17.8% patients) and radiotherapy (10.8%). The variability of administered treatments among hospitals was low. Patients with NMIBC were more likely to receive adjuvant therapy if they had a higher educational level, some comorbidities and a high-grade tumor. The number of fully active patients (ECOG 0) significantly decreased during the first year of follow-up from 58% to 36 % (OR: 2.41, 95%CI 1.82–3.20); at 12-month follow-up 10.8% patients had died from any cause. In conclusion, most of the patients had a NMIBC. Surgery alone or plus adjuvant therapy were the commonest curative options of bladder cancer. BCG therapy was the adjuvant therapy most frequently administered. Higher educational level, presence of comorbidities and a high-grade tumor were associated with adjuvant therapy. Patient performance status was worsening over time. Almost 1 of 10 patients died during the first year of follow-up.     

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.