实验性顺铂诱导急性肾功能衰竭动物模型的研究

1目的　建立顺铂 (cisplatin,CP)诱导的急性肾功能衰竭 (acute renal failure,ARF )大鼠模型 ,探讨 ARF的发病机制。2方法　 SD大鼠静脉一次性注射 CP 6 mg/ kg,动态观察大鼠血清肌酐 (Scr)、尿素氮 (BUN)变化以及肾组织形态学改变。 3结果　对照组不同时间 Scr、BUN差异不明显 (P>0 .0 5 ) ,肾组织形态学正常。模型组 Scr、BUN第 4d较第 1d明显升高 (P<0 .0 5 )。肾组织形态学显示 ,肾脏髓质外侧带大部分肾小管坏死 ,细胞核固缩、溶解、消失 ,管腔扩张 ,有坏死脱落碎屑。 4结论　 CP诱导的大鼠 ARF模型为一较为理想的 ARF模型     

适形切除保肛术与经括约肌间切除术治疗低位直肠癌的临床疗效

目的探讨适形切除保肛术(CSPO)与经括约肌间切除术(ISR)治疗低位直肠癌的临床疗效。方法采用回顾性队列研究方法。收集2011年8月至2020年4月2家医学中心收治的183例(海军军医大学附属长海医院117例、复旦大学附属华山医院66例)低位直肠癌病人的临床病理资料;男110例,女73例;年龄为(57±11)岁。183例病人中,117例行CSPO设为CSPO组,66例行ISR设为ISR组。观察指标:(1)两组低位直肠癌病人手术情况。(2)两组低位直肠癌病人术后并发症情况。(3)随访情况。(4)影响低位直肠癌病人预后因素分析。(5)影响低位直肠癌病人肛门满意度因素分析。采用门诊、问卷和电话方式进行随访,了解病人肿瘤局部复发及远处转移、病人生存、造口还纳、肛门满意度评分情况。正态分布的计量资料以x±s表示,组间比较采用t检验;偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示,组间比较采用χ²检验。等级资料比较采用秩和检验。采用Kaplan-Meier法绘制生存曲线,采用寿命表法计算生存率,采用Log-rank检验进行生存情况分析。单因素分析采用线性回归,将单因素线性回归分析中P<0.10的变量纳入多因素分析。多因素分析采用COX逐步回归分析模型和线性回归分析。结果(1)两组低位直肠癌病人手术情况:CSPO组和ISR组病人腹腔镜手术例数、手术时间、术中出血量、肿瘤远切缘、术后化疗、术后住院时间分别为44例和55例、(165±54)min和(268±101)min、(142±101)mL和(91±85)mL、(0.6±0.4)cm和(1.9±0.6)cm、76例和9例、(6.6±2.5)d和(7.9±4.7)d,两组病人上述指标比较,差异均有统计学意义(χ²=35.531,t=8.995、-3.437、-3.088,χ²=44.681,t=2.267,P<0.05)。(2)两组低位直肠癌病人术后并发症情况:CSPO组术后19例病人发生并发症,其中Ⅰ级并发症6例,Ⅱ级并发症12例,Ⅲb级并发症1例。ISR组术后14例病人发生并发症,其中Ⅰ级并发症4例,Ⅱ级并发症7例,Ⅲa级并发症1例,Ⅲb级并发症2例。两组病人术后总体并发症发生情况比较,差异无统计学意义(χ²=0.706,P>0.05)。两组病人并发症经对症支持治疗后均好转。两组病人均无围术期(术后30 d内)死亡病例。(3)随访情况:183例病人均获得随访,CSPO组和ISR组随访时间分别为(41±27)个月和(37±19)个月,两组病人比较,差异无统计学意义(t=-1.104,P>0.05)。CSPO组和ISR组病人中,肿瘤局部复发分别为2例和3例、肿瘤远处转移分别为9例和4例,两组病人上述指标比较,差异均无统计学意义(χ²=1.277、0.170,P>0.05)。CSPO组和ISR组病人3年无病生存率分别为84.0%和88.6%,3年总体生存率分别为99.0%和92.8%,两组病人无病生存情况和总体生存情况比较,差异均无统计学意义(χ²=0.218、0.002,P>0.05)。CSPO组和ISR组分别有102例和66例病人随访至CSPO或ISR术后12个月,其造口还纳率分别为92.16%(94/102)和96.97%(64/66),两组病人比较,差异无统计学意义(χ²=1.658,P>0.05)。CSPO组8例造口未还纳病人中,2例因高龄、4例主观拒绝还纳、2例因放疗致瘢痕无法还纳。ISR组2例造口未还纳病人中,术后因肝转移和主观拒绝还纳各1例。CSPO组和ISR组分别有92例和61例病人随访至造口还纳术后12个月,其中CSPO组75例和ISR组38例完成肛门功能满意度调查。CSPO组和ISR组病人肛门功能满意度评分分别为(6.8±2.8)分、(5.4±3.0)分,两组病人比较,差异有统计学意义(t=-2.542,P<0.05)。CSPO组和ISR组病人肛门功能满意度评分>5分分别为54例和21例,两组病人比较,差异无统计学意义(χ²=3.165,P>0.05)。(4)影响低位直肠癌病人预后因素分析:COX逐步回归分析结果为性别、肿瘤pT分期是影响低位直肠癌病人无病生存率的独立影响因素(风险比=2.883,1.963,95%可信区间为1.090~7.622,1.129~3.413,P<0.05);性别、肿瘤pT分期是影响低位直肠癌病人总体生存率的独立影响因素(风险比=10.963,3.187,95%可信区间为1.292~93.063,1.240~8.188,P<0.05)。(5)影响低位直肠癌病人肛门满意度因素分析:单因素分析结果显示手术方式和肿瘤分化程度是影响低位直肠癌病人肛门满意度的影响因素(偏回归系数=1.464,-1.580,95%可信区间为0.323~2.605,-2.950~-0.209,P<0.05)。多因素分析结果显示:手术方式、肿瘤分化程度、术前放疗是影响低位直肠癌病人肛门满意度的独立影响因素(偏回归系数=1.637,-1.456,-1.668,95%可信区间为0.485~2.788,-2.796~-0.116,-2.888~-0.447,P<0.05)。结论与ISR比较,低位直肠癌施行CSPO同样可实现超低位保肛,不增加术后并发症发生率,保障肿瘤学安全性,改善肛门功能,提升病人术后肛门功能满意度。     

Cr Migration Potential and Species Properties in the Soil Profile from a Chromate Production Site in the Groundwater Depression Cone Area

The relationship between the migration process and speciation distribution of Cr is important for the risk assessment in the underground environment. In this work, soil columns were collected from the chromate production site, with a 40-year operation, in the groundwater depression cone area of North China plain. The relationship between chromium pollution features and the geochemical properties of soil was established, and the migration risk of Cr(VI) was assessed based on the Nemerow composite index and Hydrus-1D model. The maximum total Cr concentration in the chromium slag dumping site reached 907 mg/kg, and that in the chromate production workshop was more than 200 mg/kg across the depth. The migration of Cr might be accelerated in the soil with abundant Mn (236–1461 mg/kg) but scarce organic matters (<?0.45%). The Hydrus simulation indicated that Cr(VI) would reach a cumulative flux of 300–729 mg/cm² after 50 years.

     

Characterisation of the IgE-binding immunodominant epitopes on Ara h1

Peanut allergy is one of the most severe food allergies due to its persistency and life-threatening character. Serum IgE from patients with documented peanut hypersensitivity reactions and synthetic peptides were used to screen the linear IgE-binding epitopes on the major peanut allergen, Ara h 1. Five major epitopes that bound peanut-specific serum IgE from more than 60% of patients tested were identified. Mutational analysis of the immunodominant epitope showed that single amino acid changes had dramatic effects on IgE-binding characteristics. Mapping and characterisation of the IgE-binding epitopes on Ara h1 could be used in future immunotherapeutic approaches for peanut allergy disease.     

Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus

Overexpression of decoy receptor (DcR) 3 protein, a recently discovered member of the tumor necrosis factor receptor superfamily, was examined in 40 esophagogastrectomy specimens containing areas of Barrett esophagus (n = 27), low-grade dysplasia (n = 27), high-grade dysplasia or carcinoma in situ (n = 22), and esophageal adenocarcinoma (EAC; n = 28) with immunohistochemical analysis. The results revealed significantly more overexpression of DcR3 in high-grade dysplasia or carcinoma in situ and EAC than in benign esophageal mucosa (both P < .0001), Barrett esophagus (both P < .001), and low-grade dysplasia (P < .01 and P = .033, respectively). Low-grade dysplasia also showed significant overexpression of DcR3 compared with benign esophagus (P < .05) but not with Barrett esophagus (P > .05). DcR3 overexpression seems to negatively correlate with the grade of EAC. Our results suggest that overexpression of DcR3 protein might aid in the diagnosis of high-grade dysplasia or carcinoma in situ and EAC and also might serve as a potential therapeutic target.     

The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzymes in normal and neoplastic human tissues. An immunohistological survey using monoclonal antibodies

The immunohistological expression of placental alkaline phosphatase (PLAP) and PLAP-like enzyme was studied in frozen sections from a wide variety (n = 254) of normal and malignant tissues using monoclonal antibodies reactive with PLAP (H317) and PLAP/PLAP-like enzyme (H17E2; H315). PLAP/PLAP-like reactivity was seen in normal thymus, and foetal and neonatal testis, and in 21 out of 22 malignant germ cell tumours (GCTs), but was also found in normal endocervix, normal Fallopian tube and in 28 out of 167 non-GCTs (particularly in ovarian and proximal gastrointestinal tract tumours). Positivity for true PLAP (as demonstrated with H317) was seen in term placenta, in endocervix, and in Fallopian tube (but not in other normal tissues) and was commonly found in ovarian and proximal gastrointestinal tract tumours. Reactivity with H317 was unusual in malignant GCTs (2 out of 22 cases). These findings confirm that PLAP/PLAP-like positivity is a highly sensitive immunohistological marker for malignant GCTs, but one which by itself is of only moderate specificity. Furthermore, expression of true PLAP is rare in GCTs and favours instead an origin from the ovary or proximal gastrointestinal tract. The results also indicate that the predominant heat-stable alkaline phosphatase species in normal foetal and neonatal testis, and in thymus has a similar immunohistological profile to that found in malignant GCTs, and is a PLAP-like enzyme ("germ cell alkaline phosphatase") distinct from true PLAP. The occurrence of this marker in GCTs would appear to reflect increased eutopic production of an enzyme present in trace amount in corresponding normal tissues rather than a genuine example of ectopic expression.     

Hydrocarbon exposure, pancreatitis, and bile acids.

The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons.     

Direct protective effect of interleukin-10 on articular chondrocytes in vitro

Objective To assess whether interleukin-10 (IL-10) is chondroprotective in vitro.Methods Chondrocytes were isolated from femoral cartilage of rats (7-10 days) by digesti on with collagenase Ⅱ.The first passage cells were grown in 24- well plates with DMEM, supplemented with 10% fetal bovine serum, for 2-4 days.The ce lls were then cultured in 0.1% fetal bovine serum DMEM medium, and given respec tively interleu kin-1 (IL-1) 100 μ/ml, IL-1 100 μ/ml+recombinant murine interleukin-10 ( rmIL-10) 20 ng/ml, rmIL-10 20 ng/ml, and cultured for 48 hours.Scanning el ectron morphology and immunohistochemical study of nitric oxide synthase 2 and matric metalloproteinase 3 mRNA in situ hybridization were performe d.Cell proliferation and morphology were observed under inverted microscope fr om the beginning of cell culture for three weeks.Results IL-1 stimulated granule production in the cytoplasma of chondrocytes, and the c ells died in the second and third weeks of culture.IL-10 antagonized IL-1, p rotected the cells from death and maintained chondrocyte proliferation.Scannin g electron morphology showed that IL-1 stimulated the formation of numerous mic rovilli on the cell surface, while thin and less numerous microvilli were found in cultures with IL-10.Immunohistochemical study and in situ hybridization sh owed that IL-10 inhibited NOS2 and MMP3 expression.Conclusion IL-10 not only inhibits the synthesis of inflammatory cytokines, but also direc tly protects chondrocytes by antagonizing IL-1.