真武汤合苓桂术甘汤改善心肾综合征大鼠模型水钠潴留的作用机制研究

[目的]研究真武汤合苓桂术甘汤对心肾综合征大鼠模型水钠潴留的作用机制。[方法]将60只雄性SD大鼠随机分为两组,即空白组与手术组,空白组大鼠常规饲养,手术组大鼠经5/6肾切除联合异丙肾上腺素皮下注射制备心肾综合征模型,剔除死亡大鼠后,将手术组剩余成模大鼠按体质量分层随机分为空白组、中药组、常规治疗组。中药组给予真武汤合苓桂术甘汤灌胃,给药量为7.29 g生药/(kg·d);常规治疗组给予贝那普利(0.45 mg/kg)+呋塞米(1.8m g/kg);空白组予以等容积生理盐水灌胃,每日1次,连续6周。观察实验过程中各组大鼠的精神状态、活动情况、灵敏度、毛发情况、食欲、大小便等一般情况及死亡情况,比较各组灌胃前、灌胃6周后的血清脑钠肽(BNP)、血肌酐(Scr)、血尿素氮(BUN)、尿水通道蛋白2(AQP2)的前后差值情况。[结果]灌胃6周后,中药组大鼠一般情况较灌胃前改善、喘息不明显,常规治疗组一般情况同样较灌胃前改善。通过比较治疗前后各组大鼠实验室指标差值发现,中药组与常规治疗组BNP均下降,中药改善大鼠心力衰竭情况接近常规治疗组水平,两组下降水平无统计学差异(P0.05);中药组Scr水平较前下降,常规治疗组Scr水平升高;中药组尿AQP2水平较前略增高,与空白组尿AQP2水平无统计学差异(P0.05),常规治疗组尿AQP2水平较前明显升高。[结论]心肾综合征大鼠尿AQP2的表达主要由肾脏调控,AQP2可作为心肾综合征水钠潴留状态的参考指标,真武汤合苓桂术甘汤改善心肾综合征大鼠水钠潴留状态的作用机制可能是通过抑制大鼠肾脏AQP2过度表达,减少水的重吸收,改善了水钠潴留状态。     

妊娠早期糖化血红蛋白联合PAPP-A对妊娠期糖尿病的预测意义

目的:探讨妊娠早期血清学指标糖化血红蛋白(glycohemoglobin,HbA1c)联合妊娠相关血浆蛋白A(pregnancy-associated plasma protein A,PAPP-A)对妊娠期糖尿病(gestational diabetes mellitus,GDM)的预测意义。方法:随机选取2018年12月1日-2019年7月30日孕11~13+6周于我院门诊产检的妊娠妇女,进行临床资料采集并记录妊娠早期(11~13+6周)空腹血糖(fasting plasma glucose,FPG)、HbA1c、PAPP-A中位数倍数(multiple of the median,MoM)水平,根据孕24~28周进行的75 g口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果将研究对象分为研究组和对照组,统计分析妊娠早期血清学指标预测GDM的最佳截断值并得出最适宜的联合预测方案。结果:多因素Logistic回归分析显示,高水平FPG和HbA1c、低水平PAPP-A、受孕方式采用辅助生殖技术、有家族糖尿病史以及妊娠早期体质量指数(BMI)为超重或肥胖均是GDM发生的独立危险因素。有糖尿病家族史和使用辅助生殖技术受孕发生GDM的风险显著增高(OR分别为7.206和47.512,均P<0.001)。分析不同预测指标的受试者工作特征(receiver operating characteristic,ROC)曲线及曲线下面积(area under the curve,AUC)显示,PAPP-A MoM联合HbA1c及FPG诊断时AUC最大(0.728),其后依次为PAPPA MoM联合HbA1c(0.721)、HbA1c联合FPG(0.717),均大于HbA1c(0.707)和FPG(0.647),而PAPP-A MoM的AUC为0.380,对GDM没有诊断意义。结论:具有高风险因素的孕妇,推荐在妊娠早期联合检测HbA1c与PAPPA MoM,以早期预测GDM。     

Genetic toxicity assessment using liver cell models: past,present, and future

ABSTRACT

Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.     

卵巢子宫内膜异位囊肿粘连程度及相关因素分析

Objective To investigate the relationship between degree of endometrioma adhesions and clinical feature, surgical treatment and postoperative recurrence. Methods From Jan 2003 to Mar 2008, 662 patients with endometrioma undergoing laparoscopic ovarian endometrioma excision in Peking Union Medical College Hospital were studied retrospectively. All patients were classified into four groups according to the extent of adhesions: 31 cases in none adhesions group, 123 cases in mild adhesions group (filmy thickness, avascular, easily separated adhesions), 310 cases in moderate adhesions group (less than a half of ovary was adjacent to dense thickness adhesions which was difficult to separate, or above a half of ovary were adjacent to filmy thickness adhesions) and 198 cases in severe adhesions group (above a half of ovary was adjacent to dense thickness, well vascularized adhesions which was difficult to separate, and always involved the other pelvic organs, observed angiogenesis). The comparison of degree, characteristics, period of pain, lab test, surgical management and postoperative recurrence was performed among those above groups. In the mean time, risk factors and multinomial logistic regression were analyzed. Results (1)Clinical characteristics: The incidence of patients with dysmenorrhea, dyspareunia, straining feeling in anus, chronic pelvic pain and the level of CA125 (>35 kU/L) was remarkably higher in moderate-to-severe adhesion groups than in none-to-mild adhesions groups (P=0.000, 0.000, 0.001, 0.006 and 0.000, respectively). Infertility rate were significantly higher in severe adhesions group(15.7%,31/198) than none adhesions group(3.2%,1/31), mild adhesions group(11.4%,14/123) and moderate adhesions group(9.7%,30/310, OR=1.728, P<0.05).(2)Operating time and blood loss: Operating time of each groups was as followed: (37±15) min in none adhesions group, (42±19) min in mild adhesions group, (50±20) min in moderate adhesions group and (63±22) min in severe adhesion group. Blood loss was (23±12) ml in none adhesion group, (31±27) ml in mild adhesion group, (40±32) ml in moderate adhesion group and (70±67) ml in severe adhesions group. Thicker adhesions result in longer operation time and more blood loss. (3)Combined with other disease: The ratio of patients who combined with adenomyosis or deeply infiltrating endometriosis in moderate-to-severer adhesion groups was higher than patients in none-to-mild adhesions groups (OR=3.466, P=0.000). (4) Postoperative recurrence: It was categorized into recurrence of pain and cyst. Moderate-to-severe adhesions was related to higher recurrence rate of pain (OR=1.685,P=0.046), but was irrelevant to recurrence of cyst. Conclusion The more extent of endometrioma adhesions was related to severer pelvic pain symptoms, longer operating time and more blood loss. Postoperative pain recurrence rate was observed in moderate-to-severe adhesion group. Extent of adhesions was irrelevant to cyst recurrence.     

上肢骨肿瘤切除后的自体骨移植重建

目的探讨应用自体骨移植对上肢骨肿瘤切除后的骨缺损修复重建的效果。方法1998年8月～2004年3月，收治上肢骨肿瘤切除后的骨缺损16例。男8例，女8例。年龄7～45岁。经病理确诊，肱骨近端尤文肉瘤和骨肉瘤各1例；肱骨远端尤文肉瘤2例；桡骨远端骨巨细胞瘤8例，高分化软骨肉瘤2例，恶性纤维组织细胞瘤和骨肉瘤各1例。2例肱骨近端肿瘤行自体锁骨代肱骨；2例肱骨远端肿瘤行自体腓骨代肱骨；12例桡骨远端肿瘤中，1例行自体髂骨移植，11例行自体腓骨代桡骨进行重建。采用MSTS系统进行术后功能评价。结果2例肱骨近端自体锁骨移植患者分别随访36个月和12个月，术后保持部分肩关节前屈和后伸功能，但外展功能丧失；MSTS评分分别为23分和22分。2例肱骨远端自体腓骨移植患者分别随访4个月和6个月，肘关节功能良好，移植骨连接处已经出现骨愈合；MSTS功能评分分别为24分和19分。12例桡骨远端自体骨移植患者中11例随访6～75个月，功能良好，无明显并发症；1例髂骨植骨的桡骨远端骨巨细胞瘤术后3个月移植骨完全愈合，至今随访75个月，肿瘤无复发。MSTS功能评分18~27分，平均22．6分。结论自体骨移植在上肢骨肿瘤切除后骨缺损的重建，尤其是儿童的骨缺损重建中，是一种较好的方法。     

磁共振质子波谱成像(1H-MRSI) 在胶质瘤诊断中的应用

目的探讨利用磁共振波谱成像(MRSI)反映胶质瘤恶性度的价值.方法41例病理证实胶质瘤,原发39例、复发2例,行MR及MRS扫描,MRS数据经残差Z分数统计模型及LLI、Lip/Cho等指标划分肿瘤边界及不同代谢区,并结合MRI结构成像,划分出肿瘤的高代谢活性区、肿瘤浸润边界、坏死区及乏氧区.结果肿瘤浸润边界均超过MR常规图像上的肿瘤边界.Ⅱ级肿瘤高代谢活性区大部分位于肿瘤区内,但Ⅲ、Ⅳ级则大部分位于肿瘤边界;随肿瘤恶性度升高,肿瘤出现了坏死区及乏氧区.结论MRSI对确定肿瘤恶性度及划分肿瘤边界具有一定价值.     

检测子宫内膜异位症患者血清中差异表达蛋白的研究

目的：检测子宫内膜异位症（内异症）患者血清中差异表达的蛋白。方法：采用表面增强激光解吸／离子化飞行时间质谱（SELDI—TOF—MS）技术，选用WCX2蛋白质芯片对50例内异症及48例对照组血清标本进行检测以筛选内异症血清中差异表达的蛋白。结果：在Mr 0～50000范围内，检测出106个蛋白峰。内异症患者血清中差异表达的蛋白峰有4个。将发现的差异蛋白峰在Swiss蛋白数据库中搜索，发现Mr 9280蛋白峰与玻璃粘连蛋白Vitronectin相符。Vitronectin属于整合素家族，在内异症的粘附、侵袭、血管形成过程中起重要作用。其他的蛋白峰没有发现与之相匹配的蛋白，提示可能为新的蛋白质。结论：内异症患者血清中存在差异表达的蛋白，其对内异症的早期诊断具有一定的临床意义。SELDI蛋白芯片技术是一种快速、简单易行、样本用量少、高通量、重复性好的分析方法，具有广阔的临床应用前景。     

PET／CT检查的护理配合

对PET／CT检查的385例患者和169例健康体检者给予精心、科学的检查前、检查后护理，并注意自身的放射性防护。结果554例均检查顺利，医务人员近期血常规正常。     

CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用

目的研究CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用。方法收集70例甲状腺良、恶性病变组织，其中包括15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌（包括9例滤泡型乳头状癌）和10例滤泡性癌，采用免疫组织化学方法检测CD10在上述组织中的表达。结果9例滤泡型乳头状癌中，7例表达CD10（77．8％），10例滤泡性癌中8例表达CD10（80．0％）；CD10在非滤泡型乳头状癌、滤泡性腺瘤、腺瘤性甲状腺肿和正常甲状腺组织中均不表达。结论对CD10表达的检测有助于对甲状腺滤泡性癌和滤泡型乳头状癌的诊断。