On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus

We have previously shown that, when administered orally to mice, bacteriophage M13 DNA, as a paradigm foreign DNA without homology to the mouse genome, can persist in fragmented form in the gastrointestinal tract, penetrate the intestinal wall, and reach the nuclei of leukocytes, spleen and liver cells. Similar results were obtained when a plasmid containing the gene for the green fluorescent protein (pEGFP-C1) was fed to mice. In spleen, the foreign DNA was detected in covalent linkage to DNA with a high degree of homology to mouse genes, perhaps pseudogenes, or to authentic E. coli DNA. We have now extended these studies to the offspring of mice that were fed regularly during pregnancy with a daily dose of 50 g of M13 or pEGFP-C1 DNA. Using the polymerase chain reaction (PCR) or the fluorescent in situ hybridization (FISH) method, foreign DNA, orally ingested by pregnant mice, can be discovered in various organs of fetuses and of newborn animals. The M13 DNA fragments have a length of about 830 bp. In various organs of the mouse fetus, clusters of cells contain foreign DNA as revealed by FISH. The foreign DNA is invariably located in the nuclei. We have never found all cells of the fetus to be transgenic for the foreign DNA. This distribution pattern argues for a transplacental pathway rather than for germline transmission which might be expected only after long-time feeding regimens. In rare cells of three different fetuses, whose mothers have been fed with M13 DNA during gestation, the foreign DNA was detected by FISH in association with both chromatids. Is maternally ingested foreign DNA a potential mutagen for the developing fetus? Received: 15 April 1998 / Accepted: 15 June 1998     

右美托咪定联合经皮穴位电刺激对混合痔剥扎术后患者肠胃功能及术后疼痛的影响

摘要 目的：探讨右美托咪定联合经皮穴位电刺激对混合痔剥扎术后患者肠胃功能及术后疼痛的影响。方法：选择2022年3月-2022年7月我院行混合痔剥扎术的患者60例,将60例患者随机分为对照组（30例）与观察组（30例）,对照组患者给予右美托咪定镇痛,观察组给予术前经皮穴位电刺激,时间为手术开始前2 min至手术结束,右美托咪定使用方法、剂量同对照组。对比两组患者术前、术后0.5 h、1 h、2 h、3 h的疼痛评分,对比两组患者的术后疼痛疗效,对比两组创面愈合时间、腐肉完全脱落时间、住院时间及胃肠功能恢复情况,对比两组术前、术后的血管活性肠肽、胃动素及胃泌素水平。结果：术前及术后3 h时,两组的疼痛评分对比无统计学意义（P>0.05）;术后0.5 h、1 h、2 h时,观察组的疼痛评分明显较对照组低（P<0.05）。观察组的术后疼痛有效率明显较对照组高,P<0.05。观察组的创面愈合时间、腐肉完全脱落时间及住院时间明显较对照组低（P<0.05）。观察组的肠鸣音恢复时间、术后恶心呕吐发生率及排气时间明显较对照组短（P<0.05）。术前,两组的血管活性肠肽、胃动素及胃泌素水平对比无统计学意义（P>0.05）;术后,两组血管活性肠肽、胃泌素水平升高,胃动素水平降低,且观察组变化幅度明显较对照组低（P<0.05）。结论：右美托咪定联合经皮穴位电刺激可改善混合痔剥扎术后患者肠胃功能及术后疼痛情况。     

胃肠道间质瘤组织中MMP-13与CD147的表达及其意义

目的探讨基质金属蛋白酶-13（Matrix metalloproteinases-13,MMP-13）和CD147的表达与胃肠道间质瘤（Gastrointestinals stromal tumors,GISTs）临床病理特征的关系。方法采用免疫组织化学检测69例GISTs组织中MMP-13及CD147的表达,分析MMP-13和CD147与各病理参数的关系。结果GISTs组织中MMP-13和CD147的表达率分别为95.7%和97.1%,MMP-13阳性表达程度与GISTs的生物学行为、CD147表达及肿瘤的大小呈正相关（P〈0.05）;CD147阳性表达程度与肿瘤的大小呈正相关（P〈0.05）。结论MMP-13表达与GISTs生物学行为关系密切,可作为GISTs生物学行为的潜在评价指标。     

IgY在胃肠感染性疾病中的应用

卵黄抗体（1mmunoglobulinofyolk,IgY）是通过使用特种抗原免疫产蛋鸡,由其卵黄中提取的抗体,与哺乳动物的IgG相似,IgY性质稳定,在控制胃肠道感染性疾病方面存在许多独特的优点,可用于相应疾病的预防和治疗。研究表明,口服特种的IgY对大肠埃希菌、沙门菌、轮状病毒等引起的胃肠感染性疾病可起到免疫保护作用,有望成为抗生素的替代制剂。目前IgY正成为生物技术领域和医药研究中的新热点。     

Innate lymphoid cells and gastrointestinal disease

Innate lymphoid cells (ILCs) are a group of innate immune cells, which constitute the first line of defense in the immune system, together with skin and mucous membrane. ILCs also play an important role in maintaining the homeostasis of the body, particularly in the complex and diverse environment of the intestine. ILCs respond to different microenvironments, maintaining homeostasis directly or indirectly through cytokines. As a result, ILCs, with complex and pleiotropic characteristics, are associated with many gastrointestinal diseases. Their ability of transition among those subgroups makes them function as both promoting and inhibiting cells, thus affecting homeostasis and disease progressing to either alleviation or deterioration. With these special characteristics, ILCs theoretically can be used in the new generation of immunotherapy as an alternative and supplement to current tumor therapy. Our review summarizes the characteristics of ILCs with respect to category, function, and the relationship with intestinal homeostasis and gastrointestinal diseases. In addition, potential tumor immunotherapies involving ILCs are also discussed to shed light on the perspectives of immunotherapy.     

Viscoelastic properties of isolated rat colon smooth muscle cells

The measurement of the biomechanical properties of gastrointestinal smooth muscle cells is important for the basic understanding of digestive function and the interaction of muscle cells with the matrix. Externally applied forces will deform the cells depending upon their mechanical properties. Hence, the evoked response mediated through stretch-sensitive ion-channels in the smooth muscle cell membrane will depend upon membrane properties and the magnitude of the external force. The aim of this study was to test the hypothesis that gastrointestinal smooth muscle cells behave in a viscoelastic manner. Smooth muscle cells were dissociated from the muscle layers of the descending colon. The viscoelastic properties of the isolated cells were characterized by measuring the mechanical deflection response of the cell membrane to a negative pressure of 1cm H(2)O applied across the cell through a micropipette and fitting the response to a theoretical viscoelastic solid model. The viscoelastic mechanical constants of the isolated cells (N=9) were found to be as follows: k(1)=19.99+/-2.86 Pa, k(2)=7.19+/-1.21 Pa, mu=25.36+/-6.14 Pas and tau=4.84+/-0.95 s. This study represents, to the best of our knowledge, the first quantitative mechanical properties of isolated living smooth muscle cells from the gastrointestinal tract. The mechanical properties determined in this study will be of use in future analytical and numerical smooth muscle cell models to better predict the mechanism between the magnitude of mechanical stimuli, mechanosensitivity and the evoked afferent responses.     

Human Papillomavirus Type 16 Integration Analysis by Real-time PCR Assay in Associated Cancers

Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16–positive specimens were used for further analysis. The DNA extraction copy number of E2 and E7 genes was calculated by qualitative real-time PCR method. Serially diluted standards that were cloned in PUC57 plasmid were used. Standard curve and melting curve analysis was used for quantification. Of the 672 specimens studied, 76 (11.3%) were HPV-16 positive. We found that 35.6% (16/45) were integrated. Statistical analysis showed that there were significant correlations between integration of HPV-16 and cervical cancer end-stage carcinogenesis (P < .0001), episomal form, and ASCUS lesions (P = .045). Significant correlation in penile cancer patients was seen between the episomal form and high-grade cancer stage (P = .037). Integration is a major factor in the carcinogenesis mechanism of HPV and has different prevalence in various cancers with a higher rate in progression except in penile cancer.     

凝结芽孢杆菌活菌片预防先兆流产保胎妇女胃肠功能紊乱的临床观察

目的观察凝结芽孢杆菌活菌片（商品名：爽舒宝）预防先兆流产保胎妇女胃肠功能紊乱的临床疗效。方法将60例先兆流产保胎妇女随机分为爽舒宝预防组和对照组,预防组30例,对照组30例,两组均给予常规服用保胎药物,出现顽固性便秘后用开塞露通便,其中预防组在此基础上同时口服凝结芽孢杆菌活菌片首次2. 1 g,以后1.05 g/次,3次/d,温水送服,疗程2-4周。观察保胎期间孕妇胃肠功能紊乱情况和使用开塞露的通便次数。结果预防组患者胃肠功能紊乱的发生率显著低于对照组,差异有统计学意义（P〈0.05 ）。结论凝结芽孢杆菌活菌片预防先兆流产保胎妇女胃肠功能紊乱疗效显著,值得临床推广。     

Challenges in assessing pathogenicity based on frequency of variants in mismatch repair genes: an extreme case of a MSH2 variant and a meta-analysis

The clinical interpretation of variants in mismatch repair (MMR) genes associated with Lynch syndrome can be confusing when the functional nature of the variant is not clearly defined. We report an extreme case where a polymorphism in the MSH2 gene which had a low minor allele frequency, was misclassified as a mutation based on low evidential methods in the database and previous publications. We expanded this experience to perform a systematic meta-analysis in order to investigate other variants that have potentially been misclassified. Our results suggested that the interpretation of pathogenicity should be more cautious and emphasized the need for solid validation through multiple analyses including functional analysis for variants in MMR genes.     

全身麻醉下不同脑电双频指数对老年胃肠道恶性肿瘤患者应激反应、炎性因子和术后认知功能的影响

摘要 目的：观察全身麻醉下不同脑电双频指数（BIS）对老年胃肠道恶性肿瘤患者应激反应、炎性因子和术后认知功能的影响。方法：选择2020年10月-2021年4月在新疆医科大学附属肿瘤医院初诊的住院老年胃肠道恶性肿瘤患者,共98例。据随机数字表法分为浅麻醉组（n=49,BIS值45~55）和深麻醉组（n=49,BIS值30~40）。对比两组苏醒质量、应激反应、炎性因子、术后认知功能、血流动力学及不良反应。结果：浅麻醉组的苏醒时间、定向力恢复时间、气管拔管时间短于深麻醉组（P<0.05）。插管后即刻（T1）~术毕（T5）时间点,两组心率（HR）、平均动脉压（MAP）均下降后升高（P<0.05）。深麻醉组T1~T5时间点HR、MAP高于浅麻醉组（P<0.05）。手术开始2 h（T4）、拔管后60 min（T6）时间点,两组皮质醇（Cor）、促肾上腺皮质激素（ACTH）水平呈升高趋势,且浅麻醉组高于深麻醉组（P<0.05）。T4、T6时间点,两组白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平持续升高,但浅麻醉组低于深麻醉组（P<0.05）。深麻醉组的术后3 d、术后7 d 简明精神状态量表（MMSE）评分低于浅麻醉组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：全身麻醉下老年胃肠道恶性肿瘤患者BIS值范围30~40可维持更平稳的血流动力学,应激反应低,但是其对认知功能影响相对较大;BIS值在45~55之间时,患者苏醒快,炎性因子水平更低;临床应结合实际情况合理调控BIS值。