妊娠期PM2.5暴露影响胎儿生长的前瞻性队列研究

目的 探讨妊娠期PM_2.5及其组分暴露对胎儿生长的影响,并进一步识别暴露效应窗口。方法 选取江苏出生队列2016年1月至2019年10月招募的4 089对母子对,收集其基线信息、妊娠期诊疗信息、妊娠期PM_2.5及其组分暴露信息、妊娠满20周后的胎儿B超检查（头围、腹围、股骨长和估计体重）信息。利用广义线性混合模型进行暴露效应的估计,利用分布滞后非线性模型探讨暴露效应窗口。结果 妊娠期PM_2.5暴露浓度每升高10 μg/m³,胎儿头围、腹围和估计体重Z评分分别减小0.025（β=-0.025,95%CI：-0.048~-0.001）、0.026（β=-0.026,95%CI：-0.049~-0.003）和0.028（β=-0.028,95%CI：-0.052~-0.004）,头围和估计体重生长受限风险分别增加8.5%（RR=1.085,95%CI：1.010~1.165）和13.5%（RR=1.135,95%CI：1.016~1.268）。PM_2.5组分中黑碳、有机物、硝酸盐、硫酸盐、铵盐暴露浓度升高均与头围Z评分减小显著相关,同时硫酸盐暴露的增加还与股骨长的Z评分减小有关。妊娠期PM_2.5暴露影响胎儿头围生长效应窗口为第2~5周,腹围为第4~13周以及第19~40周,股骨长为第4~13周以及第23~37周,估计体重为第4~12周以及第20~40周。结论 妊娠期PM_2.5及其组分暴露可能对胎儿生长产生不利影响,影响胎儿不同生长指标的效应窗口不完全一致。     

肠上皮发育稳态及其调节信号

肠上皮是哺乳动物中更新最快的组织之一,在食物消化与营养吸收、黏膜屏障维持、免疫调节以及肠道微生物防御等方面发挥着重要作用。肠上皮中丰富的细胞类型是其发挥多种功能的基础,其分化发育过程受到精密调控,关键调节信号的失调会引起肠上皮屏障功能受损并导致多种肠道疾病的发生。本文将对肠上皮的功能、细胞组成以及调控信号进行阐述。     

α2-Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver

Localization and production of alpha2-macroglobulin (alpha2M), a multifunctional binding protein with protease and cytokine scavenging properties, was studied in situ in rat livers containing experimentally induced colon carcinoma metastases by means of immunocytochemistry and in situ hybridization methods. The study was performed to investigate whether alpha2M production by hepatocytes plays a role in the defense against the growth of metastases on the basis of its protease inhibiting capacity. It was found that colon cancer cells in all developmental stages of the metastases contained large amounts of messenger RNA (mRNA) of alpha2M but hardly any alpha2M protein. Cancer cells in culture contained large amounts of both mRNA and protein of alpha2M. In contrast, stromal cells and liver cells did not show positivity for alpha2M mRNA above background levels. The exception was a few layers of hepatocytes around the latest stage of metastases. Hepatocytes contained both alpha2M mRNA and protein only when Kupffer cells were present, indicating that alpha2M mRNA production was induced via Kupffer cells. On the other hand, alpha2M protein was found in high amounts in the sinusoids and stroma of all metastases, irrespective of their developmental stage. Increased levels of alpha2M could not be detected in serum in all but one rat tested (n=8). It is concluded that production of alpha2M by hepatocytes occurs only around the latest developmental stage of metastases and that alpha2M does not play a significant role in the defense against metastatic cancer growth in rat liver. In contrast, cancer cells produce and secrete large amounts of alpha2M, which seems to be linked with their tumorigenicity. We suggest that this alpha2M captures cytokines rather than proteases by complex formation. These complexes were observed using immunocytochemical staining for alpha2M protein indicating that it was captured by either stromal cells, sinusoidal cells, or hepatocytes that are in direct contact with cancer cells, Therefore, changes in serum levels of alpha2M were limited, indicating that these levels do not reflect local production and effects of alpha2M. (Hepatology 1996 Mar;23(3):560-70)