[摘 要] 目的：探讨LINC00462招募转录因子MYC激活ABCC3对肾透明细胞癌（ccRCC）顺铂敏感性的影响及其机制。方法：数据库分析ccRCC组织中ABCC3、MYC和LINC00462的表达及其相关性，并分析ABCC3基因的富集通路。常规培养人肾小管上皮细胞（HK-2）和ccRCC细胞（A-498、786-O和Caki-2），将si-LINC00462、oe-ABCC3、si-ABCC3、si-MYC、si-LINC00462-NC、oe-ABCC3-NC、si-ABCC3-NC和si-MYC-NC核酸序列分别转染A-498或786-O细胞，分为si-LINC00462组、si-LINC00462-NC组、oe-ABCC3组、oe-ABCC3-NC组、si-ABCC3组、si-ABCC3-NC组、si-MYC组、si-MYC-NC组；用2-脱氧-D-葡萄糖（2-DG）进行回复实验，构建oe-NC+PBS组、oe-ABCC3+PBS组、oe-ABCC3+2-DG组；为探究ccRCC细胞LINC00462/MYC/ABCC3轴对顺铂敏感性的影响，构建si-NC+oe-NC组、si-LINC00462+oe-NC组、si-LINC00462+oe-ABCC3组。qPCR法检测ABCC3、MYC和LINC00462在ccRCC细胞中的表达，CCK-8法检测细胞增殖活力，CCK-8法分析梯度浓度顺铂处理ccRCC细胞后IC50值，WB法检测糖酵解代谢途径相关蛋白的表达，Seahorse XP96法检测各处理组细胞的胞外酸化率（ECAR）和耗氧率（OCR），试剂盒检测细胞中丙酮酸、乳酸、ATP水平。双荧光素酶报告基因和染色质免疫共沉淀（ChIP）实验验证ABCC3与MYC间的结合关系，RNA结合蛋白免疫沉淀（RIP）实验验证LINC00462和MYC的结合关系。结果：数据库分析和qPCR实验结果显示，ABCC3在ccRCC组织和细胞中呈高表达，差异基因富集在糖酵解通路上。敲减或过表达ABCC3能够增加A-498细胞或降低786-O细胞对顺铂的敏感性，ABCC3可通过促进有氧糖酵解抑制A-498细胞对顺铂的敏感性，2-DG处理可以逆转过表达ABCC3对ccRCC细胞对顺铂敏感性的抑制作用。MYC可直接和ABCC3结合，LINC00462可招募转录因子MYC；敲低LINC00462可抑制ABCC3的表达，敲低LINC00462可抑制ccRCC细胞的有氧糖酵解，并提高其对顺铂敏感性；而进一步过表达ABCC3可逆转敲低LINC00462对ccRCC细胞有氧糖酵解的抑制作用和顺铂敏感性的提高。结论：LINC00462通过招募转录因子MYC激活ABCC3的表达促进ccRCC细胞的糖酵解，进而促进ccRCC细胞对顺铂敏感性。

<b>Objective:b> To analyze the prevalence and co-prevalence of cardio metabolic (CM) risk factors in adults in China. <b>Methods:b> The project data of 2015 Nutritional Status and Health Transition of Chinese Residents were used, and 5 456 adults aged 18-59 years with complete socio-demographic, anthropometric, and blood biochemical data were selected as the study subjects. The definition released by the International Diabetes Federation in 2005 were used to define each CM risk factors, including central obesity, elevated TG, reduced HDL-C, elevated blood pressure and elevated FPG. The co-prevalence of the risk factors was defined as adults having ≥2 risk factors. Multivariable logistic regression analysis was performed to evaluate the relationship between CM risk and socio-demographic factors. <b>Results:b> About 80.8% of adults had at least 1 risk factor, and 54.0% had co-prevalence of risk factors. Gender, age, education level and living area were significantly associated with the prevalence of major metabolic risk factors. After adjusting for other factors, compared with men, women were more likely to have central obesity and reduced HDL-C, but not more likely to have elevated blood pressure, elevated FPG and elevated TG (P<0.01). Compared with adults aged 18-44 years, adults aged 45-59 years were more likely to have central obesity, elevated blood pressure, elevated FPG and elevated TG (P<0.01). The odds of having central obesity, elevated blood pressure and elevated fasting plasma glucose in the adults in eastern China were significantly higher than those in the central and western China. <b>Conclusions:b> In 2015, less than 20% of the adults aged 18-59 years in China had no cardio metabolic risk factors, and more than half of them had two or more risk factors. Gender, age and living areas were the major influencing factors. It is necessary to take effective intervention measures targeting adults at high-risk for the early prevention of cardiovascular disease.
Adolescent ; Adult ; Alcohol Drinking/epidemiology* ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Female ; Humans ; Male ; Metabolic Syndrome/ethnology* ; Middle Aged ; Obesity/ethnology* ; Prevalence ; Risk Factors ; Smoking/epidemiology* ; Socioeconomic Factors ; Young Adult

[摘 要] 目的：探讨低密度脂蛋白受体相关蛋白11（LRP11）在结直肠癌（CRC）组织中的表达及其对结肠癌SW480细胞增殖与凋亡的影响。方法：利用生物信息学方法分析TCGA数据库中LRP11在CRC组织中的表达水平。用慢病毒感染技术分别将sh-LRP11及sh-NC质粒转染至SW480细胞，采用qPCR、WB法检测感染后各组细胞中LRP11的mRNA和蛋白的表达，CCK-8法、流式细胞术分别检测细胞的增殖活力、凋亡率及细胞周期分布情况，WB法检测SW480细胞中cyclin D1、BAX、Bcl-2、β-catenin、活化β-catenin等蛋白的表达水平。结果：TCGA数据库数据分析显示，LRP11 mRNA在CRC组织中的表达水平显著高于正常组织（P<0.05）。与sh-NC组比较，sh-LRP11组SW480细胞的增殖活力明显降低、细胞凋亡率显著升高（均P<0.01），细胞中BAX表达显著升高、Bcl-2表达显著降低（均P<0.01）；G0/G1期细胞增多、S期细胞明显减少（均P<0.01），cyclin D1的蛋白表达显著降低（P<0.01）；Wnt/β-catenin信号通路中β-catenin和活化β-catenin的蛋白表达均显著下降（均P<0.01）。结论：LRP11 mRNA在CRC组织中呈高表达，干扰LRP11表达可抑制结肠癌SW480细胞增殖并促进其凋亡，为CRC提供了一种潜在的治疗靶点。

[Abstract] Objective: To analyze the expression of miR-185 and cell division cyclin 42 (CDC42) in osteosarcoma tissues and cells, and to preliminarily explore whether miR-185 affects the proliferation and migration of osteosarcoma MG63 cells by regulating CDC42. Methods: The cancer tissues and para-cancerous tissues of 28 patients with osteosarcoma that pathologically confirmed in the Fourth People's Hospital of Hengshui City from January 2020 to January 2021 were collected for this study. Immunohistochemistry was used to detect the expression of CDC42 in osteosarcoma tissues, and qPCR was used to detect the expression of miR-185 in osteosarcoma tissues. Dual-luciferase reporter gene experiment was applied to verify the targeting relationship between CDC42 and miR-185. According to different transfectants, MG63 cells were divided into miR-185 mimic group, miR-NC group, miR-185 inhibitor group, NC-inhibitor group, CDC42 group (transfected with CDC42 over-expression vector), and negative control (NC) group. The effects of miR-185 and CDC42 expression on the migration, proliferation and cell cycle of MG63 cells were detected by scratch healing assay, CCK-8 method and FCM, respectively. A nude mouse xenograft model was constructed by inoculating osteosarcoma MG63 cells. Immunohistochemistry, qPCR and WB methods were used to detect the effects of over-expression or knock-down of miR-185 on the expression of Ki67 and CDC42 in transplanted tumor tissues. Results: Compared with para-cancerous tissues, the expression of miR-185 in osteosarcoma tissues was significantly decreased, while the expression of CDC42 was significantly increased (all P<0.01). CDC42 was verified to be a target gene of miR-185. Compared with the control group, the migration and proliferation of MG63 cells in the miR-185 mimic group were inhibited (all P<0.01), while the migration and proliferation of MG63 cells in the CDC42 group were increased and the cell cycle was arrested in the S phase (all P<0.01). Compared with the miR-185 group, the migration and proliferation abilities of MG63 cells in the miR-185+CDC42 group were promoted, and the proportion of cells in S phase was increased (all P<0.01). Compared with the control group, the expression of Ki67 and CDC42 in the transplanted tumor tissues of miR-185 mimic group was significantly decreased (all P<0.01), while the opposite results were observed in miR-185 inhibitor group (all P<0.01). Conclusion: miR-185 is lowly expressed while CDC42 is highly expressed in osteosarcoma tissues. miR-185 can inhibit the proliferation and migration of osteosarcoma MG63 cells by negatively regulating the expression of CDC42.

<b>OBJECTIVEb>To confirm the antioxidant protective effect of peroxiredoxin 6 (Prdx6) in acute lung injury in mice.

<b>METHODSb>Lung injury or lung alveolar type II epithelial cell (AEC II) injury models were induced in mice by 100% O2 exposure or H2O2 treatments. Mice and AEC II cell survival rate or BALF analysis were applied for evaluating the degree of acute lung injury. Western Blot assay was used to determine Prdx6 or Gpx1 protein expression in lung. Annexin V staining method was applied to detect cell apoptosis on cultured AEC II cell, and thiobarbituric acid reactive substance (TBARS) measurement and diphenyl-1-pyrenyl phospholine (DPPP) assays were separately used to measure the level of lipid peroxidation in mice lung and AEC II cell membrane.

<b>RESULTSb>Under 100% O2 exposure, Prdx6-/- mice presented 24 h shorter survival time compared to wild type (WT) mice, on the contrary, Prdx6 gene over-expressed (Tg Prdx6) mice showed enhanced mice survival; meanwhile, the degree of AEC II cell injury had H2O2-dose dependent pattern with interactive relationship of Prdx6 protection. Under 100% O2 exposure for 72 h, it caused 7-fold decreased Gpx1 expression in Prdx6-/- mouse lung with no remarkable decrease of Prdx6 expression in Gpx1-/- mice. The percentage of apoptotic cells was significantly increased in AEC II cells from Prdx6-/- mice, and the percentage of AEC II apoptotic cells from Tg Prdx6 kept consistently around 10% under H2O treatments; also, the lipid peroxidation level of AEC II cell membrane was the highest in the group of Prdx6-/- mice, which was about 2 or 4-fold increased compared to the groups of WT or Tg Prdx6, separately; meanwhile, the lipid peroxidation level in Prdx6-/- mice, was also the highest compared to the other groups.

<b>CONCLUSIONSb>Prdx6 plays a critical role in defending acute oxidative lung injury and its function of defending cell apoptosis and cell membrane lipid peroxidation suggests its unique cell-based protective effect.

Acute Lung Injury ; metabolism ; prevention & control ; Animals ; Antioxidants ; metabolism ; Apoptosis ; Hydrogen Peroxide ; metabolism ; Lipid Peroxidation ; Lung ; drug effects ; metabolism ; Male ; Mice ; Mice, Knockout ; Peroxiredoxin VI ; metabolism

[摘 要] 目的：探讨过表达miR-497靶向细胞周期蛋白E1（cyclin E1，CCNE1）对肺癌A549细胞上皮间质转化（epithelial-mesenchymal transition，EMT）的影响。方法：常规培养人肺癌A549细胞，细胞实验分为正常组（不加干预）、对照组（转染miR-497 mimics-NC）、实验组（转染miR-497 mimics）。采用Transwell小室实验、免疫荧光染色、qPCR、Western blotting法分别检测各组细胞迁移和侵袭能力、蛋白间质标志物α-SMA和上皮标志物E-cadherin的表达、miR-497和CCNE1的表达水平，荧光素酶基因基因报告实验验证miR-497和CCNE1的靶向关系。结果：与对照组和正常组相比，实验组A549细胞迁移和侵袭的数量明显减少（均P<0.05），细胞的间质标志物α-SMA的绿色荧光强度明显减弱[（36.95±5.81） vs （98.69±2.36）、（97.94±2.63），均P<0.05]，上皮标志物E-cadherin的绿色荧光强度明显增强[（388.41±10.93） vs （100.95±6.37）、（102.55±3.18），均P<0.05]，miR-497的表达明显升高（均P<0.05），CCNE1的表达均明显下降（均P<0.05）。miR-497能够靶向调控CCNE1的表达。结论：在肺癌A549细胞中miR-497能够靶向调控CCNE1的表达，上调miR-497的表达后能明显抑制A549细胞迁移和侵袭能力，影响EMT相关蛋白的表达。

In the studies of modern epidemiology, exposure in a short term cannot fully elaborate the mechanism of the development of diseases or health-related events. Thus, lights have been shed on to life course epidemiology, which studies the exposures in early life time and their effects related to the development of chronic diseases. When exploring the mechanism leading from one exposure to an outcome and its effects through other factors, due to the existence of time-variant effects, conventional statistic methods could not meet the needs of etiological analysis in life course epidemiology. This paper summarizes the dynamic path analysis model, including the model structure and significance, and its application in life course epidemiology. Meanwhile, the procedure of data processing and etiology analyzing were introduced. In conclusion, dynamic path analysis is a useful tool which can be used to better elucidate the mechanisms that underlie the etiology of chronic diseases.
Chronic Disease/epidemiology* ; Epidemiologic Studies ; Humans ; Models, Theoretical ; Risk Factors ; Time

<b>Objective:b> To investigate the rates on prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014. <b>Methods:b> A cross-sectional survey was conducted in Beijing between 2013-2014. Stratified multistage random sampling method was used to select representative sample of 13 057 Chinese individuals aged over 15 years, from the general population. Blood pressure was measured for three readings at sitting position after resting for at least five minutes with an average reading recorded. A standardized structured questionnaire was developed to collect history of hypertension and antihypertensive treatment. <b>Results:b> A total of 4 663 community residents aged over 15 years were hypertensive among the 13 057 individuals, with the standardized prevalence rate as 32.7%, in Beijing area. The age-standardized prevalence rates of hypertension appeared 34.6% in men and 30.8% in women. The age-and sexstandardized prevalence of hypertension rates were 33.3% in urban and 24.6% in rural areas. The prevalence of hypertension increased with age and appeared higher in men than in women, in urban than in rural residents. Among the hypertensive patients, rates of awareness, treatment and control were 66.8%, 64.6% and 31.6%, respectively. <b>Conclusion:b> High prevalence of hypertension with low rates on awareness and treatment and control, appeared in the general population of Beijing. Related strategies should be developed regarding prevention, control and management of hypertension, to reduce the burden of this disease.
Adolescent ; Adult ; Age Distribution ; Aged ; Antihypertensive Agents/therapeutic use* ; Asian People/statistics & numerical data* ; Awareness ; Blood Pressure ; Blood Pressure Determination ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Hypertension/epidemiology* ; Male ; Middle Aged ; Prevalence ; Rural Population ; Sex Distribution ; Surveys and Questionnaires ; Urban Population ; Young Adult

<b>Objective:b> To investigate the effects of high iodine intake on thyroid function in pregnant and lactating women. <b>Methods:b> A cross sectional epidemiological study was conducted among 130 pregnant women and 220 lactating women aged 19-40 years in areas with high environment iodine level (>300 μg/L) or proper environment iodine level (50-100 μg/L) in Shanxi in 2014. The general information, urine samples and blood samples of the women surveyed and water samples were collected. The water and urine iodine levels were detected with arsenic and cerium catalysis spectrophotometric method, the blood TSH level was detected with electrochemiluminescence immunoassay, and thyroid stimulating hormone (FT(4)), antithyroid peroxidase autoantibody (TPOAb) and anti-thyroglobulin antibodies (TGAb) were detected with chemiluminescence immunoassay. <b>Results:b> The median urine iodine levels of the four groups were 221.9, 282.5, 814.1 and 818.6 μg/L, respectively. The median serum FT(4) of lactating women in high iodine area and proper iodine area were 12.96 and 13.22 pmol/L, and the median serum TSH was 2.45 and 2.17 mIU/L, respectively. The median serum FT(4) of pregnant women in high iodine area and proper iodine area were 14.66 and 16.16 pmol/L, and the median serum TSH was 2.13 and 1.82 mIU/L, respectively. The serum FT(4) levels were lower and the abnormal rates of serum TSH were higher in lactating women than in pregnant women in both high iodine area and proper iodine area, the difference was statistically significant (FT(4): Z=-6.677, -4.041, P<0.01; TSH: Z=8.797, 8.910, P<0.01). In high iodine area, the abnormal rate of serum FT(4) in lactating women was higher than that in pregnant women, the difference was statistically significant (Z=7.338, P=0.007). The serum FT(4) level of lactating women in high iodine area was lower than that in proper iodine area, the difference was statistically significant (Z=-4.687, P=0.000). In high iodine area, the median serum FT(4) in early pregnancy, mid-pregnancy and late pregnancy was 16.26, 14.22 and 14.80 pmol/L, respectively, and the median serum TSH was 1.74, 1.91 and 2.38 mIU/L, respectively. In high iodine area, the serum FT(4) level in early pregnancy was higher than that in mid-pregnancy and late pregnancy, and the serum TSH level was lower than that in mid-pregnancy and late pregnancy, the difference was statistically significant (FT(4): Z=-2.174, -2.238, P<0.05; TSH: Z=-2.985, -1.978, P<0.05). There were no significant differences in the positive rates of serum thyroid autoantibodies among the four groups of women and women in different periods of pregnancy (P>0.05). The morbidity rates of subclinical hyperthyroidism in pregnant women and lactating women in high iodine area were obviously higher than those in proper iodine areas, the difference was statistically significant (χ(2)=5.363, 5.007, P<0.05). <b>Conclusions:b> Excessive iodine intake might increase the risk of subclinical hypothyroidism in pregnant women and lactating women. It is suggested to strengthen the iodine nutrition and thyroid function monitoring in women, pregnant women and lactating women in areas with high environmental iodine.
Adult ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Hypothyroidism/epidemiology* ; Iodides/administration & dosage* ; Iodine/urine* ; Lactation ; Nutritional Status ; Pregnancy ; Prevalence ; Thyroid Diseases/epidemiology* ; Thyroid Function Tests ; Thyroid Gland/physiology* ; Young Adult

[摘 要] 目的：探讨紫甘薯花色苷（purple sweet potato anthocyanin, PSPA）是否通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。方法：选用乳腺癌MDA-MB-231细胞，将其分为对照组，200、400和800 μg/ml PSPA组，pcDNA组、pcDNA-circ_0003998组、si-NC组、si-circ_0003998组、si-circ_0003998+anti-miR-145组、PSPA+pcDNA组、PSPA+pcDNA-circ_0003998组和PSPA+anti-miR-145组。用qPCR法检测细胞中circ_0003998和miR-145的表达，CCK-8法、Transwell小室法分别检测转染前后细胞的增殖、迁移和侵袭能力，WB法检测细胞中Ki-67、MMP-2和MMP-9蛋白的表达。用双荧光素酶报告基因实验验证circ_0003998与miR-145的靶向关系。结果：与对照组比较，各剂量PSPA组MDA-MB-231细胞的增殖抑制率、miR-145表达水平均显著升高（均P<0.01），Ki-67、MMP-2、MMP-9蛋白和circ_0003998的表达水平、细胞迁移和侵袭细胞数均显著降低（均P<0.01），并呈现浓度依赖性。circ_0003998可以靶向负调控miR-145的表达。敲减circ_0003998后，MDA-MB-231细胞的增殖抑制率、miR-145表达水平显著升高，Ki-67、MMP-2和MMP-9蛋白表达水平、细胞迁移和侵袭细胞数均显著减少（均P<0.01）。共转染si-circ_0003998和anti-miR-145则可逆转敲减circ_0003998表达对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用，过表达circ_0003998或抑制miR-145表达可逆转PSPA对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用。结论：PSPA通过circ_0003998/miR-145轴抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。