OBJECTIVE:To quantitatively and qualitatively evaluate research trends and hotspots for immune checkpoint inhibitors (ICIs), according to the most frequently cited clinical trials. BACKGROUND:Numerous clinical trials have been carried out using ICIs for activating anti-tumor immunity in cancer patients. The most frequently cited clinical trials have been used as a database for achieving the objectives of this analysis. MATERIALS AND METHODS:The most frequently cited articles on ICIs meeting the inclusion criteria were extracted from the Web of Science database. Citation report information including annual outputs, most relevant journals, and country of origin together with burst references, keywords, information on co-occurrence, citation networks, and cluster topics were analyzed using standard bibliometric procedures. RESULTS:A total of 112 most frequently cited articles on clinical trials of ICIs were retrieved for the period 2013 to 2021 of which the journal JAMA Oncology had the highest number of citations. Most studies originated in the U.S., and therefore studies from this country had a determinant effect of the results of the investigation. Burst reference topics included studies on ipilimumab for melanoma, anti-PD-L1 antibody in advanced cancer, anti-PD-1 antibody in cancer, nivolumab combined with ipilimumab or as monotherapy in untreated melanoma, and pembrolizumab for PD-L1 positive non-small-cell lung cancer. Nine clusters were grouped in the citation network. The topic/keywords "cancer", "immunotherapy", "PD-1 blockade", "PD-L1", "expression", "ipilimumab", "nivolumab", "pembrolizumab", and "safety" were the search priorities, whereas "multicenter", "resistance", "adverse events", and "renal-cell carcinoma" were seen as emerging topics in this specific field. CONCLUSION:The bibliometric analysis of the most frequently cited clinical trials with ICIs provided information on the characteristics of the studies evaluated as well as hotpots and trends in evolving immunopharmacotherapy research on ICIs.

This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery occlusion(MCAO) via the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/C-X-C motif chemokine receptor 4(CXCR4) pathway. SD rats were randomized into sham, MCAO(model), and tetramethylpyrazine(TMP, 20 mg·kg~(-1) and 40 mg·kg~(-1)) groups. The neurological impairment was assessed by the modified neurological severity score(mNSS). The immunofluorescence assay was employed to detect the cells stained with both 5-bromodeoxyuridine(BrdU) and doublecortin(DCX) in the brain tissue. The effect of TMP on the migration of C17.2 cells was observed. Western blot was employed to determine the protein levels of Nrf2, HO-1, p62, NAD(P)H quinone oxidoreductase 1(NQO1), stromal cell-derived factor 1(SDF-1), and CXCR4 in the brain tissue and C17.2 cells. The results showed that after 7 days and 21 days of mode-ling, the mNSS and BrdU~+/DCX~+ cells were increased, and the expression of Nrf2 and CXCR4 in the brain tissue was up-regulated. Compared with the model group, TMP(40 mg·kg~(-1)) reduced the mNSS, increased the number of BrdU~+/DCX~+ cells, and up-regulated the expression of Nrf2, CXCR4, and SDF-1. In addition, TMP promoted the migration of C17.2 cells and up-regulated the expression of p62, Nrf2, HO-1, and NQO1 in a time-and dose-dependent manner. The expression was the highest at the time point of 12 h in the TMP(50 μg·mL~(-1)) group(P<0.01). In conclusion, TMP activates the Nrf2/HO-1/CXCR4 pathway to promote the migration of NSCs to the ischemic area, thus exerting the therapeutic effect on the ischemia-reperfusion injury. This study provides experimental support for the application of TMP in ischemic stroke.

Background:This study investigated the role and mechanisms of cullin-1 (CUL1) in chronic obstructive pulmonary disease (COPD). Methods:Cigarette smoke extract (CSE)-treated mouse pulmonary microvascular endothelial cells (mPMECs) and cigarette smoke inhalation (CSI)-stimulated mice were used to construct in vitro and in vivo COPD models, respectively. CUL1 expression was assessed using reverse transcriptase-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect cell viability and apoptosis, respectively. We conducted an enzyme-linked immunosorbent assay on mPMECs and bronchoalveolar lavage fluid (BALF) to detect inflammatory factors. Reactive oxygen species, malondialdehyde, and superoxide dismutase were detected using the corresponding kits. The histological characteristics of the lung tissues were determined by hematoxylin and eosin staining. Results:CUL1 expression was downregulated in COPD. CUL1 overexpression significantly promoted cell viability, reduced cell apoptosis, and inhibited inflammatory responses and oxidative stress in CSE-treated mPMECs. These changes were reversed by the p53 agonist nutlin-3. In addition, CUL1 overexpression significantly relieved COPD in mice, as confirmed by the reduced secretion of inflammatory factors in BALF, inhibited oxidative stress response, and improved lung function. Conclusion:CUL1 plays a protective role in CSE-treated mPMECs and CSI-stimulated mice by inhibiting the p53 signaling pathway.

Background Chronic unpredictable mild stress (CUMS) has been shown to exacerbate atherosclerosis, but the underlying mechanism remains unknown. Adipose tissue is an energy storage organ and the largest endocrine organ in the human body, playing a key role in the development of cardiovascular disease. In this research, it was hypothesized that CUMS may exacerbate the development of atherosclerosis by inducing the hypertrophy and dysfunction of white adipocytes. Methods The CUMS-induced atherosclerosis model was developed in Western diet-fed apolipoprotein E (ApoE)-/- mice. White adipose tissue (WAT), serum, aortic root, and the brachiocephalic trunk were collected and tested after 12 weeks of CUMS development. The mouse model of CUMS was evaluated for depression-like behavior using the open field test (OFT) and the elevated plus maze (EPM) test. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum noradrenaline and urine adrenaline protein levels. Serological assays were used to detect serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and free fatty acid (FFA) concentrations. Hematoxylin and eosin (H&E) staining and oil red O were used to detect atherosclerotic plaque area, lipid deposition, and adipocyte size. The mRNA levels of genes related to aberrant adipose tissue function were determined using real-time PCR. Immunofluorescence assay and western blotting were conducted to examine the expression of proteins in the adipose tissue samples. Results CUMS aggravated vascular atherosclerotic lesions in ApoE-/- mice. It decreased body weight while increasing the percentage of WAT. The serological results indicated that the concentration of HDL decreased in CUMS mice. Notably, adipocyte hypertrophy increased, whereas the mRNA levels of Pparg and its target genes (Slc2a4 (encodes for GLUT4), Adipoq, and Plin1) decreased. Further investigation revealed that CUMS increased subcutaneous inguinal WAT (iWAT) lipid synthesis and adipocyte inflammation while decreasing lipid hydrolysis and the expression of HDL-associated protein ApoA-I. Moreover, CUMS aggravated insulin resistance in mice and inhibited the insulin pathway in iWAT. Conclusions These findings indicated that CUMS induces adipose tissue dysfunction via a mechanism that leads to dyslipidemia, increased inflammation, and insulin resistance in the body, thereby exacerbating atherosclerosis. Notably, CUMS that is involved in decreasing the expression of HDL-associated proteins in adipose tissue may be a crucial link between adipose hypertrophy and advanced atherosclerosis. This study reveals a novel mechanism via which CUMS exacerbates atherosclerosis from the novel perspective of abnormal adipose function and identifies a novel potential therapeutic target for this disease.

This study analyzed total fatty acids (FAs) and their sn-2 positional distribution in triacylglycerol (TAG) in breast milk (n = 300) from three lactational stages in five regions of China, and further investigated their association with the effect of the type of edible oil consumed by lactating mothers. A total of 33 FAs including 12 saturated fatty acids (SFAs), 8 monounsaturated fatty acids (MUFAs), and 13 polyunsaturated fatty acids (PUFAs) were determined using GC. Breast milk from different regions showed significant differences in MUFAs, sn-2 MUFAs, and PUFAs (P < 0.01, P < 0.001, and P < 0.001). The results showed that 10 : 0, 18 : 0, 18 : 1 n-9, 18 : 2 n-6 (LA), and 18 : 3 n-3 (ALA) were mainly esterified at the sn-1 and sn-3 positions; 20 : 4 n-6 (ARA) seemed homogeneously esterified at all sn-positions in TAG, while 14 : 0, 16 : 0, and 22 : 6 n-3 (DHA) were primarily esterified at the sn-2 position. In breast milk, major FAs (16 : 0, 18 : 1 n-9, LA, and ALA) and the ratio of PUFAs (LA/ALA and n-6/n-3) were obviously influenced by maternal edible oils. Breast milk from mothers consuming rapeseed oil had the lowest LA (∼19%) and the highest ALA (∼1.9%). The MUFAs, especially 18 : 1 n-9, in breast milk from mothers consuming high oleic acid oils were significantly higher than those in breast milk from mothers consuming other types of edible oils. These results provide a potential nutritional strategy for better breastfeeding by specifically adjusting maternal edible oils despite other fat sources being part of the diet of lactating women.

Objective To investigate the baseline and effect of obesity and obesity trajectories on cardiovascular diseases(CVDs) in adult male with incident non-alcoholic fatty liver disease(NAFLD). Methods Adult men with newly diagnosed NAFLD and without CVDs in the Kailuan cohort study from 2006—2013 were enrolled. The subjects were divided into the nonobese group and obese group according to the definition of body mass index(BMI) or waist circumference (WC), then further divided by the obesity trajectories at the first follow-up (1-4 years). Kaplan-Meier method was used to estimate the incidence rate of CVDs for each subgroup. In addition, the Fine and Gray competing risk Cox regression model was used to compare CVDs risk in NAFLD with different baseline or trajectories in obesity measures after 1-4 years of NAFLD diagnosis. Results A total of 8 591 incident NAFLD patients were included. During a median follow-up of 9.41 years, 349 cases were found with CVDs. The 10-year cumulative incidence rates of CVDs were 3.3% and 4.3% in the nonobese and obese groups according to the definition of waist circumference, respectively (log-rank test, P＜0.05). However, the significance disappeared after adjusting the competing risk of death and other covariates. Similar results were observed based on the definition of BMI. Also, further analysis was conducted for the association trajectories in obesity measures and CVDs. The 8-year cumulative incidence rates of CVDs were 2.8%, 3.6%, 4.2%, and 3.3% in the constantly nonobese group, nonobese-obese, obese-nonobese, and constantly obese group, respectively (log-rank test, P＞0.05). Compared to the subjects with constantly nonobese defined by BMI, those who transition from nonobese to obese increased the CVDs risk by 57% (hazard ratio [HR]:1.57; 95% CI:1.03~2.38; P＜0.05). The conclusion remained even after adjusting baseline BMI (HR:1.56; 95% CI:1.02~2.37; P＜0.05). Conclusions Short-term weight gain in men with incident NAFLD led a higher CVDs risk, suggesting the importance of weight control in preventing CVDs once NAFLD occurrence.

心血管疾病(cardiovascular disease,CVDs)是全世界普遍存在的一种疾病,其发病率和死亡率均居于首位[1].高脂血症作为发生此类疾病的高危因素之一,可直接引起严重的心血管疾病,例如动脉粥样硬化等.其中脂蛋白代谢紊乱,血浆脂质如低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)异常升高可增加动脉内斑块的聚集,提高动脉粥样硬化性心血管疾病的患病风险.有研究显示,血浆甘油三酯(triglycerides,TG)的升高也是导致动脉粥样硬化发生的风险因子[2-3].随着人们生活方式的改变和生活水平的提高,心血管疾病逐渐年轻化,因此,早期发现和治疗对于降低心血管疾病的发生和发展至关重要[1].近几 年已经有多个有效降低 LDL-C 的药物上市,包括他汀类 药物和 PCSK9 抑制剂,然而针对降低血浆 TG 的疗法并不多.血管生成素样蛋白 3(angiopoietin-like protein 3, ANGPTL3)自被发现以来,一直受到人们的关注.已有文献报道,ANGPTL3 可通过抑制脂蛋白脂肪酶(lipoprotein lipase,LPL)和内皮脂肪酶(endothelial lipase,EL)等的活性,导致血浆 TG 及 LDL-C 水平升高[4-6].人类遗传学研究表明,angptl3 基因天然缺失的杂合子个体的心血管疾病患病风险下降约 40％,且其血浆 LDL-C 和 TG 水平都有显著下降.因此,ANGPTL3 被认为在脂蛋白代谢调控中发挥了关键的作用,成为调节血浆脂质水平和降低心血管疾病风险的重要研究靶标[7].本文将从以下几个方面进行综述.

目的 介绍国内外基于医疗大数据库开展上市后药品监测与评价研究的现状、存在的偏倚及其可能的控制方法,为我国药品风险监测与管理提供参考.方法 系统总结欧美发达国家基于医疗大数据开展药品上市后监测与评价的具体实践,分析我国存在的差距;评价在研究设计、数据收集与标准化、统计分析等方面存在的问题及可以改进的方法;探讨我国目前面临的机遇与挑战.结果 与结论 欧美国家已经基于医疗大数据建立了高效、可持续的药品上市后监测警戒系统;充分考虑并控制研究设计、实施和统计分析中的潜在偏倚是确定药品与不良反应因果关系的前提;应借鉴欧美先进经验,完善和整合现有医疗大数据,开展药物流行病学方法学研究.

Atherosclerosis (AS) is a potential inducer of numerous cardio-cerebrovascular diseases. However, little research has investigated the expression of TPM2 in human atherosclerosis samples. A total of 34 clinical samples were obtained, including 17 atherosclerosis and 17 normal artery samples, between January 2018 and April 2021. Bioinformatics analysis was applied to explore the potential role of TPM2 in atherosclerosis. Immunohistochemistry, immunofluorescence, and western blotting assays were used to detect the expression of TPM2 and α-SMA proteins. The mRNA expression levels of TPM2 and α-SMA were detected using RT-qPCR. A neural network and intima-media thickness model were constructed. A strong relationship existed between the intima-media thickness and relative protein expression of TPM2 (P<0.001, R=-0.579). The expression of TPM2 was lower in atherosclerosis than normal artery (P<0.05). Univariate logistic regression showed that TPM2 (OR=0.150, 95% CI: 0.026-0.868, P=0.034) had clear correlations with atherosclerosis. A neural network model was successfully constructed with a relativity of 0.94434. TPM2 might be an independent protective factor for arteries, and one novel biomarker of atherosclerosis.

Objective: Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation. Approach and Results: E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of 3 H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with 3 H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE −/− mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway. Conclusions: E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure-activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 +/- 0.5 mu M, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via downregulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1 alpha and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.

Background: Elevated serum uric acid (SUA) level is considered an independent predictor of all-cause mortality and the combined endpoint of death or readmission in cardiovascular disease patients. However, the causal relationship between uric acid-lowering therapies (ULTs) and heart failure is still controversial. Design: Meta-analyses were performed to systematically compile available evidence to determine the overall effect of ULTs on heart failure patients. Method: We conducted this systematic review following the PRISMA statement guidelines. Databases were searched to identify randomised controlled trials related to the influence of a ULT intervention in people with heart failure. Data extracted from the included studies were subjected to a meta-analysis to compare the effects of ULTs to a control. Results: Pooled analysis of left ventricular ejection fraction (LEVF) showed an insignificant result towards the ULT group (MD, 1.63%; 95%CI, −1.61 to 4.88; p = 0.32; three studies). Pooled analysis of the 6-Minute Walk Test (6MWT) showed an insignificant result towards the ULT group (MD, 4.59; 95%CI, −12.683 to 22.00; p = 0.61; four studies). Pooled analysis of BNP/NT-pro-BNP led to a nearly statistically significant result towards the ULT group (SMD, −0.30; 95%CI, −0.64 to 0.04; p = 0.08; five studies). Pooled analysis of all-cause mortality and cardiovascular death between ULTs (all XOIs) and placebo did not show a significant difference (RR, 1.26; 95% CI, 0.74 to 2.15, p = 0.39). Conclusion: ULTs did not improve LVEF, BNP/NT-pro-BNP, 6MWT, all-cause mortality, and CV death in heart failure patients. UA may just be a risk marker of heart failure.

目的 探讨初诊肺腺癌患者治疗前氟-18-脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射型计算机断层扫描显像(positron emission tomography/computed tomography,PET/CT)的左心室心肌代谢是否发生改变及其影响因素.方法 分析182例新确诊肺腺癌的患者及与其年龄和性别匹配的45例非肿瘤患者(对照组)的18 F-FDG PET/CT显像.比较两组患者左心室心肌、动脉、心外膜脂肪组织(epicardial adipose tissue,EAT)、脾脏、骨髓的代谢.采用多因素Logistic回归分析肺腺癌患者左心室心肌代谢增高的影响因素.结果 与对照组相比,初诊肺腺癌患者治疗前左心室心肌代谢显著增高(P=0.05),动脉、EAT、脾脏及骨髓的代谢在两组间差异无统计学意义(P>0.05).Logistic回归分析显示,EAT代谢与肺腺癌患者左心室心肌代谢增高具有独立的正相关性(OR=6.8,95％CI=1.1～42.4,P=0.039).结论 肺腺癌患者抗肿瘤治疗前左心室心肌代谢较非肿瘤患者显著增高,EAT代谢是肺腺癌患者左心室心肌代谢增高的独立影响因素.

Objective To investigate the association between whole blood iron, copper and their interaction with cardiovascular diseases (CVD). Methods A cohort-based case control study was conducted. Cases were 93 males with CVD in the Kailuan cohort who participated in the follow-up in 3 hospitals in 2017-2018. During the same period, 372 males with non-CVD who were 1∶4 individual matched by age and labor type were selected as controls. The concentration of blood iron and copper was determined by inductively coupled plasma mass spectrometry. Conditional logistic regression models were used to estimate the association between blood iron and copper and CVD, respectively and elastic-Net regression models to estimates interaction between the two metals and CVD. Results The whole blood iron concentration in the cases was significantly higher than the controls, while blood copper concentration was lower than the controls (both P＜0.001). After adjusting for age, smoking, drinking, overweight, hypertension, diabetes, anemia, hyperlipidemia, and high sensitivity C-reactive protein, the participants with higher iron increase 3.17 times (OR=4.17, 95% CI: 2.23-7.79, P＜0.001) risk of CVD than those with lower iron, and those with lower copper increase 3.26 times (OR=4.26, 95% CI: 1.73-10.45, P＜0.01) risk than those with the higher copper. Adaptive Elastic-net regression analysis showed that it under the simultaneous exposure of higher iron and lower copper, the risk of CVD with environment risk score ＞0.232 was 8.96 times (OR=8.96, 95% CI: 4.47-17.95, P＜0.001) than the score ≤0.232. Conclusions Higher iron and copper deficiency may be independent risk factors for CVD. Environment risk score could be a good indicator of simultaneous exposure of blood iron and copper, which should have a better predictive value of CVD.

目的 研究慢性阻塞性肺疾病(简称慢阻肺)合并焦虑抑郁患病情况,提高医务工作者对慢阻肺合并焦虑抑郁的认知.方法 收集并分析2017年1月至2019年1月参加本研究410例患者的基线资料.采用综合医院焦虑/抑郁情绪量表前瞻性测评慢阻肺合并焦虑抑郁患病情况.结果 患者年龄(60.7±10.0)岁,76.8％男性,74.3％吸烟者.检出焦虑或抑郁79例(19.3％),其中焦虑36例(8.8％),抑郁64例(15.6％),同时合并焦虑和抑郁21例(5.1％),严重焦虑11例(2.7％),严重抑郁10例(2.4％).与单纯慢阻肺患者相比,合并焦虑抑郁慢阻肺患者的CAT评分明显增高[合并焦虑(17.8±9.3)分,合并抑郁(17.4±8.4)分,单纯慢阻肺为(12.5±7.3)分,P值分别为0.002和0.000].合并抑郁患者≥2次急性加重风险增加(37.5％比22.7％,P=0.016).GOLD综合评估,合并抑郁慢阻肺患者的D组占比增高(P=0.001).结论 20％慢阻肺患者合并焦虑或抑郁,抑郁检出率几乎是焦虑两倍,严重焦虑或抑郁患病率较低.与单纯慢阻肺患者相比,合并抑郁慢阻肺患者的健康相关生活质量较差,急性加重风险增高,GOLD综合评估的D组占比增高.

目的:探讨放射性碘治疗(RAI)中131I治疗分化型甲状腺癌(DTC)功能性肺转移的短期疗效及其影响因素.方法:分析在医院行RAI的16例发生功能性肺转移的DTC患者,所有患者均行131I治疗,每次131I治疗前1月内行颈部超声、胸部CT检查,治疗前3～4 d测定血清甲状腺功能的T3、T4、FT3、FT4、Tg、抗甲状腺球蛋白抗体(TgAb)和促甲状腺激素(TSH)水平,131I治疗后5～7 d行131I单光子发射型电子计算机断层扫描/CT(SPECT/CT),治疗后2～3个月后复查并进行疗效评估,根据131I治疗的功能性肺转移的短期疗效将16例患者分为完全缓解(CR)组(11例),部分缓解(PR)组(4例),无效(NR)组(1例),并且分析不同疗效的影响因素.结果:在行131I治疗的16例功能性肺转移的DTC患者中,CR组11例,PR组4例,NR组1例.16例功能性肺转移DTC患者治疗总有效率为93.75％(15/16).3组末次手术与首次131I治疗间隔、肺外转移情况及首次131I治疗前血清Tg水平比较,差异有统计学意义(x2=4.535,x2=6.541,x2=5.403;P<0.05).病理类型、性别、诊断DTC时年龄、有无甲状腺外侵犯、有无甲状腺被膜外纤维组织和横纹肌侵犯、有无神经侵犯、有无脉管瘤栓和淋巴结转移个数、手术次数、131I治疗次数及131I累积剂量在3组间差异无统计学意义.结论:RAI是治疗DTC患者术后发生功能性肺转移的有效方法,患者短期治疗疗效良好.131I的治疗疗效与末次手术与首次131I治疗间隔时间、肺外转移情况以及首次131I治疗前Tg水平相关.

One of the characteristics on cohort studies is that exposures may change over time. The full use of information related to time-updated exposures, time-dependent covariates and their relationships to estimate the association between exposures and outcomes has become the hotspot of research. In this paper, the Kailuan cohort is used as an example to explore the association between fasting blood-glucose and hepatocellular carcinoma, based on different Cox regression models. Cox or time-dependent Cox regression models can be used to estimate the impact of exposure at baseline or on the time-updated exposures. When time-dependent confounders exist, marginal structure model is recommended. We also summarize the basic principles, conditions of applications, effect estimates, and results interpretation for each model, in this paper.

Objective: To investigate the incidence, location and etiology of abnormal cardiac uptake in patients underwent oncologic 18F-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT) imaging. Methods: The 18F-FDG PET/CT images of 2000 consecutive patients with suspected or diagnosed malignancy in Beijing Chaoyang Hospital from January 2014 to September 2016 were retrospectively analyzed. Fasting time was more than 12 hours before imaging, and fasting blood glucose level before 18F-FDG injection was less than 6.7 mmol/L. Focal uptake in the non-basal and non-papillary regions of the left ventricle, uptake in the right ventricle exceeding uptake in the left ventricle, and uptake in the atrium higher than that of the blood pool (when uptake of left ventricle was zero or low) were defined as abnormal, and all abnormal uptake was visually determined by experienced nuclear medicine physicians. General clinical data and the results of cardiac examination were collected to explore the incidence, location and etiology of cardiac diseases. Results: There were 138 patients with history of diabetes (6.90%), 228 patients with history of cardiovascular disease (11.40%) out of the 2 000 patients ((60.5±13.2) years, 1 117 male (55.85%)). The number and proportion of patients with malignancy, benign lesions, diseases of unknown etiology were 939 (46.95%), 484 (24.20%), 557 (28.85%), respectively. Abnormal cardiac uptake was detected in 145 patients (7.3%). The proportion of abnormal uptake in left ventricle, right ventricle and atrium was 52.4% (76 cases), 12.4% (18 cases), 35.2% (51 cases), respectively. Of the 76 individuals who had abnormal uptake in left ventricle, 25 cases (32.9%) were caused by coronary artery disease, and other causes included hypertrophic cardiomyopathy and myocardial damage caused by chemotherapy drugs, etc. Of the 18 cases who had abnormal uptake in right ventricle, 14 cases (14/18) were caused by pulmonary hypertension. In addition, 20 out of the 51 cases (39.3%) with abnormal uptake in atrium suffered from atrial fibrillation. Seventy-one patients with abnormal cardiac uptake (49.0%) had no clear manifestation and evidence of heart disease before imaging. Conclusions: The abnormal 18F-FDG uptake on oncologic PET/CT is not rare. The most common site of abnormal uptake is left ventricle, coronary artery disease, pulmonary hypertension and atrial fibrillation are common causes of abnormal 18F-FDG uptake.

真实世界数据研究近年来发展迅速,但目前对其认识和理解仍然还存在诸多误区。为推动真实世界数据研究的标准化,本文对真实世界数据的分类进行了更新和进一步明确,提出了真实世界数据研究的两种常用模式,构建了研究型数据体系框架,尤其厘清了对登记数据库的误区和问题,对真实世界数据研究的未来发展方向进行了展望。

Objective: To investigate the prevalence of Crohn's disease (CD) among urban employees in 24 provinces (municipalities and autonomous regions) in China in 2013. Method: The crude annual prevalence of CD among urban employees with medical insurance in 2013 was estimated by using the basic medical insurance database of 24 provinces (municipalities and autonomous regions), as well as the prevalence by sex, age and region. The age-standardized rate based on the 2010 census was also estimated. Results: The crude prevalence of CD among urban employees in 2013 was 3.2/100 000(95%CI:3.1/100 000-3.3/100 000) , and the sex-specific rate was 3.5/100 000 (95%CI:3.3/100 000-3.6/100 000) and 3.0/100 000 (95% CI:2.8/100 000-3.1/100 000) for male and female, respectively. The crude prevalence in different regions indicated that the highest crude prevalence was in the eastern region [5.6/100 000 (95% CI:5.4/100 000-5.8/100 000) ]. Conclusion: The prevalence of CD in China is still lower than that of the western countries, with difference varied in terms of age, gender and region.