Background.
Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular ...diastolic dysfunction (LVDD) and its relationship to the dose‐volume of the heart irradiated were evaluated in HER2‐positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT).
Materials and Methods.
Data from 40 breast cancer patients treated with concurrent trastuzumab and left‐sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right‐sided adjuvant RT and 71 patients treated with left‐sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified.
Results.
Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left‐sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15–D40, D60–D70, and V3–V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left‐sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left‐sided RT alone.
Conclusion.
Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose‐volume of the heart contributes significantly to the risk of LVDD in patients with left‐sided breast cancer treated concurrently with trastuzumab.
Implications for Practice:
Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose‐volume of the heart irradiated in patients with left‐sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose‐volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.
摘要
背景. 左心室射血分数（LVEF）常规用于监测与乳腺癌治疗相关的心脏功能障碍。本研究在接受曲妥珠单抗联合同期辅助放疗（RT）的HER2阳性乳腺癌患者中，对左心室舒张功能障碍（LVDD）的患病率及其与心脏照射剂量‐体积的关系进行了评价。
材料和方法. 我们前瞻性地在2011年9月至2012年10月期间收集了40例接受曲妥珠单抗联合同期左侧辅助放疗的患者数据。另外，我们还回顾性地收集了32例接受曲妥珠单抗联合同期右侧辅助放疗患者数据，以及71例仅接受左侧放疗的患者数据用于对比。在放疗前、放疗后即刻，以及放疗后3个月和6个月行超声心动图检查。确定心脏和左心室（LV）接受的照射剂量。
结果. 在给予曲妥珠单抗联合同期放疗前，基线左心室舒张功能（LVDF）正常的患者中，分别有11/29例（左侧）和8/25例（右侧）在治疗后发生了LVDD。在仅接受左侧放疗的患者中，12/61例基线LVDF正常的患者发生了LVDD。曲妥珠单抗联合同期左侧放疗后发生LVDD的患者左心室Dmean、D15‐D40、D60‐D70和V3‐V10均显著较高。相反，在接受同期治疗和仅左侧放疗的患者中，仅2例患者发生了1级LVEF下降。
结论. 通过比较LVEF检测到的LVDF改变在早期发现心脏毒性方面更为敏感。对于接受同期放疗联合曲妥珠单抗治疗的左侧乳腺癌患者而言，心脏剂量‐体积为LVDD的显著风险因素。The Oncologist 2015;20:605–614
对临床实践的意义： 在接受放疗联合同期曲妥珠单抗治疗的左侧乳腺癌患者中，舒张功能异常在发现急性心脏毒性方面比左心室射血分数改变更为敏感，且与心脏剂量‐体积相关。这项结果强调了在接受曲妥珠单抗联合同期放疗患者中，采用减少心脏照射剂量‐体积作为保护策略的重要性。对于心脏损伤，舒张功能障碍可以作为更为敏感的早期检测工具，并且应该纳入常规心脏毒性功能监测参数之中。
Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose‐volume of the heart irradiated in patients with left‐sided breast cancer receiving radiotherapy with trastuzumab, highlighting the importance of decreasing the dose‐volume as a protective strategy. Therefore, diastolic dysfunction should be incorporated as a routine parameter in the monitoring of cardiotoxicity.
Aims The brachial-ankle pulse wave velocity (baPWV) has been recognized as a marker that reflects arterial stiffness. We conducted an investigation to evaluate whether baPWV is independently ...associated with early mild diastolic heart failure (DHF) in a general middle and aged population. Methods and results From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV, echocardiography, and blood sampling were performed in the morning after a 12 h overnight fast. A total of 1929 subjects had the complete data, including questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio. Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A ratio <0.8, and E/E′ ≤ 8; finally, 482 subjects with early mild DHF and 1282 subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the subjects were male (average age was 58.0 ± 12.3), 35.8% of the subjects had hypertension, the average body mass index (BMI) was 24.2 ± 3.3 kg/m2, baPWV was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with the E/A ratio (r = −0.39, P < 0.01). There was a difference of the baPWV 1456.0 (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s between the non-DHF group and the early mild DHF group (P < 0.01). Multiple logistic-regression analyses demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall thickness (PVWT), interventricular septal thickness (IVST), E/E′ ratio, left ventricular mass index (LVMI), systolic blood pressure (≥140 mmHg), and diastolic blood pressure (≥90 mmHg) were independently correlated with early mild DHF. Conclusions The increased arterial stiffness is associated with early mild DHF in a general middle and aged population independently of age, male gender, BMI, PVWT, IVST, E/E′ ratio, LVMI, and high blood pressure. The non-invasive techniques described may allow serial measurements to be made over time to monitor baPWV changes in arteries provided the introduction of anti-arteriosclerosis therapy.
Single nucleotide polymorphism in miRNAs can alter its expression, thus can lead to the development of cancers. Many studies have explored the association between miR-146a rs2910164 (G>C) ...polymorphism and hepatocellular carcinoma (HCC) risk, but the results remains inconsistent. So, we performed this pooled analyses in order to get a precise result.
Odds ratios (OR) with 95% confidence intervals (CI), calculated by STATA software, was used to determine whether miR-146a rs2910164 polymorphism contributes to the risk of HCC. A comprehensive literature search was conducted on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure up to May 30, 2016.
A total of 14 studies including 5921 cases and 7005 controls were included in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, the miR-146a rs2910164 was associated with a decreased risk of hepatocellular carcinoma (OR=0.90; 95% CI=0.82-0.98, P=0.01, allele model).
Our meta-analysis supports that the miR-146a rs2910164 polymorphism contributes to the risk of HCC from currently available evidence.
Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its ...significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
Thiopurine dose optimization by thiopurine‐S‐methyltransferase (TPMT) or nudix hydrolase‐15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 ...months). Although laboratory monitoring of 6‐thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA‐thioguanine nucleotides (DNA‐TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA‐TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells < 3.5 × 109/L) were observed in 43 patients (14.0%), who had significantly higher DNA‐TG concentration than those without leucopenia (P = 4.1 × 10–9, 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/μg DNA). No difference in 6TGN concentrations between leucopenia and non‐leucopenia was found. With a DNA‐TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA‐TG was an independent risk factor for late leucopenia. Quantification of DNA‐TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD.
Abstract Immature Litsea mollis fruits (ILMFs) are widely used as cold appetizers and seasonings in China. The free and bound volatile components of ILMFs from five distinct regions of China were ...determined by gas chromatography-mass spectrometry (GC-MS) combined with headspace solid phase microextraction (SPME) in the present work. The results reveal sixty six free-form volatiles and fifty two bound-form volatiles in ILMFs and terpene hydrocarbons and oxygenated terpenes are the dominate components. In addition, sixty-seven volatile compounds are found in Litsea mollis fruit for the first time. The free α-pinene, eucalyptol, linalool, α,β-citral, geraniol and citronellal, and bound β-myrcene, α-citral, geraniol, citronellal and eugenol are the major odor contributors of ILMFs. Multivariate statistical analysis indicates that the free and bound volatiles profiles of ILMFs of Fujian and Guangxi in southern China are similar and those of Yunnan and Sichuan in southwestern China are similar. The odor profiles of all of the ILMFs are floral, fruity and herbaceous.
Abstract This study optimized using a headspace solid-phase microextraction (HS-SPME) method for extracting volatile aroma compounds, terpenoids in particular, from Litsea mollis Hemsl. immature ...fruit (LMIF). Gas chromatography-mass spectrometry was used to separate and identify volatile terpenoids in LMIF. The types of SPME fiber coating, salt addition, and desorption time were optimized by single factor-experiments to determine the range of extraction temperature. Built on insights from the single factor-experiments, the response surface methodology was further used to optimize the extraction temperature, extraction time, and equilibrium time of HS-SPME. The results showed that the optimal HS-SPME conditions for extracting volatile terpenoids from LMIF were: 50/30 μm of DVB/CAR/PDMS SPME fiber, 2.0 g of added sodium chloride, desorption at a temperature of 250 °C for 3 min, extraction and equilibrium temperature of 46 °C, extraction time of 36 min, and equilibrium time of 20 min. Under the above conditions, the predicted value of extraction was 66.92, while the experimental value was 65.78. The prediction value matched well with the experimental value with good repeatability. The designed model was proven to be valid, which can be applied for future extraction of aroma compounds from IMIF.
Abstract Objective Current whole genome-wide association study has identified the association of JAZF1 with type 2 diabetes; its close relation with glucose and lipid metabolism has also been ...revealed. However, to date, JAZF1 remains a relatively new gene with unknown function. Materials/Methods We constructed JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them into 3 T3-L1 adipocytes, investigated the relationship between the regulations of JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1 in glucose and lipid metabolism. Results This study found that the expression of JAZF1 was gradually but significantly upregulated during the induced differentiation of 3 T3-L1 preadipocytes, and that the trend of its expression was consistent with that of visfatin. Further studies indicated that JAZF1 promoted the expressions of visfatin, PPARα, and PPARβ/δ in adipocytes but simultaneously inhibited the expressions of TAK1 and PPARγ. Luciferase reporter assay revealed that JAZF1 activated the transcription of visfatin, but ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE. Our results also showed that the JAZF1 overexpression-increased visfatin expression was abolished by the addition of PPARα antagonist GW 6471 and PPARβ/δ antagonist GSK 3787 respectively. And these results were further confirmed by the experiment with PPARα and PPARβ/δ siRNAs. Meanwhile, we also found that JAZF1 inhibited the lipid accumulation during the differentiation of 3 T3-L1 into mature adipocyte. Conclusions Our results indicate that JAZF1 might firstly upregulated the expression of PPARα and PPARβ/δ, which in turn activated the transcription of visfatin. JAZF1 plays an important role in lipid metabolism and may thus provide a potential tool for the treatment of obesity and lipid metabolism disorders among other diseases.
Free and bound aroma volatiles from turnjujube during low temperature storage were extracted by headspace solid-phase microextraction. They were then characterized and identified using gas ...chromatography-mass spectrometry. Turnjujube was harvested and stored for 7, 14, and 21 days at 7 °C, the common temperature of display refrigerators in grocery stores. The results showed that 41 free and 24 bound aroma compounds were detected for the first time in turnjujube in both freshly harvested and stored turnjujube. The free and bound aroma compounds of turnjujube were markedly influenced by the storage time. The major free aroma compounds in turnjujube included esters, alcohols, aliphatic aldehydes, and aliphatic ketones. The major bound aroma compounds included borneol, eugenol, and isoeugenol, which contributed to sweet, floral, and herbaceous aroma after their hydrolysis. Freshly harvested turnjujube mostly had a fruity and herbaceous aroma, which diminished after storage at 7 °C. In contrast, the fatty aroma enhanced gradually over storage, and the floral aroma enhanced noticeably after storage for seven days. Foul odor was not detected even after storage at 7 °C for 21 days. The formation mechanisms of some aroma compounds were proposed.
▶ Scanning tunneling microscope (STM) images n-tetradecane (n-C14H30) and n-hexadecane (n-C16H34) self-assembled monolayers on HOPG. ▶ The molecular axes of n-C14H30 molecules tilt by 60° with ...respect to inter-lamellar trough lines on HOPG. ▶ The carbon backbones of n-C14H30 molecule chains are perpendicular to the HOPG basal plane in an all-trans conformation. ▶ The molecular axes of n-C16H34 molecules are perpendicular to lamellar borders (90°) on HOPG. ▶ Topographic effects determine STM image contrast of the methylene regions of the alkane chains on HOPG.
Two-dimensional ordered patterns of n-tetradecane (n-C14H30) and n-hexadecane (n-C16H34) molecules at liquid/graphite interface have been directly imaged using scanning tunneling microscope (STM) under ambient conditions. STM images reveal that the two different kinds of molecules self-organize into ordered lamellar structures in which alkane chains of the molecules extend along one of three equivalent lattice axes of highly oriented pyrolytic graphite (HOPG) basal plane. For n-C14H30 molecules, the molecular axes are observed to tilt by 60° with respect to inter-lamellar trough lines and the carbon backbones of the alkane chains are perpendicular to the HOPG basal plane in an all-trans conformation. However, for n-C16H34 molecules, the molecular axes are perpendicular to lamellar borders (90°) and the planes of the all-trans carbon skeletons are parallel to the graphite basal plane. The results clearly indicate that outmost hydrogen atoms of the alkane chains dominate atom-scaled features of the STM images. That is, in the case of long-chain alkane molecules, topographic effects dominantly determine STM image contrast of the methylene regions of the alkane chains that are adsorbed on HOPG.
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