In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 227, S. 112934
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 214, S. 112104
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 165, S. 270-277
Yuqian Li,1,* Wei Fang,1,* Lei Tao,2,* Min Li,1 Yanlong Yang,1 Yafei Gao,1 Shunnan Ge,1 Li Gao,1 Bin Zhang,1 Zhihong Li,1 Wei Zhou,1 Boliang Wang,3 Lihong Li11Department of Neurosurgery, 2Department of Anesthesiology, 3Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China*These authors contributed equally to this studyBackground: Nicardipine (NC) is the most commonly used antihypertensive drug in neurological patients with hypertension. Although nimodipine (NM) is widely used to treat cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage, trials exploring its antihypertensive effect after intravenous administration in subjects with intracerebral hemorrhage (ICH) are scarce.Methods: A retrospective study was carried out to compare the safety and efficacy of NC and NM administered intravenously in patients with ICH. Therapeutic responses were assessed by achievement of goal blood pressure (BP); use of additional medications for BP control; proportion of time spent within goal; variability in BP; time to goal BP; number of dose adjustments; variability in ICH volume, Glasgow Coma Scale score, and intracranial pressure; and drug-related complications.Results: A total of 87 patients were eligible for analysis (n=46 [NC]; n=41 [NM]), and baseline characteristics between groups were similar. Both agents were effective in achieving goal BP during infusion, with 93.5% and 87.8% patients in the NC and NM groups achieving goal, respectively. Fewer additional medications were needed to control BP in the NC group. BP variability was similar and no differences were observed in the mean time to goal BP and mean numbers of dose adjustments between both groups. Interestingly, intracranial pressure declined (P=0.048) during NC administration but increased (P=0.066) after NM treatment. Finally, the incidences of hematoma expansion, neurological deterioration, and adverse drug events were similar in both groups.Conclusion: NM is effective and safe for BP control in patients with ICH.Keywords: nicardipine, blood pressure, intravenous infusion
Abstract The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. l-carnitine can improve the semen microenvironment. However, the role of l-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of l-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg l-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that l-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.
In: Twin research and human genetics: the official journal of the International Society for Twin Studies (ISTS) and the Human Genetics Society of Australasia, Band 20, Heft 4, S. 355-362
The Wuhan Pre/Post-Natal Twin Birth Registry (WPTBR) is one of the largest twin birth registries with comprehensive medical information in China. It recruits women from the first trimester of pregnancy and their twins from birth. From January 2006 to May 2016, the total number of twins enrolled in WPTBR is 13,869 twin pairs (27,553 individuals). The WPTBR initiated the Wuhan Twin Birth Cohort (WTBC). The WTBC is a prospective cohort study carried out through incorporation of three samples. The first one comprises 6,920 twin pairs, and the second one, 6,949 twin pairs. Both are population-based samples linked to the WPTBR and include pre- and post-natal information from WPTBR. The second sample includes neonatal blood spots as well. Using a hospital-based approach, we recently developed a third sample with a target enrolment of 1,000 twin pairs and their mothers. These twins are invited, via their parents, to participate in a periodic health examination from the first trimester of pregnancy to 18 years. Biological samples are collected initially from the mother, including blood, urine, cord blood, cord, amniotic fluid, placenta, breast milk and meconium, and vaginal secretions, and later from the twins, including meconium, stool, urine, and blood. This article describes the design, recruitment, follow-up, data collection, and measures, as well as ongoing and planned analyses at the WTBC. The WTBC offers a unique opportunity to follow women from prenatal to postnatal, as well as follow-up of their twins. This cohort study will expand the understanding of genetic and environmental influences on pregnancy and twins' development in China.
Shukui Qin,1 Rui-Hua Xu,2 Lin Shen,3 Jianming Xu,4 Yuxian Bai,5 Lei Yang,6 Yanhong Deng,7 Zhen-dong Chen,8 Haijun Zhong,9 Hongming Pan,10 Weijian Guo,11 Yongqian Shu,12 Ying Yuan,13 Jianfeng Zhou,14 Nong Xu,15 Tianshu Liu,16 Dong Ma,17 Changping Wu,18 Ying Cheng,19 Donghui Chen,20 Wei Li,21 Sanyuan Sun,22 Zhuang Yu,23 Peiguo Cao,24 Haihui Chen,25 Jiejun Wang,26 Shubin Wang,27 Hongbing Wang,28 Ning Wang,29 Bin Zhang,29 Qiang Zhang,29 Weiguo Su,30 Xiaojun Guo,30 Jin Li31 1Cancer Center, Jinling Hospital, Nanjing, People's Republic of China; 2Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China; 3Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, People's Republic of China; 4Department of Medical Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China; 5Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China; 6Department of Medical Oncology, Nantong Cancer Hospital, Nantong, People's Republic of China; 7Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; 8Department of Medical Oncology, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China; 9Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China; 10Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China; 11Department of Medical Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 12Department of Medical Oncology, Jiangsu Provincial Hospital, Nanjing, People's Republic of China; 13Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China; 14Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, People's Republic of China; 15Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China; 16Department of Medical Oncology, Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, People's Republic of China; 17Department of Medical Oncology, Guangdong Provincial People's Hospital, Guangzhou, People's Republic of China; 18Department of Medical Oncology, The First People's Hospital of Changzhou, Changzhou, People's Republic of China; 19Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China; 20Department of Medical Oncology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, People's Republic of China; 21Department of Medical Oncology, The First Hospital of Jilin University, Changchun, People's Republic of China; 22Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, People's Republic of China; 23Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China; 24Department of Medical Oncology, The Third Xiangya Hospital of Central South University, Changsha, People's Republic of China; 25Department of Medical Oncology, Liuzhou Worker's Hospital, Liuzhou, People's Republic of China; 26Department of Medical Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China; 27Department of Medical Oncology, Peking University Shenzhen Hospital, Beijing University, Shenzhen, People's Republic of China; 28Department of Medical Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou Medical College, Xuzhou, People's Republic of China; 29Eli Lilly and Company, Shanghai, People's Republic of China; 30Hutchison MediPharma Limited, Shanghai, People's Republic of China; 31Department of Medical Oncology, Tongji University Shanghai East Hospital, Shanghai, People's Republic of ChinaCorrespondence: Jin LiDepartment of Medical Oncology, Tongji University Shanghai East Hospital, Shanghai, People's Republic of ChinaTel +8613761222111Email lijin@csco.org.cnObjective: The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy.Methods: Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups.Results: A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45– 0.77, P< 0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17– 0.30; P< 0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group.Conclusion: Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM.ClinicalTrials.gov Identifier: NCT02314819.Keywords: colorectal cancer, FRESCO trial, fruquintinib, liver metastasis
Background: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. Methods: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. Findings: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75–84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28–4·7) and 7·0% (1·2–13·0). Interpretation: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.