Search

Additional file 1: Table S1. Primers used for qPCR. Figure S1. Neither high fat diet nor leptin knockout induce depressive-like behavior. Figure S2. Neuronal activities and astrocytes reactivity in hippocampus and amygdala were not altered among ND, HFD, LM, and ob/ob mice. Figure S3. E/I balance was not altered by high fat diet or leptin knockout. Figure S4. Astrocyte reactivation was significantly upregulated by high fat diet or leptin knockout, but microglia response was not altered. Figure S5. Astrocyte reactivity was increased in susceptible mice. Figure S6. Depressive-like behaviors were increased in susceptible mice. Figure S7. Behavioral functions were not altered before CNO injection.

Wanren Peng,1,* Fenglin Zhang,2,* Zishu Wang,3,* Dongliang Li,4,* Yifu He,5,* Zhongliang Ning,6 Lili Sheng,7 Jidong Wang,8 Xiaoyang Xia,9 Changjun Yu,10 Zian Wang,3 Yong Zhao,11 Hui Liang,12 Bing Hu,13 Cuiling Sun,14 Daoqin Wang,15 Yunsheng Cheng,16 Ming Pan,17 Liming Xia,18 Xinglai Guo,19 Yanshun Zhang,20 Zhiqiang Hu,21 Xinzhong Li,22 Lin Lu,23 Jun Zhang,24 Hong Qian,8 Hua Xie,25 Guoping Sun1,* 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 2Department of Oncology, People’s Hospital of Maanshan City, Maanshan, Anhui 243000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, People’s Republic of China; 4Department of Gastrointestinal Surgery, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 6Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui 230022, People’s Republic of China; 7Department of Oncology, Yijishan Hospital of WanNan Medical College, Wuhu, Anhui 340202, People’s Republic of China; 8Department of Oncology, The Navy Anqing Hospital, Anqing, Anhui 246003, People’s Republic of China; 9Department of Oncology, The First People’s Hospital of Chuzhou City, Chuzhou, Anhui 239000, People’s Republic of China; 10Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 11Department of Oncology, People’s Hospital of Lu’an City, Lu’an, Anhui 237005, People’s Republic of China; 12Department of Oncology, Lu’an Hospital of Traditional Chinese Medicine, Lu’an, Anhui 237006, People’s Republic of China; 13Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230022, People’s Republic of China; 14Department of Oncology, People’s Hospital of Fuyang City, Fuyang, Anhui 236047, People’s Republic of China; 15Department of Gastrointestinal Surgery, Wanbei Coal-Electricity Group General Hospital, Suzhou, Anhui 234000, People’s Republic of China; 16Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, People’s Republic of China; 17Department of Oncology, People’s Hospital of Chizhou City, Chizhou, Anhui 247000, People’s Republic of China; 18Department of Oncology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, People’s Republic of China; 19Department of Oncology, Fuyang Cancer Hospital, Fuyang, Anhui 236033, People’s Republic of China; 20Department of Oncology, Huainan First People’s Hospital, Huainan, Anhui 232000, People’s Republic of China; 21Department of Oncology, Huaibei Miners General Hospital, Huaibei, Anhui 235000, People’s Republic of China; 22Department of Oncology, People’s Hospital of Huaibei, Huaibei, Anhui 235000, People’s Republic of China; 23Department of Oncology, The 901 Hospital of the Joint Logistic Support Force of the People’s Liberation Army of China, Hefei, Anhui 230033, People’s Republic of China; 24Department of Oncology, The Second People’s Hospital of Wuhu, Wuhu, Anhui 241001, People’s Republic of China; 25Department of Oncology, The People’s Hospital of Xuancheng City, Xuancheng, Anhui 242000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Sun Email sungp@ahmu.edu.cnBackground: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes.Methods: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥ 18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician’s discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile.Results: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p< 0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p< 0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (p=0.02) and experience of apatinib-related specific AEs (p< 0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported.Conclusion: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes.Trial Registration: NCT03333967.Keywords: apatinib, combination therapy, real-world, advanced gastric cancer

The present study evaluates the nutraceutical composition of muscle and calipash of Yangtze and Japanese strains of Chinese soft-shelled turtle, Pelodiscus sinensis. In general, both strains possessed high protein content (16.62–22.18 g 100 g−1 wet weight) and negligible fat content (0.22−0.95 g 100 g−1 wet weight). The ratios of total essential amino acids to total amino acids and to total nonessential amino acids in muscle of two strains were about 40 % and 84 %, while the ratios in calipash were about 20 % and 29 %, respectively. Both the values of amino acid scores and in vitro digestible indispensable amino acid scores in muscle of two strains were in the range of good protein. The unsaturated fatty acids/saturated fatty acids ratios and n-3/n-6 ratios of two strains were 1.04−2.08 and 1:3.78−1:1.11, respectively. We also found that the atherogenicity index, thrombogenicity index and hypocholesterolemic/hypercholesterolenic fatty acid values in muscle varied between 0.35−0.44, 0.41−0.46 and 2.16–2.80, respectively, while in calipash were 0.62−0.72, 1.02–1.23 and 1.26−1.56. Taken cumulatively, these results indicate that consumption of muscle of Yangtze and Japanese strains of P. sinensis is favorable to human health, while moderation needs to be exercised for the calipash consumption.

Chinese soft-shelled turtle (Pelodiscus sinensis) is a favorite food for the Asian because of its high nutritional and medicinal value. Based on an estimate production of 350,000 MT in 2015, soft-shelled turtle culture industry in China values US$5.22 billion. In central China, overwinter in greenhouse is necessary for the juvenile turtle. The use of coal boiler to heat up the water to 30 °C is a common practice, however, brings in air pollution and CO2 emission too. A modern greenhouse equipped with ground source heat pump was built in 2010 and operated during 2014–2015 for 10 months to culture juvenile turtle. Besides heating system, the other innovative features such as skirt-shaped 3-D shelter, underwater feeding platform wok-shaped tank bottom with central drainage, and semi-homemade soft shell-shaped pellet together achieved excellent rearing performance, such as high turtle productivity of 23.7 kg m−2, high survival 86%, low feed efficiency-feed conversion rate 1.26 and good water quality-dissolved oxygen >5 mg L−1, and nitrite and ammonia concentration all time within safe range. Moreover, it is a lucrative business which brought in an estimated net profit of 76%.