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Background & Aims The I148M variant (rs738409) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is by far the most important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, in the context of NAFLD, the transcriptional regulation of PNPLA3 in human liver cells is not known. In this study, we aimed to define the relationship between PNPLA3 transcription and disease characteristics of human NAFLD. Methods The abundance of PNPLA3 and collagen 1α (COL1α) transcripts was quantified in situ at single-cell resolution using RNAscope® in 87 patients with NAFLD. We examined the association of PNPLA3 and COL1α transcript levels with NAFLD disease severity, defined by histology. Results While the majority of PNPLA3 transcripts were found in hepatocytes, approximately 7% of PNPLA3-positive cells co-express COL1α, representing activated myofibroblasts. There is no association between the rs738409 genotype and the level of PNPLA3 transcript. The overall PNPLA3 transcript abundance is lower in zone 1 hepatocytes, patients with higher body mass index, and those with advanced liver fibrosis. The negative association between the PNPLA3 transcript levels and liver fibrosis is largely driven by COL1α-positive cells. A significant proportion of PNPLA3 mRNA is seen in the nucleus. The cytoplasmic-to-nuclear PNPLA3 mRNA ratio is inversely associated with NAFLD disease activity. Conclusions PNPLA3 transcript abundance and nuclear-to-cytoplasmic translocation are negatively associated with hepatic steatosis and NAFLD disease activity, while its abundance in activated myofibroblasts is inversely associated with the stage of liver fibrosis. Lay summary A genetic variant in patatin-like phospholipase domain-containing protein 3 (or PNPLA3) is the most important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, it is not known how transcriptional regulation of the PNPLA3 gene contributes to the disease characteristics of human NAFLD. Herein, we show that the mRNA levels of PNPLA3, particularly in the cytoplasm, are negatively associated with the severity of NAFLD in humans., Highlights • Relationships between PNPLA3 transcription and the severity of human non-alcoholic fatty liver disease was unknown. • PNPLA3 transcript abundance is negatively associated with hepatic steatosis and non-alcoholic fatty liver disease activity. • Nuclear-to-cytoplasmic translocation of PNPLA3 is also negatively associated with non-alcoholic fatty liver disease severity. • PNPLA3 transcript abundance in activated myofibroblasts is inversely associated with the stage of liver fibrosis.

Purpose Recent evidence suggests that there is a correlation between the micro- and macrovascular complications of diabetes mellitus. The aim of this study is to investigate the molecular mechanisms by which diabetes promotes the development of microvascular disease (diabetic retinopathy [DR]) through characterization of the effects of hyperglycemia in the retina of mouse models of diabetic atherosclerosis. Methods Hyperglycemia was induced in apolipoprotein E-deficient (ApoE-/-) mice, a model of accelerated atherosclerosis, either through streptozotocin (STZ) injection or introduction of the Ins2Akita mutation (ApoE-/-Ins2+/Akita). Another subset of ApoE-/- mice was supplemented with glucosamine (GlcN). To attenuate atherosclerosis, subsets of mice from each experimental group were treated with the chemical chaperone, 4-phenylbutyric acid (4PBA). Eyes from 15-week-old mice were either trypsin digested and stained with periodic acid-Schiff (PAS) or frozen for cryostat sectioning and immunostained for endoplasmic reticulum (ER) stress markers, including C/EBP homologous protein (CHOP) and 78-kDa glucose-regulated protein (GRP78). PAS-stained retinal flatmounts were analyzed for microvessel density, acellular capillaries, and pericyte ghosts. Results Features of DR, including pericyte ghosts and reduced microvessel density, were observed in hyperglycemic and GlcN-supplemented mice. Treatment with 4PBA reduced ER stress in the retinal periphery and attenuated DR in the experimental groups. Conclusions Mouse models of diabetic atherosclerosis show characteristic pathologies of DR that correlate with atherosclerosis. The increased magnitude of these changes and responses to 4PBA in the peripheral retina suggest that future studies should be aimed at assessing regional differences in mechanisms of ER stress-related pathways in these mouse models.

1. The study objectives were to determine the direct effects of gonadotropin-releasing hormone (GnRH) on the proliferation of ovarian granulosa cells (GCs) and the development of follicles in geese...

The objective of the study was to investigate the mechanism by which dietary energy concentration regulates laying performance in geese. Eighty 558-day-old female Sichuan White geese were randomly allotted to two dietary treatments, each treatment was fed 1 of 2 experimental diets containing 10.00 (deficient) or 11.80MJ/kg metabolizable energy (sufficient) for 30 days. Laying performance, hormone concentration and gene expressions in hypothalamus-pituitary-gonadal axis were examined in geese. Birds fed the sufficient-energy diet had significantly higher average egg weight, daily laying rate, and lower feed to egg ratio than those fed the deficient-energy (p

BackgroundThe tourniquet is a common medical instrument used in total knee arthroplasty (TKA). However, there has always been a debate about the use of a tourniquet and there is no published meta-analysis to study the effects of a tourniquet on blood loss in primary TKA for patients with osteoarthritis.MethodsWe performed a literature review on high-quality clinical studies to determine the effects of using a tourniquet or not on blood loss in cemented TKA. PubMed, Web of Science, MEDLINE, Embase, and the Cochrane Library were searched up to November 2018 for relevant randomized controlled trials (RCTs). We conducted a meta-analysis following the guidelines of the Cochrane Reviewer’s Handbook. We used the Cochrane Collaboration’s tool for assessing the risk of bias of each trial. The statistical analysis was performed with Review Manager statistical software (version 5.3).ResultsEleven RCTs involving 541 patients (541 knees) were included in this meta-analysis. There were 271 patients (271 knees) in the tourniquet group and 270 patients (270 knees) in the no tourniquet group. The results showed that using a tourniquet significantly decreased intraoperative blood loss (P P P P > 0.05), total blood loss (P > 0.05), the rate of transfusion (P > 0.05), and of deep vein thrombosis (DVT) (P > 0.05) in TKA.ConclusionsUsing a tourniquet can significantly decrease intraoperative blood loss, calculated blood loss, and operation time but does not significantly decrease the rate of transfusion or the rate of DVT in TKA. More research is needed to determine if there are fewer complications in TKA without the use of tourniquets.

Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase expression in male focal ischemia.

Introduction: Objective to summarize the work flow list during epidemic period, and to discuss and summarize the process management and prevention and control methods of each link in Tumor area during epidemic period of novel coronavirus pneumonia (NCP), in order to achieve the orderly completion of radiotherapy and chemotherapy for tumor patients, and prevent a tumor patient from contracting novel coronavirus pneumonia Methods: According to the characteristics of the transmission of NCP and the relevant documents of the National Health Commission, the list of management work was carded out, to establish various prevention and control processes in tumor wards, control key population, establish correct infection control measures, scientifically protect key personnel and effectively manage protective materials Results: During the epidemic period of NCP, the tumor inpatients could complete the radiotherapy and chemotherapy in time and effectively, and the infection of NCP was avoided The ability and knowledge of prevention and control of hospital infection of new pneumonia were improved [Formula presented] Conclusion: The nursing managers adopt and implement correct measures to prevent and control NCP infection through the management work list system, which can effectively ensure the safety of tumor patients and the occupational safety of medical workers The purpose of this study is to provide practical experience for the establishment of infectious emergency nursing management system in common disease areas Keywords: List of management, Oncology ward, coronavirus pneumonia

Background:Behcet’s disease (BD) is a chronic and relapsing vasculitis, in which major vessel involvement is a main cause of mortality and morbidity. The therapeutic arsenal is mainly composed of classical immunosuppressants. However, when faced with resistance to these drugs, no alternative therapeutic strategy is currently recommended.Objectives:To assess the efficacy and safety of interleukin 6 receptor inhibitor tocilizumab (TCZ) in refractory arterial involvement of BD in a real-life observational setting.Methods:10 patients were enrolled in our center between 2014 and 2019. All patients met the international criteria for BD and had severe arterial involvement evaluated by echocardiography, angio-Computerized Tomography scan and vascular Doppler. The diagnosis of refractory arterio-BD was based on objective vascular symptoms not explained by any other known disease and non-response to conventional immunosuppressants combined with glucocorticoids therapy. All patients underwent TCZ infusions at 8mg/kg every 4 weeks. Concomitant therapy with immunosuppressants and glucocorticoids was continued. Clinical and imaging findings were assessed before and after TCZ therapy. All adverse events were recorded during follow-up.Results:All the patients were males, with a mean age of 44.3±10.5 years in this study. The mean age at presentation of arterial involvement was 40.8±9.2 years old. The patterns of arterial involvement were aneurysm (n=9), stenosis (n=3) and aortic valve lesion (n=2). After a mean follow-up of 26.8±7.2 months, TCZ yielded rapid and maintained clinical improvement in 9 patients, with complete remission in 6 of them and partial response in 3 of them. Discontinuation of TCZ treatment due to relapse occurred in one case as the enlargement of abdominal aortic aneurysm. The mean glucocorticoid dosage was tapered from 54.5±20.6mg/d to 8.3±3.6mg/d (pConclusion:TCZ was a safe and effective therapeutic option for refractory arterial involvement of BD, with a favorable steroid-sparing effect.References:[1]G Hatemi, R Christensen, D Bang, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018;77(6):808-818.[2]Y Ozguler, P Leccese, R Christensen, et al. Management of major organ involvement of Behcet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford). 2018;57(12):2200-2212.[3]M Akiyama, Y Kaneko, T Takeuchi. Effectiveness of tocilizumab in Behcet’s disease: A systematic literature review. Semin Arthritis Rheum. 2020;50(4):797-804.Table 1.Tocilizumab therapy in ten cases of refractory arterio-BDPatientAge, yearDisease duration, monthsClinical features*Arterial lesionsPrevious therapyResponse at week 24134228O, G, P, S, IStenosis of CA/ SMA/RA/SCA, aortic valve prolapsePred/CYC/MMFCR22024O, SDissecting aneurysm of AA (Debakey I)Pred/MMFPR367276O, G, P, S, Athoracoabdominal aortic aneurysmPred/CYC/TACCR46775O, S, UStenosis of LAD/LCX/RCAPred /CYCCR55080O, G, AAbdominal and coronary aortic aneurysmsPred /CYCRelapse64826O, GAortic insufficiencyPred /CYCPR726147O, P, S, VIliac artery aneurysmPred /MMFCR849466O, S, VThoracoabdominal and coronary aortic aneurysmsPred /CYC/AZACR927181O, P, SPseudoaneurysm of CCAPred /CYCPR10Male/55354O, P, SAbdominal aneurysm, stenosis of LAD/LCX/RCAPred /CYC/AZACR*O: oral ulcer; G: genital ulcer; P: pathergy test; S: skin lesions; I: intestinal ulcer; A: arthritis; U: uveitis; V: venous thrombosisFigure 1.Changes from baseline in BSAS, BDCAF, ESR, CRP and steroid daily dose at 24 weeksDisclosure of Interests:None declared

Introduction Data on prophylactic cranial irradiation (PCI) after complete resection of SCLC are limited. The purpose of this study was to investigate the impact of PCI in this population. Methods We retrospectively identified completely resected SCLC at the Shanghai Chest Hospital between January 2006 and January 2014. Results A total of 349 patients (115 patients who received PCI [the PCI-treated cohort] and 234 patients who did not [the non–PCI-treated cohort]) were included in the study. The results demonstrated that the PCI-treated cohort had longer overall survival than the non–PCI-treated cohort among patients with pathologic stage (p-stage) II (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.30–0.99, p = 0.047) and p-stage III (HR = 0.54, 95% CI: 0.34–0.86, p = 0.009) disease. Among patients with p-stage III disease, there was a significantly higher risk for cerebral recurrence from the time of diagnosis in the non–PCI-treated cohort ( p = 0.018). With regard to patients with p-stage I disease, neither overall survival benefit (HR = 1.61, 95% CI: 0.68–3.83, p = 0.282) nor risk for cerebral recurrence ( p = 0.389) was significant between the PCI-treated and non–PCI-treated cohorts. Conclusions The data presented in the current study support using PCI in patients with p-stage II/III disease but not in patients with p-stage I disease. A relatively lower risk for brain metastases in p-stage I patients might explain the inferior efficacy of PCI in this population.

This retrospective study was to investigate whether radiomics feature come from radiotherapy treatment planning CT can predict prognosis in locally advanced rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery. Four-hundred-eleven locally advanced rectal cancer patients which were treated with neoadjuvant chemoradiation enrolled in this study. All patients’ radiotherapy treatment planning CTs were collected. Tumor was delineated on these CTs by physicians. An in-house radiomics software was used to calculate 271 radiomics features. The results of test-retest and contour-recontour studies were used to filter stable radiomics (Spearman correlation coefficient > 0.7). Twenty-one radiomics features were final enrolled. The performance of prediction model with the radiomics or clinical features were calculated. The clinical outcomes include local control, distant control, disease-free survival (DFS) and overall survival (OS). Model performance C-index was evaluated by C-index. Patients are divided into two groups by cluster results. The results of chi-square test revealed that the radiomics feature cluster is independent of clinical features. Patients have significant differences in OS (p = 0.032, log rank test) for these two groups. By supervised modeling, radiomics features can improve the prediction power of OS from 0.672 [0.617 0.728] with clinical features only to 0.730 [0.658 0.801]. In conclusion, the radiomics features from radiotherapy CT can potentially predict OS for locally advanced rectal cancer patients with neoadjuvant chemoradiation treatment.

The objective of this study was to determine bile acid metabolism and its association with fetal pig death in pregnant gilts. A total of 430 gilts/sows with similar genetic background (Landrace×Yorkshire) were included in this study, 407 of them from parity 1 to 9 were selected to evaluate the critical time of fetal death, 12 gilts implanted with cephalic vein catheters were used to determine the relationship of bile acid metabolism with fetal death, and additional 11 pregnant gilts at gestation day 60 (G60) and 90 (G90), respectively, were sacrificed at 8h postprandial for determination of mechanism accounting for disrupted bile acid homeostasis and fetal death. Pregnant gilts had raised serum total bile acids (TBA), which reached peak levels (7.10–67.00 μmol/L) at G90, and was ~1–8 time that at G60 (4.10–20.00 μmol/L). Moreover, fetal death predominantly occurred during late pregnancy, with 70.67% of dead fetuses observed from G76 to farrowing. Fetal mortality was positively correlated with the increasing of TBA ratio of G90/G60, and significant difference in fetal survival appeared between the ratio “

// Panpan Hu 1, 2 , Jiazhou Wang 1, 2 , Haoyu Zhong 1, 2 , Zhen Zhou 1, 2 , Lijun Shen 1, 2 , Weigang Hu 1, 2 , Zhen Zhang 1, 2 1 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China Correspondence to: Zhen Zhang, email: zhenzhang6@gmail.com Keywords: radiomics, rectal cancer, reproducibility, textural features Received: July 26, 2016 Accepted: September 16, 2016 Published: September 22, 2016 ABSTRACT Purpose: To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Results: Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC ≥ 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC ≥ 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). Methods: 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. Conclusions: Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction.

SummaryBackground and Aim Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4+ adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post-OLT. Methods A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6–36 months post-OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time. Results Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post-OLT, and the average ImmuKnow assay in these patients was 190 ± 48 ng/ml, which was less (p

OBJECTIVES To study the potential pathogenesis of endometriosis (EMs) in an area of estrogen receptors (ERs) and tyrosine kinase receptor type B (TrkB) expressions in tissues from patients with EMs. STUDY DESIGN The authors examined the expressions of ERα, ERβ, TrkB, brain-derived neurotrophic factor (BDNF), and SGPL1 in tissues with EMs, using real-time PCR, western blot, and immunohistochemistry. RESULTS ERα and SGPL1 were mainly expressed in eutopic endometrium than that in ectopic endometrium of patients with ovarian endometriosis (p < 0.05), while ERβ, BDNF, and TrkB were adverse, mainly detected in ectopic endometrium of the same patients with EMs (p < 0.01 and p < 0.05 ) by real-time PCR and western blot. ERβ, ERα, TrkB, and SGPL1 proteins were mainly expressed in eutopic endometrium of proliferative phase with EMs than that in eutopic endometrium of secretory phase (p < 0.05 ). TrkB, BDNF, and SGPL1 were not found in endometrium of proliferative or secretory phase in control group. CONCLUSIONS ERβ expressed in cytoplasm may mediate pathogenesis of EMs.

Three out of four people with diabetes will die of cardiovascular disease. However, the molecular mechanisms by which hyperglycemia promotes atherosclerosis, the major underlying cause of cardiovascular disease, are not clear.Three distinct models of hyperglycemia-associated accelerated atherosclerosis were used to identify commonly altered metabolites and pathways associated with the disease.Normoglycemic apolipoprotein-E-deficient mice served as atherosclerotic control. Hyperglycemia was induced by multiple low-dose streptozotocin injections, or by introducing a point-mutation in one copy of insulin-2 gene. Glucosamine-supplemented mice, which experience accelerated atherosclerosis to a similar extent as hyperglycemia-induced models without alterations in glucose or insulin levels, were also included in the analysis. Untargeted plasma metabolomics were used to investigate hyperglycemia-associated accelerated atherosclerosis in three disease models. The effect of specific significantly altered metabolites on pro-atherogenic processes was investigated in cultured human vascular cells.Hyperglycemic and glucosamine-supplemented mice showed distinct metabolomic profiles compared to controls. Meta-analysis of three disease models revealed 62 similarly altered metabolite features (FDR-adjusted p 0.05). Identification of shared metabolites revealed alterations in glycerophospholipid and sphingolipid metabolism, and pro-atherogenic processes including inflammation and oxidative stress. Post-multivariate and pathway analyses indicated that the glycosphingolipid pathway is strongly associated with hyperglycemia-induced accelerated atherosclerosis in these atherogenic mouse models. Glycosphingolipids induced oxidative stress and inflammation in cultured human vascular cells.Glycosphingolipids are strongly associated with hyperglycemia-induced accelerated atherosclerosis in three distinct models. They also promote pro-atherogenic processes in cultured human cells. These results suggest glycosphingolipid pathway may be a potential therapeutic target to block or slow atherogenesis in diabetic patients.

Background PD-L1 immunohistochemistry (IHC) data in China was less reported. We systematically investigated PD-L1 IHC data of Chinese patients generated by Origimed. Methods PD-L1 was stained using IHC on cancer samples from 2060 Chinese patients in Origimed since 2017. Written informed consent was obtained from each patient. IHC staining was performed on FFPE tissue sections using anti-PD-L1 antibody 28-8. Tumor Proportion Score (TPS) was applied on all the samples. We investigated PD-L1 TPS in lung adenocarcinoma (n = 893), lung squamous carcinoma (n = 172), liver cancer (n = 404), esophageal cancer (n = 186), colorectal cancer (n = 166), pancreatic cancer (n = 136) and gastric cancer (n = 103). We then further applied PD-L1 combined positive score (CPS) on the 103 gastric cancer samples. All the slides were reviewed by the same senior pathologist. 95% confidence interval (CI) was obtained by bootstrap. Information entropy (Shannon’s formula) was measured in natural units. Results The highest proportion of PD-L1 TPS > = 1% was observed in lung squamous carcinoma (49%; 95% CI: [43%, 59%]), followed by lung adenocarcinoma (25%; 95% CI: [22%, 28%]), liver cancer (14%; 95% CI: [11%, 18%]), esophageal cancer (12%; 95% CI: [8.1%, 17%]), pancreatic cancer (11%; 95% CI: [5.9%, 16%]), gastric cancer (7%; 95% CI: [1.9%, 12%]) and colorectal cancer (4%; 95% CI: [1.2%, 6.6%]). The proportion of PD-L1 CPS > = 1 for gastric cancer was 17% (95% CI: [9.7%, 24%]). In gastric cancer, information entropy of TPS and CPS was 0.40 and 0.78, respectively. Conclusions The proportion of PD-L1 TPS > = 1% in Chinese lung squamous cell carcinoma (49%) was much higher than that in lung adenocarcinoma (25%). PD-L1 CPS contained more information than TPS in gastric cancer. Thus, we recommend applying CPS to gastric cancer in China. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure X. Pan: Full / Part-time employment: Origimed. Y. Dai: Full / Part-time employment: Origimed. D. Chen: Full / Part-time employment: Origimed. K. Wang: Full / Part-time employment: Origimed. X. Dong: Full / Part-time employment: Origimed. All other authors have declared no conflicts of interest.

The objective of this work was to investigate the effect of feeding conditions on methylation status of FATP1 gene, which is an important candidate gene of Intramuscular fat and important indicator of chicken meat quality. We selected Daninghe (DNH) and Qingjiaoma (QJM) chickens under scatter-feeding and captivity-feeding conditions as experimental animals, and detected the methylation status of FATP1 genes in chicken breast muscle using Bisulfite Sequencing PCR method. The results showed that the methylation level of FATP1 in scatter-fed chicken was lower than in captivity-fed conditions in DNH and QIM chicken breast tissues; DNA methylation in the promoter and exon1 region was demonstrated to negatively regulate the expression of the FATP1 gene. These results suggested that feeding conditions affect the methylation status and expression level of FATP1, thereby affecting the Intramuscular fat content in DNH and QJM chicken breast muscle.

The poor egg-laying rate of geese hinders the development of the goose industry; therefore, the reproductive performance of geese is an important area of investigation. To evaluate the relationship between photoperiod, reproductive hormones, and reproductive activity during the egg-laying cycle in geese under natural conditions, we collected blood samples from Sichuan white geese and Xupu geese to quantify changes in prolactin (PRL), estradiol (E2), vasoactive intestinal polypeptide (VIP), follicle stimulating hormone (FSH), gonadotropin-inhibitory hormone (GnIH), and luteinizing hormone (LH). We also calculated the rate of egg laying for the two populations during the egg-laying cycle. We show that the egg-laying rate and the serum concentration of some hormones (PRL, E2, VIP, FSH, GnIH, and LH) differed significantly between the two populations during the pre-laying, laying, and ceased-laying periods. Serum LH concentrations may be associated with maturation of the ovary and oviducts, whereas FSH, PRL, and GnIH play important roles in egg laying. These results provide a useful resource for future studies examining the laying rate in geese.

The efficacy of EGFR tyrosine kinase inhibitors (TKIs) varies among different EGFR mutations. Here, we directly compared the efficacy of first-line TKIs to chemotherapy for non-small cell lung cancer (NSCLC) patients with the L858R mutation. The progression-free survival (PFS) for patients receiving TKIs as first-line therapy was longer than those who received chemotherapy (hazard ratio [HR]: 0.44, P

Background The epidemiologic profiles of chronic urticaria (CU) vary considerably among regions, and few such data are available from China. Methods We performed a multicenter open questionnaire investigation about the clinical and laboratory features of CU, defined as recurrent wheals with/without angioedema lasting for ≥6 weeks, among 3027 patients. Results Female preponderance was observed (female/male ratio, 1.46 : 1). The mean age at diagnosis was 34.7 ± 13.8 years, and the mean disease duration was 18.5 ± 46.1 months (range, 1.5–127 months). Patients were classified as having chronic spontaneous urticaria (CSU, 61.0% of patients), physical urticaria (PU, 26.2%), or other urticaria types (OU, 2.3%). Nocturnal attacks were reported by 60% of cases. The Urticaria Activity Score (UAS) in patients with CSU was 3.8 ± 1.4. The mean Dermatology Life Quality Index was 7.3 ± 3.4 (range 0–30). Induction or exacerbation of wheals with alcohol drinking was reported by 55.7% of patients. Chronic hepatitis B was less prevalent in our CU patients compared with the general Chinese population (2.7% vs 7%). Positive autologous serum skin tests (ASSTs) were observed in 66.9% of patients. Patients with positive ASST had higher UAS, greater angioedema frequencies, longer disease durations, and poorer QoL compared with patients with negative ASST (P

The present study was conducted to determine the alteration of bile acid profile and signaling in piglets during transition periods and the potential association with gut microbiome. A total of 24 piglets were included in this study. Twelve suckling piglets euthanized at 21 or 28 days of age were designated as D21 or D28 group respectively. Twelve piglets weaned at 21 days of age and fed solid feed until 28 days of age were designated as low feed intake (LFI, ingested nutrients could hardly meet maintenance requirements) group or normal feed intake (NFI, ingested nutrients higher than maintenance requirements) group, respectively. Jugular concentrations of conjugated deoxycholic acid (DCA) and lithocholic acid (LCA) were higher (P

To evaluate the feasibility and safety of a revised technique of botulinum toxin type A (BTA) injections for the treatment of infantile esotropia.Forty-seven patients with infantile esotropia were randomly divided into two groups. In group A, 23 cases were treated with a bilateral injection of 2.5-3.75 U BTA combined with sodium hyaluronate (SH) to the medial rectus muscle. In group B, 24 cases were treated with a bilateral injection of 2.5-3.75 U BTA solution alone to the medial rectus muscle. Electromyography was not used in the study. All patients received one injection and were evaluated 2 weeks, 3 months, and 6 months following injection.The measured changes between groups A and B included the frequencies of good alignment 6 months after injections (30.4% vs 37.5%), complicated ptosis (2.2% vs 20.8%), and vertical deviation (2.2% vs 2.1%).BTA injections combined with or without SH in the absence of electromyography demonstrated effectiveness and feasibility in the treatment of infantile esotropia. A relative decrease in the frequency of complicated ptosis resulted from injections of BTA+SH.

Previous studies reported that aerobic-type exercise such as walking or cycling with blood flow restriction (BFR) has been shown to elicit increases in leg muscle hypertrophy and strength, as well as improved aerobic capacity. Although previous studies investigated cardiovascular responses during a relatively short duration of exercise (∼5 min), the effects of prolonged leg muscular BFR have remained unknown. The purpose of this study was to examine the cardiovascular effects of longer duration low intensity exercise combined with BFR. Eight men performed 30 min of exercise at 40% of a predetermined maximal oxygen uptake under both BFR and normal flow (CON) conditions. Cardiovascular parameters were measured at rest and every 10 min during exercise. The main findings were that 1) the SV and HR did not change significantly between 10 to 30 min of exercise in BFR and CON conditions, although BFR-induced reduction of SV and increased HR were found at 10 min exercise compared with normal flow, 2) blood pressure was increased at 10 min of exercise in BFR compared to the CON, however the blood pressure decreased gradually with BFR from 10 to 30 min of exercise, and 3) blood lactate and RPE increased gradually during exercise with BFR. In conclusion, our results suggest that the BFR-induced reduction of SV and increased HR within the first 10 min of exercise are representative of changes in these parameters.

Atherosclerosis is the major underlying cause of most cardiovascular diseases. Despite recent advances, the molecular mechanisms underlying the pathophysiology of atherogenesis are not clear. In this study, comprehensive plasma metabolomics were used to investigate early-stage atherosclerotic development and progression in chow-fed apolipoprotein E-deficient mice at 5, 10 and 15 weeks of age. Comprehensive plasma metabolomic profiles, based on 4365 detected metabolite features, differentiate atherosclerosis-prone from atherosclerosis-resistant models. Metabolites in the sphingomyelin pathway were significantly altered prior to detectable lesion formation and at all subsequent time-points. The cytidine diphosphate-diacylglycerol pathway was up-regulated during stage I of atherosclerosis, while metabolites in the phosphatidylethanolamine and glycosphingolipid pathways were augmented in mice with stage II lesions. These pathways, involving glycerophospholipid and sphingolipid metabolism, were also significantly affected during the course of atherosclerotic progression. Our findings suggest that distinct plasma metabolomic profiles can differentiate the different stages of atherosclerotic progression. This study reveals that alteration of specific, previously unreported pathways of glycerophospholipid and sphingolipid metabolism are associated with atherosclerosis. The clear difference in the level of several metabolites supports the use of plasma lipid profiling as a diagnostic tool of atherogenesis.

Preeclampsia (PE) is one of the pregnancy metabolic diseases. Since Gut microbiota play important roles in the hosts’ metabolism, it is necessary to investigate the gut microbiota in PE patients, so that some intestinal dysbiosis might be detected as a biomarker for PE early diagnosis or as a target for intervention. One hundred subjects were categorized into four groups: 26 PE patients in late pregnancy, healthy individuals in early, middle, and late pregnancy (26/24/24 women). Gut microbiota were analyzed by sequencing the V4 region of the 16S rDNA gene using Illuminal MiSeq. Data were analyzed by multivariate statistics. Bacteroidetes was the dominant bacterium (47.57–52.35%) in the pregnant women in South China. Tenericutes increased while Verrucomicrobia almost disappeared in late pregnancy. In the PE patients, there was an overall increase in pathogenic bacteria, Clostridium perfringens (p = 0.03) and Bulleidia moorei (p = 0.00) but a reduction in probiotic bacteria Coprococcus catus (p = 0.03). Our research suggests that there is a significant structural shift of the gut microbiota in PE patients, which might be associated with the occurrence and development of the disease. However, further studies are required to understand the underlying mechanisms.

Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has been implicated in the development of diabetic complications, including atherosclerosis and hepatic steatosis. In this study, we investigate the potential relationship between the effects of glucosamine on lipid-linked oligosaccharide (LLO) biosynthesis, N-linked glycosylation, and ER homeostasis. Mouse embryonic fibroblasts (MEFs) were cultured in the presence of 0–5 mM glucosamine for up to 18 h, and LLO biosynthesis was monitored by fluorescence-assisted carbohydrate electrophoresis. ER stress was determined by quantification of unfolded protein response (UPR) gene expression. We found that exposure of MEFs to ≥1 mM glucosamine significantly impaired the biosynthesis of mature (Glc3Man9GlcNAc2) LLOs before the activation of the UPR, which resulted in the accumulation of an LLO intermediate (Man3GlcNAc2). The addition of 4-phenylbutyric acid (4-PBA), a chemical chaperone, was able to alleviate ER stress but did not rescue LLO biosynthesis. Other ER stress-inducing agents, including dithiothreitol and thapsigargin, had no effect on LLO levels. Together, these data suggest that elevated concentrations of glucosamine induce ER stress by interfering with lipid-linked oligosaccharide biosynthesis and N-linked glycosylation. We hypothesize that this pathway represents a causative link between hyperglycemia and the development of diabetic complications.

Ertapenem is a broad-spectrum antibiotic that is increasingly being utilized. Its dosing convenience renders it suitable for outpatient therapy, and its pharmacokinetic characteristics favour its use against complicated urinary tract infections (cUTIs). Despite this, sufficient clinical data are lacking for its use against cUTIs in the outpatient setting. We assessed the microbiological and clinical cure rates associated with ertapenem treatment for cUTIs in two outpatient parenteral antimicrobial therapy (OPAT) departments.We undertook a prospective observational study of adult patients who received ertapenem for cUTIs between August 2010 and August 2014. Data on patient characteristics, clinical progress and microbiological results were collected and analysed.Sixty-one patients were enrolled. The median age was 59 years (range 24, 83) and 61% were male. The most common diagnoses were pyelonephritis (39%) and prostatitis (15%). The most common causative organism was Escherichia coli (67%). Extended-spectrum β-lactamase (ESBL)-producing organisms were detected in 72% of infections. Microbiological cure was achieved in 67% overall, and was less likely in those with Klebsiella pneumoniae infection (OR = 0.21 [95%CI: 0.05 to 0.85] p = 0.029). Clinical cure was observed in 92% of patients.In this study of treating cUTIs with ertapenem, we have demonstrated good clinical outcomes. A lower than expected microbiological cure rate was observed in those with Klebsiella pneumoniae infection.

1-[2-(2,4-Dimethylphenyl-sulfanyl)-phenyl]-piperazine (Lu AA21004) is a human (h) serotonin (5-HT)(3A) receptor antagonist (K(i) = 3.7 nM), h5-HT(7) receptor antagonist (K(i) = 19 nM), h5-HT(1B) receptor partial agonist (K(i) = 33 nM), h5-HT(1A) receptor agonist (K(i) = 15 nM), and a human 5-HT transporter (SERT) inhibitor (K(i) = 1.6 nM) (J Med Chem 54:3206-3221, 2011). Here, we confirm that Lu AA21004 is a partial h5-HT(1B) receptor agonist [EC(50) = 460 nM, intrinsic activity = 22%] using a whole-cell cAMP-based assay and demonstrate that Lu AA21004 is a rat (r) 5-HT(7) receptor antagonist (K(i) = 200 nM and IC(50) = 2080 nM). In vivo, Lu AA21004 occupies the r5-HT(1B) receptor and rSERT (ED(50) = 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT(3) receptor antagonist in the Bezold-Jarisch reflex assay (ED(50) = 0.11 mg/kg s.c.). In rat microdialysis experiments, Lu AA21004 (2.5-10.0 mg/kg s.c.) increased extracellular 5-HT, dopamine, and noradrenaline in the medial prefrontal cortex and ventral hippocampus. Lu AA21004 (5 mg/kg per day for 3 days; minipump subcutaneously), corresponding to 41% rSERT occupancy, significantly increased extracellular 5-HT in the ventral hippocampus. Furthermore, the 5-HT(3) receptor antagonist, ondansetron, potentiated the increase in extracellular levels of 5-HT induced by citalopram. Lu AA21004 has antidepressant- and anxiolytic-like effects in the rat forced swim (Flinders Sensitive Line) and social interaction and conditioned fear tests (minimal effective doses: 7.8, 2.0, and 3.9 mg/kg). In conclusion, Lu AA21004 mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation. In vivo, this results in enhanced release of several neurotransmitters and antidepressant- and anxiolytic-like profiles at doses for which targets in addition to the SERT are occupied. The multimodal activity profile of Lu AA21004 is distinct from that of current antidepressants.