Transcriptome profiling reveals morphogenesis-related candidate genes and pathways in the chick embryonic small intestine.

1. A better understanding of intestinal development is essential for the intestinal health of poultry. Intestinal villification starts on embryo day E15 and is generally completed before hatching (E21). The development of lymphoid organs in the intestine starts during embryogenesis. However, transcriptional information on the processing of intestinal morphogenesis and immune development during chick embryogenesis is limited.2. In this work, RNA-sequencing was performed using 12 biological replicates to investigate Hy-Line brown chick embryonic small intestinal transcription at E15 and E21. Differentially expressed genes (DEGs) between E15 and E21 were identified. GO and KEGG enrichment analyses, based on the DEGs, were performed to identify key GO terms in the biological process category and key KEGG pathways. PPI networks were constructed based on the DEGs in the key pathways to screen hub genes. The embryonic small intestinal morphology and IgA distribution were observed by histological processing. The serum levels of IgA and lysozyme were measured by ELISA.3. A total of 76.38 Gb of high-quality RNA-sequencing data were generated and uploaded. A total of 2,676 DEGs, between E15 and E21, were identified. Structural development and villification of the small intestine at E15 tended to proceed via the expression of nervous system development-related genes. A combination of the histological and serological results with the transcriptome data indicated that the identified genes and pathways may be strong candidates for intestinal morphogenesis-regulation.4. The small intestine appears to have developed a relatively complete morphology and transport, metabolism, digestion and immunity functions by E21. This work provided a transcriptome profile of the chick embryonic small intestine and provided insights into the intestinal development and health of poultry.

[Incidence and risk factors of thromboembolism in patients with lung cancer receiving immunotherapy].

Objective: To evaluate the incidence of thromboembolism in a cohort of patients with lung cancer who received immune checkpoint inhibitors (ICIs), and explore relevant clinical risk factors. Methods: We retrospectively collected and analyzed the clinical data of patients with confirmed primary lung cancer and treated with ICIs between March 2018 and June 2021 at three hospitals in China (Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Fudan University Shanghai Cancer Center and Zhongshan Hospital of Fudan University). The cumulative incidence and risk factors of thromboembolism in these patients were analyzed using a competitive risk model. Results: A total of 804 patients were enrolled, there were 623 males and 181 females, with a median age of 59 years (ranged 28-86 years). Of these, 62 patients encountered 65 thromboembolic events, including 51 venous thromboembolism events (VTE) and 14 arterial thromboembolism events. The cumulative incidence of thromboembolism events at 3, 6, 12 and 24 months were 4.3%, 6.1%, 10.1% and 16.8%, respectively. And the cumulative incidence of venous thromboembolism events at 3, 6, 12 and 24 months were 3.4%, 4.7%, 9.0% and 13.3%, respectively. Multivariate analysis showed that history of thromboembolism (HR=6.345, 95%CI: 2.917-13.802,P<0.001),liver metastasis (HR=2.249, 95%CI: 1.123-4.502,P=0.022) and peripherally inserted central venous catheter (HR=3.674, 95%CI: 1.751-7.712, P<0.001) were independent risk factors for venous thromboembolism during ICIs therapy in patients with lung cancer. Conclusions: Patients with lung cancer under ICIs therapy are at high risk of thromboembolism. And history of thromboembolism, liver metastasis and peripherally inserted central venous catheter are risk factors of venous thromboembolism.

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China.

BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0-70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086-15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498-19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

3.7 kW monolithic narrow linewidth single mode fiber laser through simultaneously suppressing nonlinear effects and mode instability.

In this paper, we report a 3.7 kW all fiber narrow linewidth single mode fiber laser. The full width at half-maximum is about 0.30 nm, and the beam quality is Mx2=1.358, My2=1.202 at maximum output power. The laser is achieved by simultaneously suppressing nonlinear effects and mode instability (MI). Different seeds are injected into the main amplifier to study stimulated Raman scattering (SRS) effect. The results show that the phase modulated single frequency seed is benefit to suppress the SRS effect. For the phase modulated single frequency seed, inserting a filter in preamplifier will suppress amplified spontaneous emission (ASE) and decrease the backward power. By optimizing the coiling of active fiber, the MI effect is suppressed.

Modified Folfox6 as Adjuvant Chemotherapy in Vietnamese Patients With Colorectal Cancer.

Colorectal cancer is the third most common cancer and the second leading cause of death from cancer worldwide. In Vietnam, the disease is the fifth leading cancer (8.9%), with 14 733 new cases in 2018. In recent years, the mFolfox6 regimen has been indicated commonly as the adjuvant chemotherapy after curative resection for patients with colorectal cancer. However, the efficacy of the regimen in Vietnamese patients has not been assessed and reported. In this retrospective study, we reviewed medical records of 83 patients with stage II or stage III colorectal cancer who received mFOLFOX6 regimen in order to investigate simultaneously survival and safety of this chemotherapy regimen. Three-year overall and disease-free survival were 84.3% and 79.5%, respectively. Our data revealed that postoperative Carcinoma Embryonic Antigen (CEA) level was a significant prognostic factor for survival, with hazard ratio of 3.83 and 3.67, respectively (P < .05), for overall survival and disease-free survival in the elevated CEA level group when compared to the normal CEA level group. The regimen also demonstrated to be well tolerated and can be used in routine practice as an adjuvant chemotherapy.

[Effects and mechanism of lncRNA serving as ceRNA in non-obstructive azoospermia].

Objective: To investigate the mechanisms of lncRNA on the occurrence and development of NOA by constructing ceRNA regulation network of lncRNA, miRNA and mRNA. Methods: Samples of adult human testis were obtained from NOA patients and OA patients with normal spermatogenesis (controls), recruited from the Reproductive Medicine Center of Nanfang Hospital from June 2017 to June 2018. Differentially expressed lncRNAs and mRNAs in testicular tissues from patients with NOA were identified by microarray analysis in previous association study. In this study, differentially expressed lncRNAs and mRNA were used to construct the ceRNA regulatory network in NOA and clarify the interaction relationship among lncRNA, miRNA and mRNA. GeneMANIA database was used to construct Protein-Protein Interaction (PPI) of the mRNAs in ceRNA regulatory network. WebGestalt toolkit was employed to perform gene function and pathway enrichment analyses of those coding genes. Finally, qRT-PCR and dual luciferase reporter system were employed for further experimental validation. Results: The ceRNA regulatory network of lncRNA, miRNA and mRNA consists of 21 nodes and 26 edges, of which 4 lncRNAs, 13 miRNAs and 4 mRNAs. 19 proteins were found to interact with the mRNA coding proteins in ceRNA regulatory network by PPI analysis. Gene oncology and KEGG pathway enrichment analyses indicate these coding genes were significantly enriched in pentose metabolic process and pentose phosphate pathway. Furthermore, lncRNA ANXA2P3 was found binding with miR-613 and miR-206 to inhibit mRNA TKT expression. Conclusion: lncRNAs exert an important role in the occurrence and development of NOA via ceRNA regulatory network, which could be used as new biomarkers for NOA treatment.

Level of neutral alpha-1,4-glucosidase in seminal plasma of Chinese men.

Neutral alpha-1,4-glucosidase (NAG) is a crucial biomarker for the function of epididymis and is reported to be associated with semen quality. However, the correlation between NAG and Chinese semen quality has never been reported. This study aimed to investigate the level of NAG in the seminal plasma of Chinese men. A total of 394 cases of seminal plasma samples from normal, subfertile and infertile men were enrolled in this study. Male subfertility was caused by teratozoospermia, asthenospermia, severe oligozoospermia, asthenoteratozoospermia, oligoasthenospermia and oligoasthenoteratozoospermia. Male infertility was resulted from azoospermatism. The level of NAG was detected by spectrophotometry. Results showed that the level of NAG in normal men was significantly higher than that in subfertile and infertile men (p = .000). Meanwhile, the level of NAG in subfertile men was significantly greater than that in infertile men (p = .000). In addition, a significant difference was observed in normozoospermia, teratozoospermia, asthenospermia, severe oligozoospermia, asthenoteratozoospermia, oligoasthenospermia, oligoasthenoteratozoospermia and azoospermatism (p < .05). In conclusion, these data indicate that NAG is a crucial marker for assessing seminal plasma quality in Chinese men, which might be helpful for the assistant diagnosis of male infertility.

Abnormal placentation: the role of MRI in diagnosis and therapeutic planning.

AIM: To evaluate the role of magnetic resonance imaging (MRI) for diagnosis and therapeutic planning in patients with abnormal placentation (AP). MATERIALS AND METHODS: Overall, 168 consecutive patients with suspected placenta previa and AP were referred for MRI before caesarean section (CS). The ability of MRI to properly detect and assess abnormal placentation was correlated with findings at CS, which were considered the reference standard diagnostic tool. For each patient, MRI was used to determine whether the AP was suitable for complete/incomplete delivery, hysterectomy, or conservative treatment. Treatment planning with MRI was prospectively compared with the actual treatment that had been carried out in each patient decided at CS. RESULTS: Placenta previa was detected at MRI in 63 patients and AP in 105 patients; 16 patients had false-positive MRI findings, and three had false-negative findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI compared to findings at CS were 88.9% (149 of 168), 96.7% (89 of 92), 78.9% (60 of 76), 84.8% (89 of 105), and 95.2% (60 of 63), respectively. Treatment planning could be correctly made on the basis of MRI with accuracy, sensitivity, specificity, PPV, and NPV of 97%, 100%, 92.6%, 95.2%, and 100%, respectively. CONCLUSIONS: MRI offers high diagnostic accuracy in the detection of AP, and it may be helpful in the detailed planning of treatment.

Genetic differences in oestrous signs and oestrogen metabolism-related genes between Chinese Mi and European Landrace-Large White pigs.

Oestrous signs affect timely mating and reproductive efficiency in swine breeding herds. To study the genetic difference of oestrous signs between Chinese and European pigs, 100 Landrace-Large White (LLW) cross gilts and 50 Chinese Mi gilts were assessed for oestrous signs and the concentrations of serum estradiol-17ß and progesterone were determined. The genotype of 39 single nucleotide polymorphisms (SNPs) in 11 oestrogen metabolism and function-related genes was determined by Sequenom iPLEX platform. Compared with LLW gilts, Mi gilts had longer time of standing reflex (p < .001), higher scores of vulva reddening (p = .001) and greater serum estradiol-17ß concentration (p < .01). Gilts with greater serum estradiol-17ß concentrations also had greater (p < .05) scores for oestrous signs. Genetic polymorphisms of nine genes in oestrogen metabolism pathways had significant differences (p < .05) between LLW and Mi gilts. There were three and six haploblocks of SNPs in LLW and Mi, respectively. Compared with LLW, the distribution of haplotypes was more centralized in Mi pigs. Genetic polymorphisms of oestrogen metabolism-related genes have considerable differences between Chinese Mi and European LLW pigs. Because of the important roles of oestrogen during the oestrus, some genes of oestrogen metabolism pathway could be considered as candidate genes for oestrous signs.

A phase II study of SB939, a novel pan-histone deacetylase inhibitor, in patients with translocation-associated recurrent/metastatic sarcomas-NCIC-CTG IND 200†.

BACKGROUND: A subgroup of sarcomas is characterized by defining chromosomal translocations, creating fusion transcription factor oncogenes. Resultant fusion oncoproteins associate with chromatin-modifying complexes containing histone deacetylases (HDAC), and lead to epigenetic transcriptional dysregulation. HDAC inhibitors were shown to be effective in vitro, reversing gene repression by these complexes, restoring PTEN expression and apoptosis via the PI3K/Akt/mTOR pathway. PATIENTS AND METHODS: SB939 is an oral inhibitor of classes 1 and 2 HDAC. Eligible patients with recurrent or metastatic translocation-associated sarcoma (TAS) by local pathology were treated with 60 mg/day every other day for 3 of 4 weeks. Central pathology review was conducted with fusion oncogenes characterized, and HDAC2 expression correlated with efficacy in pre-specified methods. RESULTS: Twenty-two patients were treated with a median of 2 cycles. Fourteen patients were assessable for response with confirmed specific chromosomal translocations; 8 had a best response of stable disease (SD) (median duration 5.4 months) with no confirmed objective responses. The 3-month progression-free survival (PFS) rate was 49%. Among those with HDAC2 score ≥5, 7/10 had SD, versus 0/3 with HDAC2 score <5. SB939 was considered as well tolerated with <10% patients experienced ≥grade 3 toxicity. CONCLUSION: This study was stopped prematurely due to prolonged unavailability of SB939. No objective responses were seen. Although the observed SD in HDAC2 high patients was interesting, due to the small sample size, no definitive conclusion can be drawn about the efficacy of SB939 in this patient population. CLINICAL TRIAL: NCT01112384.

Caesarean section combined with temporary aortic balloon occlusion followed by uterine artery embolisation for the management of placenta accreta.

AIM: To determine the efficacy and safety of caesarean section combined with temporary aortic balloon occlusion followed by uterine artery embolisation (UAE) for the treatment of patients with placenta accreta. MATERIALS AND METHODS: This retrospective study involved 42 patients with placenta accreta. All patients underwent caesarean section combined with temporary aortic balloon occlusion followed by UAE through the right femoral approach. RESULTS: All patients were confirmed to have placenta praevia and accreta, including five patients with placenta percreta, at the time of delivery. The technical success rate of the combined treatment was 97.6% (41/42). Forty-one patients underwent successful caesarean section with conservation of the uterus. Hysterectomy was required in one (3.1%) patient. The amount of blood loss and blood transfusion, and the operation time were was 586 ± 355 ml, 422 ± 83 ml and 65.5 ± 10.6 minutes, respectively. The mean postoperative hospital stay, occlusion time and fetal radiation dose were 5.5 ± 2.6 days, 22.4 ± 7.2 minutes and 4.2 ± 2.9 mGy, respectively. There were no significant changes before and 7 days after the endovascular procedure in creatinine levels (56.8 ± 13.8 µmol/l versus 63.4 ± 16.7 µmol/l, p = 0.09) or urea nitrogen (6.3 ± 2.5 µmol/l versus 7.4 ± 3.8 µmol/l, p = 0.17). There were no access-site complications after the endovascular procedure and no complications related to the intervention during follow-up. CONCLUSION: Temporary aortic balloon occlusion followed by UAE can effectively control postpartum haemorrhage during placental dissection, and reduce transfusion requirements, hysterectomy rate, and operation time in patients with placenta accreta.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Effects of photoperiod on broodiness, egg-laying and endocrine responses in native laying hens.

1. The effects of photoperiod on broodiness, egg-laying and endocrine responses in native laying hens were investigated. A total of 648, 18-week-old native laying hens (Beijing You Chicken, BYC) were randomly allocated to 6 groups with 3 replicates. The birds were exposed to 1 of 6 different photoperiods, including 16L:8D (06:00 to 22:00 h) for group 1; 12L:2D:4L:6D for group 2; 8L:4D:4L:8D for group 3; 16L:8D (03:00 to 19:00 h) for group 4; 14L:10D for group 5; and 18L:6D for group 6. 2. The broodiness rate and egg-laying rate for weeks 20-26, 27-33, 34-40, 41-47, 48-54 and 55-61 were calculated, and serum prolactin (PRL), luteinising hormone (LH), 17-beta-oestradiol (E2), melatonin (Mel) and progesterone (P4) concentrations were measured at the end of each stage. 3. Significant effects were observed on the rate of broodiness by the photoperiod and stage, but the interaction of photoperiod and stage was not significant. The rate of broodiness for group 3 (5.9%) was significantly higher than other groups, with group 2 being the lowest (2.8%). Broodiness rate was the highest for weeks 41-47 (9.9%). Significant effects were observed on average egg-laying rate by photoperiod and stage: the rate of egg-laying of groups 2 and 5 were significantly higher than groups 1, 4 and 6. 4. There were no significant effects of photoperiod on PRL, LH and Mel concentrations at 26, 33, 40 and 54 weeks of age (P > 0.05), but at 47 weeks of age, PRL and LH concentrations of group 1 were significantly lower than those in other groups. 5. The study suggests that the photoperiod of group 2 (12L:2D:4L:6D) is optimal for the birds' performance to give the lowest broodiness rate and the highest egg-laying rate during the whole laying period, and 41-47 weeks may be a key stage for the photomodulation of broodiness.

Dietary metabolizable energy and crude protein levels affect pectoral muscle composition and gut microbiota in native growing chickens.

The experiment aimed to study effects of dietary metabolizable energy (ME) and crude protein (CP) levels alone and in interaction on performance, pectoral muscle composition and gut microbiota in native growing chickens. A total of 648 10-wks-old Beijing-You Chicken (BYC) female chickens were randomly allocated to 9 groups with 6 replicates per group and 12 chickens per replicate, and the chickens were fed with a 3 × 3 factorial diets (3 levels of dietary ME: 11.31 MJ/kg, 11.51 MJ/kg, 11.71 MJ/kg; and 3 levels of dietary CP: 14%, 15%, 16%). The results showed that dietary ME and CP levels didn't affect average feed intake (AFI), body weight gain, feed gain ratio (P > 0.05), but ME level significantly affected the AFI (P < 0.05); mortality rate of 11.31 MJ/kg group was the highest (P < 0.05). Dietary ME, CP levels, and the interaction significantly affected pectoral CP and crude fat (CF) content of the growing chickens (P < 0.01). Dietary CP level had opposite effects on pectoral CP and CF content (P < 0.01). The 16% CP increased the pectoral CF content, which may have a negative impact on meat flavor. Dietary ME level affected 11 types of pectoral free amino acids (FAA) contents, including aspartic acid, L-threonine (P < 0.05), also amino acid classification, for example, total amino acid (TAA) and essential amino acid (EAA) content (P < 0.05). The 11.51 MJ/kg group had the highest TAA, EAA, delicious amino acid (DAA) content and EAA percentage (P < 0.05), while 11.31 MJ/kg group had the lowest bitter amino acid (BAA) content and BAA percentage and the highest fresh and sweet amino acid (FSAA) percentage (P < 0.05). Dietary CP level significantly affected glutamine and tyrosine content (P < 0.05). The interaction of dietary ME and CP level affected C20:3n6 content, saturated fatty acid (SFA), and unsaturated fatty acid (UFA) percentage (P < 0.05). The CP level significantly affected SFA percentage (P < 0.05). The 16% CP level increased the diversity of gut microbiota, but at the same time increased the relative abundance of Proteobacteria (P < 0.05), which is a sign of microbiota disorder. The increase of dietary ME level resulted in a gradual decrease in the diversity and relative abundance of gut microbiota. In conclusion, the present study suggested that the medium dietary ME (11.51 MJ/kg) and low CP (14-15%) levels can be helpful for enhancing pectoral muscle composition, increase meat quality such as flavor and nutritional value, and benefit for gut microbiota in native growing chickens.

Dietary calcium and non-phytate phosphorus levels affect the performance, serum biochemical indices, and lipid metabolism in growing pullets.

This experiment aimed to study the effects of dietary calcium (Ca) and non-phytate phosphorus (NPP) levels on performance, serum biochemical indices, and lipid metabolism in Beijing You Chicken (BYC), a local chicken. A 3 × 3 factorial design was adopted, dietary Ca levels were 0.66, 0.71, and 0.76%, NPP levels were 0.25, 0.30, and 0.35%. A total of 648 ten-wk-old BYC growing pullets were randomly divided into 9 groups with 6 replicates per group, and 12 birds per replicate. Growth performance, serum biochemical indices, and lipid metabolism indicators from 10 to 16 wk were measured. The results showed as follows: 1) Dietary Ca and NPP alone did not affect growth performance, but the interaction of dietary Ca and NPP affected average feed intake (AFI) of growing pullets (P < 0.05). The AFI was the lowest for the group with 0.71% Ca and 0.25% NPP (3,550.0 g, P = 0.036). 2) Dietary Ca level significantly affected serum P content (P < 0.05); dietary NPP had an influence trend on serum Ca content (P= 0.054). Dietary NPP levels and the interaction of Ca and NPP significantly affected alkaline phosphatase (AKP) activity. 3) Dietary Ca levels significantly affected TC content and HDL-C content (P < 0.05). Dietary NPP level significantly affected TG content (P < 0.05), the TG content in 0.25% and 0.30% NPP groups was significantly lower than that in 0.35% NPP group (P < 0.05). The interaction of dietary Ca and NPP significantly affected TG, TC and HDL-C contents (P < 0.05). TG, TC, and LDL-C levels were lower and HDL-C levels were the highest in the group with 0.66% Ca and 0.25% NPP. In summary, appropriate dietary Ca level can regulate serum TG, TC, and HDL-C content. Dietary Ca and NPP levels can be adjusted in pullet phase to avoid excessive obesity during the egg-laying period. This study recommended that dietary 0.66% Ca and 0.25% NPP benefit for the lipid metabolism of BYC growing pullets without affecting the performance.

Lighting pattern and photoperiod affect the range use and feather cover of native laying hens under free range condition.

The study aimed to investigate the effects of lighting pattern and photoperiod on range use, feather cover and gait score of native laying hens. Six hundred and thirty 19-wks-old Beijing You Chicken (BYC) pullets were randomly allocated to 6 groups with 105 birds each, 3 replicates per group, reared in individually lit indoor pens with separate covered shed and outdoor areas. A 2 × 3 factorial experiment (2 lighting patterns: continuous and intermittent lighting; 3 photoperiods: 16 h, 14 h, 12 h) was arranged indoors, including 16L:8D (6:00-22:00) for group 1; 12L:2D:4L:6D (6:00-18:00,20:00-24:00) for group 2; 14L:10D (6:00-20:00) for group 3; 10L:2D:4L:8D (6:00-16:00,18:00-22:00) for group 4; 12L:12D (6:00-18:00) for group 5, and 8L:4D:4L:8D (6:00-14:00,18:00-22:00) for group 6, respectively. The number of hens in indoor pen, covered shed and outdoor area were counted at 8:00, 9:00, 10:00, 11:00, 12:00, 13:00, 14:00 for consecutive 3 sunny days at 34 wks and 36 wks of age, feather cover and gait score of the laying hens were assessed at the end of 36 wks. The results showed that daily average hen percentage was the highest in continuous 12 h group (63.67%), and the lowest in intermittent 14 h group (58.36%) in indoor pen (P < 0.05); the daily average hen percentage was the lowest in continuous 12 h group (16.05%), and the highest in intermittent 14h group (21.22%) in outdoor area (P < 0.05). Lighting pattern significantly affected hen percentage in indoor pen and outdoor area, the hen percentage in indoor pen was higher in continuous lighting groups than in intermittent lighting groups (62.09% vs. 59.23%) (P < 0.05), the hen percentage in outdoor area was lower in continuous lighting groups than in intermittent lighting groups (16.60% vs. 19.95%) (P < 0.05). Photoperiod had no effect on the hen percentage (P > 0.05), but time of day affected the hen percentage in different areas (P < 0.05). The feather cover score was higher in intermittent lighting groups than in continuous lighting groups (17.43 vs. 15.04, P < 0.05). The average hen percentage in indoor pen is strongly negatively correlated with the feather cover score (r = -0.880, P = 0.050), and the hen percentage in outdoor area is strongly positively correlated with the feather cover score in intermittent lighting condition (r = 0.811, P < 0.05). The present study suggested that more range use is beneficial for the feather cover and physical health of laying hens under free range condition, and intermittent lighting is more conducive to range use and feather cover of native laying hens, which may be related to its affecting hens' rhythmic activities, increasing adaptation to outdoor environment, and reducing the incidence of feather pecking and parasites.

A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer.

BACKGROUND: Bcl-2 family genes are frequently amplified in small cell lung cancer (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy. METHODS: Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, ≤ 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients were treated with escalating doses of obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m(-2), days 1-3). The primary endpoint was to determine the maximum tolerated dose of obatoclax. RESULTS: Twenty-five patients (56% male; median age 66 years) were enrolled in three dose cohorts for each schedule. Maximum tolerated dose was established with the 3-h infusion at 30 mg per day and was not reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts had higher incidence of central nervous system (CNS) adverse events (AEs); dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS AEs were transient, resolving shortly after the end of infusion, and without sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion cohorts. CONCLUSION: Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. Though patient numbers were small, there was a suggestion of improved efficacy in the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 consecutive days will be utilised in future SCLC studies.

Effects of light regime on circadian rhythmic behavior and reproductive parameters in native laying hens.

The paper aimed to study the effects of light regime on circadian rhythmic behavior and reproductive parameters in a native laying hen, Beijing You Chicken (BYC) during 22 to 30 wk. A total of 630 19-wk-old BYC female chicken were allocated to 6 light regime groups with 3 replicates per group and 35 birds per replicate, reared in individually lit floor pens with separate outdoor areas. A 2 × 3 factorial experiment (2 lighting patterns: continuous and intermittent lighting; 3 photoperiods: 16 h, 14 h, 12 h) was arranged, including 16L:8D for group 1; 12L:2D:4L:6D for group 2; 14L:10D for group 3; 10L:2D:4L:8D for group 4; 12L:12D for group 5, and 8L:4D:4L:8D for group 6, respectively. The circadian rhythmic behavior of the hens, including feeding, egg-laying and sleeping behaviors were observed by scan sampling and target sampling method for consecutive 3 d every other week during 22 to 30 wk. Infrared cameras were set outside each pen to record the rhythmic behaviors of the birds every other hour (6:00-7:00;8:00-9:00;10:00-11:00;12:00-13:00;14:00-15:00;16:00-17:00;18:00-19:00;20:00-21:00;22:00-23:00;0:00-1:00;2:00-3:00;4:00-5:00). Theovarian weight, oviduct weight, oviduct length, the number of large yellow follicles (LYF), and small yellow follicles (SYF) were measured at the end of 30 wk. The egg-laying rate during 22 to 30 wk was measured. The results showed that the highest feeding frequency was given by the 16L:8D, and the lowest given by the 12L:12D (P < 0.05). The average feeding duration was the longest in the 8L:4D:4L:8D at 6:00 to 8:00 (18.67 min/hen) (P < 0.05), and the shortest in the 8L:4D:4L:8D at 18:00 to 20:00 (3.75 min/hen) (P < 0.05). The highest egg-laying frequency was given by the 8L:4D:4L:8D (0.28), the lowest given by the 10L:2D:4L:8D (0.21) (P < 0.05). The shortest egg-laying duration occurred at 6:00 to 8:00, was given by the 16L:8D (8 min/hen), and the longest egg-laying duration occurred at 18:00 to 20:00, was given by 16L:8D and 8L:4D:4L:8D (>20.5 min/hen) (P < 0.05). The highest sleeping frequency was given by the 12L:2D:4L:6D, the lowest was given by the 12L:12D (P < 0.05). At 6:00 to 8:00, the shortest sleeping duration was given by 12L:2D:4L:6D (1.5 s/hen), at 18:00 to 20:00, the longest given by 8L:4D:4L:8D (14.3 s/hen) (P < 0.05). Lighting pattern and photoperiod alone or in interaction had no effect on egg-laying rate during 22 to 30 wk (P > 0.05), but had significant effects on ovarian weight, oviduct weight, oviduct length, the number of LYF and SYF (P < 0.05), and the continuous groups were all significantly higher than the intermittent groups (P < 0.05). The present study indicated that light regimes affected the frequency and duration of circadian behavior in BYC laying hens, and the continuous light was more beneficial to the reproductive development than the intermittent light in the early laying period.