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Papillary thyroid microcarcinoma (PTMC) is a malignant thyroid tumor of less than 1 cm in size. Ultrasound (US) is the preferred imaging modality for PTMC. This study retrospectively evaluated the US results from 113 consecutive cases of PTMC with 127 nodules and correlated the results with the histopathologic findings. The results showed none of the PTMC nodules had a cystic element. Half of the PTMC nodules had a well-defined boundary and the remaining half had an ill-defined boundary. A percent (6.3%) of the nodules had a halo sign. Microcalcification was present in approximately half of the PTMC nodules. The cancerous tissue with a papillary structure was hypoechogenic and the amount of fibrous stroma determined whether the nodule echogenicity was heterogeneous or homogeneous. Heterogeneous echogenicity was associated with a fibrous stroma proportion of >20%. Only PTMC nodules with predominantly follicular structures containing a large proportion of colloid demonstrated isoechogenicity. Well-defined boundaries on US were associated with well-defined histologic margins, with or without the presence of an intact fibrous pseudo-capsule. A halo sign with a well-defined boundary detected by US was associated with the presence of an intact fibrous pseudo-capsule. Half of the PTMC nodules with ill-defined boundaries exhibited infiltration into the surrounding thyroid tissue, while the remaining half of the PTMC nodules with ill-defined boundaries on US presented irregular nodule margins by histology, rather than nodule infiltration. Psammoma bodies detected at a frequency ≥5 per ×200 microscopic field of view were detectable on US as microcalcifications. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the prognostic significance of the modified diagnostic biopsy-adapted immunoscore (mIS b ) in determining the outcomes for patients with locally advanced rectal cancer (LARC) in a neoadjuvant setting., Methods and Materials: We included 181 patients with LARC from a single subcenter of a prospective study comparing total neoadjuvant therapy (TNT) based on short-course radiation therapy with long-term chemoradiation therapy (CRT). Tumor biopsies at baseline were stained for CD8+ and CD3+ T-cell densities. The mIS b was developed using mean percentile of CD8+ T-cell density and CD8/CD3 ratio. Patients were classified into low (0%-25%), intermediate (>25%-70%), and high (>70%-100%) in both groups. The relativity among different lymphocytes and their correlation with survival were illustrated. Survival analyses and Cox regression models were used to compare the prognostic values of mIS b and diagnostic biopsy immunoscore for survival outcomes and to assess the role of mIS b in TNT and CRT subgroups, respectively., Results: In this study, 151 (83.4%) patients received surgery, and 30 (16.6%) followed a watch and wait strategy. A strong correlation was found between CD8+ and CD3+ T-cell densities (R = 0.86; P < .001), whereas a weak correlation was witnessed between CD8+ and CD8/CD3 ratio (R = 0.45). The 3-year disease-free survival for the entire cohort was 69.9%, with 57.2%, 68.6%, and 85.5% for the low, intermediate, and high mIS b groups, respectively (P = .01), whereas diagnostic biopsy immunoscore failed to distinguish survival outcomes. Multivariate analysis revealed mIS b to be an independent prognostic factor for disease-free survival in surgically treated patients (P = .01). Specifically, patients with high mIS b score showed longer progression-free survival than other subgroups in the TNT cohort (P = .049), but no significant difference was found in the CRT population., Conclusions: In this study, mIS b demonstrated significant prognostic value in patients with LARC receiving preoperative therapies, especially in the TNT subgroup. These findings may help tailor the intensity of neoadjuvant therapy for patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was high. These drug-resistant strains showed good replication capacity without serious loss of fitness. In the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. Pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased (1) replication ability in MDCK( P < 0.05) and A549( P < 0.05), (2) neuraminidase enzyme activity, (3) binding ability to both α2,3 and α2,6 receptor, (4) pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), (5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titre). It indicated that through the fine-tuning of HA-NA balance, R229I increased the fitness and changed the antigenicity of H7N9 virus bearing NA 292K. Public health attention to this mechanism needs to be drawn.

The blunt snout bream (Megalobrama amblycephala) is a typical hypoxia-sensitive fish, and hypoxia stress leads to reduced vitality and yield during aquaculture. To explore the specific adaptation mechanism under hypoxia, the blunt snout bream was treated with hypoxia (DO = 2.0 ± 0.1 mg/L) for 24 h, followed by 3 h of recovery. Our results depicted that the gill filament structure of blunt snout bream changed after hypoxia. During hypoxia for 24 h, the gill filament structure was altered, including a more than 80% expansion of the lamellar respiratory surface area and a proportionate apoptosis decrease in interlamellar cell mass (ILCM) volume. Thus, the water-blood diffusion distance was shortened to less than 46%. During hypoxia for 24 h, the activity of ROS in gill tissue increased significantly (p < 0.05), while the mitochondrial membrane potential decreased significantly (p < 0.05). During hypoxia, mRNA expression level of anti-apoptotic gene Bcl-2 in the gills of blunt snout bream decreased significantly (p < 0.05), while the expression of pro-apoptotic gene Bax mRNA increased significantly (p < 0.05). Thus, the ratio of Bax/Bcl-2 mRNA increased in the gills of blunt snout bream to promote the activity of Caspase-3. Together, our results indicated hypoxia-induced apoptosis in the gills of blunt snout bream through the mitochondrial pathway. In addition, a decreased expression of Phd1 and an increased expression of Hif-1α in gills under hypoxia stress indicates that blunt snout bream may cope with hypoxia-induced apoptosis by enhancing the HIF pathway. These results provide new insights into fish's adaptation strategies and mechanisms of hypoxia., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

With the gradual decrease in freshwater resources, the available space for freshwater aquaculture is diminishing. As a result, saline-alkaline water aquaculture has emerged as a crucial method to fulfill the increasing demand. This study investigates the impact of alkaline water on the growth performance, tissues (gill, liver, and kidney), digestive enzyme activity, and intestinal microbiology in grass carp (Ctenopharyngodon idella). The aquarium conditions were set with sodium bicarbonate (18 mmol/L (LAW), 32 mmol/L (HAW)) to simulate the alkaline water environment. A freshwater group was the control (FW). The experimental fish were cultured for 60 days. The findings revealed that NaHCO 3 alkaline stress significantly reduced growth performance, caused alterations in the structural morphology of gill lamellae, liver, and kidney tissues, and led to decreased activity of intestinal trypsin and lipase amylase (P < 0.05). Analysis of 16S rRNA sequences demonstrated that alkalinity influenced the abundance of dominant bacterial phyla and genera. Proteobacteria showed a significant decrease under alkaline conditions, while Firmicutes exhibited a significant increase (P < 0.05). Furthermore, alkalinity conditions significantly reduced the abundance of bacteria involved in protein, amino acid, and carbohydrate metabolism, cell transport, cell decomposition, and environmental information processing. Conversely, the abundance of bacteria associated with lipid metabolism, energy metabolism, organic systems, and disease functional flora increased significantly under alkalinity conditions (P < 0.05). In conclusion, this comprehensive study indicates that alkalinity stress adversely affected the growth performance of juvenile grass carp, likely due to tissue damage, reduced activity of intestinal digestive enzymes, and alterations in intestinal microorganisms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups ( P >0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation ( P <0.05). Multivariate regression analysis showed that only erosion or rupture ( OR =4.028, 95% CI: 1.468, 11.050, P =0.007), localized depression ( OR =3.105, 95% CI: 1.584, 6.088, P =0.001), infiltrative JNET staging ( OR =5.622, 95% CI: 3.029, 10.434, P <0.001), and infiltrative Pit pattern ( OR =2.722, 95% CI: 1.347, 5.702, P =0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

A new hypoxia-tolerant variety of blunt snout bream was obtained by successive breeding of the wild population, which markedly improved hypoxia tolerance. In this study, the hypoxia-tolerant variety was exposed to hypoxia (2.0 mg O 2 ·L -1 ) for 4, 7 days. The contents of blood biochemical indicators including the number of red blood cells (RBC), total cholesterol (T-CHO), total protein (TP), triglyceride (TG), glucose (GLU), and lactic acid (LD) increased significantly (P < 0.05) under hypoxia. The glycogen content in the liver and muscle decreased significantly (P < 0.05) and the LD content in the brain, muscle and liver increased significantly (P < 0.05) under hypoxia. The levels of oxidative stress-related indicators i.e., superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T-AOC) also changed significantly (P < 0.05) in the heart, liver, and intestine of the new variety under hypoxia. Additionally, hypoxia has caused injuries to the heart, liver, and intestine, but it shows amazing repair ability during reoxygenation. The apoptotic cells and apoptosis rate in the heart, liver, and intestine increased under hypoxia. Under hypoxia, the expression of the B-cell lymphomas 2 (Bcl-2) gene in the heart, liver, and intestine was significantly (P < 0.05) down-regulated, while the expression of the BCL2-associated agonist of cell death (Bad) gene was significantly (P < 0.05) up-regulated. These results are of great significance for enriching the basic data of blunt snout bream new variety in response to hypoxia and promoting the healthy development of its culture industry., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia environment. Hypoxia-inducible factor (HIF) is the most critical factor in the HIF pathway, which strictly regulates the hypoxia stress process of fish. In this study, we found six hifα genes in blunt snout bream that demonstrated different expressions under hypoxia conditions. In HEK293T cells, all six hifαs were detected to activate the HRE region by luciferase reporter assay. More importantly, we identified two linkage-disequilibrium SNP sites at exon 203 and 752 of the hif2αb gene in blunt snout bream. Haplotype II (A 203 A 752 ) and its homozygous diplotype II (A 203 A 203 A 752 A 752 ) appeared frequently in a selected strain of blunt snout bream with hypoxia tolerance. Diplotype II has a lower oxygen tension threshold for loss of equilibrium (LOE crit ) over a similar range of temperatures. Moreover, its erythrocyte number increased significantly (p < 0.05) than those in diplotype I and diplotype III strains at 48 h of hypoxia. The enzymes related with hypoxia tolerant traits, i.e., reduced glutathione, superoxide dismutase, and catalase, were also significantly (p < 0.05) induced in diplotype II than in diplotype I or III. In addition, the expression of epo in the liver of diplotype II was significantly (p < 0.01) higher than that in the diplotype I or III strains at 48 h of hypoxia. Taken together, our results found that the hypoxia-tolerant-related diplotype II of hif2αb has the potential to be used as a molecular marker in future genetic breeding of hypoxia-tolerant strain., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The theory of knowledge, attitude and practice (KAP) can well explain the whole process of pregnant females' practice to obtain balanced nutrition. However, the process of KAP works very differently in populations with different sociodemography. This study aims to investigate the sociodemographic determinants associated with pregnant females' nutritional KAP and find a way to locate the vulnerable pregnant females who would benefit most from intervention. A cross-sectional survey was conducted on pregnant females' KAP regarding food nutrition at the University of Chinese Academy of Science Shenzhen Hospital from December 2020 to February 2021. A total of 310 pregnant females aged 18-40 years were interviewed. And we assessed the influence of sociodemographic factors on KAP and built a model for screening the vulnerable group who would benefit most from intervention. The results showed that on nutritional knowledge and practice, only 15.2% and 47.3% were above 0.6 respectively, while 91% were above 0.75 on attitude. Age, Husband's Education Degree, Monthly Income of Family, Nutritional Knowledge and Nutritional Attitude were statistically significant predictors of the vulnerable group. There was a gap between knowledge (3.8% were good or above) and attitude (91% were good or above), attitude and practice (16.8% were good or above). Age, household registry, education level, monthly income, and nutrition knowledge were associated with nutrition practices. This study highlights that nutritional education interventions targeting certain populations may improve the conversion rate of nutrition practices, and presents a predictive model to locate the vulnerable group., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group ( P <0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

Seasonal changes, diurnal variations, and eutrophication result in periodic hypoxia in fish habitats, thus affecting the success of commercial aquaculture. In this study, the grass carp (Ctenopharyngodon idella) presented moderate hypoxia tolerance; they showed a medium critical oxygen tension during the loss of equilibrium. In response to 7 d of hypoxic exposure, the erythrocyte count and hemoglobin (Hb) concentration significantly increased (p < 0.01). To cope with the hypoxic environment, the grass carp underwent gill remodeling marked by reduction in the interlamellar cell mass (ILCM) and an increase in respiratory surface area. The gill remodeling under hypoxia was enabled by apoptosis induction. Although apoptotic signals were not found on ILCM cells, transferase dUTP nick end labeling (TUNEL) assay results indicated that after 1 d of hypoxic exposure, the number of TUNEL-positive cells per lamella increased until 4 d and then began to decrease. Consistent with the results of the TUNEL assay, the mRNA expression of apoptosis-related genes, caspase-3, Bax, and Bcl-2, increased at 1, 4, and 7 d of the hypoxia treatment. In addition, gill remodeling significantly (p < 0.01) decreased the concentration of sodium and chloride ions in the fish serum. These findings provide evidence that grass carps increase their respiratory surface area through gill remodeling by apoptosis in the gill filaments to acclimate to a hypoxic environment. This study expands our understanding of the morphological and physiological changes in grass carp in response to a hypoxic environment; therefore, it could be useful for maintaining grass carp production., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer., Materials and Methods: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m 2 , once a day] on day 1 and capecitabine [1,000 mg/m 2 , twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS)., Results: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P < .001)., Conclusion: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer., Competing Interests: Chen HuConsulting or Advisory Role: Merck Sharp & Dohme, D1 Medical Technology Ai-Ping ZhouConsulting or Advisory Role: Pfizer, NovartisNo other potential conflicts of interest were reported.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial., Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate., Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively., Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT., Trial Registration: ClinicalTrial.gov NCT02301481., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Yang, Chi, Zhao, Jiang, Jiang, Tang, Li, Liu, Dou, Zou, Xue, Ren, Tian, Che, Guo, Bai, Sun, Wang, Song, Liu, Fang, Li and Jin.)

Background: The grass carp has great economic value and occupies an important evolutionary position. Genomic information regarding this species could help better understand its rapid growth rate as well as its unique body plan and environmental adaptation., Results: We assembled the chromosome-level grass carp genome using the PacBio sequencing and chromosome structure capture technique. The final genome assembly has a total length of 893.2 Mb with a contig N50 of 19.3 Mb and a scaffold N50 of 35.7 Mb. About 99.85% of the assembled contigs were anchored into 24 chromosomes. Based on the prediction, this genome contained 30,342 protein-coding genes and 43.26% repetitive sequences. Furthermore, we determined that the large genome size can be attributed to the DNA-mediated transposable elements which accounted for 58.9% of the repetitive sequences in grass carp. We identified that the grass carp has only 24 pairs of chromosomes due to the fusion of two ancestral chromosomes. Enrichment analyses of significantly expanded and positively selected genes reflected evolutionary adaptation of grass carp to the feeding habits. We also detected the loss of conserved non-coding regulatory elements associated with the development of the immune system, nervous system, and digestive system, which may be critical for grass carp herbivorous traits., Conclusions: The high-quality reference genome reported here provides a valuable resource for the genetic improvement and molecular-guided breeding of the grass carp., (© 2022. The Author(s).)

Background: Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia. A new blunt snout bream strain, "Pujiang No.2", was developed to overcome this shortcoming. As a proteasome inhibitor, bortezomib (PS-341) has been shown to affect the adaptation of cells to a hypoxic environment. In the present study, bortezomib was used to explore the hypoxia adaptation mechanism of "Pujiang No.2". We examined how acute hypoxia alone (hypoxia-treated, HN: 1.0 mg·L - 1 ), and in combination with bortezomib (hypoxia-bortezomib-treated, HB: Use 1 mg bortezomib for 1 kg fish), impacted the hepatic ultrastructure and transcriptome expression compared to control fish (normoxia-treated, NN)., Results: Hypoxia tolerance was significantly decreased in the bortezomib-treated group (LOE crit , loss of equilibrium, 1.11 mg·L - 1 and 1.32 mg·L - 1 ) compared to the control group (LOE crit , 0.73 mg·L - 1 and 0.85 mg·L - 1 ). The HB group had more severe liver injury than the HN group. Specifically, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the HB group (52.16 U/gprot, 32 U/gprot) were significantly (p < 0.01) higher than those in the HN group (32.85 U/gprot, 21. 68 U/gprot). In addition, more severe liver damage such as vacuoles, nuclear atrophy, and nuclear lysis were observed in the HB group. RNA-seq was performed on livers from the HN, HB and NN groups. KEGG pathway analysis disclosed that many DEGs (differently expressed genes) were enriched in the HIF-1, FOXO, MAPK, PI3K-Akt and AMPK signaling pathway and their downstream., Conclusion: We explored the adaptation mechanism of "Pujiang No.2" to hypoxia stress by using bortezomib, and combined with transcriptome analysis, accurately captured the genes related to hypoxia tolerance advantage., (© 2022. The Author(s).)

Blunt snout bream plays an important role in freshwater aquaculture in China, but the development of its culture industry has been restricted by increasing hypoxia problem. Through the breeding of wild blunt snout bream populations (F0), a hypoxia-tolerant new variety (F6) was obtained. In this study, the new variety was stressed under low oxygen concentration (2.0 mg·L -1 ) for 4 and 7 days, the morphological structure of the gill tissue showed a striking change, the interlamellar cell mass (ILCM) volume reduced significantly (P < 0.05), and the lamellar respiratory surface area enlarged significantly (P < 0.05), compared to normoxic controls. After 7 days of oxygen recovery, gill remodeling was completely reversed. Additionally, the TUNEL-positive apoptotic fluorescence signals increased in the gills exposed to hypoxia up to 4 and 7 days; the apoptosis rate also increased significantly (P < 0.05). Under 4 and 7 days of hypoxia stress, the expression of anti-apoptotic gene Bcl-2 in the gills downregulated significantly (P < 0.05), with the significantly (P < 0.05) upregulated expression of pro-apoptotic gene Bad. Furthermore, under hypoxia stress, the activity or content of oxidative stress-related enzymes (superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione (GSH)) in gill tissue increased to varying degrees compared to normoxic controls. These results offer a new perspective into the cellular and molecular mechanism of hypoxia-induced gill remodeling in blunt snout bream and a theoretical basis for its hypoxia adaptation mechanism., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

N-ethyl-N-nitrosourea (ENU) selection is a useful technique to generate new mutations that may cause some functional changes in the gene. Through our previous genomic bulked segregant analysis (BSA), one single nucleotide polymorphism (SNP) at the 3' UTR of Toll interacting protein gene (TOLLIP 982T>C ) was identified in grass carp (Ctenopharyngodon idella) subjected to ENU-induced mutagenesis. We found that the overexpression of cid-miR-nov-1043 mimics significantly suppressed the luciferase activity of the TOLLIP 3' UTR, but TOLLIP 982T>C mutation at the target site can decrease the binding affinity between the miRNA cid-miR-nov-1043 and TOLLIP 3' UTR, reducing the inhibition of TOLLIP mRNA transcription in grass carp subjected to ENU-induced mutagenesis. More importantly, we demonstrated that TOLLIP mRNA transcription levels in the gills, liver, kidney and the isolate white cells of the mutant grass carp were significantly (p < 0.01) higher than those in the corresponding tissues from the wild-type grass carp following infection with Grass Carp Reovirus (GCRV) for seven days, while the downstream gene of TOLLIP transforming growth factor β-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1), were higher expressed in wild-type grass carp. As a negative regulator in the pro-inflammatory pathway of NF-κB, TOLLIP inhibits the excessive inflammation in ENU grass carp after GCRV infection. Consistent with the TOLLIP expression, histopathological results demonstrated more severe inflammation in wild-type grass carp, compared to the TOLLIP 982T>C mutant grass carp on the seventh day. Severe inflammation will lead to thoroughly infiltration of chloride and inflammatory cells in the gill filaments. This seriously hindered the exchange of oxygen, which ultimately disrupted blood circulation. Meanwhile, the survival rate of the mutant grass carp was significantly (p < 0.01) higher than that of the wild-type grass carp, indicating that the TOLLIP 982T>C mutants showed strong anti-viral abilities. Our results revealed that an SNP in the TOLLIP 3' UTR may contribute to the suppression of serve inflammation subjected to ENU-induced mutagenesis following GCRV infection, which may be helpful for future resistant breeding development of grass carp., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Lynch-syndrome-associated cancer is caused by germline pathogenic mutations in mismatch repair genes. The major challenge to Lynch-syndrome screening is the interpretation of variants found by diagnostic testing. This study aimed to classify the MLH1 c.1989 + 5G>A mutation, which was previously reported as a variant of uncertain significance, to describe its clinical phenotypes and characteristics, to enable detailed genetic counselling., Methods: We reviewed the database of patients with Lynch-syndrome gene detection in our hospital. A novel variant of MLH1 c.1989 + 5G>A identified by next-generation sequencing was further investigated in this study. Immunohistochemical staining was carried out to assess the expression of MLH1 and PMS2 protein in tumour tissue. In silico analysis by Alamut software was used to predict the MLH1 c.1989 + 5G>A variant function. Reverse transcription-polymerase chain reaction and sequencing of RNA from whole blood were used to analyse the functional significance of this mutation., Results: Among affected family members in the suspected Lynch-syndrome pedigree, the patient suffered from late-stage colorectal cancer but had a good prognosis. We found the MLH1 c.1989 + 5G>A variant, which led to aberrant splicing and loss of MLH1 and PMS2 protein in the nuclei of tumour cells. An aberrant transcript was detectable and skipping of MLH1 exon 17 in carriers of MLH1 c.1989 + 5G>A was confirmed., Conclusions: MLH1 c.1989 + 5G>A was detected in a cancer family pedigree and identified as a pathological variant in patients with Lynch syndrome. The mutation spectrum of Lynch syndrome was enriched through enhanced genetic testing and close surveillance might help future patients who are suspected of having Lynch syndrome to obtain a definitive early diagnosis., (© The Author(s) 2021. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: N-ethyl-N-nitrosourea (ENU) mutagenesis is a useful method for the genetic engineering of plants, and the production of functional mutants in animal models including mice and zebrafish. Grass carp reovirus (GCRV) is a haemorrhagic disease of grass carp which has caused noteworthy losses in fingerlings over the last few years. To overcome this problem, we used ENU mutant grass carp in an attempt to identify functional resistance genes for future hereditary rearing projects in grass carp., Results: This study used ENU-mutated grass carp to identify genetic markers associated with resistance to the haemorrhagic disease caused by GCRV. Bulked segregant analysis (BSA) was performed on two homozygous gynogenetic ENU grass carp groups who were susceptible or resistant to GCRV. This analysis identified 466,162 SNPs and 197,644 InDels within the genomes of these mixed pools with a total of 170 genes annotated in the associated region, including 49 genes with non-synonymous mutations at SNP sites and 25 genes with frame shift mutations at InDel sites. Of these 170 mutated genes, 5 randomly selected immune-related genes were shown to be more strongly expressed in the resistant group as compared to the susceptible animals. In addition, we found that one immune-related gene, EPHB2, presented with two heterozygous SNP mutations which altered the animal's responded to GCRV disease. These SNPs were found in the intron region of EPHB2 at positions 5859 (5859 G > A ) and 5968 (5968 G > A ) and were significantly (p = 0.002, 0.003) associated with resistance to GCRV. These SNP sites were also shown to correlate with the GCRV-resistant phenotype in these ENU grass carp. We also evaluated the mortality of the different ENU fish genotypes in response to GCRV and the SNPs in EPHB2. The outcomes of these evaluations will be useful in future selections of GCRV-resistant genes for genetic breeding in grass carp., Conclusion: Our results provide a proof of concept for the application of BSA-sequence analysis in detecting genes responsible for specific functional genotypes and may help to develop better methods for marker-assisted selection, especially for disease resistance in response to GCRV.

Objective: To investigate the effect of VDR gene silencing on proliferation of airway smooth muscle cells (ASMCs) and elucidate the role of NF-κB. Methods: A recombinant lentiviral vector specifically targeting VDR gene in rat was constructed by RNA interference. Rat ASMCs were divided into blank group, empty vector group and interference group. ASM cell line model stably silencing the VDR gene RNA expressing was selected by puromycin. Then MTT colorimetric assay and cell cycle analysis by flow cytometry were used to examine cell proliferation. The activation of nuclear factor-κB was determined by immunofluorescence double label method. Moreover, NF-κB-dependent transcription activity was tested through luciferase reporter gene assay. Western blotting was used for IκBα and phospho-IκBα protein levels and actinomycin D treatment was used to determine IκBα mRNA stability. All statistical analyses were performed using SPSS version 23.0 software. Differences between groups were analyzed using one-way ANOVA analysis. Multiple comparisons among groups were made by Student-Newman-Keuls test. Results: (1) As compared with those in the blank group and the empty vector group, the cell proliferation index (PI) and the percent of ASMCs at G 2 /M phase in the interference group were markedly increased ( P <0.05), but their percent at G 0/1 phase was decreased ( P <0.05).(2) In the interference group, the nuclear translocation of NF-κB p65 in ASMCs was obviously induced. And its level of receptor gene NF-κB p65 (1.37±0.28) was significantly higher than that in the blank group (1.00±0.19, P =0.031) and in the empty vector group (0.96±0.18, P =0.027).(3) In the interference group, the IκBα protein level in ASMCs (0.13±0.04) was obviously less than that in the blank group (0.29±0.05, P =0.023) and in the empty vector group (0.32±0.07, P =0.014). Oppositely, the p-IκBα/IκBα level in the interference group (0.86±0.04) was much more than that in the blank control group (0.41±0.07, P =0.026) and in the empty vector group (0.37±0.05, P =0.017). (4) In the interference group, IκBα mRNA showed a shorter half-life, (171.31±9.67) min, compared to that in the blank group [(224.69±7.95) min, P =0.032] and in the empty vector group [(230.41±6.37) min, P =0.035]. Conclusion: VDR gene silencing could promote ASMC proliferation and the underlying mechanism may involve the activation of NF-κB signaling pathway.

Background: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited., Methods: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records., Results: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan., Conclusions: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China., (© 2021 American Cancer Society.)

Objective: To explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment. Methods: Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors. Results: Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis ( P <0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology ( P =0.002), including mucus or not ( P <0.001), and MR-N evaluation ( P <0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95% CI: 0.720~0.852). Conclusions: Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

Background Accurate differentiation of stage T0-T1 rectal tumors from stage T2 rectal tumors facilitates the selection of appropriate surgical treatment. MRI is a recommended technique for local staging, but its ability to distinguish T1 from T2 tumors is poor. Purpose To explore the value of a submucosal enhancing stripe (SES), an uninterrupted enhancing band between the rectal tumor and the muscular layer on contrast material-enhanced T1-weighted images, as a potential imaging feature to differentiate T0-T1 from T2 rectal tumors. Materials and Methods This retrospective study included patients with pT0-T1 and pT2 rectal tumors who underwent pretreatment MRI and rectal tumor resection between January 2012 and November 2019. Two radiologists independently evaluated tumor characteristics (SES; status of muscularis propria [SMP]; and tumor shape, location, and size) at MRI. The associations of clinical and imaging characteristics with stage T0-T1 or T2 tumors were assessed, β values were calculated, and predictive models were built. The diagnostic accuracies for the differentiation of T0-T1 tumors from T2 tumors with SES and SMP were compared. Results Data from 431 patients (mean age, 60 years ± 10 [standard deviation]; 261 men) were evaluated. SES (β = 3.9; 95% CI: 3.1, 4.7; P < .001), SMP (β = 1.3; 95% CI: 0.7, 1.9; P < .001), and carpetlike shape (β = 1.6; 95% CI: 0.5, 2.8; P = .01) were independent factors distinguishing T0-T1 tumors from T2 tumors. The diagnostic accuracy was 87% (95% CI: 84, 90; 376 of 431) for SES and 67% (95% CI: 63, 72; 290 of 431) for SMP ( P < .001). Conclusion Submucosal enhancing stripe (SES) at contrasted-enhanced MRI, status of muscularis propria (SMP) on T2-weighted images, and tumor shape can serve as independent imaging features to differentiate stage T0-T1 rectal tumors from stage T2 rectal tumors. Moreover, SES is a more accurate feature than is SMP. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for cytological and histological diagnosis. The objective of this study was to explore the role of cytological diagnosis in EBUS-TBNAs., Methods: Eight hundred and thirteen consecutive cases performed EBUS-TBNA with both cytological and histological diagnoses were retrospectively reviewed. All patients were followed up for clinical data., Results: Before immunohistochemical examination, the cytological sensitivity, specificity, and diagnostic accuracy of EBUS-TBNAs were 92.9% (421/453), 98.9% (348/352), 95.5% (769/805), respectively. After immunohistochemical examination, the sensitivity, specificity, and diagnostic accuracy were 93.0% (423/455), 99.4% (348/350), 95.8% (771/805), respectively. The majority of false-negative were cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate." "Neoplastic" were also prone to false-negative cytology. The diagnostic accordance rate of cytological subtyping was 90.3% for squamous-cell carcinoma, 99.2% for adenocarcinoma, and 98.1% for small-cell carcinoma before immunohistochemical examination, and became 85.9%, 98.5%, and 98.2% after immunohistochemical examination, respectively., Conclusion: Cytological diagnosis in EBUS-TBNAs had a good sensitivity and high specificity. The sensitivity and specificity of cytological diagnosis were proved to be higher after the immunohistochemical examination. At the same time, cytology had high accordance rate in subtype diagnosis. False-negative results occurred more commonly in cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate" or the corresponding histological diagnosis was "Neoplastic.", (© 2020 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Objective: To evaluate the diagnostic performance of quantitative fecal immunochemical testing (FIT) and to provide reference for designing effective colorectal cancer (CRC) screening strategy in China. Methods: Based on an ongoing randomized controlled trial comparing the colorectal cancer screening strategies, this current study involved 3 407 participants aged 50-74 years who had undergone colonoscopies. All the feces samples were collected from the participants prior to receiving the colonoscopy. Fecal hemoglobin (Hb) was tested by FIT following a standardized operation process. Diagnosis-related indicators of FIT were calculated using the colonoscopy results as the gold standard. Results: Among the 3 407 participants, the mean age (SD) as 60.5 (6.3) years and 1 753 (51.5%) were males. The participants involved 28 (0.8%) CRCs, 255 (7.5%) advanced adenomas, 677 (19.9%) nonadvanced adenomas, and 2 447 (71.8%) benign or negative findings. With an overall positivity rate of 2.8% (96/3 407) at the recommended cutoff value of 20 μg Hb/g, the sensitivities of FIT for both CRC and advanced adenoma were 57.1% (95 %CI : 37.2%-75.5%) and 11.0% (95 %CI : 7.4%-15.5%), respectively, with the corresponding specificity as 98.4% (95 %CI : 97.8%-98.8%). At a decreased cut-off value of 5 μg Hb/g, the sensitivities for detecting CRC and advanced adenoma increased to 64.3% (95 %CI : 44.1%-81.4%) and 16.5% (95 %CI : 12.1%-21.6%), respectively, but the specificity reduced to 95.2% (95 %CI : 94.4%-95.9%). The areas under the ROC curve for CRC and advanced adenoma were 0.908 (95 %CI : 0.842-0.973) and 0.657 (95 %CI : 0.621-0.692), respectively. Of the diagnostic performance, there were no significant differences noticed by different sex and age groups. Conclusions: In our study, the quantitative FIT showed modest sensitivity in detecting CRC but limited sensitivity in detecting advanced adenoma. In population-based CRC screening programs, the quantitative FIT had the advantage of adjusting the positive threshold based on the targeted detection rate and available resource load of colonoscopy.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Objective: To compare the rates of acceptance of colonoscopy, fecal immunochemical test (FIT), or a novel risk-adapted screening approach in the colorectal cancer (CRC) screening program. Related risk factors were also studied. Methods: The study has been based on an ongoing randomized controlled trial on colorectal cancer screening programs in six centers of research since May 2018. The involved participants were those who presented at the baseline screening phase. All the participants were randomly allocated into one of the following three intervention arms in a 1∶2∶2 ratio: colonoscopy group, FIT group, and a novel risk-adapted screening group. All the participants underwent risk assessment on CRC by an established risk score system. The subjects with high-risk were recommended to undertake the colonoscopy while the low-risk ones were receiving the FIT. Detailed epidemiological data was collected through questionnaires and clinical examinations. Rates of participation and compliance in all three groups were calculated. Multivariate logistic regression models were used to explore the potential associated factors related to the acceptance of screening. Results: There were 19 546 eligible participants involved in the study, including 3 916 in the colonoscopy group, 7 854 in the FIT group, and 7 776 in the novel risk-adapted screening group, respectively. Among the 19 546 participants, the mean age was 60.5 years ( SD =6.5), and 8 154 (41.7 % ) were males. The rates of participation in the colonoscopy, FIT and the novel risk-adapted screening groups were 42.5 % , 94.0 % and 85.2 % , respectively. In the novel risk-adapted screening group, the participation rate was 49.2 % for the high-risk participants who need to undertake colonoscopy and was 94.0 % for the low-risk ones who need to undertake FIT. Results from the multivariate logistic regression models demonstrated that there were several factors associated with the rates of participation in CRC screening, including age, background of education, history of smoking cigarettes, previous history of bowel examination, chronic inflammatory bowel disease and family history of CRC among the 1(st)-degree relatives. Conclusions: FIT and the novel risk-adapted screening approach showed superior participation rates to the colonoscopy. Further efforts including health promotion campaign for specific target population are needed to improve the engagement which ensures the effectiveness of CRC screening programs.

Human infections with highly pathogenic avian influenza (HPAI) H7N9 virus were detected in late 2016. We examined the drug resistance profile of 30 HPAI H7N9 isolates from Mainland of China (2016-2019). Altogether, 23% (7/30) carried neuraminidase inhibitors (NAIs) - resistance mutations, and 13% (4/30) displayed reduced susceptibility to NAIs in neuraminidase (NA) inhibition test. An HPAI H7N9 reassortment virus we prepared was passaged with NAIs for 10 passages. Passage with zanamivir induced an E119G substitution in NA, whereas passage with oseltamivir induced R292K and E119V substitutions that simulated that seen in oseltamivir -treated HPAI H7N9 cases, indicating that the high frequency of resistant strains in the HPAI H7N9 isolates is related to NAIs use. In presence of NAIs, R238I, A146E, G151E and G234T substitutions were found in HA1 region of HA. No amino acid mutations were found in the internal genes of the recombinant virus., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection. Methods: During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated. Results: The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 μm were 33 cases, ≥1 000 μm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 μm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors. Conclusions: The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.

Background: Claudin 7 is often abnormally expressed in cancers and promotes the progression of some malignancies. However, the role of claudin 7 in stage II colorectal cancer (CRC) has not been studied., Aim: To assess the expression and prognostic value of claudin 7 in stage II CRC., Methods: We retrospectively studied 231 stage II CRC patients who underwent radical surgery at our hospital from 2013 to 2014. The protein expression level of claudin 7 was assessed and its relationship with clinicopathological features and prognosis was statistically analyzed. The independent prognostic factors were identified by Cox proportional hazards models. A prognostic grading system was constructed to stratify the survival of CRC patients., Results: The expression of claudin 7 was significantly reduced in cancer tissues compared with normal tissues ( P < 0.001), and its low expression was closely related to recurrence of the disease ( P = 0.017). Multivariate analysis confirmed that claudin 7 low expression (claudin 7-low) ( P = 0.028) and perineural invasion positivity (PNI+) ( P = 0.026) were independent predictors of poor disease-free survival (DFS). A prognostic grading system based on the status of claudin 7 and PNI classified the patients into three prognostic grades: grade A (claudin 7-high and PNI-), grade B (claudin 7-low and PNI-, claudin 7-high and PNI+), and grade C (claudin 7-low and PNI+). The DFS was significantly different among the three grades (grade B vs grade A, P = 0.032; grade C vs grade A, P < 0.001; grade C vs grade B, P = 0.040)., Conclusion: Claudin 7 can be used as a new prognostic marker to predict the DFS of patients with stage II CRC. The prognostic grading system with the addition of claudin 7 can further improve prognosis stratification of patients., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China. Methods: Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated. Results: A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n =20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n =10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n =11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n =3), than at the 40 year-olds (0.781, 0.321-2.459, n =8). Conclusions: Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.

The suppressor of cytokine signaling 3 (SOCS3) negatively regulates the responses of various immune cytokines. In this study, we identified socs3s genes of blunt snout bream. 209- and 216-aa long peptides are encoded by socs3a and socs3b genes, respectively. The socs3s mRNAs are expressed consistently during the entire process of embryonic development. Whole-mount in situ hybridization detected socs3a in the eyes and posterior somites at 12 h post fertilization (hpf), transcribed at the otic vesicle at 24 hpf, and transcribed at the eyes, brain, and otic vesicle at 36 hpf; while the socs3b mRNA was transcribed at the notochord at 12 hpf, expressed in the brain, eyes, and tailbud at 24 hpf, and detected in the brain at 36 hpf. The expression of socs3a is slightly different from that of socs3b in tissues of juvenile and adult blunt snout bream. After recombinant human growth hormone (hGH) treatment, the transcript levels of socs3s of blunt snout bream were increased in gills, spleen, kidney, and gonads. After Aerononas hydrophila infection, the mRNA levels of socs3s of blunt snout bream were significantly increased in the liver, spleen, intestine, and kidney tissues. Blunt snout bream were susceptible to various pathogenic microorganisms, we intraperitoneally injected blunt snout bream with A. hydrophila to explore the immune mechanism of socs3s. These results suggested that socs3s of blunt snout bream plays important roles in the regulation of embryonic development and tissue growth, and that socs3s may also play key roles in regulating the bacterial-induced congenital immune response. Socs3s genes has the potential to be used as targeted genes to improve the immunity against bacteria, which is conducive to the improvement of production and breeding., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The suppressor of cytokine signaling 1 (SOCS1) is an essential feedback regulator extensively involved in many different cytokine signaling pathways, such as regulation of the immune system and growth of organism. However, the molecular and functional information on socs1 genes in freshwater fish is unclear. In the present paper, we identified and characterized the full-length closely related but distinct socs1 genes (socs 1a and -1b) in blunt snout bream (Megalobrama amblycephala). The bioinformatic analysis results showed that duplicated socs1s shared majority conserved motifs with other vertebrates. Both socs1a and -1b mRNAs were detected throughout embryogenesis, and gradually increase and then constantly expressed after 16 hpf. Whole-mount in situ hybridization demonstrated that socs1a and socs1b mRNAs were detected in the brain at 12hpf and 24hpf, and in the notochord and brain at 36hpf. In adult fish, the socs1a mRNA were strongly expressed in the heart, eye, kidney, spleen and gonad, but were found to be relatively low in the intestine and liver. On the other hand, the expression of socs1b mRNA was significantly high in the muscle, eye and spleen, and relatively low in the intestine, liver, skin and heart. The results of hGH treatment experiment showed that socs1a and 1b mRNAs were upregulated markedly in the kidney, muscle and liver. Overexpression of socs1s significantly inhibit the GH and JAK/STAT factor stat3 and the inhibitory effect of SOCS1s on GH may be involved in JAK-STAT signaling pathway. These results indicate that SOCS1 plays an important role in regulating growth and development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Locally advanced breast cancer (LABC) is one of the subgroups of invasive breast cancer. The treatment of LABC is neoadjuvant chemotherapy (NAC) before surgery, which is different from the others. The study aimed to analyze and compare the characteristics of conventional ultrasound, contrast-enhanced ultrasonography (CEUS) and strain elastography (SE) in LABC patients who have different treatment outcomes, and to provide help for LABC in the imaging diagnosis and clinic treatment., Methods: From May 2018 to April 2019, 36 patients (40 lesions) of LABC were enrolled, which diagnosed by puncture biopsy. According to the clinical evaluation, these patients were recommended to undergo pre-operative NAC followed by surgery. All patients underwent conventional ultrasound, CEUS and SE before puncture. According to postoperative pathological grading and follow-up, the patients were divided into effective and ineffective groups. We summarized and compared the features of conventional ultrasound, CEUS and SE of patients in two groups. The correlation between the imaging characteristics and the postoperative pathological grading was also analyzed., Results: Conventional ultrasonic features of LABC: the most lesions of LABC were mass type (32/40, 80.0%), and all lesions were irregular. Most of lesions showed unclear boundaries (39/40, 97.5%), heterogeneous echoes (38/40, 95.0%), and internal calcifications (24/40, 60.0%). Most of lesions had hyperechoic halos (31/40, 77.5%), aspect ratio less than or equal to 1 (34/40, 85.0%), and blood flow grading was III (36/40, 90.0%). CEUS features of LABC: compared with the surrounding normal tissues, all the lesions (40/40,100.0%) were highly enhanced. Most of lesions (35/40, 87.5%) were uneven enhanced. The main enhancement mode was "fast in and slow out" (39/40, 97.5%). There were totally 25 lesions which had "solar sign" (25/40, 62.5%). SE features of LABC: the average visual elastography score of the lesions was 4.28±0.67, the maximum strain rate (E1) of the lesions averaged 4.88±0.54, and the overall strain rate of the lesion averaged 4.14±0.72. There was no significant difference between effective and ineffective groups in the characteristics of conventional ultrasound, CEUS and SE. There was a correlation between the appearance of "solar sign" in CEUS and postoperative pathological grading, and the contingency coefficient was 0.564 (P<0.05). The pathological grading of patients without solar sign was higher. The other characteristics of conventional ultrasound, CEUS and SE in LABC patients had no correlation with postoperative pathological grading., Conclusions: In LABC, the conventional ultrasound usually shows irregular shape and unclear boundaries. The aspect ratio is less than or equal to 1. CEUS showed uneven enhancement of "fast in and slow out", and "solar sign" was often seen. Elastography showed that the texture of the lesion was significantly stiffer than the surrounding normal tissue. Ultrasound imaging before NAC had no relationship with pathological complete response or not. However, "solar sign" in CEUS was an important feature and had correlation with postoperative pathological grading., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Objective: To acknowledge the availability and rates of annual transition of outcomes during the progression and regression stages of colorectal cancer (CRC) and related diseases, by pooling global follow-up studies on the natural history of CRC. Methods: Till March, 2017, data was collected through systematic literature review over multiple databases, including PubMed, Embase, Cochrane and Chinese Biology Medicine (CBM) disc. Information regarding the characteristics, classification system of health states, related outcomes and incidence rates on CRC or high-risk adenoma for the surveillance cohorts of the studies, were extracted and summarized. Both Meta and sensitivity analyses were performed on those outcomes if they appeared in more than 3 studies, using the random effects model. Annual transition rate with 95 %CI was used to estimate each of the outcomes, Quality of the studies was assessed, using the Newcastle-Ottawa Scale. Results: A total of 29 cohort studies were included, with the mean follow-up period as 5.7 years. All studies except one, focused on adenoma-carcinoma pathway and reported the outcome parameters of adenomas by different risk, and some reported the findings on different sizes ( n =6) of adenomas. These cohorts were divided into three groups (normal status, with low-risk or high-risk adenoma) according to the status of baseline endoscopic pathologic findings. Their available outcome parameters, corresponding number of involved articles, aggregated sample size and pooled annual transition rates were presented. Six parameters were obtained in the normal cohorts, including those from normal to low-risk adenoma (16 articles, 58 235, 0.030: 0.024-0.037), to high-risk adenoma (17 articles, 62 089, 0.003: 0.002-0.004), to diminutive adenoma (<5 mm, 4 articles, 1 277, 0.021: 0.013-0.029), to small adenoma (6-9 mm, 4 articles, 1 277, 0.006: 0.001-0.010), to large adenoma (≥10 mm, 7 articles, 3 531, 0.002: 0.000-0.003) and to CRC (19 articles, 104 836, 0.000 3: 0.000 2-0.000 5). Three parameters were obtained in low-risk adenoma in cohorts with polypectomy findings, including recurrence (9 articles, 4 788, 0.109: 0.062-0.157) from low-risk adenoma after polypectomy to high-risk adenoma (10 articles, 5 736, 0.009: 0.004-0.013) and to CRC (12 articles, 11 347, 0.000 6: 0.000 4-0.000 8). Three parameters were obtained on high-risk adenoma from cohorts with polypectomy findings, including recurrence (12 articles, 7 030, 0.038: 0.028-0.048) from high-risk adenoma after polypectomy to low-risk adenoma (8 articles, 2 489, 0.133: 0.081-0.185) and CRC (14 articles, 14 899, 0.002: 0.001-0.003). Except for normal to low-risk adenomas, results from the sensitivity analysis for the other parameters showed stable. Of the included studies, two presented incidence rates of CRC in different clinical stages and the another two were focusing on the parameters related to serrated pathway. Conclusions: Globally, follow-up studies reported data on natural history of colorectal cancer is of paucity. Compared to the "adenoma-carcinoma" pathway, transition parameters of the serrated lesion pathway are more limited. This Meta-analysis provided convincing evidence for optimizing the strategies regarding follow-up program on the disease, using the baseline endoscopic findings from global CRC Screening Program. These results also offered strong data-related support for Chinese population- specific interventional model on colorectal cancer.

The CITED3 protein is a non-DNA-binding transcriptional co-regulator involved in the regulation of various transcriptional responses against hypoxia stress. Here, we characterized two paralogs Cited3 genes (Cited3a and Cited3b) from blunt snout bream (Megalobrama amblycephala), which is a hypoxia-sensitive species. Both genes have an open reading frame of 756 and 723 bp; encoded a protein of 251 amino acid and 240 amino acid, respectively; and they shared a sequence identity of 67%. In adult fish, both Cited3a and Cited3b mRNAs were highly expressed in kidney tissues. In contrast, they were detected in the skin, muscle, and gonad at extraordinarily low levels. During embryogenesis, both Cited3a and Cited3b mRNAs were maternally deposited in eggs and fluctuated from the zygote to the 44-hpf (hours post-fertilization) larvae. Whole-mount in situ hybridization demonstrated that both Cited3a and Cited3b mRNAs were transcribed in the brain, gut, and tailbud at 12 hpf, and at the brain and gut at 24 hpf, and at the brain at 36 hpf embryos. Hypoxic treatment led to upregulated expression of the Cited3 genes during embryogenesis. Under hypoxia, both Cited3a and Cited3b genes in the kidney and brain and Cited3a genes in the liver were significantly upregulated. These results suggest that hypoxia was associated with increases in mRNA levels for both Cited3a (kidney, brain, liver) and Cited3b (kidney and liver).

Two-dimensional gel electrophoresis (2-DE) was combined with liquid chromatography-mass spectrometry (LC-MS/MS) to identify the differential proteomics of grass carp gills after hypoxic stress to better understand the roles of proteins in the hypoxic response and to explore the possible molecular mechanisms. Protein spots were obtained from a hypoxia-stressed group (372 ± 11 individuals) and a control group (406 ± 14 individuals) using the lmage Master 2D Platinum 7.0 analysis software. Fifteen protein spots were expressed differentially in the hypoxia-stressed group and varied significantly after exposure to the hypoxic conditions. In addition, these differential proteins were identified by mass spectrometry and then searched in a database. We found the expression and upregulation of the toll-like receptor 4, ephx1 protein, isocitrate dehydrogenase, L-lactate dehydrogenase, GTP-binding nuclear protein Ran, and glyceraldehyde-3-phosphate dehydrogenase; however, the expression of the keratin type II cytoskeletal 8, type I cytokeratin, ARP3 actin-related protein 3 homolog, thyroid hormone receptor alpha-A, ATP synthase subunit beta, citrate synthase, tropomyosin 2, and tropomyosin 3 were downregulated. Six proteins were found in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. We concluded that the grass carp gill is involved in response processes, including energy generation, metabolic processes, cellular structure, antioxidation, immunity, and signal transduction, to hypoxic stress. To our knowledge, this is the first study to conduct a proteomics analysis of expressed proteins in the gills of grass carp, and this study will help increase the understanding of the molecular mechanisms involved in hypoxic stress responses in fish at the protein level.

The grass goldfish appeared early in the evolutionary history of goldfish, and shows heritable stability in the development of the caudal fin. The twin-tail phenotype is extremely rare, however, some twin-tail individuals were produced in the process of breeding for ornamental value. From mutations in the twin-tail goldfish genome, we identified two kinds of Tgf2 transposons. One type was completely sequenced Tgf2 and the other type was ΔTgf2, which had 858 bp missing. We speculate that the bifurcation of the axial skeletal system in goldfish may be caused by an endogenous ΔTgf2 insertion mutation in Chordin A, as ΔTgf2 has no transposition activity and blocks the expression of Chordin A. The twin-tail showed doubled caudal fin and accumulation of red blood cells in the tail. In addition, in situ hybridization revealed that ventral embryonic tissue markers (eve1, sizzled, and bmp4) were more widely and strongly expressed in the twin-tail than in the wild-type embryos during the gastrula stage, and bmp4 showed bifurcated expression patterns in the posterior region of the twin-tail embryos. These results provide new insights into the artificial breeding of genetically stable twin-tail grass goldfish families.

Aim: To identify the clinicopathological characteristics of pT1N0 esophageal squamous cell carcinoma (ESCC) that are associated with tumor recurrence., Methods: We reviewed 216 pT1N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrence-free survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence (≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models., Results: Forty-seven (24%) patients had a recurrence at 3 to 178 (median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence (Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence., Conclusion: These results should be useful for designing optimal individual follow-up and therapy for patients with T1N0 ESCC., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

Purpose: To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method., Methods: The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing., Results: Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS., Conclusion: The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.

Objective: To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods: Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios ( ORs ) and 95% confidence intervals ( CIs ), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios ( HR s) and 95% CIs by Cox proportional regression model. Results: Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P =0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P =0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer ( HR =0.44, 95% CI: 0.20-0.96, P =0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time ( HR =1.74, 95% CI: 1.06-2.84, P =0.028; HR =1.64, 95% CI: 1.01-2.66, P =0.046; HR =1.71, 95% CI: 1.01-2.91, P =0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis. Conclusions: Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Midkine (Mdk) is a heparin-binding growth factor that is involved in regulating cell growth, differentiation and migration. Here, we report the isolation and characterization of duplicated mdk genes in blunt snout bream (Megalobrama amblycephala). The mdka and -b genes encode 146 aa and 147 aa peptides, respectively, sharing a sequence identity of 64%. During embryogenesis, mdka mRNA is detectable after 12 h post-fertilization (hpf) and mdkb mRNA can be detected after 8 hpf, about 4 h prior to mdka mRNA. Whole-mount in situ hybridization demonstrated that two paralogs of mdk mRNA were detected in the brain and dorsal neural tube at 16 hpf. At 22 hpf, mdka mRNA was abundant in the brain and dorsal neural tube, whereas mdkb mRNA were transcribed in the brain and tailbud. Later, at 55 hpf, both paralogs were mainly expressed in the brain. Furthermore, both the mdk genes were highly expressed in multiple adult tissues except in the skin and a low expression of mdka in the muscle. In addition, they were differentially inhibited in the liver and intestine with exogenous recombinant human growth hormone, while their mRNA levels were up-regulated in the brain. During starvation, both the mdk genes were significantly up-regulated in the intestine, brain and liver and returned to the control levels following 6 days of refeeding. Our results suggest that duplicated mdk genes may play conserved and divergent roles in embryonic development and tissue growth regulation in blunt snout bream., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate the compliance rate of screening colonoscopy and associated factors in high-risk populations of colorectal cancer (CRC) in urban China. Methods: CRC screening data from the Program of Cancer Screening in Urban China conducted in 12 provinces in 2012-2014 was used in the present study. All 97 445 participants were asked to take epidemiological questionnaire survey to evaluate their cancer risk. Participants who were evaluated as "high risk for CRC" were recommended to receive colonoscopy at designated hospitals. Chi-square tests were used to compare the differences of participation rates between groups. Multivariate logistic regression models were applied to explore the potential factors associated withthe compliance rate of screening colonoscopy. Results: Overall, 97 445 participants of CRC high-risk were included in this analysis, and 14 949 of them took screening colonoscopy, yielding a participation rate of 15.3%. The participation rate varied greatly across provinces, ranging from 25.2% (2 785/11 071) in Heilongjiang to 9.7% (1 698/17 515) in Liaoning. Moreover, the participation rate in 2013-2014 was significantly higher than that in 2012-2013 (17.1%(9 766/57 280) vs 12.9% (5 183/40 165), χ(2)=57.67, P< 0.001) . The multivariate logistic regression analyses showed that: compared with individuals of 40-49 years old, individuals of 50-59 or 60-69 years old were more willing to accept screening colonoscopy, with OR of 1.17 (95 % CI: 1.12-1.22) and 1.13 (95 % CI: 1.08-1.19), respectively; compared with uneducated individuals, individuals with good educational background of equivalent to high school or higher ( OR= 1.29, 95 % CI: 1.10-1.50) were more willing to accept screening colonoscopy; compared with individuals who never took fecal occult blood tests (FOBT) before, individuals with previous positive FOBT results ( OR= 1.40, 95 % CI: 1.31-1.50) were more willing to accept screening colonoscopy; compared with individuals with no inflammatory bowel diseases (IBD), individuals with IBD ( OR= 1.63, 95 %CI: 1.56-1.69) were more willing to accept screening colonoscopy; Compared with individuals without polyp history, individuals having history of previous polyp detection ( OR= 1.43, 95 % CI: 1.37-1.50) were more willing to accept screening colonoscopy; compared to individuals with no family history of CRC, individuals with history of CRC ( OR= 1.60, 95 % CI: 1.53-1.66) were more willing to accept screening colonoscopy. Conclusion: The overall participation rate of screening colonoscopy among high-risk population of CRC in the 12 participating sites was 15.3%. The study findings indicated that age, education level, history of past fecal occult blood test, IBD, history of polyp, family history of CRC were associated with the compliance rate of colonoscopy in this population-based CRC screening program.

The proteins CITED belong to a family of non-DNA-binding transcriptional co-regulators involved in the regulation of various transcriptional responses. Previous studies suggest that members of CITED family may function in response to hypoxia in mammals. however, the molecular and functional information on CITED genes in aquaculture fish is unclear. Here, we characterized and examined the transcriptional patterns of CITED1 and CITED2 genes in the hypoxia-sensitive blunt snout bream ( Megalobrama amblycephala ). Blunt snout bream CITED1 and CITED2 genes shared a relatively low sequence identity of 45%. CITED1 and CITED2 mRNAs were widely transcribed in adult tissues. During embryogenesis, CITED1 mRNA was significantly transcribed at 4, 24, 28, 40, and 44 hpf, whereas CITED2 mRNA levels fluctuated from the zygote to 44 hpf larval stage. Whole-mount in situ hybridization demonstrated that CITED1 and CITED2 mRNAs were detected in the brain at 12 hpf, brain and gut at 24 hpf, and brain at 36 hpf. In addition, low expression of CITED1 mRNA was detected in the tailbud at 24 hpf. The results of acute hypoxia experiment showed that CITED1 and CITED2 mRNAs were markedly upregulated in the kidney and downregulated in the liver, brain, gill, and heart under hypoxia. Embryos in hypoxic conditions at different developmental stages showed a significant increase in mRNA levels of CITED1 and CITED2 . These results provide a new insight into the divergence of CITED1 and CITED2 genes and their transcriptional responses to hypoxia.

Background: Although primary thyroid lymphoma (PTL) and anaplastic thyroid carcinoma (ATC) both account for a rare portion of the morbidity of all thyroid malignancies, the therapeutic methods and prognosis for these two diseases are different. The purpose of this study was to investigate the sonographic characteristics of PTL and ATC and to compare the sonographic findings of PTL and ATC., Methods: The study included 42 patients with histopathologically proven PTL (n=27) and ATC (n=15). The Clinical characteristics and sonographic findings were retrospectively reviewed and compared between the two groups., Results: The mean age of patients with ATC was not significantly different from that in patients with PTL (P=0.601). The female-to-male ratio of patients with ATC was significantly lower than that of patients with PTL (P=0.029). Both PTL and ATC commonly present as a relatively large, solid mass on sonography with compressive symptoms, in which hoarseness was seen more frequently in ATC group (66.7%) than in PTL group (14.8%) (P=0.001). There is no significant difference in thyroid size, nodular size, margin, shape, echo texture, echogenicity, cystic change, vascularity and local invasion on sonography between ATC and PTL groups. Echogenic strands, markedly hypoechoic and enhanced posterior echo were seen more frequently in PTL group (92.6%, 92.6%, and 85.2%, respectively) than those in ATC group (6.7%, 60.0%, and 33.3%, respectively) (P<0.05), and calcification was seen more frequently in ATC group (80.0%) than in PTL group (0%) (P<0.001). Three ultrasound patterns were observed for PTL including diffuse type (25.9%), nodular type (48.2%) and mixed type (25.9%), while all ATC cases presented with nodular type (100.0%). Associated Hashimoto's thyroiditis occurred more frequently in PTL group (59.3%) than in ATC group (20.0%) (P=0.023)., Conclusions: Certain sonographic features as a markedly hypoechogenicity, the presence of an enhanced posterior echo and linear echogenic strands, lack of calcification and associated Hashimoto's thyroiditis were valuable for distinguishing PTL from ATC. In contrast, heterogeneous echogenicity, uncircumscribed margin, irregular shape, and vascular pattern were not specific features for differential diagnosis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Heme oxygenase (HO) that catalyzes the degradation of heme, is involved in responding and using oxygen in teleost fish. Physiologic heme degradation can be catalyzed by two isozymes of HO (HO-1 and HO-2). In fish, the molecular constructions, expression characteristics and hypoxic regulation of HO-2 are still not well known. Here, we report the isolation and characterization of duplicated HO-2 genes in blunt snout bream, a hypoxia sensitive fish species. Blunt snout bream HO-2a and -2b genes shared a relatively low sequence identity of 67%. The HO-2a and -2b mRNAs were widely expressed in adult tissues. During embryogenesis, HO-2a mRNAs was significantly upregulated at 16hpf and then maintained with high lever, while HO-2b mRNAs was gradually increased at 12hpf and then reduced significantly. Whole-mount in situ hybridization demonstrated that HO-2a and -2b mRNAs mainly detected in brain and eyes at different embryonic stages. The results of acute hypoxia experiment showed that both HO-2a and -2b mRNAs have significant changes in different tissues. Both HO-2a and -2b mRNAs were significantly up-regulated in the brain, but down-regulated in the gill and liver during hypoxia. Under hypoxia, HO-2a mRNA in the heart was significantly increased while HO-2b mRNA was decreased. Embryos in hypoxic conditions at different developmental stages strongly induced the mRNA expression of HO-2a and -2b. These results provide new insights into the functional conservation and divergence of HO-2 genes and improve our understanding of HO-2 responses to hypoxia., (Copyright © 2017. Published by Elsevier B.V.)

The heme oxygenase (HO)-1 is a cytoprotective enzyme that can be involved in cytoprotection against hypoxia stress. In this study, we cloned duplicated HO-1a and HO-1b cDNAs in hypoxia-sensitive blunt snout bream (Megalobrama amblycephala). HO-1a and HO-1b encode peptides with 272 amino acids and 246 amino acids, respectively, and they share a low sequence identity of 55%. HO-1a and HO-1b mRNAs were maternally deposited in the zygote, and the mRNAs decreased to the lowest levels at 8 hpf. Both mRNAs were significantly (p < 0.01) expressed from 12 hpf and fluctuated but maintained a high level after 16 hpf. Using in situ hybridization, HO-1a and HO-1b mRNAs were ubiquitously expressed in embryos at 12 hpf. At 24 and 36 hpf, HO-1b transcripts were detected in the mid- and hindbrain, respectively, whereas HO-1a was mainly transcribed in the eyes and endoderm at 24 hpf and in the brain at 36 hpf. In adult fish, HO-1a was abundantly expressed in the heart, liver, gill, kidney, spleen, and brain, while HO-1b mRNA was detected mainly in the kidney. After exposure to hypoxic stress, both HO-1a and HO-1b mRNAs were upregulated significantly in the gill and liver but downregulated significantly in the brain (p < 0.01). These findings suggest that duplicated HO genes have evolved divergently and yet play overlapping biological roles in regulating the response to hypoxia in M. amblycephala.

Objective: To review the worldwide studies on natural history models among colorectal cancer (CRC), and to inform building a Chinese population-specific CRC model and developing a platform for further evaluation of CRC screening and other interventions in population in China. Methods: A structured literature search process was conducted in PubMed and the target publication dates were from January 1995 to December 2014. Information about classification systems on both colorectal cancer and precancer on corresponding transition rate, were extracted and summarized. Indicators were mainly expressed by the medians and ranges of annual progression or regression rate. Results: A total of 24 studies were extracted from 1 022 studies, most were from America ( n =9), but 2 from China including 1 from the mainland area, mainly based on Markov model ( n =22). Classification systems for adenomas included progression risk ( n =9) and the sizes of adenoma ( n =13, divided into two ways) as follows: 1) Based on studies where adenoma was risk-dependent, the median annual transition rates, from ' normal status' to ' non-advanced adenoma', 'non-advanced' to ' advanced' and ' advanced adenoma' to CRC were 0.016 0 (range: 0.002 2-0.020 0), 0.020 (range: 0.002-0.177) and 0.044 (range: 0.005-0.063), respectively. 2) Median annual transition rates, based on studies where adenoma were classified by sizes, into <10 mm and ≥10 mm ( n =7), from ' normal' to adenoma <10 mm, from adenoma <10 mm to adenoma ≥10 mm and adenoma ≥ 10 mm to CRC, were 0.016 7 (range: 0.015 0-0.037 0), 0.020 (range: 0.015-0.035) and 0.040 0 (range: 0.008 5-0.050 0), respectively. 3) Median annual transition rates, based on studies where adenoma, were classified by sizes into diminutive (≤5 mm), small (6-9 mm) and large adenoma (≥10 mm) ( n =6), from ' normal' to diminutive adenoma,'diminutive' to ' small','small' to ' large', and large adenoma to CRC were 0.013 (range: 0.009-0.019), 0.043 (range: 0.020-0.085), 0.044 (range: 0.020-0.125) and 0.033 5 (range: 0.030-0.040), respectively. Staging system of CRC mainly included LRD (localized/regional/distant, n =10), Dukes' ( n =7) and TNM ( n =3). When using the LRD classification, the median annual transition rates from ' localized' to ' regional' and ' regional' to 'distant' were 0.28 (range: 0.20-0.33) and 0.40 (range: 0.24-0.63), respectively. Under the Dukes' classification, the median annual transition rates appeared as 0.583 (range: 0.050-0.910), 0.656 (range: 0.280-0.720) and 0.830 (range: 0.630-0.865) from Dukes' A to B, B to C and C to Dukes' D, respectively. Again, when using the TNM classification, very limited transition rate was reported. Serrated pathway was only described in one study. Conclusions: Studies on the natural history model of colorectal cancer was still limited worldwide. Adenoma seemed the most common status setting for precancer model, and the risk-dependent classification for adenoma was consistent with the most commonly used system in clinical practice as well as major cancer screening programs in China. Since the staging systems of cancers varied, and shortage of transition rates based on TNM classification (commonly used in China), there will be a challenge for building Chinese population-specific natural history model of colorectal cancer, information from other classification systems could be conditionally applied.

Insulin-like growth factor binding-protein 5 (igfbp5), the most conserved member of the IGFBP family in vertebrates, plays a critical role in controlling cell survival, growth, differentiation, and apoptosis. Here, we characterized the expression patterns of igfbp5a and igfbp5b in grass carp (Ctenopharyngodon idella), which are retained in many fish species, likely from the teleost-specific whole-genome duplication. Both igfbp5a and igfbp5b encode 268- and 263-aa peptides, respectively, which share a sequence identity of 71%. Their mRNAs are not detected in zygotes. At 14hpf, grass carp igfbp5b mRNA was detected in the somites, while igfbp5a mRNA has some possible signal around the eye and head region. At 24hpf, both igfbp5a and igfbp5b mRNA appear to be limited to the presomitic mesoderm. At 36hpf, igfbp5a mRNA was only detected in the midbrain, while igfbp5b mRNA was detected in both the midbrain and notochord. Overall, both mRNAs were expressed in most adult tissues. igfbp5a and igfbp5b were significantly upregulated in the muscle and liver after injection of 10μg per kilogram body weight of zebrafish growth hormone (zGH), while their hepatic expression was downregulated by 50μg zGH. During fasting, both igfbp5a and igfbp5b mRNAs were significantly downregulated in the muscle but upregulated in the liver. Collectively, the results suggest that the two igfbp5 genes play important but different roles in the regulation of growth and development in grass carp., (Copyright © 2016 Elsevier Inc. All rights reserved.)