A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

[Relationship between promoting effect of Zuogui Pills on angiogenesis of reproductive organs and mobilization factors GM-CSF, SDF-1, and their receptors of EPCs in early-aging rats].

This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 µg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P<0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P<0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P<0.05), decreased number of atresia follicles(P<0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P<0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.

Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020.

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

Association analysis of polymorphisms of G protein-coupled receptor 54 gene exons with reproductive traits in Jiaxing Black sows.

OBJECTIVE: The aim of this study was to detect single nucleotide polymorphisms (SNP) of G protein-coupled receptor 54 (GPR54) gene and explore association of this candidate gene with reproductive traits in Jiaxing Black sows. METHODS: Six pairs of primers of the gene were designed to amplify all exons thus sequences of which were detected by means of direct sequencing and then SNP loci were scanned. The effects of SNPs on total number of piglets born (TNB), number of piglets born alive (NBA), number of still born piglets (NSB), and litter weight at birth (LWB) of Jiaxing Black sows were analyzed. RESULTS: Three SNP loci, including T3739C, C3878T and T6789C, were identified via comparison of sequencing and two genotypes (AB, BB) at each SNP site were observed. T3739C resulted in the change of amino acid (Leu→Pro) in corresponding protein, and C3878T resulted in synonymous mutation (Ile→Ile). Statistical results demonstrated that allele B was the preponderant allele at the three SNP loci and Genotype BB was the preponderant genotype. Meanwhile, Chi-Square test of these three SNPs indicated that all mutation sites fitted in Hardy-Weinberg equilibrium (p>0.05). For GPR54-T3739C locus, Jiaxing Black sows with genotype BB had 1.23 TNB and 1.28 NBA (p<0.01) that were more than those with genotype AB, respectively. Jiaxing Black sows that had the first two parities with genotype BB had additional 2.23 TNB, 2.27 NBA (p<0.01), and 1.94 LWB (p<0.05) compared to those with genotype AB, respectively. However, for other two loci, no significant difference was found between TNB, NBA, NSB, and LWB, and different genotypes of Jiaxing Black sows. CONCLUSION: In conclusion, the polymorphisms of GPR54-T3739C locus were significantly associated to TNB, NBA, and LWB and could be used as a potential genetic marker to improve reproductive function of Jiaxing black sows.

Scalable and reconfigurable true time delay line based on an ultra-low-loss silica waveguide.

A scalable and reconfigurable on-chip optical true time delay line consisting of Mach-Zehnder interferometer (MZI) switches and delay waveguides is proposed and demonstrated with the ultra-low-loss silica waveguide platform. The MZI switches provide the reconfiguration of the light traveling paths and hence different delays. Our proposed structure can be easily scaled to an M bit delay line with a slight increase in dimensions. The footprint of our fabricated 1 bit delay line is 33 mm×13 mm (length×width) and can provide a delay of 6.0 ps with an insertion loss of 1.2 dB at the operating wavelength of 1550 nm, while the footprint of the 4 bit delay line is 43 mm×14 mm and can provide a discrete delay tuning from 6.0 to 90.2 ps with a delay deviation lower than 0.2 ps and a tuning response time of 0.84 ms. The insertion losses are lower than ∼2.34 dB, and the extinction ratios are greater than 20.42 dB. The average switching power is ∼132.6 mW. Our proposed optical true time delay lines could find applications for optical beamforming in phased array antennas.

Low-power total internal reflection thermo-optic switch based on hybrid SiON-polymer X-junction waveguides.

We propose and demonstrate a low-power 2×2 total internal reflection thermo-optic switch based on an X-junction configuration formed with a silicon oxynitride (SiON) core and polymer cladding. Unlike X-junctions reported thus far, our proposed configuration features a slot formed on the center of the X-junction and filled with polymer cladding. With such a configuration, the opposite thermo-optic characteristics of SiON and polymer and, hence, heat utilization efficiency can be fully utilized. Our fabricated proof-of-principle switch shows extinction ratios of larger than 15.34 dB and switching powers of less than ∼59.6 mW. The rise time and fall time of switching are 1.42 and 0.85 ms, respectively. The insertion losses are less than 10.6 dB for all channels, and the polarization-dependent loss is ∼0.3 dB.

Local curative effect of MRI-guided radiofrequency ablation on small hepatocellular carcinoma.

Radiofrequency ablation (RFA) is one of the treatment modes for liver cancer. The trauma caused by RFA is small, and its local curative effect is reliable. Computed tomography (CT) can only be used for axial scans, and parts of the lesion are unclear on plain scans. The aim of this study is to compare the local curative effect of RFA percutaneously guided by MRI and ultrasound for small hepatocellular carcinoma (HCC). This study is a retrospective study. In this study, we examined 60 cases of 88 liver lesions and 50 cases of 52 lesions, in which RFA was guided by MRI and ultrasound, respectively. All cases were clinically diagnosed. The therapeutic effect of ablation lesions was examined by postoperative imaging follow-up. The results indicated that there were 5 (5/88) recurrences of liver lesions with MRI-guided RFA and 14 (14/52) recurrences of liver lesions with ultrasound-guided RFA. The median time to recurrence in the case of recurrent lesions was 7 months. Postoperative ablation lesions showed a low-intensity signal surrounded by a thin high-intensity signal ring on T2WI images. On T1WI images, the ablation lesion showed a concentric pattern and the central area of the original lesion continued to show a low-intensity signal with a clear ring of high-intensity signal that had a clear boundary. In conclusion, the local curative effect of MRI-guided RFA for small HCC is superior to that of ultrasound-guided RFA.

[Distribution of Typical Resistant Bacteria and Resistance Genes in Source Water of the Middle and Lower Reaches of the Yellow River].

The Yellow River water of an urban area located in the middle and lower reaches of the Yellow River was taken as the research object， in which the seasonal and along-range distribution of total culturable bacteria， typical antibiotic resistant bacteria （amoxicillin resistant bacteria and sulfamethoxazole-resistant bacteria）， and their corresponding typical resistance genes ï¼»ß-lactam resistance gene （blaCTX-M） and sulfamamide resistance genes （sulI and sulⅡ）， as well as intⅠ1 were investigated. The results showed that the total culturable bacteria， ß-lactam-resistant bacteria and sulfonamide-resistant bacteria in the Yellow River Basin were significantly affected by temperature and human activities. The composition and quantity of their genera had obvious spatiotemporal distribution characteristics， in which Bacillus and Pseudomonas were dominant in the composition and number of bacteria. The abundance of resistance genes decreased with the decrease in temperature. The proportion of ß-lactam resistance genes in the total genes was higher than that of sulfanilamide genes， and sulI was the dominant gene in sulfanilamide genes. Correlation analysis showed that class Ⅰ integron played an important role in accelerating the spread of resistance genes. This study offers insight into the status quo of water resistance pollution in the Yellow River and provides theoretical support for the risk assessment of resistance genes in the middle and lower reaches of the Yellow River Basin.

Harnessing the potential of long non-coding RNAs in breast cancer: from etiology to treatment resistance and clinical applications.

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.

Evaluation of the four breeds in synthetic line of Jiaxing Black Pigs and Berkshire for meat quality traits, carcass characteristics, and flavor substances.

To investigate breed characteristics and the effect of hybridization of Jiaxing Black Pig (JBP) with Western breeds, the carcass and meat quality traits and flavor substances such as inosinic acids (IMP), intramuscular fat (IMF) in longissimus muscle (LM) from five breeds including JBP, Berkshire, Berkshire × JBP (BJBP), Duroc × Berkshire × JBP (DBJBP), Duroc × Landrace × JBP (DLJBP) were compared in this study. It was found that water holding capacity (WHC) of LM in JBP was significantly higher than that in the other strains (p < 0.01). Dressing out percentage and lean percentage of JBP were both significantly lower than those in the others (p < 0.01) in connection with their lighter carcass weight and higher subcutaneous fat percentage (p < 0.01). Heterosis was realized in DJBP, DBJBP, and DLJBP since their carcass weight, lean percentage, and loin eye muscle area (LEMA) were markedly higher when compared to JBP, whereas lower than those in Berkshire. Among the breeds, the content of IMF and IMP in the LM of JBP were the highest. These traits were also palpably improved in the crossbreds, especially for DBJBP, of which pork was considered outstanding for containing the most abundant essential amino acids (EAA) and total amino acids (TAA).

Genetic variation in the glucocorticoid pathway involved in interindividual differences in the glucocorticoid treatment.

Glucocorticoids (GCs) are widely used for treating asthma, rheumatoid arthritis, nephrotic syndrome, acute lymphoblastic leukemia and other autoimmune diseases. However, in a subgroup of patients, failure to respond to GCs is known as GC resistance or GC insensitivity. This represents an important barrier to effective treatment and a clinical problem requiring an urgent solution. Genetic variation in the GC pathway is a significant factor in interindividual differences in GC treatment. This article reviews the pharmacogenetics of GCs in diverse diseases based on the GC pathway.

Dog to dog transmission of a novel influenza virus (H5N2) isolated from a canine.

In 2009, an influenza virus (IV), A/canine/Shandong/JT01/2009 (CA/SD/JT01/09), was isolated from the dog exhibiting respiratory signs in China, and was a novel H5N2. Intraspecies transmission of the virus in dog population had thus far remained unclear. To determine whether the novel H5N2 was transmitted among dogs, we conducted contact exposure and inoculation experiments. Susceptible dogs were housed in the room which the novel H5N2 infected dogs were housed in. As a result, the direct contact resulted in intraspecies transmission. Most of the infected dogs and the sentinel animals developed mild respiratory syndrome, including transient increased body temperatures, conjunctivitis, sneezing, nasal discharge and mild coughing, virus shedding and seroconversion, but no fatal disease. These data suggest that dogs may play a role in transmission and spread of influenza virus.