[Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma].

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Excitation functions for fast neutron induced reactions on iron and lead.

Cross sections of the 54Fe(n,p)54Mn, 54Fe(n,α)51Cr, 56Fe(n,p)56Mn and 204Pb (n,2n)203Pb reactions induced by D-T neutrons were obtained with activation method and γ-ray spectrometry technique. Experimental values measured in this work are consistent with most of the previous literature data. These reactions cross sections were theoretically calculated by using the TALYS-1.96 and EMPIRE-3.2.3 codes from threshold up to 20 MeV, and significant discrepancies were found between calculated results and experiment data. In addition, experimental values are compared with evaluated nuclear data of the CENDL-3.2, ENDF/B-VIII.0, JENDL-5, BROND-3.1 and JEFF-3.3 libraries, and significant difference was found for the 54Fe(n,α)51Cr reaction in ENDF/B-VIII.0 library but not for other reactions.

[Colorectal cancer with ß-catenin protein expression deficiency: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and molecular characteristics of ß-catenin-deficient colorectal cancer. Methods: The clinical, pathological and molecular features of 11 colorectal cancers with ß-catenin protein loss diagnosed at the 960th Hospital of People's Liberation Army of China, from January 2012 to November 2022 were analyzed. Results: Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. ß-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of ß-catenin protein expression. Conclusion: ß-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

[Comparison of short-term safety of two anastomotic techniques when resecting Siewert type II adenocarcinoma of the esophagogastric junction: a multicenter retrospective cohort study].

Objective: In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups. Results: There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant (t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ²=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences (Z=0.406, P=0.685). Conclusions: Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Fast neutron induced reaction cross sections on natural manganese and tantalum.

The cross sections for the 55Mn(n,2n)54Mn, 181Ta(n,2n)180gTa, and 181Ta(n,p)181Hf reactions were measured to be 705.1 ± 26.1 mb at 14.0 MeV, 1362.7 ± 87.2 mb at 13.6 MeV, and 2.31 ± 0.09 mb at 13.6 MeV, respectively, by using an off-line γ-ray spectroscopic technique. The neutrons were produced via the 3H(d,n)4He reaction. The monitor reactions 27Al(n,α)24Na and 93Nb(n,2n)92mNb were used for neutron flux determination. The results from the present work were compared with those of the literature and the evaluated data from ENDF/B-VIII.0, JEFF-3.3, JENDL-5, CENDL-3.2, and BROND-3.1 libraries. Besides, the cross sections were also estimated with the TALYS-1.96 nuclear model code using different level density models for a better description of the present work and literature data. The present experimental results were found to be in good agreement with most of the available literature data and with the evaluated data.

[Predictor of clinical response to subcutaneous immunotherapy with dust mites in polysensitized allergic rhinitis patients].

Objective: To evaluate the efficacy of 1-year subcutaneous immunotherapy (SCIT) with dust mites in polysensitized allergic rhinitis (AR) patients and to analyze the serological markers associated with clinical response. Methods: A retrospective analysis of data from 69 polysensitized AR patients who completed 1-year SCIT with dust mites from Oct 2020 to Mar 2022 in Shandong Provincial ENT Hospital was conducted. The median patient age was 21 years, including 41 males and 28 females. The changes in symptoms and serum IgE, IgG4 assessed before and after treatment were evaluated. The differences in serological markers between effective and ineffective groups were analyzed. Multivariate regression analysis was used to investigate the predictors of clinical response. SPSS 22.0 software was used for data processing. Results: After immunotherapy, there was a significant reduction in symptom scores and a substantial improvement in the quality of life of polysensitized AR patients (all P<0.001). Dust mite specific IgG4 (sIgG4) significantly increased and dust mite specific IgE (sIgE)/sIgG4 significantly decreased (all P<0.05). sIgE, total IgE (tIgE), sIgE/tIgE and sIgE/sIgG4 were significantly lower in ineffective group than those in effective group (all P<0.05). The clinical response of SCIT related only to dust mite sIgE (r=0.29, P=0.036), and sIgE≥53.86 kU/L had the best sensitivity (77.78%) and specificity (57.89%) to predict effective SCIT in polysensitized AR patients. Conclusions: One-year dust mite SCIT is effective for polysensitized AR patients. Pre-treatment serum dust mite sIgE≥53.86 kU/L may play a role in predicting clinical response of dust mite SCIT in polysensitized AR patients.

[Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis].

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 µg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1ß in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

Activation cross sections for reactions induced by 14 MeV neutrons on natural titanium.

Cross sections for the neutrons around 14 MeV interaction with natural titanium were precisely measured by neutron activation and off-line measurement technique. The fast neutrons were produced by 3H(d,n)4He reaction and the neutron energy was obtained by using the cross section ratio method of 90Zr(n,2n)89Zr to 93Nb(n,2n)92mNb reactions. Experimental cross sections have been acquired for natTi(n,x)46Sc, natTi(n,x)47Sc, 50Ti(n,x)47Ca and 48Ti(n,x)48Sc reactions. The measured cross section data are compared with the experimental data available in the previous literature and evaluated nuclear data from the ENDF/B-VIII.0, JEFF-3.3, JENDL-5, BROND-3.1, CENDL-3.2 and FENDL-3.2b libraries. Furthermore, excitation functions for these reactions were calculated by using the theoretical model based on Talys-1.96 code with default and adjusted parameters. Within experimental error, evaluated nuclear data are mostly consistent with experimental data. The excitation function with adjusted parameters can roughly reproduce the experimental data.

Excitation functions for fast-neutron induced reactions on zinc.

Cross sections of the 64Zn(n, p)64Cu, natZn(n, x)67Cu, 66Zn(n, 2n)65Zn and 70Zn(n, 2n)69mZn reactions have been measured by using the activation technique at 14.0 MeV neutron energy. The neutrons were produced via the 3H(d, n)4He reaction. The present experimental data illustrated satisfactory agreement with most of the previously reported experimental data. Experimental data are compared with evaluated nuclear data of the CENDL-3.2, ENDF/B-VIII.0, JENDL-5, BROND-3.1 and JEFF-3.3 libraries. Besides, these excitation functions were calculated by using theoretical model of the TALYS-1.96 code from thresholds up to 20 MeV. A group set of parameters was obtained which better reproduce the experimental data than the default parameters.

Efficacy of non-surgical periodontal treatment on patients with coronary artery disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Coronary artery disease (CAD) is defined as one of the most common cardiovascular diseases (CVDs). Periodontitis is one of the risk factors for CAD. MATERIAL AND METHODS: PubMed, Embase and Cochrane Library databases were carefully and thoroughly retrieved until October 2021. On the basis of the inclusion and exclusion criteria, eligible articles were selected strictly to identify randomized controlled trials (RCTs). Using Cochran's Q statistic, Review Manager 5.4 and Stata 16, data were extracted, and a comprehensive analysis was carried out. RESULTS: Six RCTs of 619 patients were included in this study, including 360 in the intervention group (IG) and 259 in the control group (CG). Meta-analysis showed significant difference for C-reactive protein (CRP) (1.20mg/L, 95% CI: 1.13 to 1.27, p < 0.00001) after non-surgical periodontal therapy (NSPT), but showed no significant difference for interleukin-6 (IL-6) (1.19mg/L, 95% CI: -1.03 to 3.40, p=0.29), flow-mediated dilation (FMD) (-1.64%, 95% CI: -4.95 to 1.67, p=0.33), triacylglycerol (TG) (-0.02mg/dL, 95% CI: -0.31 to 0.27, p=0.90), total cholesterol (TC) (0.04mg/dL, 95% CI: -0.25 to 0.33, p=0.90), low-density lipoprotein cholesterol (LDL-C) (0.00mg/dL, 95% CI: -0.29 to 0.29, p=0.99) and high-density lipoprotein cholesterol (HDL-C) (0.11mg/dL, 95% CI: -0.18 to 0.40, p=0.46). CONCLUSIONS: The impact of NSPT on the reduction of CRP in patients of CAD with periodontitis is significant. NSPT can be considered as an important preventive strategy for major cardiovascular events in CAD.

Thick target yields of proton induced reactions on natural molybdenum.

This work presents the thick target production yields of 94gTc, 95gTc, 95mTc, 96m+gTc, 99mTc and 99Mo radionuclides produced by 8.0-18.0MeV proton induced reactions on natural molybdenum targets. The measurements were carried out at the superconducting linear accelerator of the Institute of Modern Physics, Chinese Academy of Sciences by using the stacked-foil activation technique. In addition, the proton beam current was determined by the natTi(p,x)48V monitor reaction. The obtained results were compared with the available literature data from EXFOR database, the calculation results using our fitted experimental cross-sections data and the theoretical calculations predicted by TALYS-1.95 and FLUKA-2020.0. Our measurements are in good agreement with the calculations results using our fitted data. Besides, our data have similar trends with the theoretical calculations predicted by TALYS-1.95 and FLUKA-2020.0 although there are discrepancies between them for the radionuclides 94gTc, 99mTc and 99Mo.

[Multimodality-based super-resolution reconstruction for routine brain magnetic resonance images].

OBJECTIVE: To propose a multi-modality-based super-resolution synthesis model for reconstruction of routine brain magnetic resonance images (MRI) with a low resolution and a high thickness into high-resolution images. METHODS: Based on real paired low-high resolution MRI data (2D T1, 2D T2 FLAIR and 3D T1), a structure-constrained image mapping network was used to extract important features from the images with different modalities including the whole T1 and subcortical regions of T2 FLAIR to reconstruct T1 images with higher resolutions. The gray scale intensity and structural similarities between the super-resolution images and high-resolution images were used to enhance the reconstruction performance. We used the anatomical information acquired from segment maps of the super-resolution T1 image and the ground truth by a segmentation tool as a significant constraint for adaptive learning of the intrinsic tissue structure characteristics of the brain to improve the reconstruction performance of the model. RESULTS: Our method showed the performance on the testing dataset than other methods with an average PSNR of 33.11 and SSIM of 0.996. The anatomical structure of the brain including the sulcus, gyrus, and subcortex were all reconstructed clearly using the proposed method, which also greatly enhanced the precision of MSCSR for brain volume measurement. CONCLUSION: The proposed MSCSR model shows excellent performance for reconstructing super-resolution brain MR images based on the information of brain tissue structure and multimodality MR images.

Quantitative Collateral Assessment on CTP in the Prediction of Stroke Etiology.

BACKGROUND AND PURPOSE: Patients with stroke etiology of large-artery atherosclerosis were thought to have better collateral circulation compared with patients with other stroke etiologies. We aimed to investigate the association between stroke etiology and collateral circulation with a new quantitative collateral assessment method. MATERIALS AND METHODS: This retrospective study reviewed data from consecutive patients with proximal anterior artery occlusion who underwent CTP before reperfusion therapy. CBF maps were derived from CTP. A new indicator, maximum CBF of collateral vessels within the Sylvian fissure (cCBFmax), was applied to quantitatively assess the collateral status. The relationship between collateral status and stroke etiology was investigated. RESULTS: A total of 296 patients were finally analyzed. The median cCBFmax was significantly higher in patients with large-artery atherosclerosis than in those without it (92 [interquartile range, 65-123] mL/100 g/min versus 62 [interquartile range, 46-82] mL/100 g/min; P < .001). Multivariable analysis revealed that a higher cCBFmax score was independently associated with large-artery atherosclerosis etiology (OR, 1.010; 95% CI, 1.002-1.018; P = .017) after adjustment. The area under the curve, sensitivity, and specificity of the final model in predicting the etiology of large-artery atherosclerosis were 0.870, 89.7%, and 75.2%, respectively. CONCLUSIONS: Patients with large-artery atherosclerosis had a more adequate collateral perfusion supply with the new quantitative collateral assessment. The new quantitative collateral measurement might contribute to the prediction of stroke etiology in the acute clinical scenario for patients with acute ischemic stroke.

[Relationship between preoperative inflammatory indexes and prognosis of patients with rectal cancer and establishment of prognostic nomogram prediction model].

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

[Impact of probiotics on the lung development of Bama minipig after premature birth].

Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) µm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) µm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) µm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.

[Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system].

Objective: To explore the impact of different referral timing on postponing early-onset pre-eclampsia (PE), postponing severe pre-eclampsia (SPE), reducing SPE severe complications and improving maternal and neonatal outcomes by analyzing the pregnancy outcomes of SPE patients who were referred from primary hospitals to tertiary referral center in the referral system. Methods: The clinical data of 159 SPE patients who were referred from primary hospitals, treated and then terminated their pregnancy in Peking University Third Hospital from January 2020 to October 2021, were observed and analyzed in this clinical observational study. According to the clinical stage of PE at the time of referral, they were divided into four groups: 38 cases were referred after onset of SPE severe complications (SPE-C group), 72 cases were referred after onset of SPE (a-SPE group), 15 cases were referred after onset of PE (a-PE group) and 34 cases were referred after detection of PE early warning-signs (Warn-s group). And then these 159 cases were divided into different color groups according to the project management system for high-risk pregnant women. Patients of Red color (highest risk) and Orange color (higher risk) were required to be referred to tertiary hospitals (Red-Orange group, 113 cases), and patients of Yellow color (high risk) could be treated under tertiary hospitals (Yellow group, 46 cases). The maternal and neonatal outcomes of different referral timings were analyzed and compared. Results: (1) Pregnancy outcomes of different referral timings grouped by PE clinical stage at the time of referral: the later the referral timing, the higher the rate of SPE severe complications, the shorter the interval from referral to termination of pregnancy. The rate of SPE severe complications in the SPE-C group was significantly higher than those of the other three groups, and the interval from referral to termination of pregnancy in the SPE-C group was significantly shorter than those of the other three groups (all P<0.05). The referral gestational age of Warn-s group was earlier than those of the other three groups (all P<0.05). The average gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications were all after 34 gestational weeks, and were later than those of a-SPE group and SPE-C group; the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, neonatal intensive care unit (NICU) hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group, and its rate of take-home-babies was 100%, significantly higher than those in a-SPE group and SPE-C group (all P<0.05). The gestational ages for onset of SPE and termination of pregnancy in a-PE group were later than those in a-SPE group and SPE-C group, the rates of SPE onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, and NICU hospitalization were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group (all P<0.05). (2) Pregnancy outcomes of different referral timings grouped by the color classification of PE clinical characteristics: among the 159 cases of SPE, 113 cases (71.1%, 113/159) were in the Red-Orange group which were required to be referred to tertiary hospitals, and 46 cases (28.9%, 46/159) were in the Yellow group,which were not in the range of referral requirements, but actually referred to the tertiary hospital and eventually developed SPE. Gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications in the Yellow group were later than those of the Red-Orange group, while the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, NICU hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of the Red-Orange group, the length of NICU stay was shorter than that of the Red-Orange group, and its rate of take-home-babies was higher than that in the Red-Orange group (all P<0.05). (3) Analysis of different clinical referral timings in the Yellow group: among these 159 SPE patients, 46 cases (28.9%, 46/159) would be excluded from the range of referral requirements which belonged to the Yellow color grade, but 6 cases still developed SPE severe complications (4 cases in Warn-s group and 2 cases in a-PE group), 17 cases were terminated pregnancy before 34 weeks of gestation (12 cases in Warn-s group and 5 cases in a-PE group), and 23 cases developed SPE before 34 weeks of gestation (17 cases in Warn-s group and 6 cases in a-PE group). (4) Multivariate analysis: referral after detection of PE early warning signs was the independent protective factor for postponing the onset of SPE severe complications (P<0.05). Referral after detection of PE early warning signs and referral after onset of PE were both protective factors for postponing the onset of SPE and early-onset PE (all P<0.05). Conclusions: Different referral timing in the referral system is one of the key points that affect the maternal and neonatal outcomes of SPE. Referral after detection of PE early warning signs and timely referral after onset of PE would reduce early-onset PE, postpone the onset of SPE and reduce the severe complications of SPE. The clinical development and evolution of PE is really complicated, and referral based on specific clinical situations is better than referral based on fixed mode.

Activation cross sections for 13.6 MeV neutron induced reactions on natural tin.

Cross sections of the  112Sn(n,x)111In,  114Sn(n,2n)113Sn,  natSn(n,x)117mSn and  124Sn(n,2n)123gSn reactions have been measured by using the activation technique at 13.6 MeV neutron energy. The neutrons were produced via the  3H(d,n)4He reaction. The present experimental data illustrated satisfactory agreement with most of the available literature data. Experimental data are compared with the corresponding evaluated nuclear data from the ENDF/B-VIII.0, JENDL-4.0/HE, BROND-3.1, CENDL-3.2 and JEFF-3.3 libraries, and the agreement are generally acceptable. Besides, different nuclear level density models have been used for the estimation of the desired excitation functions with TALYS-1.95 code.

[Studies on resistance of Schistosoma to praziquantel XVIII Sensitivity to praziquantel in filial generations of praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections].

OBJECTIVE: To investigate the sensitivity of adult worms of filial generations from praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections to praziquantel. METHODS: Mice were infected with the cercariae of an experimentally generated praziquantel-resistant S. japonicum isolate [median effective dose (ED50) = 277.4 mg/kg] and a laboratory-maintained praziquantel-sensitive S. japonicum isolate (ED50 = 99.6 mg/kg) at a mixture ratio of 1:1 and 2:1, which was maintained in the laboratory via the mouse-snail cycle for 8 generations. Then, mice were infected with the cercariae of the 8th filial-generation parasite, and grouped 35 days post-infection. Mice in the 5 treatment groups were given praziquantel treatment by gavage at a single oral dose of 37.5, 75, 150, 300 mg/kg and 600 mg/kg, while animals in the control group was administered orally with 2.5% cremophor EL. All mice were sacrificed 14 days post-treatment and adult worms were collected by perfusion of the portal vein. The worm burden reductions and praziquantel ED50 values were calculated. The praziquantel-resistant S. japonicum isolate generated from experimental induction with 12 rounds of praziquantel treatment with sub-curative doses was maintained in the laboratory via the mouse-snail cycle, and mice were infected with the cercariae of the 8th filial-generation parasite. The praziquantel ED50 value against the 8th filial-generation adults was measured. RESULTS: After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 1:1, the praziquantel ED50 was 135.2 mg/kg against the adults of the 8th filial-generation parasite. After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 2:1, the praziquantel ED50 was 129.2 mg/kg against the adults of the 8th filial-generation parasite. In addition, the praziquantel ED50 was 208.4 mg/kg against the adults of the 8th filial-generation S. japonicum without the selection pressure of praziquantel. CONCLUSIONS: Compared with the experimentally induced praziquantel-resistant S. japonicum isolate, the adult worms of the filial-generation S. japonicum show a reduced sensitivity to praziquantel in the same host following infection with the mixture of cercariae of praziquantel-resistant and -sensitive S. japonicum isolates. The adult worms of the filial generation of the praziquantel-resistant S. japonicum isolate without the selection pressure of praziquantel may still maintain the resistance to praziquantel.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.