Prenatal exome sequencing analysis in fetuses with central nervous system anomalies.

OBJECTIVE: To evaluate the utility of prenatal exome sequencing (pES) in fetuses with central nervous system (CNS) abnormalities. METHODS: This was a retrospective cohort study of fetuses identified to have CNS abnormality on prenatal ultrasound and/or magnetic resonance imaging. All fetuses were first analyzed by chromosomal microarray analysis (CMA). Fetuses with a confirmed aneuploidy or causal pathogenic copy-number variant (CNV) on CMA did not undergo pES analysis and were excluded, while those with a negative CMA result were offered pES testing. RESULTS: Of the 167 pregnancies included in the study, 42 (25.1%) were identified to have a pathogenic or likely pathogenic (P/LP) variant. The diagnostic rate was significantly higher in fetuses with a non-isolated CNS abnormality than in those with a single CNS abnormality (35.7% (20/56) vs 14.5% (8/55); P = 0.010). Moreover, when a fetus had three or more CNS abnormalities, the positive diagnostic rate increased to 42.9%. A total of 25/42 (59.5%) cases had de-novo mutations, while, in the remaining cases, mutations were inherited and carried a significant risk of recurrence. Families whose fetus carried a P/LP mutation were more likely to choose advanced pregnancy termination than those with a variant of uncertain significance, secondary/incidental finding or negative pES result (83.3% (25/30) vs 41.3% (38/92); P < 0.001). CONCLUSION: pES improved the identification of genetic disorders in fetuses with CNS anomalies without a chromosomal abnormality or CNV identified on CMA, regardless of the number of CNS anomalies and presence of extracranial abnormality. We also demonstrated that pES findings can significantly impact parental decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Host response of Nicotiana benthamiana to the parasitism of five populations of root-lesion nematode, Pratylenchus coffeae, from China.

In a recent survey of nematodes associated with tobacco in Shandong, China, the root-lesion nematode Pratylenchus coffeae was identified using a combination of morphology and molecular techniques. This nematode species is a serious parasite that damages a variety of plant species. The model plant benthi, Nicotiana benthamiana, is frequently used to study plant-disease interactions. However, it is not known whether this plant species is a host of P. coffeae. The objectives of this study were to evaluate the parasitism and pathogenicity of five populations of the root-lesion nematode P. coffeae on N. benthamiana.N. benthamiana seedlings with the same growth status were chosen and inoculated with 1,000 nematodes per pot. At 60 days after inoculation, the reproductive factors (Rf = final population densities (Pf)/initial population densities (Pi)) for P. coffeae in the rhizosphere of N. benthamiana were all more than 1, suggesting that N. benthamiana was a good host plant for P. coffeae.Nicotiana. benthamiana infected by P. coffeae showed weak growth, decreased tillering, high root reduction, and noticeable brown spots on the roots. Thus, we determined that the model plant N. benthamiana can be used to study plant-P. coffeae interactions.

[Association of greenness exposure with waist circumference and central obesity in Chinese adults aged 65 years and over].

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [ß (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (Pinteraction=0.022). Compared with the Q1 group in NDVI, WC of Q2 and Q3 groups in rural decreased, and the ß (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (Pinteraction=0.284). Compared with the Q1 group in NDVI, the risk of central obesity in the Q2 and Q3 groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (Pnonlinear=0.006) and central obesity (Pnonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

The association of coffee consumption with the risk of osteoporosis and fractures: a systematic review and meta-analysis.

To elucidate the association of coffee and bone health would help fracture risk reduction via dietary intervention. Although those who had higher coffee consumption were less likely to have osteoporosis, the associations between coffee consumption and fracture risk need further investigations with better study designs. INTRODUCTION: The associations between coffee consumption and the risk of osteoporosis and fracture remain inconclusive. We aimed to better quantify these associations by conducting meta-analyses of observational studies. METHODS: Relevant studies were systematically searched on PubMed, Web of Science, Cochrane library, and Embase Database up to November 25, 2021. The odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CI) was pooled and a dose-response analysis was performed. RESULTS: Four studies with 7114 participants for osteoporosis and thirteen studies with 391,956 participants for fracture incidence were included in the meta-analyses. High versus low coffee consumption was associated with a lower risk of osteoporosis [pooled OR (95% CI): 0.79 (0.65-0.92)], while it was non-significantly associated with fracture incidence [pooled OR (95% CI): 0.86 (0.67-1.05) at hip and 0.89 (0.42-1.36) at non-hip]. A non-linear association between the level of coffee consumption and hip fracture incidence was shown (P = 0.004). The pooled RR (95% CI) of hip fracture risk in those who consumed 1, 2-3, 4, and ≥ 9 cups of coffee per day was 0.92 (0.87-0.97), 0.89 (0.83-0.95), 0.91 (0.85-0.98), and 1.10 (0.76-1.59), respectively. The significance in the association between coffee consumption and the hip fracture incidence decreased in those studies that had larger sample size, higher quality, and more adjustments. CONCLUSIONS: A dose-dependent relationship may exist between coffee consumption and hip fracture incidence. The effect of high versus low coffee consumption was influenced by study designs. Further studies with dedicated designs are needed to confirm the independent effects of coffee consumption on bone health.

Fano-like Resonance due to Interference with Distant Transitions.

Narrow optical resonances of atoms or molecules have immense significance in various precision measurements, such as testing fundamental physics and the generation of primary frequency standards. In these studies, accurate transition centers derived from fitting the measured spectra are demanded, which critically rely on the knowledge of spectral line profiles. Here, we propose a new mechanism of Fano-like resonance induced by distant discrete levels and experimentally verify it with Doppler-free spectroscopy of vibration-rotational transitions of CO_{2}. The observed spectrum has an asymmetric profile and its amplitude increases quadratically with the probe laser power. Our results facilitate a broad range of topics based on narrow transitions.

A comparative study for the evaluation of CT-based conventional, radiomic, combined conventional and radiomic, and delta-radiomic features, and the prediction of the invasiveness of lung adenocarcinoma manifesting as ground-glass nodules.

AIM: To investigate and compare the performance of conventional, radiomic, combined, and delta-radiomic features to predict the invasiveness of lung adenocarcinoma manifesting as ground-glass nodules (GGNs). MATERIALS AND METHODS: The present retrospective study included 216 GGNs confirmed surgically as pulmonary adenocarcinomas. All the thin-section computed tomography (CT) images were imported into the software of the United Imaging Intelligence research portal, and radiomic features were extracted with three-dimensional (3D) regions of interest. Least Absolute Shrinkage and Selection Operator was used to select the optimal radiomic features. Four models were constructed, including conventional, radiomic, combined conventional and radiomic, and delta-radiomic models. The receiver operating characteristic curves were built to evaluate the validity of these. RESULTS: The type, long diameter, shape, margin, vacuole, air bronchus, vascular convergence, and pleural traction exhibited significant differences between pre-invasive lesions (PILs)/minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) groups were selected for conventional model building. Nine radiomic features were selected to build the radiomic model. The four models indicated optimal performance (AUC > 0.7). The radiomic and combined models exhibited the highest diagnostic efficiency, and their AUC were 0.89 and 0.88 in the training set, and 0.87 and 0.88 in the validation set, respectively. The delta-radiomic model indicated that the AUC was 0.83 in the training set, and 0.76 in the validation set. Finally, the conventional model exhibited an AUC in the training and validation sets of 0.78 and 0.76. CONCLUSIONS: The radiomic model and combined model, in particular, and the delta-radiomic model all demonstrated improved diagnostic efficiency in differentiating IA from PIL/MIA than that of the conventional model.

Antifungal activity of puroindoline protein from soft wheat against grain molds and its potential as a biocontrol agent.

Mold growth reduces the quality of stored grains, besides producing toxins that pose a potential threat to human health. Therefore, prevention of grain mold growth during storage is important to ensure a safe and high-quality product, preferably using an eco-friendly antifungal agent. The puroindoline (PIN) protein was extracted by Triton X-114 and identified by QE mass spectrometry. Aspergillus flavus has attracted much attention because of its toxic secondary metabolites, and PIN protein showed a significant inhibition on A. flavus growth. Scanning electron microscopy revealed altered spore morphology of A. flavus following PIN protein treatment, and propidium iodide staining showed incomplete spore cell membranes. The disruption and deformation of A. flavus spores suggest that the cell walls and cell membranes were compromised. Decreased mitochondrial membrane potential and increased levels of intracellular reactive oxygen specieswere detected using JC-1 and 2,7-dichlorodihydrofluorescein diacetate staining, respectively. PIN protein could effectively inhibit the growth and aflatoxins B1 production of A. flavus in stored grains, such as wheat and rice. PIN proteins can inhibit the growth of many common grain storage molds, including Penicillium, Aspergillus spp. (A. flavus, A. glaucus, A. kawachii, A. ochraceus and A. niger), Alternaria and Fusarium graminearum, in a dose-dependent manner. PIN protein has a significant inhibitory effect on the growth of grain molds, with a stronger inhibitory effect noted in wheat and rice. Our study provides a novel and simple theoretical basis for the selection and storage of mold resistance in grains and food during storage.

[Related factors of revision of distal femoral fractures treated with lateral locking plate].

OBJECTIVE: To analyze the factors related to the need for revision surgery due to nonunion or internal fixation failure after the treatment of distal femoral fracture with lateral locking plate (LLP). METHODS: Retrospective analysis was made of the clinical data of 130 cases with distal femoral fracture treated in our hospital from March 2005 to March 2019. SPSS 17.0 software (univariate analysis and Logistic regression analysis) was used to analyze the general condition [gender, age, body mass index (BMI), comorbidities, smoking history], injury related factors (energy of injury, open or closed injury, AO/OTA classification of fracture, fracture area distribution), operation related factors (operation time, reduction quality, postoperative infection) and construct characteristics of internal fixation. RESULTS: Twelve of 130 patients who were included in the study underwent revisional surgery, with a revision rate 9.2%. Univariate analysis showed that there were significant differences in age, BMI, AO/OTA classification, fracture area distribution, operation time, reduction quality, length of plate/fracture area, length of plate/fracture area above condylar between the two groups (P < 0.05). Logistic regression analysis showed that AO/OTA classification (A3), supracondylar involved fracture, operation time, reduction quality and the length of the plate/fracture area above the condylar were the possible related factors (P < 0.05). Destruction of the medial support ability of the femur in comminuted type A3 fracture, supra-condylar cortex area fracture involvement, increase of the bending stress of the LLP due to poor fracture reduction quality, damage of the blood supply of fracture end due to long-time operation, and stress concentration caused by insufficient length of plate might be risk factors of revisional operation after the treatment of distal femoral fracture with LLP. For the patients who needed revision after LLP treatment, additional use of medial minimally invasive plate fixation and autologous bone transplantation, change to intramedullary nail fixation were commonly used clinical treatment strategies. CONCLUSION: AO/OTA classification (A3), supracondylar involved fracture, long operation time, poor reduction quality and the length of the plate/fracture area above the condylar were the possible predictive factors of the revision in distal femoral fractures treated with lateral locking plate. The appropriate application of the locking plate and operation strategy are the key to reduce the revision rate in distal femoral fractures.

A New Berberine Preparation Protects Pancreatic Islet Cells from Apoptosis Mediated by Inhibition of Phospholipase A2/p38 MAPK Pathway.

We studied an amorphous solid dispersion of berberine with absorption enhancer sodium caprate (Huang-Gui solid dispersion preparations, HGSD). A therapeutic effect of HGSD was revealed in mice with type 2 diabetes mellitus and palmitate-induced injury to MIN6 ß-cells. HGSD treatment (150 mg/kg) improved glucose metabolism and decreased ß-cell apoptosis in diabetic mice. Furthermore, the effective component of HGSD berberine significantly attenuated the palmitate-induced decrease in MIN6 ß-cells viability and insulin secretion. Moreover, molecular docking analysis and Western blotting showed that berberine decreased cell apoptosis and expression of group VIA phospholipase A2 (iPLA2), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3. These data suggest that HGSD treatment protected ß-cells via inhibiting the iPLA2/p38 MAPK pathway.

Identification of DNA methylation-driven genes and construction of a nomogram to predict overall survival in pancreatic cancer.

BACKGROUND: The incidence and mortality of pancreatic cancer (PC) has gradually increased. The aim of this study was to identify survival-related DNA methylation (DNAm)-driven genes and establish a nomogram to predict outcomes in patients with PC. METHODS: The gene expression, DNA methylation database, and PC clinical samples were downloaded from TCGA. DNAm-driven genes were identified by integrating analyses of gene expression and DNA methylation data. Survival-related DNAm-driven genes were screened via univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to develop a risk score model for prognosis. Based on analyses of clinical parameters and risk score, a nomogram was built and validated. The independent cohort from GEO database were used for external validation. RESULTS: A total of 16 differentially expressed methylation-driven genes were identified. Based on LASSO Cox regression and multivariate Cox regression analysis, six genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) were chosen to develop the risk score model. In the Kaplan-Meier analysis, age, T stage, N stage, AJCC stage, radiation therapy history, tumor size, surgery type performed, pathological type, chemotherapy history, and risk score were potential prognostic factors in PC (P < 0.1). In the multivariate analysis, stage, chemotherapy, and risk score were significantly correlated to overall survival (P < 0.05). The nomogram was constructed with the three variables (stage, chemotherapy, and risk score) for predicting the 1-year, 2-year, and 3-year survival rates of PC patients. Nomogram performance was assessed by receiver operating characteristic (ROC) curves and calibration curves. 1-year, 2-year and 3-year AUC of nomogram model was 0.899, 0.765 and 0.776, respectively. CONCLUSIONS: In our study, we successfully identified the six DNAm-driven genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) with a relationship to the outcomes of PC patients. The nomogram including stage, chemotherapy, and risk score could be used to predict survival in PC patients.

The analysis of osteosarcopenia as a risk factor for fractures, mortality, and falls.

Osteosarcopenia is defined as the concomitant occurrence of sarcopenia and osteoporosis/osteopenia. This study aimed to clarify whether osteosarcopenia implies a greater risk of fractures, mortality, and falls and to draw attention to osteosarcopenia. INTRODUCTION: Osteosarcopenia, which is characterized by the co-existence of osteoporosis/osteopenia and sarcopenia, is one of the most challenging geriatric syndromes. However, the association between osteosarcopenia and the risk of falls, fractures, disability, and mortality is controversial. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from their inception to March 18, 2021, for cohort studies on the relationship between osteosarcopenia and fractures, falls, and mortality. Two reviewers independently extracted data and assessed study quality. A pooled analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using fixed or random-effects models. RESULTS: Eight cohort studies including 19,836 participants showed that osteosarcopenia significantly increased the risk of fracture (OR 2.46, 95% CI 1.83-3.30, Pheterogeneity = 0.006, I2 = 63.0%), three cohort studies involving 2601 participants indicated that osteosarcopenia significantly increased the risk of mortality (OR 1.66, 95% CI 1.23-2.26, Pheterogeneity = 0.214, I2 = 35.2%), and three cohort studies involving 3144 participants indicated that osteosarcopenia significantly increased the risk of falls (OR 1.62, 95% CI 1.28-2.04, Pheterogeneity = 0.219, I2 = 34.1%). No publication bias existed among the studies regarding the association between osteosarcopenia and fractures. The findings were robust according to the subgroup and sensitivity analyses. CONCLUSIONS: This pooled analysis demonstrated that osteosarcopenia significantly increased the risk of fractures, falls, and mortality, thus highlighting its relevance in daily life. Therefore, we suggest that elderly persons should be aware of the risks associated with osteosarcopenia.

Nomogram to predict survival of patients with advanced and metastatic pancreatic Cancer.

BACKGROUND: Nomograms are rarely employed to estimate the survival of patients with advanced and metastatic pancreatic cancer (PC). Herein, we developed a comprehensive approach to using a nomogram to predict survival probability in patients with advanced and metastatic PC. METHODS: A total of 323 patients with advanced and metastatic PC were identified from the Chinese People's Liberation Army (PLA) General Hospital. A baseline nomogram was constructed using baseline variables of 323 patients. Additionally, 233 patients, whose tumors showed initial responses to first-line chemotherapy, were enrolled in the chemotherapy response-based model. 128 patients and 108 patients with advanced and metastatic PC from January 2019 to April 2021 were selected for external validating baseline model and chemotherapy response-based model. The 1-year and 2-year survival probability was evaluated using multivariate COX regression models. The discrimination and calibration capacity of the nomograms were assessed using C-statistic and calibration plots. The predictive accuracy and net benefit of the nomograms were evaluated using ROC curve and DCA, respectively. RESULTS: In the baseline model, six variables (gender, KPS, baseline TB, baseline N, baseline WBC and baseline CA19-9) were used in the final model. In the chemotherapy response-based model, nine variables (KPS, gender, ascites, baseline N, baseline CA 19-9, baseline CEA, change in CA 19-9 level at week, change in CEA level at week and initial response to chemotherapy) were included in the final model. The C-statistics of the baseline nomogram and the chemotherapy response-based nomogram were 0.67 (95% CI, 0.62-0.71) and 0.74 (95% CI, 0.69-0.77), respectively. CONCLUSION: These nomograms were constructed to predict the survival probability of patients of advanced and metastatic PC. The baseline model and chemotherapy response-based model performed well in survival prediction.

Potential probiotics Lactobacillus casei K11 combined with plant extracts reduce markers of type 2 diabetes mellitus in mice.

AIMS: Probiotics and plant extracts have been used to prevent the development of type 2 diabetes mellitus (T2DM). The study aimed to explore the effect of the interaction between potential probiotics and bitter gourd extract (BGE) or mulberry leaf extract (MLE) on T2DM. METHODS AND RESULTS: Potential probiotics were tested for their gastrointestinal tract viability and growth situation combined with BGE and MLE in vitro. The diabetes model was constructed in C57BL/6 mice, and the potential effect and mechanism of regulating blood glucose were verified. Hematoxylin-eosin staining (HE), gas chromatography (GC), ELISA, and RT-PCR were also used for analysis. The results showed that Lactobacillus casei K11 had outstanding gastrointestinal tract viability and growth situation with plant extracts. Administration of L. casei K11 combined with BGE and MLE significantly reduced blood glucose levels and ameliorated insulin resistance in diabetic mice than the administration of Lactobacillus paracasei J5 combined with BGE and MLE. Moreover, in L. casei K11 combined with BGE and MLE groups, lipid metabolism, oxidative stress, and proinflammatory cytokine levels were regulated. Furthermore, the results indicated that L. casei K11 combined with BGE and MLE improved free fatty acid receptor 2 (FFAR2) upregulation, glucagon-like peptide-1 (GLP-1) secretion, and short-chain fatty acid (SCFA) levels. CONCLUSIONS: These findings showed that L. casei K11 combined with BGE and MLE modified the SCFA-FFAR2-GLP-1 pathway to improve T2DM. SIGNIFICANCE AND IMPACT OF THE STUDY: This study identified a new modality for evaluating interactions between potential probiotics and plant extracts. Our findings revealed that L. casei K11 combined with BGE and MLE significantly promoted the SCFA-FFAR2-GLP-1 pathway to inhibit T2DM.

A radiomics study to predict invasive pulmonary adenocarcinoma appearing as pure ground-glass nodules.

AIM: To establish a machine-learning model to differentiate adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC) appearing as pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This retrospective study enrolled 136 patients with histopathologically diagnosed with AIS, MIA, and IAC. All pGGNs were divided randomly into a training and a testing dataset at a ratio of 7 : 3. Radiomics features were extracted based on the unenhanced computed tomography (CT) images derived from the last preoperative CT examination of each patient. The F-test and least absolute shrinkage and selection operator (LASSO) logistic regression were applied to select the most valuable features to establish a support vector machine (SVM) model. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUROC), and the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance of radiologists and the SVM model. RESULTS: Six significant radiomics features were selected to develop the SVM model and showed excellent ability to differentiate AIS/MIA from IAC in both the training dataset (AUROC=0.950, 95% confidence interval [CI]: 0.886-0.984) and the testing dataset (AUROC=0.945, 95% CI: 0.826-0.992). Compared with two radiologists, the proposed model possessed significant advantages with higher accuracy (90.24% versus 75.61% and 80.49%), sensitivity (91.67% versus 50% and 75%), and specificity (89.66% versus 86.21% and 82.76%). CONCLUSION: A machine-learning model based on radiomics features exhibits superior diagnostic performance in differentiating AIS/MIA from IAC appearing as pGGNs.

[A Luciferase-EGFP Reporter System for the Evaluation of DNA Methylation in Mammalian Cells].

DNA methylation is an essential epigenetic modification involved in numerous biological processes. Here, we present a cell-based system pLTR-Luc2P-EGFP for evaluation of DNA methylation in mammalian cells. In this system, the expression of reporter gene luciferase2P (Luc2P)-EGFP is under the control of HIV-1 promoter 5' long terminal repeat (LTR), which contains multiple CpG sites. Once these sites are methylated, the expression of Luc2P-EGFP is turned off, which may be visualized under fluorescence microscopy, with quantification performed in luciferase activity assay. As a proof of principle, pLTR-Luc2P-EGFP was methylated in vitro, and transfected into 293T cells, where the reduction of Luc2P-EGFP expression was confirmed. Premixed reporter DNA samples with the methylation levels varying from 0 to 100% were used for quantitative measurements of DNA methylation. The resulting standard curves indicated the accuracy of luciferase activity exceeding that of the Western blotting against EGFP. The Bland-Altman analysis showed that data from luciferase activity assay were in good agreement with the actual DNA methylation levels. In summary, we have established a reporter system coupled with reliable detection technique capable of efficient quantifying the changes in methylation in mammalian cells. This system may be utilized as a high throughput screening tool for identifying molecules that modulate DNA methylation.

Are left ventricular muscle area and radiation attenuation associated with overall survival in advanced pancreatic cancer patients treated with chemotherapy?

AIM: To evaluate whether cardiac muscle area and radiation attenuation, determined using pre-chemotherapy computed tomography (CT), are associated with therapeutic response and overall survival (OS) in chemotherapy-treated advanced pancreatic cancer (APC) patients. MATERIALS AND METHODS: Ninety-eight chemotherapy-treated APC patients who underwent pre-chemotherapy CT between 2009 and 2018 were considered. Left ventricular muscle area (LVMA) and left ventricular muscle radiation attenuation (LVMRA) were measured using pre-chemotherapy arterial-phase CT. OS and progression-free survival (PFS) were analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse potential factors affecting OS and PFS. RESULTS: Patients with low LVMRA, low LVMA at baseline CT, and multiple metastases had a significantly shorter median OS than patients with high LVMRA, high LVMA, and without multiple metastases (8.8 versus 14 months, p=0.017; 12.2 versus 18.1 months, p=0.038; 7.3 versus 13.5 months, p<0.001, respectively). Patients with low LVMRA and distant metastasis had a shorter median PFS than patients with high LVMRA and those without distant metastasis (4.9 versus 8.3 months, p=0.032; 5.4 versus 9.9 months, p=0.002, respectively). Moreover, the mean LVMRA was the highest in the partial response group (p=0.028). CONCLUSION: LVMRA could well predict PFS and OS in chemotherapy-treated APC patients.

Effects of crocin on frozen-thawed sperm apoptosis, protamine expression and membrane lipid oxidation in Yanbian yellow cattle.

Glycerol is used as a bovine semen osmotic cryoprotectant that greatly improves the quality of frozen and thawed bovine sperm. However, high glycerol concentrations can have a toxic effect on frozen and thawed bovine sperm. Therefore, this experiment investigated the effect of replacing a portion of the glycerol in a cryoprotectant solution with crocin on the sperm apoptosis, protamine deficiency and membrane lipid oxidation of frozen and thawed Yanbian yellow cattle sperm. The experiment included a control group (6% glycerol) and four treatment groups: I (3% glycerol), II (3% glycerol +0.5 mM crocin), III (3% glycerol + 1 mM crocin) and IV (3% glycerol + 2 mM crocin). Computer assisted semen analysis was used to detect sperm motility, Hoechst 33,342, propidium iodide, and JC-1 staining were used to analyse sperm viability and mitochondrial membrane potential, chromomycin A3 staining was used to detect protamine deficiency and DNA damage, flow cytometry was used for sperm membrane lipid disorder detection and analysis, and real-time quantitative RT-qPCR was used to detect the mRNA expression levels of protamine-related genes (PRM2, PRM3), sperm acrosome-associated genes (SPACA3), oxidative stress-related genes (ROMO1) and apoptosis-related genes (BCL2, BAX). Compared to the control group, replacing a portion of glycerol with 1 mM crocin significantly improved sperm motility, plasma membrane integrity, membrane lipid disorders (p < .05) and viability, mitochondrial membrane potential, protamine deficiency (p < .01). The expression level of PRM2, PRM3, SPACA3 and BCL2 significantly increased (p < .05), while the expression levels of ROMO1 and BAX significantly decreased (p < .05). Accordingly, the BCL2/BAX ratio significantly increased (p < .05). In summary, the substitution of a portion of glycerol with crocin in cryoprotective solution improved the quality of Yanbian yellow cattle sperm after freezing and thawing.

[Risk factors of recurrent kyphosis in thoracolumbar burst fracture patients treated by short segmental pedicle screw fixation].

OBJECTIVE: To analyze the risk factors of recurrent kyphosis after removal of short segmental pedicle screw fixation in patients with thoracolumbar burst fractures. METHODS: Retrospective analysis was conducted of 144 cases of thoracolumbar burst fractures without neurological impairment treated in Peking University Third Hospital from January 2010 to December 2017. There were 74 males and 70 females, with an average age of (39.1±13.2) years. The distribution of the injured vertebrae was T12: 42, L1: 72 and L2: 30, with fracture types of A3: 90, B1: 25 and B2: 29. The patients were divided into two groups: Recurrent kyphosis group (n=92) and non-recurrent kyphosis group (n=52). SPSS 26.0 software was used for univariate analysis and Logistic regression analysis. RESULTS: The average follow-up time was 28 (20-113) months. The imaging indexes of pre-operation, 3 days post-operation, 12 months post-operation and the last follow-up were measured and compared. Anterior vertebral body height, segmental kyphosis, vertebral wadge angle and Gardner deformity were significantly improved after operation (P < 0.05), and there were some degrees of loss in the 1-year follow-up; anterior vertebral body height and vertebral wadge angle were no longer changed after the removal of the screws; however, segmental kyphosis and Gardner deformity were still aggravated after the removal of the screws (P < 0.05). There were some degrees of collapse of the height of the upper and lower discs during the follow-up. Univariate analysis showed that there were statistically significant differences (P < 0.05) between the two groups in gender, age (36.9 years vs. 43.0 years), upper disc injury, CT value (174 vs. 160), segmental kyphosis (16.6° vs. 13.3°), vertebral wadge angle (16.7° vs. 13.6°), Gardner deformity (19.1° vs. 15.2°) and ratio of anterior vertebral body height (0.65 vs. 0.71). Logistic regression analysis showed that male (OR: 2.88, 95%CI: 1.196-6.933), upper disc injury (OR: 2.962, 95%CI: 1.062-8.258) and injured vertebral wedge angle were risk factors of recurrent kyphosis after removal of internal fixation for thoracolumbar burst fracture (P < 0.05). CONCLUSION: The patients with thoracolumbar burst fracture can obtain satisfactory effect immediately after posterior short segmental pedicle screw fixation, however, there may be some degree of loss during the follow-up. Male, upper disc injury and injured vertebral wedge angle are the risk factors of recurrent kyphosis after removal of internal fixation for thoracolumbar burst fracture.

[Analysis of risk factors for necrosis of femoral head after internal fixation surgery in young and mid-aged patients with femoral neck fracture].

OBJECTIVE: To retrospectively analyze the risk factors of avascular necrosis of femoral head (ANFH) after internal fixation in young and mid-aged adults. METHODS: From January 2007 to December 2017, femoral neck fracture patients (18-60 years old) treated by reduction and internal fixation were retrospectively studied in Peking University Third Hospital. We recorded their gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) grade, reason of injury, fracture side, interval between injury and surgery, location of fracture line, Garden classification, Pauwels classification, reduction method (open or closed), internal fixation and reduction quality. The diagnosis of ANFH was confirmed based on X-ray and MRI images during the follow-up. The internal fixation method included cannulated compression screw (CCS) or dynamic hip screw (DHS, with or without anti-rotation screw). χ2 test and Logistic regression analysis were used to analyze the relationship between the various factors and postoperative ANFH. RESULTS: A total of 113 patients were included in this study, including 63 males and 50 females with an average age of (43.17 ± 12.34) years. They were followed up by (25.08 ± 16.17) months. ASA grade included grade I (21 cases), grade II (55 cases) and grade III (37 cases). The reasons of injury included low-energy trauma (76 cases) and high-energy (37 cases). The fracture line included subcapital type (37 cases), transverse type (74 cases) and basal type (2 cases). Garden classification included type I (3 cases), type II (46 cases), type III (39 cases) and type IV (25 cases). Pauwels classification included type I (21 cases), type II (55 cases) and type III (37 cases). Interval between injury and surgery was (3.88 ± 3.66) days, 108 patients and 5 patients performed closed and open reduction respectively. 63 patients performed CCS, and 50 patients performed DHS. The reduction quality included grade A (91 cases), grade B (18 cases) and grade C (4 cases). 18 patients developed ANFH after surgery, the incidence rate was 15.93% (18/113). The result of χ2 test showed the reason of injury (OR=0.19, P < 0.01), Garden classification (OR=0.13, P < 0.01), Pauwels classification (OR=0.12, P = 0.02), internal fixation method (OR=3.29, P = 0.04) and reduction quality (OR=0.33, P < 0.01) were significantly associated with ANFH. These five factors were further included into the Logistic regression analysis, and its results showed that the reason of injury (OR=4.11, P = 0.03) and Garden classification (OR=4.85, P = 0.04) were statistically significant. CONCLUSION: The reason of injury, Garden classification, Pauwels classification, internal fixation and reduction quality may increase the risk of ANFH after surgery, and the reason of injury and Garden classification were much more significant.

Notch3 signaling activation in smooth muscle cells promotes extrauterine growth restriction-induced pulmonary hypertension.

BACKGROUND AND AIMS: Early postnatal life is a critical developmental period that affects health of the whole life. Extrauterine growth restriction (EUGR) causes cardiovascular development problems and diseases, including pulmonary arterial hypertension (PAH). PAH is characterized by proliferation, migration, and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs). However, the role of PASMCs in EUGR has not been studied. Thus, we hypothesized that PASMCs dysfunction played a role in EUGR-induced pulmonary hypertension. METHODS AND RESULTS: Here we identified that postnatal nutritional restriction-induced EUGR rats exhibited an elevated mean pulmonary arterial pressure and vascular remodeling at 12 weeks old. PASMCs of EUGR rats showed increased cell proliferation and migration features. In EUGR-induced PAH rats, Notch3 signaling was activated. Relative mRNA and protein expression levels of Notch3 intracellular domain (Notch3 ICD), and Notch target gene Hey1 in PASMCs were upregulated. We further demonstrated that pharmacological inhibition of Notch3 activity by using a γ-secretase inhibitor DAPT, which blocked the cleavage of Notch proteins to ICD peptides, could effectively inhibit PASMC proliferation. Specifically knocked down of Notch3 in rat PASMCs by shRNA restored the abnormal PASMC phenotype in vitro. We found that administration of Notch signaling inhibitor DAPT could successfully reduce mean pulmonary arterial pressure in EUGR rats. CONCLUSIONS: The present study demonstrated that upregulation of Notch3 signaling in PASMCs was crucial for the development of EUGR-induced PAH. Blocking Notch3-Hey1 signaling pathway in PASMCs provides a potential therapeutic target for PAH.