Copper-Catalyzed Difluoroalkylation Reaction.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

Esophageal wall thickness on CT scans: can it predict the T stage of primary thoracic esophageal squamous cell carcinoma?

BACKGROUND: CT is the most commonly used method to stage esophageal cancer (EC). However, the reported CT T-staging criteria for EC are controversial. PURPOSE: To determine and validate the optimal esophageal wall thickness (EWT) threshold on CT to distinguish lesions with different T stages in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One thousand, one hundred-two consecutive patients with histopathologically confirmed ESCC between July 2014 and April 2020 were retrospectively reviewed. All patients underwent a preoperative CT examination and surgical treatment. The maximal EWT of the lesions on CT was measured. Patients were divided into pT1, pT2, pT3 and pT4 subgroups according to the pathologic stage. We employed the support vector machine, where linear kernels were leveraged to determine the optimal threshold to classify samples with different T stages. 90% of samples from each subgroup were randomly selected as the training set, while the remainder comprised the testing set. RESULTS: The mean EWTs of the pT1, pT2, pT3 and pT4 subgroups were 4.9 ± 2.6 mm, 8.1 ± 2.3 mm, 12.4 ± 3.6 mm, and 18.6 ± 4.4 mm, respectively. Differences in the EWT between the four subgroups or between adjacent subgroups were significant (p < 0.001), and esophageal wall became thicker with increasing pT stage. We utilized MATLAB 2020a to implement the SVM model and ran the code 10 times. The accuracy of the model was 60.29 ± 2.33%. The thresholds between samples from pT1/pT2, pT2/pT3 and pT3/pT4 lesions were 5.5 ± 0.3 mm, 10.8 ± 0.8 mm and 15.9 ± 0.5 mm, respectively. CONCLUSIONS: Possibility of predicting T stage of ESCC by EWT on CT scans was limited to 60% by model examination with large sample size.

Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma.

Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase (NAMPT) expression is associated with the development and prognosis of many cancers, but it remains unknown regarding its role in oral squamous cell carcinoma (OSCC). In the present study, the results from tissue microarray showed that NAMPT was overexpressed in OSCC patients and its expression level was directly correlated with differential grades of cancer. Interestingly, treatment of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels of NAMPT protein and increased cellular death in an ATO dose- and time-dependent manner. Most importantly, combination of low concentration ATO with FK866 (a NAMPT inhibitor) exerted enhanced inhibitive effect on NAMPT protein and mRNA expressions, leading to synergistic cytotoxicity on cancer cells through increasing cell apoptosis and depleting intracellular nicotinamide adenine dinucleotide levels. These findings demonstrate the crucial role of NAMPT in the prognosis of OSCC and reveal inhibition of NAMPT as a novel mechanism of ATO in suppressing cancer cell growth. Our results suggest that ATO can significantly enhance therapeutic efficacy of NAMPT inhibitor, and combined treatment may be a novel and effective therapeutic strategy for OSCC patients.

Flavor compounds and sensory profiles of a novel Chinese marinated chicken.

BACKGROUND: Marinating is a Chinese traditional meat-processing method using aged brine that brings popular flavor together with food safety issues. In this study a novel method named quantitative marinating (QM) was developed to improve Chinese traditional marinating (TM). Flavor compounds and sensory profiles of two marinated products were determined to verify if the improved marinating method could maintain the characteristic flavors of TM. RESULTS: Fifty-four, 60, 60, 60 and 44 volatile flavor compounds were identified from four processing stages of QM and TM respectively. Contents of taste compounds first increased and then decreased in the processing stages of QM. The total free amino acid contents of QM and TM products were 789 and 536 mg per 100 g respectively. The total nucleotide content of QM product (22.21 mg per 100 g) was higher than that of TM (20.75 mg per 100 g), while the fatty acid content of QM product (26.66 mg g(-1)) was lower than that of TM (44.43 mg g(-1)). Finally, QM received higher sensory scores than TM. CONCLUSION: Volatile flavor compounds, taste compounds and sensory properties of QM were richer than those of TM, indicating that QM can not only maintain the original aroma of TM but also have advantages in taste compounds.

Dynamic changes in cardiac biomarkers in radiotherapy for oesophageal cancer and their correlations with cardiac radiation dosimetry.

Background and purpose: To investigate the dynamic changes in cardiac enzymes, high-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (pro-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy (RT) and 6 months after RT for oesophageal squamous cell carcinoma (ESCC) in the middle and lower locations and to analyse the correlations between these indicators and cardiac radiation dosimetry parameters. Methods: For 35 patients with ESCC in the middle and lower locations receiving radical concurrent chemoradiotherapy (cCRT), intensity-modulated RT was performed at 1.8 Gy or 2.0 Gy per day, and the totle dose was 50.4 Gy or 60 Gy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (α-HBDH), hs-TnT, pro-BNP and LVEF were measured before, during, and at the end of RT and 1, 3 and 6 months after RT, and correlations of these indicators with mean heart dose (MHD) and heart V5-V50 were analysed. Results: hs-TnT during, at the end and 6 months after RT for oesophageal cancer showed increasing trends, however, LVEF showed a downward trend. pro-BNP showed an increasing trend during RT and gradually returned to normal after RT. CK and CK-MB showed decreasing trends during RT and continued until one month after RT and then gradually returned to normal. Compared with the low-dose group (MHD < 2000 cGy), the high-dose group (MHD ≥ 2000 cGy) had larger increases in hs-TnT and pro-BNP, a more significant decrease in LVEF, and a longer recovery time for these indicators. MHD and V35 were positively correlated with dynamic changes in hs-TnT. Conclusions: Cardiac injury caused by cCRT for ESCC in the middle and lower locations led to increased hs-TnT and pro-BNP levels and a decrease in LVEF in the early stage of treatment, effects that were more pronounced in the high-dose group. MHD and V35 may be potential indicators to predict the degree of cardiac damage. hs-TnT and pro-BNP are sensitive indicators reflecting cardiac injury in RT for oesophageal cancer. Continuous dynamic monitoring of these markers can provide a reference for cardiac protection in clinical RT.

Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 µg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Background: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. Methods: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. Results: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). Conclusions: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Type I Mirizzi syndrome treated by electrohydraulic lithotripsy under the direct view of SpyGlass: A case report.

BACKGROUND: Mirizzi syndrome is an uncommon clinical complication for which the available treatment options mainly include open surgery, laparoscopic surgery, endoscopic retrograde cholangiopancreatography (ERCP), electrohydraulic lithotripsy, and laser lithotripsy. Here, a patient diagnosed with type I Mirizzi syndrome was treated with electrohydraulic lithotripsy under SpyGlass direct visualization, which may provide a reference to explore new treatments for Mirizzi syndrome. CASE SUMMARY: This paper describes a middle-aged female patient with suspected choledocholithiasis who complained for over 1 mo of intermittent abdominal pain, dark yellow urine, jaundice, and was proposed to undergo ERCP lithotomy. Mirizzi syndrome was found during the operation and confirmed by SpyGlass. Electrohydraulic lithotripsy was performed under the direct vision of SpyGlass. After the lithotripsy, the stones were extracted using the stone extraction basket and balloon. After the operation, the patient developed transient hyperamylasemia. Through a series of symptomatic treatments (such as fasting, fluids and anti-inflammation medications), the symptoms of the patient improved. Finally, laparoscopic cholecystectomy or open cholecystectomy was performed after a half-year post-operatively. CONCLUSION: Direct visualization-guided laser or electrohydraulic lithotripsy with SpyGlass is feasible and minimally invasive for type I Mirizzi syndrome without apparent unsafe outcomes.

miR-16 integrates signal pathways in myofibroblasts: determinant of cell fate necessary for fibrosis resolution.

Liver fibrosis is characterized by the transdifferentiation of hepatic stellate cells (HSCs) to myofibroblasts and poor response to treatment. This can be attributed to the myofibroblast-specific resistance to phenotype reversal. In this study, we complemented miR-16 into miR-16-deficient myofibroblasts and analyzed the global role of miR-16 using transcriptome profiling and generating a pathway-based action model underlying transcriptomic regulation. Phenotypic analysis of myofibroblasts and fibrogenic characterization were used to understand the effect of miR-16 on phenotypic remodeling of myofibroblasts. miR-16 expression altered the transcriptome of myofibroblasts to resemble that of HSCs. Simultaneous targeting of Smad2 and Wnt3a, etc. by miR-16 integrated signaling pathways of TGF-ß and Wnt, etc., which underlay the comprehensive regulation of transcriptome. The synergistic effect of miR-16 on the signaling pathways abolished the phenotypic characteristics of myofibroblasts, including collagen production and inhibition of adipogenesis. In vivo, myofibroblast-specific expression of miR-16 not only eliminated mesenchymal cells with myofibroblast characteristics but also restored the phenotype of HSCs in perisinusoidal space. This phenotypic remodeling resolved liver fibrosis induced by chronic wound healing. Therefore, miR-16 may integrate signaling pathways crucial for the fate determination of myofibroblasts. Its global effect induces the reversal of HSC-to-myofibroblast transdifferentiation and, subsequently, the resolution of fibrogenesis. Taken together, these findings highlight the potential of miR-16 as a promising therapeutic target for liver fibrosis.

A comparative study of the normal oesophageal wall thickness based on 3-dimensional, 4-dimensional, and cone beam computed tomography.

BACKGROUND: The study aimed to compare normal oesophageal wall thickness based on 3-dimensional computed tomography (3DCT), 4-dimensional computed tomography (4DCT) and cone beam computed tomography (CBCT). METHODS: Contrast-enhanced 3DCT, 4DCT, and CBCT scans were acquired from 50 patients with lung cancer or metastatic lung cancer. The outer oesophageal wall was manually contoured on each 3DCT, the maximum intensity projection of 4DCT (4DCTMIP) the end expiration phase of 4DCT (4DCT50) (the end expiration phase of 4DCT) and the CBCT data sets. The average wall thicknesses were measured (defined as R3DCT, R50, RMIP, and RCBCT). RESULTS: Whether for thoracic or for intra-abdominal segments, there were no significant differences between R3DCT and R50, but significant differences between R3DCT and RMIP, R3DCT and RCBCT. For upper and middle oesophagus, RCBCT were larger than RMIP. There was no significant difference between upper and middle segments on 3DCT, 4DCT, and CBCT. Intra-abdominal oesophageal wall thickness was greater than that of thoracic oesophagus. There were no differences between upper and lower, and middle and lower oesophagus on CBCT. CONCLUSION: Our findings indicate normal oesophageal wall thickness differed along the length of oesophagus whatever it was delineated on 3DCT, 4DCT (4DCT50 and 4DCTMIP) or CBCT. It is reasonable to use uniform criterion to identify normal esophageal wall thickness when delineating gross tumor volume on 3DCT and 4DCT50, the same is true of delineating internal gross tumor volume on 4DCTMIP or CBCT images for lower and intra-abdominal oesophagus. But, in spite of using contrast-enhanced scanning, relatively blurred boundary on the CBCT images is noteworthy, especially for upper and middle thoracic esophagus.

[Effects of sustained military physical related activity on balance ability].

OBJECTIVE: To evaluate the effects of sustained military physical related activity on balance abilities and the role of visual system in it, so as to provide the basis for precise training. METHODS: Fifty-four healthy males (age: 20.28±3.72 y, height: 173.21±5.67 cm; weight: 64.29±5.12 kg) were recruited in this experiment. Multiple military subjects were completed within 36 hours, and the workload was recorded (randomly select 11 people). After military activity, the balance abilities with opened eyes (54 people) and closed eyes (randomly selected 27 people) were evaluated. RESULTS: In terms of internal load, the heart rates (HR), excess post-exercise oxygen consumption (EPOC) and training impulse (TRIMP) for all exercises were increased significantly in military activity compared with rest (P＜0.05). Regard to balance abilities, compared to the rest with eyes-opened, the sway path-total (SPT), sway path-A-P ( SPAP ), sway path-M-L (SPML), sway V-total (SVT), sway V-A-P (SVAP), and sway V-M-L (SVML)after sustained military activity with eyes-opened were increased significantly (P＜0.05), while sway maximal amplitude-A-P (SMAAP), sway maximal amplitude-M-L (SMAML), and area of 100% ellipse (AE) had no significant changes; Compared to the rest, all indicators after the military activity with eyes-closed were significantly increased (P＜0.05). So vision could control the amplitude and area after the military activity. CONCLUSION: Sustained military related activity can damage the balance ability. After sustained military activity, the degree of damage of the balance ability in the closed-eyes is greater than that of the open-eyes, the amplitude and range of the center of gravity are increased, indicates that the visual system plays major role in controlling attitude stability.

Definition of Internal Mammary Node Target Volume Based on the Position of the Internal Mammary Sentinel Lymph Nodes Presented on SPECT/CT Fusion Images.

Purpose: Mapping the distribution of internal mammary sentinel lymph nodes (IM-SLNs) presented on single photon emission computed tomography in conjunction with computed tomography (SPECT/CT) images to explore the value of IM-SLN to guide tailored clinical target volume (CTV) delineation of postoperative prophylactic IMNI. Materials and methods: Ninety-seven patients who underwent preoperative lymphoscintigraphy by SPECT/CT and had imaging of IM-SLN were selected in this study. The imaging IM-SLNs on SPECT/CT of eligible patients were projected onto corresponding anatomical positions of a representative axial CT image. The IMN CTVs were delineated on the representative axial CT images according to the Radiation Therapy Oncology Group (RTOG) and Danish Breast Cancer Cooperative Group (DBCG) guideline, and defined as CTVRTOG and CTVDBCG. The location of the IM-SLNs was compared with the RTOG and DBCG guidelines of IMN target volume delineations, respectively. The intercostal space distribution of IM-SLNs was recorded. The distances from the CTVRTOG and CTVDBCG to the IM-SLNs were measured, respectively. Results: The total number of imaging IM-SLNs was 136. IM-SLNs were mostly found in the first intercostal space (40.4%), with 30.2, 24.3, 4.4, and 0.7% of IM-SLNs in the second, third, fourth, and fifth intercostal space, respectively. The average distance from the edge of the CTVRTOG and the edge of CTVDBCG to the central points of the IM-SLNs was 4.10 mm (SD, 3.3 mm) and 1.60 mm (SD, 2.6 mm), respectively (t = 16.640, P = 0.000). The average distance from the edge of CTVRTOG and the edge of CTVDBCG to the lateral border IM-SLN was 6.40 mm (SD, 3.5 mm) and 3.34 mm (SD, 3.3 mm), respectively (t = 19.815, P = 0.000). Only 18.4% of IM-SLN central points were included in the CTVRTOG, and 60.3% of IM-SLN central points were included in the CTVDBCG. When covering 90 and 100% of the IM-SLN center points, the CTVRTOG needs to expand 8 and 15 mm, respectively, and the CTVDBCG needs to expand 5 and 13 mm, respectively. Conclusion: Neither the RTOG nor DBCG consensus guideline about the delineation of IMN CTV was sufficient to cover 90% of IM-SLNs. For 90% coverage of IM-SLN central points, CTVRTOG needed to be expanded by 8 mm, and CTVDBCG needed to be expanded by 5 mm.

Time-Course Responses of Muscle-Specific MicroRNAs Following Acute Uphill or Downhill Exercise in Sprague-Dawley Rats.

Objective: The physiological characteristics and acute responses underpinning uphill running differ from those of downhill running and remain less understood. This study aimed to evaluate time-course changes of muscle-specific microRNA (miRNA) responses in striated muscle or circulation in response to uphill and downhill running. Methods: Male Sprague-Dawley rats (n = 84) were randomly assigned to a sedentary group (n = 12) and an exercise group (n = 72). The exercise group performed 90 min of uphill or downhill running. The striated muscle (quadriceps, gastrocnemius, soleus, and cardiac muscle) or circulation (plasma, exosome, exosome-free) levels of six muscle-specific miRNAs (miR-1, miR-133a, miR-133b, miR-206, miR-208a, and miR-499) were assessed at rest, immediately following exercise, and during recovery (1 h and 48 h). Results: Our results show that miR-1 and miR-133a levels are both decreased in quadriceps following downhill running (p < 0.05) while there is no change after uphill running (p > 0.05). In gastrocnemius, both uphill and downhill running decreased miR-1 level immediately after exercise and returned to baseline during recovery (p < 0.05): interestingly, only miR-499 significantly increased following uphill running (p > 0.05). Of the cell-free miRNAs in circulation, only the miR-133b levels in plasma were not affected following uphill running (p > 0.05); the other miRNA levels significantly increased immediately after exercise (p < 0.05), decreased at 1 h and significantly increased at 48 h after exercise (p < 0.05). All selected miRNA levels in exosomes were not affected following uphill running (p > 0.05), while all selected miRNA levels significantly increased during early recovery after downhill running (p > 0.05). In addition, only the miR-133a level in the exosome-free condition showed significant changes following uphill running (p < 0.05), while miR-1, miR-133a, and miR-499 levels showed significant changes after downhill running (p < 0.05). Conclusion: The results indicate that miRNA undergoes dynamic changes in tissue may play an important role in regulating different stress/adaptation following uphill and downhill running. It is likely that changed miRNA levels in plasma may act as a new biomarker for monitoring whole muscular stress during recovery.

PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has now become the leading cause of chronic liver disease with its growing incidence worldwide. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C > G reflects one of the critical genetic factors that confers high-risk to NAFLD. However, the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain. Here, the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409 (PNPLA3 148M variant) are sensitive to therapies of lifestyle modification, dipeptidyl peptidase-4 inhibitors, and bariatric surgery. They exhibit much significant reduction of liver fat content, in concurrence with weigh loss and abolished insulin resistance, as compared to those of C-allele carriers. In contrast, patients bearing PNPLA3 rs738409 C-allele (PNPLA3 148I variant), instead of G-allele, demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention. Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409 related diversities in therapeutic efficacy. Therefore, PNPLA3 rs738409 underlies the response to a variety of treatments, which warrants a personalized, precise medicine in NAFLD on the basis of genotype stratification.

Exosomes in the Oncobiology, Diagnosis, and Therapy of Hepatic Carcinoma: A New Player of an Old Game.

Exosomes are emerging as essential vehicles mediated cross-talk between different types of cells in tumor microenvironment. The extensive exploration of exosomes in hepatocellular carcinoma (HCC) enhances our comprehension of cancer biology referring to tumor growth, metastasis, immune evasion, and chemoresistance. Besides, the versatile roles of exosomes provide reasonable explanations for the propensity for liver metastasis of gastric cancer, pancreatic ductal adenocarcinoma, breast cancer, and colorectal cancer. The selective-enriched components, especially some specific proteins and noncoding RNAs in exosomes, have great potential as noninvasive biomarkers of HCC with high sensitivity and specificity. The characteristics of exosomes further inspire frontier research to interrupt intercellular malignant signals by controlling the biogenesis, release, or contents of exosomes.

Changes in cardiac volume determined with repeated enhanced 4DCT during chemoradiotherapy for esophageal cancer.

BACKGROUND: Concurrent chemoradiotherapy is considered curative intent treatment for patients with non-operative esophageal cancer. Radiation-induced heart damage receives much attention. We performed repeated four-dimensional computed tomography (4DCT) to detect changes in cardiac volume during radiotherapy for esophageal cancer patients, and explored potential factors responsible for those changes. METHODS: Forty-six patients with esophageal cancer underwent enhanced 4DCT and three-dimensional (3D) CT scans before radiotherapy and every 10 fractions during treatment. The heart was contoured on 3DCT images, 4DCT end expiratory (EE) images and 4DCT maximum intensity projection (MIP) images by the same radiation oncologist. Heart volumes and other relative parameters were compared by the SPSS software package, version 19.0. RESULTS: Compared with its initial value, heart volume was smaller at the 10th fraction (reduction = 3.27%, 4.45% and 4.52% on 3DCT, EE and MIP images, respectively, p < 0.05) and the 20th fraction (reduction = 6.05%, 5.64% and 4.51% on 3DCT, EE and MIP images, respectively, p < 0.05), but not at the 30th fraction. Systolic and diastolic blood pressures were reduced (by 16.95 ± 16.69 mmHg and 7.14 ± 11.64 mmHg, respectively, both p < 0.05) and the heart rate was elevated by 5.27 ± 6.25 beats/min (p < 0.05) after radiotherapy. None of the potential explanatory variables correlated with heart volume changes. CONCLUSIONS: Cardiac volume reduced significantly from an early treatment stage and maintained the reduction until the middle stage. The heart volume changes observed on 3DCT and 4DCT were consistent during radiotherapy. The changes in heart volume, blood pressure and heart rate may be valuable indicators of cardiac impairment and target dose changes.

Effects of Hot-Pressure Extraction Time on Composition and Gelatin Properties of Chicken Bone Extracts.

Hot-pressure extraction was utilized in this study to extract proteins from chicken bones at 130 °C. The obtained extracts were further used to prepare gelatin gels. Results demonstrated that the extraction time can significantly affect the composition of the chicken bone extracts (P < 0.05). High-performance liquid chromatography (HPLC) analysis indicated that the protein fraction of molecular weight (MW) >30 KDa was only visible in the extracts collected between 40 and 60 min. The highest contents of hydroxyproline, imino acids, and hydrophobic amino acids were all achieved in the chicken bone extracts after 120 min of extraction, being 3.9, 7.7, and 16.0 mg/g, respectively. The prepared gelatin properties were evaluated in terms of viscosity, storage and loss modulus, stability, gel strength, and their microstructures. Results indicated that gelatins made from chicken bone extracts of 20, 40, and 60 min extraction had better properties compared to that of 90 and 120 min. Significant correlations were identified between gelatin's composition and properties (P < 0.05). The abundance of proteins with MW of <10 KDa and 10 to 30 KDa was found to be the predominant factor that can affect the gelatin's properties. This study illustrated a promising and natural way to obtain edible gelatins from chicken bones.

Comparison of gross tumor volume of primary oesophageal cancer based on contrast-enhanced three-dimensional, four-dimensional, and cone beam computed tomography.

BACKGROUND: To explore motion information included in 3DCT, 4DCT and CBCT by comparing volumetric and positional differences of GTV. RESULTS: Independent of tumor location, significant differences were observed among volumes [IGTV10 > (IGTVCBCT or IGTVMIP) > (GTV3D or GTV4D50)]. The underestimations or overestimations between IGTV10 and IGTVCBCT were larger than those between IGTV10 and IGTVMIP (p < 0.001-0.011; p < 0.001-0.023). For upper oesophageal tumors, GTV4D50/IGTVCBCT negatively correlated with motion vector (r = -0.756, p = 0.011). In AP direction, the centroid coordinates of IGTVCBCT differed from GTV3D, GTV4D50, IGTVMIP and IGTV10 (p = 0.006, 0.013, 0.038, and 0.010). For middle oesophageal tumors, IGTV10/IGTVCBCT positively correlated with motion vector (r = 0.695, p = 0.006). The centroid coordinates of IGTVCBCT differed from those of IGTV10 (p = 0.046) in AP direction. For distal oesophageal tumors, the centroid coordinates of IGTVCBCT showed significant differences to those of IGTVMIP (p = 0.042) in LR direction. For both middle and distal tumors, the degrees of associations of IGTV10 outside IGTVCBCT significantly correlated with the motion vector (r = 0.540, p = 0.046; r = 0.678, p = 0.031). MATERIALS AND METHODS: Thirty-four oesophageal cancer patients underwent 3DCT, 4DCT and CBCT. GTV3D, GTV4D50, internal GTVMIP (IGTVMIP) and IGTVCBCT were delineated on 3DCT, 4DCT50, 4DCTMIP and CBCT. GTVs from 10 respiratory phases were combined to produce GTV10. Differences in volume, position for different targets, correlation between volume ratio and motion vector were evaluated. The motion vector was the spatial moving of the target centroid position. CONCLUSIONS: IGTVCBCT encompasses more motion information than GTV3D and GTV4D50 for upper oesophageal tumors, but slightly less than IGTV10 for middle and distal oesophageal tumors. IGTVCBCT incorporated similar motion information to IGTVMIP. However, motion information encompassed in CBCT and MIP cannot replace each other.

Upregulation and biological function of transmembrane protein 119 in osteosarcoma.

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-ß signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-ß pathway-related factors (BMP2, BMP7 and TGF-ß). TGF-ß application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-ß inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-ß/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.