Multidimensional analysis using low-dose computed tomography to evaluate the severity of Mycoplasma pneumoniae pneumonia in children.

Background: It is unclear whether local pathological pulmonary changes truly reflect the severity of childhood Mycoplasma pneumoniae infection, which is characterized by rapid progress and potential mortality. This study multi-dimensionally analyzed low-dose computed tomography findings to assess the severity of Mycoplasma pneumoniae infection and predict its progress in such patients. Methods: In all, 752 children with Mycoplasma pneumoniae pneumonia (MPP) who underwent low-dose computed tomography examinations from February 2016 to July 2020 were retrospectively enrolled to conduct a cohort study. Clinical and radiological variables were analyzed using univariate analysis, and radiological variables were further analyzed using multivariable logistic regression in severe cases. Then, the correlation between the key computed tomography features and clinical symptoms, laboratory indicators, and medical costs were assessed using the chi-squared and Kruskal-Wallis H tests. Kaplan-Meier curves and Cox regression models were created to evaluate the correlations between the key computed tomography features, fever duration, and the length of hospital stay. Results: Of the 752 included patients, 16.2% (122/752) developed severe MPP. Atelectasis, pleural effusion, and lung consolidation occurred in 9.7% (73/752), 15.8% (119/752), and 90.3% (679/752) of patients, respectively. In addition to pleural effusion, the number of lobes of lung consolidation was the highest risk feature of severe MPP. Patients with consolidation in 2, 3, and 4 lobes had a 1.0-, 3.1-, and 7.5-fold increased risk of severe MPP, compared with patients with consolidation in fewer than 1 lobe. The duration of fever prior to admission had no effect on the proportions of the lobar consolidation (P=0.14) but did have significant effect on the incidence of pleural effusion (P=0.004). Levels of inflammatory markers and medical costs rose consistently with the increase in the number of lobar consolidations (P<0.001). After adjustments for pleural effusion, 1, 2, 3, and 4 lobes of consolidation remained positively associated with fever duration [1 lobe: hazard ratio (HR) =1.55, 95% CI: 1.10-2.18; 2 lobes: HR =1.65, 95% CI: 1.13-2.42l; 3 lobes: HR =1.82, 95% CI: 1.11-2.98; 4 lobes: HR =2.87, 95% CI: 1.25-6.61] compared to 0 lobes of consolidation. Compared to 0 lobes of consolidation, 1, 2, 3, and 4 lobes of consolidation were also positively correlated with the length of hospital stay (1 lobe: HR =2.24, 95% CI: 1.73-2.89; 2 lobes: HR =2.56, 95% CI: 1.91-3.43; 3 lobes: HR =2.87, 95% CI: 1.90-4.32; 4 lobes: HR =4.12, 95% CI: 2.01-8.46). Conclusions: Lobar consolidation is a stable and reliable computed tomography feature that can be used to assess the severity of MPP in children. Quantitative analysis of lobar consolidation can comprehensively and accurately predict the progression of Mycoplasma pneumoniae. Low-dose computed tomography is recommended for children with severe MPP with complicated courses.

Effects of radiofrequency balloon angioplasty on the abdominal aorta in atherosclerotic rabbits.

OBJECTIVES: A novel temperature-controlled intravascular radiofrequency balloon angioplasty (RFBA) technique was designed and developed for atherosclerosis (AS) management. METHODS: After establishing an AS model based on a balloon denudation injury of the abdominal aorta and a high cholesterol diet in rabbits, 46 animals were randomly assigned to the RFBA group (n = 28) or the plain balloon angioplasty (PBA) group (n = 28). The groups were further subdivided based on post-treatment euthanasia times (1 hour, 7 days, 14 days, and 28 days). Histopathological changes were observed by hematoxylin and eosin and Masson's staining. Immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction were used to detect changes in pro-inflammatory, anti-inflammatory, and apoptotic factors; TGF-ß/Smad-2 pathway protein Immune levels; and mRNA levels in tissues, respectively. RESULTS: The vascular lumen area in the RFBA group was larger than that in the PBA group at the same time points, although the change in the vascular lumen area was not different between groups. The expression of Bax, TGF-ß, Smad-2, and Caspase-3 in the RFBA group was significantly higher than that in the PBA group. The expression levels of Bcl-2 in the RFBA group were significantly lower than those in the PBA group. CONCLUSIONS: At 28 days, RFBA dilated the atherosclerotic blood vessels and thickened the fibrous cap of atherosclerotic plaques to promote plaque stability. RFBA was also found to activate apoptotic factors and the TGF-/Smad-2 inflammatory pathway.

The class B heat shock factor HSFB1 regulates heat tolerance in grapevine.

Grape is a widely cultivated crop with high economic value. Most cultivars derived from mild or cooler climates may not withstand increasing heat stress. Therefore, dissecting the mechanisms of heat tolerance in grapes is of particular significance. Here, we performed comparative transcriptome analysis of Vitis davidii 'Tangwei' (heat tolerant) and Vitis vinifera 'Jingxiu' (heat sensitive) grapevines after exposure to 25°C, 40°C, or 45°C for 2 h. More differentially expressed genes (DEGs) were detected in 'Tangwei' than in 'Jingxiu' in response to heat stress, and the number of DEGs increased with increasing treatment temperatures. We identified a class B Heat Shock Factor, HSFB1, which was significantly upregulated in 'Tangwei', but not in 'Jingxiu', at high temperature. VdHSFB1 from 'Tangwei' and VvHSFB1 from 'Jingxiu' differ in only one amino acid, and both showed similar transcriptional repression activities. Overexpression and RNA interference of HSFB1 in grape indicated that HSFB1 positively regulates the heat tolerance. Moreover, the heat tolerance of HSFB1-overexpressing plants was positively correlated to HSFB1 expression level. The activity of the VdHSFB1 promoter is higher than that of VvHSFB1 under both normal and high temperatures. Promoter analysis showed that more TATA-box and AT~TATA-box cis-elements are present in the VdHSFB1 promoter than the VvHSFB1 promoter. The promoter sequence variations between VdHSFB1 and VvHSFB1 likely determine the HSFB1 expression levels that influence heat tolerance of the two grape germplasms with contrasting thermotolerance. Collectively, we validated the role of HSFB1 in heat tolerance, and the knowledge gained will advance our ability to breed heat-tolerant grape cultivars.

Have residents adapted to heat wave and cold spell in the 21st century? Evidence from 136 Chinese cities.

Global climate change has increased the probability and intensity of extreme weather events. The adverse health effect of extreme temperature has gone through a temporal variation over years. Time-series data including city-level daily cardiovascular death records and meteorological data were collected from 136 Chinese cities during 2006 and 2019. A time-varying distributed lag model with interaction terms was applied to assess the temporal change of mortality risk and attributable mortality of heat wave and cold spell. The mortality effect of heat wave generally increased and that of cold spell decreased significantly in the total population during the study period. The heat wave effect increased especially among the female and people aged 65 to 74. As for the cold spell, the reduced susceptibility was detected both in the temperate and cold climatic zone. Our findings appeal for counterpart measures corresponding to sub-populations and regions responding to future extreme climate events from the public and individuals.

The pattern of alternative splicing and DNA methylation alteration and their interaction in linseed (Linum usitatissimum L.) response to repeated drought stresses.

BACKGROUND: Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. RESULTS: We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. CONCLUSION: Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.

Integrated whole transcriptome analysis for the crucial regulators and functional pathways related to cardiac fibrosis in rats.

BACKGROUND: Cardiac fibrosis has gradually gained significance in the field of cardiovascular disease; however, its specific pathogenesis remains unclear. This study aims to establish the regulatory networks based on whole-transcriptome RNA sequencing analyses and reveal the underlying mechanisms of cardiac fibrosis. METHODS: An experimental model of myocardial fibrosis was induced using the chronic intermittent hypoxia (CIH) method. Expression profiles of long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) were acquired from right atrial tissue samples of rats. Differentially expressed RNAs (DERs) were identified, and functional enrichment analysis was performed. Moreover, a protein-protein interaction (PPI) network and competitive endogenous RNA (ceRNA) regulatory network that are related to cardiac fibrosis were constructed, and the relevant regulatory factors and functional pathways were identified. Finally, the crucial regulators were validated using qRT-PCR. RESULTS: DERs, including 268 lncRNAs, 20 miRNAs, and 436 mRNAs, were screened. Further, 18 relevant biological processes, such as "chromosome segregation, " and 6 KEGG signaling pathways, such as "cell cycle, " were significantly enriched. The regulatory relationship of miRNA-mRNA-KEGG pathways showed eight overlapping disease pathways, including "pathways in cancer." In addition, crucial regulatory factors, such as Arnt2, WNT2B, GNG7, LOC100909750, Cyp1a1, E2F1, BIRC5, and LPAR4, were identified and verified to be closely related to cardiac fibrosis. CONCLUSION: This study identified the crucial regulators and related functional pathways in cardiac fibrosis by integrating the whole transcriptome analysis in rats, which might provide novel insights into the pathogenesis of cardiac fibrosis.

AI-powered drone-based automated inspection of FAST.

Automated optical inspection of FAST is realized by exploiting advances in drone technology and deep-learning techniques. The AI-powered drone-based automated inspection is time-efficient and reliable, which guarantees the stable operation of FAST.

Sintilimab plus Lenvatinib conversion therapy for intermediate/locally advanced hepatocellular carcinoma: A phase 2 study.

Introduction: Patients with intermediate or locally advanced hepatocellular carcinoma (HCC) who are not eligible for radical treatment typically have a poor overall prognosis. Treatment strategies that can convert unresectable HCC into resectable HCC may improve patient survival. We conducted a single arm phase 2 trial to evaluate the efficacy and safety of Sintilimab plus Lenvatinib as conversion therapy for HCC. Methods: A single-arm, single-center study conducted in China (NCT04042805). Adults (≥18 years) with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC ineligible for radical surgery with no distant/lymph node metastasis received Sintilimab 200 mg IV on day 1 of a 21-day cycle plus Lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) orally once daily. Resectability was based on imaging and liver function. The primary endpoint was objective response rate (ORR), assessed using RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), event-free survival (EFS) in patients who underwent resection, surgical conversion rate, and safety. Results: Overall, 36 patients were treated between August 1, 2018, and November 25, 2021; the median age was 58 years (range, 30-79), and 86% were male. The ORR (RECIST v1.1) was 36.1% (95% CI, 20.4-51.8) and the DCR was 94.4% (95% CI, 86.9-99.9). Eleven patients underwent radical surgery and one received radiofrequency ablation and stereotactic body radiotherapy; after a median follow up of 15.9 months, all 12 were alive and four had recurrence, median EFS was not reached. Median PFS among 24 patients who did not undergo surgery was 14.3 months (95% CI, 6.3-26.5). Treatment was generally well tolerated; two patients had serious adverse events; there were no treatment-related deaths. Conclusions: Sintilimab plus Lenvatinib is safe and feasible for the conversion treatment of intermediate to locally advanced HCC initially unsuitable for surgical resection.

Promotion of healthy adipose tissue remodeling ameliorates muscle inflammation in a mouse model of sarcopenic obesity.

A large subset of elders is classified as having sarcopenic obesity, a prevalence of obesity in combination with sarcopenia which places an aging population at the risk of adverse health consequences from both conditions. However, its complex etiology has restrained the development of effective therapeutic strategies. Recent progress has highlighted that the mode by which adipose tissue (AT) remodels is a determinant of metabolic health in the context of obesity. Healthy AT remodeling confers metabolic protection including insulin-sensitizing and anti-inflammatory effects to non-adipose tissues including skeletal muscle. Here, we employed a doxycycline-inducible adipocyte Hif1a knockout system to evaluate the muscle-protective effects associated with HIF1α inactivation-induced healthy AT remodeling in a model of sarcopenic obesity. We found that adipocyte HIF1α inactivation leads to improved AT metabolic health, reduced serum levels of lipids and pro-inflammatory cytokines, and increase of circulating adipokine (APN) in ovariectomized obese mice fed with obesogenic high-fat diet (HFD). Concomitantly, muscle inflammation is evidently lower in obese OVX mice when adipocyte HIF1α is inactivated. Furthermore, these protective effects against muscle inflammation can be mimicked by the administration of adiponectin receptor agonist AdipoRon. Collectively, our findings underscore the importance of AT metabolic health in the context of concurrent sarcopenia and obesity, and promotion of healthy AT remodeling may represent a new therapeutic strategy to improve muscle health in sarcopenic obesity.

Loss of life expectancy due to stroke and its subtypes in urban and rural areas in China, 2005-2020.

Stroke is characterised by high mortality and disability rate in China. This study aimed to explore the temporal trends in years of life lost (YLL) and loss of life expectancy due to stroke and its subtypes in urban and rural areas in China during 2005-2020. Data were obtained from China National Mortality Surveillance System. Abbreviated life and stroke-eliminated life tables were generated to calculate loss of life expectancy. The YLL and loss of life expectancy due to stroke in urban and rural areas at both national and provincial level during 2005-2020 were estimated. In China, the age-standardised YLL rate due to stroke and its subtypes were higher in rural areas than in urban areas. The YLL rate due to stroke showed a downward trend in both urban and rural residents from 2005 to 2020, decreased by 39.9% and 21.5%, respectively. Loss of life expectancy caused by stroke decreased from 1.75 years to 1.70 years from 2005 to 2020. During which, loss of life expectancy due to intracerebral haemorrhage (ICH) decreased from 0.94 years to 0.65 years, while that of ischaemic stroke (IS) increased from 0.62 years to 0.86 years. A slightly upward trend was observed in loss of life expectancy caused by subarachnoid haemorrhage (SAH), from 0.05 years to 0.06 years. Loss of life expectancy due to ICH and SAH was always higher in rural areas than in urban areas, whereas that of IS was higher in urban areas than in rural areas. Rural males suffered the greatest loss of life expectancy due to ICH and SAH, while the highest loss of life expectancy caused by IS was found in urban females. Furthermore, Heilongjiang (2.25 years), Tibet (2.17 years) and Jilin (2.16 years) were found to have the highest loss of life expectancy caused by stroke in 2020. Loss of life expectancy caused by ICH and SAH was higher in western China, while the disease burden of IS was heavier in northeast China. Stroke remains a major public health problem in China, although the age-standardised YLL rate and loss of life expectancy due to stroke decreased. Evidence-based strategies should be conducted to reduce the premature death burden caused by stroke and prolong life expectancy in Chinese population.

Analysis of factors that influence the occurrence of otitis media with effusion in pediatric patients with adenoid hypertrophy.

Objective: Adenoid hypertrophy (AH) and otitis media with effusion (OME) are common pediatric otolaryngological diseases and often occur concurrently. The purpose of this study was to comprehensively analyze the factors that influence the occurrence of OME pediatric patients with AH. Methods: Patients younger than 12 years with AH, who were hospitalized for treatment at Beijing Tsinghua Changgung Hospital in Beijing, China, between March 2018 and February 2022 were enrolled. The patients were divided into an AH group and an AH + OME group based on the presence of OME. The authors collected the following clinical data for univariable analysis: sex; age; body mass index (BMI); comorbid nasal congestion/rhinorrhea, recurrent tonsillitis, or allergic rhinitis (AR); adenoid and tonsil grade; tonsillar hypertrophy; food/drug allergy; history of adenoidectomy and congenital diseases; breastfeeding status; preterm birth; exposure to environmental tobacco smoke (ETS); family history of adenotonsillectomy, otitis media, and AR; main data of polysomnography and oropharyngeal conditional pathogen culture data of some patients. Univariate analysis was performed as a basis for logistic regression analysis. Results: A total of 511 children (329 boys and 182 girls) were included, their mean age was 5.37 ± 2.10 years. Of them, 407 (79.6%) were in the AH group and 104 (20.4%) in the AH + OME group. Univariate analysis revealed statistically significant differences in age, BMI, adenoid grade, AR, breastfeeding status, and ETS exposure between the two groups. Multivariate stepwise logistic regression analysis showed that age, adenoid grade, AR, breastfeeding status, and ETS influenced the occurrence of OME in pediatric patients with AH. The risk of OME decreased with increasing age. High adenoid grade, ETS exposure, and comorbid AR were risk factors for OME in pediatric patients with AH, but breastfeeding was a protective factor. The final analytical results of the oropharyngeal conditional pathogen culture data showed that Streptococcus pneumoniae positivity was associated with OME in AH. Conclusion: The pathogenesis of AH with OME is complex. Young age, high adenoid grade, ETS exposure, non-breastfed status, comorbid AR, and the presence of S. pneumoniae in the oropharynx are risk factors for OME in pediatric patients with AH.

Controlled Deformation of Soft Nanogel Particles Generates Artificial Biominerals with Ordered Internal Structure.

Biominerals can exhibit exceptional mechanical properties owing to their hierarchically-ordered organic/inorganic nanocomposite structure. However, synthetic routes to oriented artificial biominerals of comparable complexity remain a formidable technical challenge. Herein we design a series of soft, deformable nanogels that are employed as particulate additives to prepare nanogel@calcite nanocomposite crystals. Remarkably, such nanogels undergo a significant morphological change-from spherical to pseudo-hemispherical-depending on their degree of cross-linking. Such deformation occurs normal to the direction of growth of the (104) face of the calcite and the underlying occlusion mechanism is revealed by in situ atomic force microscopy studies. This model system provides new mechanistic insights regarding the formation of oriented structures during biomineralization and offers new avenues for the design of synthetic nanocomposites comprising aligned anisotropic nanoparticles.

DNA barcoding of Chinese snakes reveals hidden diversity and conservation needs.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1,638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbor distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 Operational Taxonomic Units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most likely caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes.

MiRNA and Potential Prognostic Value in Non-Smoking Females with Lung Adenocarcinoma by High-Throughput Sequencing.

Background: Non-smoking females with lung adenocarcinoma (LUAD) account for a unique disease entity and miRNA play critical roles in cancer development and progression. The purpose of this study is to explore prognosis-related differentially expressed miRNA (DEmiRNA) and establish a prognostic model for non-smoking females with LUAD. Methods: Eight specimens were collected from thoracic surgery of non-smoking females with LUAD and implemented the miRNA sequencing. The intersection of our miRNA sequencing data and TCGA database were identified as common DEmiRNA. Then, we predicted the target genes of the common DEmiRNAs (DETGs) and explored the functional enrichment and prognosis of DETGs. A risk model by overall survival (OS)-related DEmiRNA was constructed based on multivariate Cox regression analyses. Results: A total of 34 overlapping DEmiRNA were obtained. The DETGs were enriched in pathways including "Cell cycle" and "miRNAs in cancer". The DETGs (KPNA2, CEP55, TRIP13, MYBL2) were risk factors, significantly related to OS, progression-free survival (PFS), and were also hub genes. ScRNA-seq data also validated the expression of the four DETGs. Hsa-mir-200a, hsa-mir-21, and hsa-mir-584 were significantly associated with OS. The prognostic prediction model constructed by the 3 DEmiRNA could effectively predict OS and can be used as an independent prognostic factor of non-smoking females with LUAD. Conclusion: Hsa-mir-200a, hsa-mir-21, and hsa-mir-584 can serve as potential prognostic predictors in non-smoking females with LUAD. A novel prognostic model based on the three DEmiRNAs was also constructed to predict the survival of non-smoking females with LUAD and showed good performance. The result of our paper can be helpful for treatment and prognosis prediction for non-smoking females with LUAD.

Health Behaviours among Travellers Regarding Risk Compensation Following COVID-19 Vaccination in Taizhou, China.

Background: During the COVID-19 pandemic, public transport was restricted in many countries because of the transmission risk. According to the risk compensation theory, travellers post-COVID-19 vaccination may encounter higher risks; however, no real-world studies provide such evidence. Therefore, we conducted a survey to assess whether risk compensation would occur among travellers' health-related behaviours after COVID-19 vaccination, potentially aggravating the transmission of the virus. Materials and Methods: A self-administered online survey was designed and distributed over WeChat to identify the difference in health behaviours before and after COVID-19 vaccination among travellers at a train station in Taizhou, China, from 13 February to 26 April 2022. Results: A total of 602 individuals completed the questionnaire. The results revealed no statistical difference between the health behaviours reported by the vaccinated and unvaccinated groups. Participants who received the first dose of the vaccine earlier showed no statistical difference in harmful health behaviours (hand washing frequency decreased by 4.1% (P=0.145) and the duration of public transport travel increased by 3.4% (P=0.437)), but showed better protective health behaviours (mask-wearing duration increased by 24.7% (P=0.014)). Compared to those vaccinated less than three times, participants vaccinated against COVID-19 three times showed no statistical differences in harmful health behaviours mask-wearing duration decreased by 7.0% (P=0.927), their hand washing frequency decreased by 4.8% (P=0.905), and the duration of public transport travel increased by 2.5% (P=0.287). After vaccination, when compared to themselves before vaccination, participants exhibited better health behaviours (increased hand washing frequency and mask-wearing duration, and decreased duration of public transport travel) to some extent. Conclusion: In conclusion, this study found no evidence of risk compensation among travellers. After being vaccinated, health behaviours partly improved among travellers.

Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.

BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. STUDY TYPE: Retrospective. SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days). FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database.

Objective To screen for antigen targets for immunotherapy by analyzing over-expressed genes and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis and PPI network and survival analysis based on the Gene Expression Omnibus (GEO) database. Methods By screening with highly expressed genes, we analyzed two proteins with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis and PPI network and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation. Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1, and ZBTB7C were screened with significant P value of survival curve. Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1, and ZBTB7C may play important roles in the development of esophageal cancer.

Five-year survival post hepatectomy for colorectal liver metastases in a real-world Chinese cohort: Recurrence patterns and prediction for potential cure.

BACKGROUND: Patients with a 5-year recurrence-free survival post liver resection for colorectal cancer liver metastases (CRLM) are considered to be potentially cured. However, there is a deficit of data on long-term follow-up and the recurrence status among these patients in the Chinese population. We analyzed real-world follow-up data of patients with CRLM who underwent hepatectomy, explored the recurrence patterns, and established a prediction model for a potential cure scenario. METHODS: Patients who underwent radical hepatic resection for CRLM during 2000-2016, with actual follow-up data for at least 5 years, were enrolled. The observed survival rate was calculated and compared among the groups with different recurrence patterns. The predictive factors for 5-year non-recurrence were determined using logistic regression analysis; a recurrence-free survival model was developed to predict long-term survival. RESULTS: A total of 433 patients were included, of whom 113 patients were found non-recurrence after 5 years follow-up, with a potential cure rate of 26.1%. Patients with late recurrence (>5 months) and lung relapse showed significantly superior survival. Repeated localized treatment significantly improved the long-term survival of patients with intrahepatic or extrahepatic recurrences. Multivariate analysis showed that RAS wild-type CRC, preoperative CEA <10 ng/ml, and liver metastases ≤3 were independent factors for a 5-year disease-free recurrence. A cure model was developed based on the above factors, achieving good performance in predicting long-term survival. CONCLUSIONS: About one quarter patients with CRLM could achieve potential cure with non-recurrence at 5-year after surgery. The recurrence-free cure model could well distinguish the long-term survival, which would aid clinicians in determining the treatment strategy.

Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response.

Background: Radiodynamic therapy (RDT) is an emerging novel anti-cancer treatment based on the generation of cytotoxic reactive oxygen species (ROS) at the lesion site following the interaction between low-dose X-ray and a photosensitizer (PS) drug. For a classical RDT, scintillator nanomaterials loaded with traditional PSs are generally involved to generate singlet oxygen (1O2). However, this scintillator-mediated strategy generally suffers from insufficient energy transfer efficiency and the hypoxic tumor microenvironment, and finally severely impedes the efficacy of RDT. Methods: Gold nanoclusters were irradiated by low dose of X-ray (called RDT) to investigate the production of ROS, killing efficiency of cell level and living body level, antitumor immune mechanism and biosafety. Results: A novel dihydrolipoic acid coated gold nanoclusters (AuNC@DHLA) RDT, without additional scintillator or photosensitizer assisted, has been developed. In contrast to scintillator-mediated strategy, AuNC@DHLA can directly absorb the X-ray and exhibit excellent radiodynamic performance. More importantly, the radiodynamic mechanism of AuNC@DHLA involves electron-transfer mode resulting in O2 -• and HO•, and excess ROS has been generated even under hypoxic conditions. Highly efficient in vivo treatment of solid tumors had been achieved via only single drug administration and low-dose X-ray radiation. Interestingly, enhanced antitumor immune response was involved, which could be effective against tumor recurrence or metastasis. Negligible systemic toxicity was also observed as a consequence of the ultra-small size of AuNC@DHLA and rapid clearance from body after effective treatment. Conclusions: Highly efficient in vivo treatment of solid tumors had been achieved, enhanced antitumor immune response and negligible systemic toxicity were observed. Our developed strategy will further promote the cancer therapeutic efficiency under low dose X-ray radiation and hypoxic conditions, and bring hope for clinical cancer treatment.