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Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher’s exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.

Tumor heterogeneity in breast cancer hinders proper diagnosis and treatment, and the identification of molecular subtypes may help enhance the understanding of its heterogeneity. Therefore, we proposed a novel integrated multi-omics approach for breast cancer typing, which led to the identification of a hybrid subtype (Mix_Sub subtype) with a poor survival prognosis. This subtype is characterized by lower levels of the inflammatory response, lower tumor malignancy, lower immune cell infiltration, and higher T-cell dysfunction. Moreover, we found that cell-cell communication mediated by NCAM1-FGFR1 ligand-receptor interaction and cellular functional states, such as cell cycle, DNA damage, and DNA repair, were significantly altered and upregulated in patients with this subtype, and that such patients displayed greater sensitivity to targeted therapies. Subsequently, using differential genes among subtypes as biomarkers, we constructed prognostic risk models and subtype classifiers for the Mix_Sub subtype and validated their generalization ability in external datasets obtained from the GEO database, indicating their potential therapeutic and prognostic significance. These biomarkers also showed significant spatially variable expression in malignant tumor cells. Collectively, the identification of the Mix_Sub breast cancer subtype and its biomarkers, based on the driving relationship between omics, has deepened our understanding of breast cancer heterogeneity and facilitated the development of breast cancer precision therapy.

To investigate the different imaging features of contrast-enhanced multidetector-row-computed tomography (MDCT) for distinguishing between silicosis and tuberculosis involving the mediastinal lymph nodes.86 silicosis patients and 61 tuberculosis patients with mediastinal lymphadenopathy based on contrast-enhanced MDCT were included. The enhanced patterns, anatomical distribution and calcification features of the enlarged lymph nodes were retrospectively compared between the groups using the Pearson chi-square test or Fisher's exact test.Homogeneous enhancement of the mediastinal lymph nodes was more commonly observed in silicosis (94.2%, 81/86) than in tuberculosis (19.7%, 12/61). Peripheral enhancement was more frequent in tuberculosis (n = 44, 72.1%) than in silicosis involving the mediastinal lymph nodes (n = 1, 1.2%), and multilocular appearance was more frequent in TB than in silicosis. Tuberculosis was more likely to affect regions 1R, 2R, 2L, 3A, 5 and 6 than silicosis (all p 0.05), especially region 2R. Calcification of the lymph nodes was more common in the silicosis group than in tuberculosis group. The sensitivity, specificity, and accuracy of silicosis with lymphadenopathy with homogeneous enhanced pattern were 94.2%, 80.3% and 88.4%, respectively. The sensitivity, specificity, and accuracy of tuberculosis lymphadenopathy with peripheral enhanced pattern were 72.1%, 98.8%, and 87.7%, respectively.The predominant enhanced patterns, anatomical distribution, and calcification features of mediastinal lymph nodes were different between tuberculosis and silicosis. These radiographic features might help differentiate tuberculosis from silicosis, which provides imaging information for the differential diagnosis of the two diseases in a clinical setting.

Dysregulation of signaling pathways plays an essential role in cancer. However, there is not a comprehensive understanding on how oncogenic signaling pathways affect the occurrence and development with a common molecular mechanism of pan-cancer. Here, we investigated the oncogenic signaling pathway dysregulation by using multi-omics data on patients from TCGA from a pan-cancer perspective to identify commonalities across different cancer types. First, the pathway dysregulation profile was constructed by integrating typical oncogenic signaling pathways and the gene expression of TCGA samples, and four molecular subtypes with significant phenotypic and clinical differences induced by different oncogenic signaling pathways were identified: TGF-β+ subtype; cell cycle, MYC, and NF2− subtype; cell cycle and TP53+ subtype; and TGF-β and TP53− subtype. Patients in the TGF-β+ subtype have the best prognosis; meanwhile, the TGF-β+ subtype is associated with hypomethylation. Moreover, there is a higher level of immune cell infiltration but a slightly worse survival prognosis in the cell cycle, MYC, and NF2− subtype patients due to the effect of T-cell dysfunction. Then, the prognosis and subtype classifiers constructed by differential genes on a multi-omics level show great performance, indicating that these genes can be considered as biomarkers with potential therapeutic and prognostic significance for cancers. In summary, our study identified four oncogenic signaling pathway–driven patterns presented as molecular subtypes and their related potential prognostic biomarkers by integrating multiple omics data. Our discovery provides a perspective for understanding the role of oncogenic signaling pathways in pan-cancer.

Mitral regurgitation (MR) is a comorbidity of myocardial infarction (MI), which may promote the incidence of adverse cardiovascular clinical events. However, it is not yet completely understood how MR in MI patients is associated with impaired myocardial deformation.To determine the damaging myocardium effects of MR in MI patients in terms of the global peak strain (PS) and left ventricular (LV) function, and evaluate the independent risk factors impacting LV deformation after MI.Retrospective.One hundred eighty-six MI patients (17.7% female) and 84 normal control subjects (27.4% female).3.0T; late gadolinium enhancement sequence, balanced steady-state free precession.LV function and LV global PS (global radial peak strain [GRPS]; global circumferential peak strain [GCPS]; and global longitudinal peak strain [GLPS]) were compared among normal controls, MI without MR (MR-) and MI with MR (MR+, mild, moderate, severe) patients.One-way analysis of variance (ANOVA) test, Mann-Whitney U test, Kruskal-Wallis test, and multiple linear regressions were used. A P value0.05 indicated statistically significant difference (two-tailed).The MI (MR+) patients showed significantly lower LV global PS than both MI (MR-) and control groups in three directions (GRPS 16.66 ± 7.43%; GCPS -11.27 ± 4.27%; GLPS -7.75 ± 3.44%), and significantly higher LV end-systolic (128.85 [87.91, 188.01] mL) and end-diastolic volumes (210.29 [164.07, 264.00] mL) and significantly lower LV ejection fraction (38.23 ± 13.02%). Multiple regression analysis demonstrated that MR was independently associated with LV GCPS (β = -0.268) and GLPS (β = -0.320). LV infarct size was an independent indicator of LV GRPS (β = -0.215) and GCPS (β = -0.222). LV end-diastolic volume was an independent indicator of LV GRPS (β = -0.518), GCPS (β = -0.503), and GLPS (β = -0.331).MR may further exacerbate the reduction of LV global peak strains and function. The MR, infarct size, and LV end-diastolic volume can be used as independent association indicators for LV global PS in MI (MR+) patients.4 Technical Efficacy Stage: 2 TOC Category: Chest.

Background Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluate myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of myocardial scar on left ventricular (LV) deformation. Methods Overall, 202 T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI−)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), were compared among these groups. Correlation and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation. Results Decreases were observed in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Reduced LV deformation (p p p p 2 = 0.37) and circumferential PS (β = 0.339 and β = 0.530, respectively, all p 2 = 0.41), LV anterior wall infarction was independently associated with LV global longitudinal PS (β = 0.398, p = 0.006). Conclusions The myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, particularly in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened.

Objectives More than 50% of congenital hearing loss is attributed to genetic factors. Data of gene mutation associated with hearing loss from large population studies in Chinese population are scarce. In this study, we conducted a comprehensive newborn genetic screening in China to establish the carrier frequency and mutation spectrum of deafness-associated genes. Methods A total of 53,033 newborns were screened for hearing defects associated mutations. Twenty hot spot mutations in GJB2, GJB3, SLC26A4 and mitochondria12S rRNA were examined using suspension array analysis. Results 14,185 newborns (26.75%) were identified with at least one mutated allele. 872 (1.64%) neonates carried homozygous mutations including 112 (0.21%) mitochondrial DNA homoplasmy, 228 (0.43%) were compound heterozygotes, and 11,985 (22.59%) were heterozygotes including 11 (0.02%) mitochondrial DNA heteroplasmy. Top five mutations included 109 G > A, 235 delC, 299–300 delAT in GJB2, IVS7-2 A > G in SLC26A4 and 1555 A > G in mitochondria12S rRNA. Notably, a total of 10,995 neonates (20.73%) carried 109 G > A in GJB2. Moreover, the allele frequencies of 109 G > A were detected 11.61% in Guangdong, 10.44% in Sichuan and 2.88% in Shandong, respectively, a significant difference in prevalence among these geographic regions (p A in GJB2 was confirmed by a TaqMan probe-based qPCR assay. Very recently, the ClinGen Hearing Loss Expert Panel reached a consensus and confirmed its pathogenic role in hearing impairment. Conclusion We delineated the mutation profile of common deafness-causing genes in the Chinese population and highlighted the high prevalence of 109 G > A pathogenic mutation. Our study may facilitate early diagnosis/intervention and genetic counseling for hearing impairment in clinical practice.

Objective To investigate the clinical value of multi-slice spiral CT(MSCT) in the diagnosis of mild digestive tract hemorrhage. Methods Thirty-five patients with mild gastrointestinal hemorrhage were examined by enhanced MSCT.CT signs were observed and compared with pathologic examination findings.Results Diseases in these 35 patients included gastric and duodenal ulcer and inflammation(n=4,11.4%),esophagogastric variceal rupture(n=7,20.0%),gastric carcinoma(n=3,8.6%),gastric stromal tumor(n=3,8.6%),gastric polyp(n=1,2.9%),colonic malignancy(n=5,14.2%),small intestinal stromal tumor(n=6,17.1%),rectal cancer(n=2,5.7%),intestinal Crohn disease(n=3,8.6%),and jejunum diverticulum combined with hemorrhage(n=1,2.9%).All of them were diagnosed by endoscopy of the digestive tract and confirmed by operation and pathology.The accuracy rate of CT was 100%.The coincidence rate of CT diagnosis was 97.1%.Conclusion MSCT is a promising technique in the localization,qualitative diagnosis,and clinical treatment of mild gastrointestinal hemorrhage.

Urinary crystals in normal and kidney stone patients often contain a larger proportion of micron/nano calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals. However, the effect of their varying sizes and crystal phases in inducing the formation of kidney stones remains unclear. This study aims to comparatively investigate the cytotoxicity and aggregation capabilities of micron/nano COM and COD in vitro to reveal the mechanism of kidney stone formation. The effects of the exposure of African green monkey renal epithelial (Vero) cells to 50 nm (COM-50 nm and COD-50 nm) and 10 μm (COM-10 μm and COD-10 μm) calcium oxalate crystals were investigated by determining cell viability, cell membrane integrity, cell morphology change, adhesion and internalization, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), cell cycle progression, and cell death rate by apoptosis and/or necrosis. The cell viability and cytomembrane integrity of Vero cells were significantly decreased, in size- and concentration-dependent manners, after the treatment with micron/nano COM and COD crystals. Cell injury increased with the reduction in crystal size and increase in crystal concentration; COM caused a more serious injury in Vero than COD of the same size. COM-10 μm and COD-10 μm caused mild injury in Vero cells because they could only adhere on the cell surface and could not be completely internalized into cells. Meanwhile, the adhered COM-50 nm and COD-50 nm were internalized into cells, caused severe injury, and the effects were more concentration-dependent. Excessive expression of ROS led to a decrease in Δψm and cell cycle dysregulation; a series of cell responses ultimately caused a significant number of necrotic cell deaths and few apoptotic cell deaths. Micron-sized COM and COD crystals induced cell injury by damaging the membrane integrity. Nano-COM and COD crystals could damage membrane integrity by adhering to the cell surface, as well as directly damage the mitochondria via internalized crystals. Thus, nano-sized crystals possess greater toxicity than micron-sized crystals.

The effects of potassium citrate (K3cit) on sedimentation and aggregation of 50 nm calcium oxalate dihydrate (COD) crystals was studied in order to explore the mechanism of formation and inhibition of kidney stone. In four different systems, including pure water, urine of healthy person and CaOx stone former before and after taking medicine K3cit, the influences of K3cit on average size (), Zeta potential and optical density of nanoCOD suspensions were studied by nanoparticle size Zeta potential analyzer and ultraviolet spectrophotometer. It was showed that K3cit could specifically adsorb on nanoCOD crystals, and also competed with the inhibitor molecules in urine. Due to the decrease of inhibitors in urine of patients, K3cit can be better to fulfill its inhibitory effect, leading to the largest reduced values of the diameter of COD crystal and the optical density of urine suspension. In conclusion, the inhibitory effect of K3cit on aggregation and sedimentation of calcium oxalate crystals is better in urine of patients, whereas the inhibitory effect has been reduced in urine of control group and patients after taking k3cit.

The property difference of urine crystallites with different sizes in the urines of calcium oxalate (CaOx) calculi patients and healthy controls was comparatively investigated. Nanoparticle size analyzer was used to study the mobility of urine crystallites. Fast Fourier transformation (FFT) and and energy dispersive X-ray spectroscopy (EDS) was performed to detect the components of urinary crystallites. The specific surface area (Sg) of nanoscale urinary crystallites is greater than that of micron-grade urinary crystals. The mobility of the controls was more negative than that of the calculi patients. The effect of particle size on mobility was greater than that of the charges on surface of the particles. The amount of small-sized urine crystallites in the healthy subjects was significantly higher than that of the patients. However, the number of large micron-scale crystals in the controls was reduced remarkably. These results showed that the formation of CaOx calculi was closely related to the presence of UA and calcium phosphate crystallites in urine. The urinary system of calculi patients is unstable and very susceptible to urine crystallite aggregation.

Objectives: The effects of sodium citrate (Na3cit) on sedimentation and aggregation of calcium oxalate dihydrate (COD) nanocrystallites with a size of about 50 nm was studied in order to explore the mechanism of Na3cit to inhibit calcium oxalate stone formation. Methods: The influence of concentration of Na3cit (c(Na3cit)) on size, Zeta potential, aggregation, and sedimentation of COD nanoparticles in aqueous solution was studied using nanoparticle size Zeta potential analyzer and ultraviolet spectrophotometer. Results: In lowc(Na3cit) (< 0.8 mmol/L), the inhibition effect of Na3cit on aggregation and sedimentation of nanoCOD increased with the increase ofc(Na3cit); while in highc(Na3cit), COD was gradually dissolved by Na3cit. The former was due to the specific adsorption of citrate ions (cit3-) on COD surface, which made the absolute Zeta-potential increased, therefore inhibited the aggregation and sedimentation of nanocrystallites; the later was because the high concentration of cit3-made Ca2+ions dissociated from the crystal surface, leading to COD dissolution. Conclusions: Na3cit can inhibit the aggregation and sedimentation of nanoCOD in low concentration and dissolve COD in high concentration, indicating that Na3cit can inhibit the formation of calcium oxalate stones.

High-resolution transmission electron microscopy, X-ray diffraction, selected area electron diffraction (SAED), and energy dispersive spectroscopy (EDS) were accurately performed to analyze the components of nanocrystals in the urine of patients with calcium oxalate (CaOx) stones. XRD, SAED and FFT detected the presence of calcium oxalate monohydrate (COM), uric acid (UA), and calcium phosphate (CaP). EDS detected the elements of C, O, Ca, with a small amount of N and P. These results showed that the main components of urinary nanocrystals were COM, with a small amount UA and phosphate. HRTEM observation showed that the particle size of urinary nanocrystals was dozens of nanometers. The result was consistent with the calculation by Debye-Scherrer equation. When the urine was filtered through a microporous membrane of 0.45, 1.2, and 3 μm, respectively, the number of diffraction peaks of the obtained urine crystallites increased with the increased pore size, indicating the increase of urinary crystallite species. Crystal nucleation, growth, aggregation, and adhesion of crystals to the renal epithelial cells are important processes for CaOx stone formation. The presence of a large amount of COM crystals in patients' urine is a critical factor for CaOx stones formation. Nano UA and CaP crystallite can induce the CaOx stone formation as central nidus.

Purpose) To study the component change of urine crystallites with different sizes in the urines of calcium oxalate (CaOx) calculi patients and healthy controls with placement time. (Methods) A combination of high-resolution transmission electron microscopy (HRTEM), fast Fourier transformation (FFT), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) was performed to detect the component of urinary crystallites. Different sizes of urine crystallites were obtained after filtration of urine through microporous membrane with different pore sizes (0.22, 0.45, 1.2, 3, and 8 μm). (Results) The main components of urine crystallites in patients with CaOx calculi are calcium oxalate monohydrate (COM), uric acid, and calcium phosphate. As the placement time increases, the deposition quality of crystallites increased. TEM analysis showed that the amount of small-sized urine crystallites (approximately 100 nm) in the healthy subjects was significantly higher than that of the patients. However, the number of large micron-scale crystals in the controls was reduced remarkably. (Conclusion) The rapid aggregation of urine crystallites may be an important factor affecting the growth of crystallites in CaOx calculi patients. The increase of COM in patient's urine was crucial factors affecting the formation of uroliths.

Intelligent information twenty-first Century needs a great number of electric information engineers and technical personnel with engineering practice and innovation ability. On the basis of CDIO, PBL and accreditation of engineering education theory, the training target is determined according to the information age talent demand. To change the teaching idea as the foundation, construct the teaching system for content, reform the teaching methods, means of engineering experiment as an example, exploration and research theme clues are carried out. After 3 years practice, from the aspects of training objectives, theoretical foundation, teaching contents and methods to implement the integration of personnel training, to achieve the goal of cultivating engineering talents, the dilemma of difficult employment and talent shortage is effectively solved and good results were obtained.

The three-phase inverter with the conventional space-vector pulse width modulation (SVPWM) algorithm has fast dynamic response, but the complex coordinate transformations, trigonometric function calculations, and sector number identification should be performed. In this paper, the relationship between SVPWM and three-phase carrier-based PWM is comprehensively analyzed. A zero-vector distribution variable k1, which changes from zero to one, is introduced, and the influence of k1 on characteristics of the PWM is investigated. The continuous SVPWM is generated when 0

Static synchronous compensator (STATCOM) is a flexible ac transmission system (FACTS) device for generating or absorbing reactive power. In this paper, the general mathematical model for the multi-pulse three-level STATCOM which consists of m three-phase three-level dc-ac converters connected together through a interphase transformer is proposed by use of the switching function concept. With the assumption of constant dc-link voltage, the harmonic voltage amplitude expressions of three types of the STATCOM under the fundamental frequency modulation (FFM) control are presented and employed to analyze the output voltage harmonic characteristics of the STATCOM. Furthermore, the developed model is implemented and the STATCOM output voltage harmonic spectra are simulated with the help of Matlab/Simulink. Meanwhile, taking the dual three-point STATCOM (m=2) for example, the steady-state and dynamic performance of the STATCOM are investigated by the digital simulation method. Both analytical and simulation results show the STATCOM can compensate the reactive power needed by load effectively and increase the power system stability quickly, and the proposed model is feasible and will be helpful to the design and development of the power electronic system with high voltage and large capacity.