Nanomechanical-based classification of prostate tumor using atomic force microscopy.

BACKGROUND: The loss of mechanical homeostasis between tumor cells and microenvironment is an important factor in tumor metastasis. In the process, mechanical forces affect cell proliferation, differentiation, migration and tissue development. AIMS: Using high spatial resolution of Atomic force microscopy (AFM) technology, our study provides the direct measurement of the nanomechanical properties of prostate cancer clinical tissue specimens. MATERIALS AND METHODS: AFM was used to determine the biomechanical properties of prostate tissue with different grade scores. K-means clustering method and fuzzy C-means were used to distinguish the cellular component in prostate tissue from non-cellular component based on their viscoelasticity. Futhermore, AFM measurements in vitro cells, including metastatic prostate cells (PC-3) and normal human prostate cells (PZ-HPV-7) were carried out. RESULTS: The Young's modulus was decreased in prostate cancer progression, and the elasticity of cellular component in prostate cancer tissue was smaller than that of normal prostate tissue. PC-3 cells were softer than PZ-HPV-7 cells. Further mechanism investigation showed that the difference in modulus between cancerous and normal prostate tissue may be associated with a greater actin cytoskeleton distribution inside the cancer cells. CONCLUSION: The results suggests that the nanomechanical properties can classify the prostate tumor, which could be used as an index for the identification and classification of cancer at cellular level.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification.

BACKGROUND: There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. METHODS: A total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. RESULTS: The scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. CONCLUSIONS: The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.

Development of pre and post-operative nomograms to predict individual survival for ideal liver resection candidates with hepatocellular carcinoma.

BACKGROUND: Liver resection is currently the only recommended treatment option for solitary hepatocellular carcinoma (HCC) at an early stage, with well-preserved liver function and no clinically significant portal hypertension. However, this population is heterogeneous, rendering it crucial to develop a risk stratification tool. Therefore, this study aimed to develop preoperative and post-operative nomograms to predict individual survival and stratify patient risk in the ideal candidates for liver resection. METHODS: A total of 1405 ideal liver resection candidates were recruited. Independent risk factors were identified by Cox regression model and used to establish two ideal liver resection for overall survival (IROS) nomograms in training cohort. Model performance was assessed by discrimination, calibration, clinical usefulness. The two model also compared with six other prognostic nomograms and six other staging systems. RESULTS: Multivariate COX analysis revealed that ALP, ln(AFP), NrLR, PNI, ln(tumor size), microvascular invasion, Edmondson-Steiner grade and tumour capsular were the independent risk factors associated with mortality. 5 preoperative variables were incorporated to construct IROS-pre model; All eight available variables were used to draw IROS-post model. The C-index, K-index, time-dependent AUC and DCA of the two models showed significantly better predictive performances than other models. The models could stratify patients into three different risk groups. The web-based tools are convenient for clinical practice. CONCLUSIONS: These two nomograms were developed to estimate survival probability and stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts, as well as different subgroups. Both IROS models will help guide individualized follow-up.

Extra-Thyroid Extension Prediction by Ultrasound Quantitative Method Based on Thyroid Capsule Response Evaluation.

BACKGROUND The aim of this study was to assess the interaction between thyroid malignancies and thyroid anterior capsule by ultrasound quantification to determine extra-capsular invasion. MATERIAL AND METHODS A total of 145 patients preoperatively diagnosed with malignant nodules under the thyroid anterior capsule were selected and routinely examined by ultrasound. The length of the nodules (from the junction of the nodule capsule to the deepest point of the nodule, vertical diameter, V) and the distance between the nodule protruding from thyroid capsule and the highest protruding (ledge length, L) nodule were used to obtain the L/V ratio. These parameters where then used to compare the efficacy of predicting extra-thyroid extension (ETE) between L/V, the aspect ratio of the tumor, and manual judgment. RESULTS Out of 145 nodules, there were 63 ETEs and 82 non-ETEs determined by ultrasound. Extra-capsular invasion was associated with L//V ratio, but there was no significant correlation between capsular invasion and AR (aspect ratio), age, location, or presence of clustered calcification. The ability of the ratio of L/V to predict extra-capsular invasion was superior to the predictive ability of the AR ratio. With a Youden index of 0.593, the L/V ratio was 0.2325. The use of the L/V ratio to determine the presence of ETE was superior to subjective visual judgment. CONCLUSIONS The calculation of L/V ratio by ultrasound could more precisely predict the ETE compared with manual judgment, which indirectly reflects the interaction between thyroid capsule and malignant nodules. The above conclusions need to be confirmed by a range of cases.

Sonography Is Superior to Serum-Based Biomarkers for Measuring Disease Status in Experimental Rheumatoid Arthritis.

OBJECTIVES: Progress in developing novel rational treatments for rheumatoid arthritis (RA) critically depends on preclinical work in experimental animals. However, there is lack of insight into the most appropriate mode of noninvasive measurement of disease status in experimental RA. This study compared sonography with serum biomarkers in a rabbit model of RA. METHODS: Six-month-old male New Zealand White rabbits were randomized into 2 groups: antigen-induced arthritis group (n = 25), which was subjected to ovalbumin immunization and intra-articular injection; and control group (n = 5). Pathologic changes in the knee joints were evaluated by sonography, and serum C-reactive protein, tumor necrosis factor TNF-α, and interleukin 1 were measured by enzyme-linked immunosorbent assay. Synovial pathologic scores were obtained by ultrasound-guided biopsy. RESULTS: A total of 23 rabbits (2 rabbits died before the end of the study) in the antigen-induced arthritis group and 5 rabbits in the control group completed the study. Sonographic scores for all rabbits were graded from 0 to 3, according to grayscale sonography, synovitis, and blood flow. Synovial lesions were evident on sonography before week 4; however, serum biomarkers slowly increased until weeks 5 and 6 (P < .05). Although both sonography and serum biomarkers correlated significantly with synovitis scoring, the correlations for the sonographically derived parameters were better. The correlation indices between pathologic scores and synovial membranes thickness, blood flow, and resistive index were 0.798, 0.557, and -0.320, respectively, whereas the correlation indices between pathologic scores and tumor necrosis factor α, interleukin 1, and C-reactive protein levels were 0.451, 0.503, and 0.529. CONCLUSIONS: Sonographic findings had better correlations with histologic scoring than serologic biomarkers of disease activity in the RA rabbit model, especially at early stages. Local pathologic assessment of disease status by sonography is possible.

Acute physiological, perceived exertion and enjoyment responses during a 4-week basketball training: a small-sided game vs. high-intensity interval training.

Introduction: Although previous research found that small-sided game (SSG) training was more enjoyable than high-intensity interval training (HIT) in various sports, no data were provided during longer training period in basketball. Furthermore, the comparison of internal loads between the two training approaches needs to be further examined. Thus, this study aimed to examine the acute physiological, perceived exertion and enjoyment responses during 4-week progressive basketball SSG or HIT programs. Methods: Nineteen female collegiate basketball players were randomly assigned to two groups that performed either HIT (n = 10) or SSG (n = 9) 3 times per week for 4 continuous weeks. Average and percentage of maximal heart rate (HRmean and %HRmax), rating of perceived exertion (RPE), and physical activity enjoyment (PACES) were determined during each training session. Results: There was a main group effect in PACES (p < 0.001; ηp2 = 0.44, moderate), and SSG had higher PACES than HIT in each week (p < 0.05). There were no significant interactions or main group effects in HRmean, %HRmax or RPE, but a main time effect was found in HRmean (p = 0.004; ηp2 = 0.16, minimum), %HRmax (p < 0.001; ηp2 = 0.25, minimum), and RPE (p < 0.001; ηp2 = 0.31, moderate), respectively. In the SSG group, although no significant differences were found in HR responses, %HRmax was below 90% in week 1 and week 2. Accompanied with changes in %HRmax, RPE in week 1 and week 2 was lower than that in week 3 and week 4 (p < 0.05). Conclusion: Our findings suggest that SSG and HIT elicit similar acute HR response and RPE level, but SSG is perceived as more enjoyable and therefore it is more likely to increase exercise motivation and adherence comparing to HIT. Moreover, it seems that half-court, 2 vs. 2 SS Gtraining format with modified rules and lasting ≥ 7.5 min should be prescribed as an enjoyable training alternative to provide optimal cardiovascular stimuli (> 90% of HRmax) for female basketball players.

Exercise-Induced Muscle Damage and Protein Intake: A Bibliometric and Visual Analysis.

Numerous studies have covered exercise-induced muscle damage (EIMD) topics, ranging from nutritional strategies to recovery methods, but few attempts have adequately explored and analyzed large volumes of scientific output. The purpose of this study was to assess the scientific output and research activity regarding EIMD and protein intake by conducting a bibliometric and visual analysis. Relevant publications from 1975-2022 were retrieved from the Web of Science Core Collection database. Quantitative and qualitative variables were collected, including the number of publications and citations, H-indexes, journals of citation reports, co-authorship, co-citation, and the co-occurrence of keywords. There were 351 total publications, with the number of annual publications steadily increasing. The United States has the highest total number of publications (26.21% of total publications, centrality 0.44). Institutional cooperation is mostly geographically limited, with few transnational cooperation links. EIMD and protein intake research is concentrated in high-quality journals in the disciplines of Sport Science, Physiology, Nutrition, and Biochemistry & Molecular Biology. The top ten journals in the number of publications are mostly high-quality printed journals, and the top ten journals in centrality have an average impact factor of 13.845. The findings of the co-citation clusters and major keyword co-occurrence reveal that the most discussed research topics are "exercise mode", "nutritional strategies", "beneficial outcomes", and "proposed mechanisms". Finally, we identified the following research frontiers and research directions: developing a comprehensive understanding of new exercise or training models, nutritional strategies, and recovery techniques to alleviate EIMD symptoms and accelerate recovery; applying the concept of hormesis in EIMD to induce muscle hypertrophy; and investigating the underlying mechanisms of muscle fiber and membrane damage.

Emerging Trends and Hotspots in Tai Chi Fall Prevention: Analysis and Visualization.

Recently, substantial studies have increased around the topic of the tai chi fall-prevention field. Few studies, however, have revealed the current progress and hotspots under a bibliometric analysis. Therefore, the present study aimed to conduct Citespace, a significant application for bibliometric analysis, to carry out the situation and trend in this field. This study has identified the core countries are the United States, China, Australia, and England, which are also the origins of the core institutions. Besides this, we also have found two large research groups led by Li and Sherrington. Moreover, the result has revealed that J Aging Phys Act and J Am Geriatr Soc are the primary journals. Geriatrics and gerontology, sport sciences, rehabilitation, and gerontology are the leading categories. Furthermore, one of the more important findings to come out in this study are that "elderly", "Parkinson's disease", "vestibular rehabilitation", "frail patient", and "community fall prevention" are the research hotspots. "Women", "proprioception", "cognitive impairment", "dementia", "osteoarthritis", and "stroke" are the potential research trend in the future. These findings suggest that the tai chi fall-prevention field has a broad research prospect. Although several questions remain uncertain currently, it is worthy for scholars to do further study.

Value of a quantitative model of axillary venous blood flow spectrum for the detection of central venous stenosis in patients undergoing hemodialysis via radiocephalic arteriovenous fistula.

Background: Central venous stenosis (CVS) of radiocephalic arteriovenous fistula (RCAVF) affects RCAVF function and longevity. Ultrasound screening for CVS is limited by acoustic window. Herein, we analyzed the quantitative axillary venous (AxV) spectrum in hemodialysis patients via RCAVF, and constructed central venous stenosis index (CVSI) model based on the spectrum parameters to early detect resting asymptomatic CVS. Methods: From August 2017 to May 2021, stage 5 chronic kidney disease (CKD) patients dialysed via RCAVF at the First Affiliated Hospital of Fujian Medical University were included in this study. No CVS-related symptoms were found and the pulsation at the arteriovenous anastomosis was normal. However, the patients had the sensation of swelling in the ipsilateral upper limb during dialysis; the venous pressure advanced upon the completion of dialysis; or both (n=52). The inclusion criteria were as follows: (I) Ultrasound (US) showed that the temporal phases of the AxV spectrum were "normal"; and (II) CVS was confirmed by digital subtraction angiography (DSA). The exclusion criteria were as follows: (I) stent placement; (II) multiple stenosis; and (III) placement of central venous catheter. A total of 37 patients participated in the analysis. Eighteen patients were included in the CVS group, and 19 cases without CVS were included in the control group. Independent sample t-test was used to screen each parameter of the AxV spectrum, and a CVSI model was constructed by principal component analysis (PCA). The receiver operating characteristic curve (ROC) was applied to analyze the diagnostic value of CVSI. Results: According to the independent sample t-test, 9 parameters were found to have statistical significance (all P<0.05); they were analyzed by PCA, and the CVSI model was constructed. The ROC showed that CVSI had diagnostic value for CVS. When the cut-off value of CVSI was 7.13, the maximum value of the Youden index was 0.842, with a sensitivity of 100% and a specificity of 84.2%. Conclusions: The CVSI helps to early detect resting asymptomatic CVS and dramatically increases the detection rate of CVS.

Hypoxic Exercise Exacerbates Hypoxemia and Acute Mountain Sickness in Obesity: A Case Analysis.

Acute mountain sickness (AMS) is a common syndrome characterized by headache, dizziness, loss of appetite, weakness, and nausea. As a major public health issue, obesity has increased in high altitude urban residents and intermittent commuters to high altitudes. The present study investigated acute hypoxic exposure and hypoxic exercise on hypoxemia severity and AMS symptoms in a physically active obese man. In this case analysis, peripheral oxygen saturation (SpO2) was used to evaluate hypoxemia, heart rate (HR) and blood pressure (BP) were used to reflect the function of autonomic nervous system (ANS), and Lake Louise scoring (LLS) was used to assess AMS. The results showed that acute hypoxic exposure led to severe hypoxemia (SpO2 = 72%) and tachycardia (HRrest = 97 bpm), and acute hypoxic exercise exacerbated severe hypoxemia (SpO2 = 59%) and ANS dysfunction (HRpeak = 167 bpm, SBP/DBP = 210/97 mmHg). At the end of the 6-h acute hypoxic exposure, the case developed severe AMS (LLS = 10) symptoms of headache, gastrointestinal distress, cyanosis, vomiting, poor appetite, and fatigue. The findings of the case study suggest that high physical activity level appears did not show a reliable protective effect against severe hypoxemia, ANS dysfunction, and severe AMS symptoms in acute hypoxia exposure and hypoxia exercise.

The Value of Relative Size in the Ultrasound Diagnosis of Follicular Thyroid Neoplasm.

PURPOSE: Ultrasonography as the first choice for thyroid nodules is still difficult to distinguish between solid follicular thyroid neoplasm (FTN) and solid nodular goiter (NG). We tried to investigate the value of relative size (M/S, M: the maximum diameter of target nodule, S: the maximum diameter of the largest of the remaining nodules) that may help to differentiate FTN from NG. METHODS: T test and chi-square test were used to retrospectively analyze the differences of the clinical and ultrasonographic characteristics between FTN and NG in 422 cases in our hospital. T test was used to analyze the difference of M/S value in the two kinds of nodules. ROC was used to evaluate the accuracy of M/S value in distinguishing the two. RESULTS: There were statistically significant differences in age, echogenicity, calcification, peripheral halo and blood supply between the two. The M/S value is not only significantly different in the two kinds of nodules but also can be used as a quantitative indicator to guide ultrasound diagnosis. ROC analysis showed that the cutoff point and AUC of M/S value were 1.94 and 0.709, respectively. CONCLUSION: In the ultrasound diagnosis of multiple thyroid nodules, the M/S value can better distinguish FTN and NG. We need to be aware of FTN when the M/S value of the nodule is greater than 2.

Ultrasonographic evaluation of extracapsular vascular invasion for subcapsular nodules of the thyroid.

BACKGROUND: Ultrasound provides a high-frequency spatial resolution. In this study, we used the combined pathological features of extrathyroid extension (ETE) measured by ultrasound to evaluate the vascular manifestations of subcapsular differentiated thyroid cancer. Our study aims to explore the value of high-frequency ultrasonography in the evaluation of extracapsular vascular invasion for the evaluation of both benign and malignant nodules and the prediction of ETE. METHODS: A total of 167 thyroid nodules were enrolled in this study. High-frequency ultrasonography was used to observe the relationship between the blood flow of the nodules and the capsules. The blood flow was divided into two types according to the relationship: non-extracapsular invasive blood flow and extracapsular invasive blood flow. Non-extracapsular blood flow was defined as any flow seen inside or around the nodule that did not extend beyond the thyroid gland. Extracapsular invasive blood flow was defined as any blood flow seen inside or around the nodule that flowed across the capsule and extended beyond the thyroid gland. A comparison of the different types of blood flow to judge the nature of thyroid nodules for predicting ETE was performed. RESULTS: Out of 167 nodules, 81 cases of nodules were the non-extracapsular invasive blood flow type, while the remaining 86 cases of nodules were classified as the extracapsular invasive blood flow type. Nodules with distinct types of blood flow were significantly different in malignancy rates between the nodules (P<0.001). The incidence rate of ETE was also significantly different between the malignant nodules with distinct types of blood flows. CONCLUSIONS: Extracapsular vascular invasion is a good indicator for the evaluation of benign and malignant nodules. Using it as an indicator provides physicians with a potential tool for the prediction of ETE.

Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy.

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

Surface-enhanced Raman scattering analysis of serum albumin via adsorption-exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening.

Combining serum albumin via adsorption-exfoliation on hydroxyapatite particles (HAp) with surface-enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS-SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp-adsorbed-exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.

Quantitative analysis of breast cancer diagnosis using a probabilistic modelling approach.

BACKGROUND: Breast cancer is the most prevalent cancer in women in most countries of the world. Many computer-aided diagnostic methods have been proposed, but there are few studies on quantitative discovery of probabilistic dependencies among breast cancer data features and identification of the contribution of each feature to breast cancer diagnosis. METHODS: This study aims to fill this void by utilizing a Bayesian network (BN) modelling approach. A K2 learning algorithm and statistical computation methods are used to construct BN structure and assess the obtained BN model. The data used in this study were collected from a clinical ultrasound dataset derived from a Chinese local hospital and a fine-needle aspiration cytology (FNAC) dataset from UCI machine learning repository. RESULTS: Our study suggested that, in terms of ultrasound data, cell shape is the most significant feature for breast cancer diagnosis, and the resistance index presents a strong probabilistic dependency on blood signals. With respect to FNAC data, bare nuclei are the most important discriminating feature of malignant and benign breast tumours, and uniformity of both cell size and cell shape are tightly interdependent. CONTRIBUTIONS: The BN modelling approach can support clinicians in making diagnostic decisions based on the significant features identified by the model, especially when some other features are missing for specific patients. The approach is also applicable to other healthcare data analytics and data modelling for disease diagnosis.

Quantitative analysis of the cell-surface roughness and viscoelasticity for breast cancer cells discrimination using atomic force microscopy.

Breast cancer has been one of the most common malignant tumors threatening female health with high incidence. Cell mechanics is becoming an important issue and could serves as a potential indicator for early cancer diagnosis. In this study, atomic force microscopy (AFM) was applied to characterize and compare the surface nanostructure and viscoelasticity of different breast cell lines. Our results show that breast cancerous cells MCF-7 exhibit more disorganized filamentous cytoskeleton structure with increased membrane roughness compared to benign breast cells MCF-10A (P < 0.05). The viscoelastic properties, including elasticity and viscosity, are significantly different between the two cell lines. MCF-7 displays reduced elasticity and viscosity, indicating that breast cancer cells are softer and more fluid than benign counterpart. Our findings provide new insights into the biophysical changes of cells during tumor transformation and suggest it could be used for early cancer detection at single cell level. SCANNING 38:558-563, 2016. © 2016 Wiley Periodicals, Inc.