Controlling Nutritional Status (CONUT) score is a prognostic marker in III-IV NSCLC patients receiving first-line chemotherapy.

BACKGROUND: To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy. METHODS: We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: A high CONUT score was significantly associated with older age(P = 0.003), worse ECOG-PS(P = 0.018), advanced clinical stage(P = 0.006), higher systematic inflammation index (SII) (P < 0.001)and lower prognostic nutritional index (PNI) (P < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (Pall < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (Pall < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753). CONCLUSION: CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.

Evaluating the mitigation strategies of COVID-19 by the application of the CO2 emission data through high-resolution agent-based computational experiments.

The negative consequences, such as healthy and environmental issues, brought by rapid urbanization and interactive human activities result in increasing social uncertainties, unreliable predictions, and poor management decisions. For instance, the Coronavirus Disease (COVID-19) occurred in 2019 has been plaguing many countries. Aiming at controlling the spread of COVID-19, countries around the world have adopted various mitigation and suppression strategies. However, how to comprehensively eva luate different mitigation strategies remains unexplored. To this end, based on the Artificial societies, Computational experiments, Parallel execution (ACP) approach, we proposed a system model, which clarifies the process to collect the necessary data and conduct large-scale computational experiments to evaluate the effectiveness of different mitigation strategies. Specifically, we established an artificial society of Wuhan city through geo-environment modeling, population modeling, contact behavior modeling, disease spread modeling and mitigation strategy modeling. Moreover, we established an evaluation model in terms of the control effects and economic costs of the mitigation strategy. With respect to the control effects, it is directly reflected by indicators such as the cumulative number of diseases and deaths, while the relationship between mitigation strategies and economic costs is built based on the CO2 emission. Finally, large-scale simulation experiments are conducted to evaluate the mitigation strategies of six countries. The results reveal that the more strict mitigation strategies achieve better control effects and less economic costs.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Carotid stiffness and atherosclerotic risk: non-invasive quantification with ultrafast ultrasound pulse wave velocity.

OBJECTIVES: To evaluate the value of ultrafast pulse wave velocity (ufPWV) for the quantitative assessment of carotid stiffness and its associated with atherosclerosis (AS) risk. METHODS: The present study included 233 patients with hyperlipoidaemia (AS risk group) and 114 healthy adults as the control group. The carotid (n = 694) intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS) and pulse wave velocity-end of systole (PWV-ES) were measured on sample images. Differences, distributive characteristics and correlation evaluation were assessed in patients (ages 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70) and carotids (control group vs AS risk group). RESULTS: The cIMT, PWV-BS and PWV-ES increased with age; PWV-ES and cIMT showed an early significant increase in the 30-39 years group, whereas PWV-BS displayed a significant increase at 40-49 years compared with the 18- to 29-years group. Besides, PWV-ES correlated well with age compared with PWV-BS and cIMT. For carotid level, cIMT, PWV-BS and PWV-ES measurements were higher in the AS risk group compared with control. To compare the value of ufPWV and cIMT in early AS assessment, we subdivided groups into cIMT subgroups using a cut-off thickness of 0.050 cm. PWV-ES measurements were higher in the AS risk group compared with the control in the 0.040-0.050 cm (not thickened) and 0.051-0.060 cm (thickened) cIMT subgroups. CONCLUSIONS: Carotid ufPWV measurement at PWV-ES is a novel modality for the early diagnosis and quantitative assessment of arterial stiffness associated with atherosclerotic risk. KEY POINTS: • ufPWV technique is real-time and well repeatable for assessing carotid stiffness • ufPWV measurements increase and correlate well with age • PWV-ES is a quantitative predictor for the early assessment of AS.

Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal angiomyolipoma from renal cell carcinoma: a meta-analysis.

OBJECTIVES: To determine the performance of chemical shift signal intensity index (CS-SII) values for distinguishing minimal-fat renal angiomyolipoma (mfAML) from renal cell carcinoma (RCC) and to assess RCC subtype characterisation. METHODS: We identified eligible studies on CS magnetic resonance imaging (CS-MRI) of focal renal lesions via PubMed, Embase, and the Cochrane Library. CS-SII values were extracted by lesion type and evaluated using linear mixed model-based meta-regression. RCC subtypes were analysed. Two-sided p value <0.05 indicated statistical significance. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Eleven articles involving 850 patients were included. Minimal-fat AML had significantly higher CS-SII value than RCC (p < 0.05); there were no significant differences between mfAML and clear cell RCC (cc-RCC) (p = 0.112). Clear cell RCC had a significantly higher CS-SII value than papillary RCC (p-RCC) (p < 0.001) and chromophobe RCC (ch-RCC) (p = 0.045). The methodological quality was relatively high, and Begg's test data points indicated no obvious publication bias. CONCLUSIONS: The CS-SII value for differentiating mfAML from cc-RCC remains unproven, but is a promising method for differentiating cc-RCC from p-RCC and ch-RCC. KEY POINTS: • RCC CS-SII values are significantly lower than those of mfAML overall. • CS-SII values cannot aid differentiation between mfAML and cc-RCC. • CS-SII values might help characterise RCC subtypes.

Use of atropine in four-dimensional hysterosalpingo-contrast sonography: Does it suppress pain during infertility examination?

This study aimed to ascertain if atropine is useful for suppressing the pain suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) when assessing infertility in women. A total of 252 patients were divided into 2 groups to receive or not receive atropine (0.5 mg) injection 30 minutes before 4D-HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D-HyCoSy; upon 2-dimensional transvaginal sonography; before catheter insertion; upon insertion and fixation of the catheter into the uterine cavity; 30 minutes after 4D-HyCoSy. According to the degree of patency of Fallopian tubes, the 6 patterns observed were integrated further into 3 patient groups: all-negative (both Fallopian tubes were negative), positive-and-negative (one Fallopian tube showed patency and the other showed stenosis or non-patency), and all-positive (both Fallopian tubes showed stenosis or non-patency). We compared the NRS scores and prevalence of side-effects other than pain between the atropine-injection and non-atropine-injection groups within the three groups mentioned above. The NRS score showed no significant differences among the groups at any time point (all P > .05). The different prevalence of side-effects other than pain was significant between the atropine-injection and atropine-non-injection groups (P = .012). These data suggest that atropine does not reduce pain in patients during 4D-HyCoSy. However, atropine may reduce the prevalence of other side-effects during 4D-HyCoSy, which needs a further, large, prospective, multi-cohort study to verify.

Continuous infusion of a large dose of CF (folinic acid) and 5-FU combined with CDDP in the treatment of advanced esophageal cancer.

5-fluorouracil (5-FU) and cisplatin (CDDP) are common chemotherapy drugs used in the treatment of patients with advanced esophageal cancer. We investigated the efficacy of adding a continuous infusion of a large dose of a common adjuvant, citrovorumfactor (CF), to the traditional 5-FU/wCDDP regimen. 50 patients with advanced esophageal cancer were treated with a continuous infusion of CF, 5-FU, and CDDP, and the short-term effects, adverse reactions, and survival periods after treatment were analyzed. Overall, the treatment was effective in 58% of patients, and the therapeutic effects of the first-line of chemotherapy were significantly better than the second-line (u = 4.121, p < 0.05). Patients experienced severe nausea and vomiting in 18.7% of the treatment cycles and experienced severe hair loss or leucopenia in 1.9% of the treatment cycles. The majority of the treatment cycles produced only mild side effects. The median survival period following chemotherapy treatment was 10.6 months (95% confidence interval was 8.146 ~ 13.054 months), with the median survival time of patients with a Karnofsky Performance Status (KPS) score ≥ 80 being significantly longer than that of patients with KPS scores < 80 (χ2 = 41.595, p < 0.05). The median survival time of patients with metastasis to the lymph nodes and surrounding tissue was significantly longer than that of patients with visceral metastasis (χ2 = 32.246, p < 0.05). Cox regression analysis showed that KPS scores before the treatment < 80 (relative risk (RR= = 1.635) and the incidence of visceral metastasis (RR = 1.875) were associated with survival time (p < 0.05). These results suggest that the continuous infusion of a large dose of CF, 5-FU, and CDDP as chemotherapy treatment of advanced esophageal cancer can produce promising short-term results and decrease adverse reactions.

Forkhead box O1 mediates defects in palmitate-induced insulin granule exocytosis by downregulation of calcium/calmodulin-dependent serine protein kinase expression in INS-1 cells.

AIMS/HYPOTHESIS: The transcription factor forkhead box O1 (FOXO1) induces pancreatic islet beta cell endoplasmic reticulum stress and is involved in fatty-acid-induced insulin-secretion defects. Cask is a downstream target gene of FOXO1. Using INS-1 cells with palmitate-induced insulin-release defects, we investigated the relationship between FOXO1 and Cask. METHODS: The expression levels and location of calcium/calmodulin-dependent serine protein kinase (CASK) and FOXO1 were evaluated by real-time PCR, western blotting and immunofluorescence. The regulation of Cask by FOXO1 was examined using chromatin immunoprecipitation (ChIP) and luciferase assays. Potassium-stimulated insulin-secretion assays were used to verify the function of INS-1 cells and islets. Electron microscopy was used to establish the anchoring process of the insulin granules after CASK knockdown in islets. RESULTS: Palmitic acid reduced CASK levels and increased FOXO1 levels. ChIP and luciferase assays demonstrated FOXO1 binding with the Cask promoter, which was enhanced by palmitate treatment. CASK knockdown reduced insulin release in INS-1 cells and primary islets, and Cask overexpression reversed the palmitate-induced insulin reduction. CASK knockdown attenuated forskolin-enhanced insulin release, but Cask overexpression did not change the insulin-secretion suppression induced by nifedipine. In pancreatic islet beta cells, CASK knockdown reduced the anchoring of insulin vesicles to cell membranes. CONCLUSIONS/INTERPRETATION: The induction of beta cell insulin-secretion defects by fatty acids is mediated, at least in part, by FOXO1 via downregulation of Cask expression. It is characterised mainly as an obstruction of the anchoring of insulin granules to beta cell membranes.

[Magnetic resonance evaluations of correlation of iron overload and osteoporosis in ovariectomized rats].

OBJECTIVE: To explore the correlation between liver T(2)(*) value and bone mineral density (BMD) in ovariectomized (OVX) rats. METHODS: A total of 60 rats, including sham (n = 25) and OVX (n = 35) groups, underwent dual-energy X-ray absorptiometry (DEXA) and liver magnetic resonance (MR)-T(2)(*) mapping for lumbar vertebra BMD and T(2)(*) values before and after operation monthly for 4 timepoints. Also micro-computed tomography (micro-CT) and biochemical measurements were performed. The sensitivity of liver T(2)(*) relaxation time detecting early osteoporosis were estimated and the correlation between liver T(2)(*) values and BMD analyzed. RESULTS: BMD of lumber vertebra in OVX group decreased compared to control group at Month 2 postoperation ((554 ± 27) mg/cm³ vs (722 ± 19) mg/cm³, P < 0.05) in synchrony with an elevation of serum ferritin concentration ((521 ± 41) ng/ml vs (441 ± 29) ng/ml, P < 0.01) and liver iron concentration ((291 ± 18) µg/g vs (237 ± 27) µg/g, P < 0.01). A significant inter-group difference of liver T(2)(*) was detected at Month 1 postoperation ((13.2 ± 0.7) ms vs (13.9 ± 0.4) ms, P < 0.01). Liver T(2)(*) was significant positively correlated with BMD in sham group (r = 0.410, P < 0.01) and OVX group (r = 0.434, P < 0.01). CONCLUSION: Liver T(2)(*) relaxation time may a valuable detection tool of assessing pathophysiological changes of osteoporosis in early stage.

Protective effect of N-acetylcysteine (NAC) on renal ischemia/reperfusion injury through Nrf2 signaling pathway.

The aim of this study was to investigate whether N-acetylcysteine (NAC), a known antioxidant, can protect kidney against ischemic injury through regulating Nrf2 signaling pathway. The expression of Nrf2, HO-1 and cleaved caspase 3 were analyzed by Western blot analysis. Apoptosis of renal tubular epithelial cells was assessed by the TUNEL method. Malondialdehyde (MDA) levels were measured by the thiobarbituric acid reaction. Blood serum creatinine and blood urea nitrogen levels were measured with an Olympus automatic multi-analyzer. We found that NAC significantly increased Nrf2 and downstream HO-1 expression. Furthermore, NAC significantly decreased cleaved caspase 3, p53 and renal epithelial tubular cell apoptosis. In addition, NAC reduced the MDA level. These findings suggest that the protective action of NAC on ischemia renal injury is associated closely with Nrf2 signaling pathway.

Hepatic magnetic resonance imaging with T2* mapping of ovariectomized rats: correlation between iron overload and postmenopausal osteoporosis.

OBJECTIVE: To explore the correlation between liver iron overload and bone mineral density (BMD) in an ovariectomy (OVX) rat model, using liver magnetic resonance (MR)-T2* and dual-energy X-ray absorptiometry (DEXA). METHODS: Sprague-Dawley rats received deferoxamine (DFO) or phosphate-buffered saline 3 months after bilateral OVX. MRI and DEXA were performed pre- and postoperatively. Five rats per group were killed every month for micro-CT, histopathology and biochemical examinations. Statistical analysis was performed with independent-samples t tests, box plots and Pearson's correlation analysis. RESULTS: At 2 months postoperatively, BMD was significantly lower in the OVX group than in the control group (P < 0.01), corresponding to the increased serum ferritin concentration (SFC; P < 0.01) and liver iron concentration (LIC; P < 0.01). Liver T2* values significantly differed between the two groups at 1 month postoperatively (P < 0.001) and improved 1 month after DFO injection (P < 0.05). These values were significantly and positively correlated with BMD in the control (r = 0.527, P < 0.001) and OVX (r = 0.456, P < 0.001) groups. CONCLUSION: Liver MRI T2* changed markedly earlier than BMD, LIC and SFC, and correlated well with osteoporosis; it may thus be a valuable early indicator of osteoporosis. KEY POINTS: • Iron overload plays a vital role in the pathogenesis of postmenopausal osteoporosis. • Liver T2* relaxation time is a sensitive value in reflecting iron overload. • Liver T2* mapping elucidates changes in postmenopausal osteoporosis earlier than BMD. • Iron chelation increases BMD in ovariectomized rats. • Liver T2* has a moderate positive correlation with BMD.

Predicting cardiovascular risk stratification in apparently healthy population by using noninvasive ultrafast ultrasound imaging.

BACKGROUND: To investigate the association between cardiovascular risk estimated using the Framingham Risk Score (FRS) and carotid stiffening determined using ultrafast pulse wave velocity (ufPWV) measurements in apparently healthy individuals. METHODS: We enrolled 1034 apparently healthy participants without known cardiovascular disease who underwent ufPWV measurements. Clinical and laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (PWV-BS), and pulse wave velocity at the end of systole (PWV-ES) were assessed. In FRS assessments based on major cardiovascular risk factors (CVRFs), participants were assigned into three risk categories: low risk (<10%, n = 679), intermediate risk (10-20%, n = 191), and high risk (>20%, n = 164); the low-risk category was further subdivided into three subcategories: < 1% (n = 58), 1%- 5% (n = 374) and > 5% (n = 247). Multivariate logistic regression analyses with crude and adjusted odds ratios (ORs) were used to evaluate the association of carotid stiffening and FRS-based risk stratification. RESULTS: Carotid stiffening indicated by PWV-BS and PWV-ES differed notably between the FRS-estimated low-risk vs. intermediate-risk and high-risk categories, but only PWV-ES differed notably among the low-risk subcategories (all p < 0.010), and correlated notably with the FRS-estimated risk most obviously in low-risk participants (r = 0.517). In participants with cIMT < 0.050 cm, only PWV-ES differed significantly among the FRS-estimated risk categories (all p < 0.001). Increased PWV-BS (adjusted OR: 1.49; p = 0.003) and PWV-ES (adjusted OR: 1.29; p = 0.007) were both associated with FRS categories independent of conventional CVRFs in low- vs. intermediate-risk categories, but not in low- vs. high-risk categories (all p > 0.050). CONCLUSION: In vivo imaging of carotid stiffening by ufPWV measurements is independently linked to FRS categories, and ufPWV indices may help stratify differing levels of cardiovascular risk in apparently healthy young people. AVAILABILITY OF DATA AND MATERIAL: Data generated or analyzed during the study are available from the corresponding author by reasonable request.

Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching.

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

Quantifying carotid stiffness in a pre-hypertensive population with ultrafast ultrasound imaging.

PURPOSE: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). METHODS: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)-normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292). Correlation analyses and comparisons were performed among the groups and in the cIMT subgroups (cIMT ≥0.050 cm and <0.050 cm). RESULTS: cIMT and PWV-ES significantly differed among the BP groups (P<0.05). The BP groups had similar PWV-BS when cIMT <0.050 cm or cIMT ≥0.050 cm (all P>0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P<0.001 and P=0.024) and HT (all P<0.001) groups in both cIMT categories, while the PWV-ES in the PHT group were not significantly lower than in the HT group (all P>0.05). CONCLUSION: Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.

Toward parallel intelligence: An interdisciplinary solution for complex systems.

The growing complexity of real-world systems necessitates interdisciplinary solutions to confront myriad challenges in modeling, analysis, management, and control. To meet these demands, the parallel systems method rooted in the artificial systems, computational experiments, and parallel execution (ACP) approach has been developed. The method cultivates a cycle termed parallel intelligence, which iteratively creates data, acquires knowledge, and refines the actual system. Over the past two decades, the parallel systems method has continuously woven advanced knowledge and technologies from various disciplines, offering versatile interdisciplinary solutions for complex systems across diverse fields. This review explores the origins and fundamental concepts of the parallel systems method, showcasing its accomplishments as a diverse array of parallel technologies and applications while also prognosticating potential challenges. We posit that this method will considerably augment sustainable development while enhancing interdisciplinary communication and cooperation.

Formononetin attenuates IL-1ß-induced apoptosis and NF-κB activation in INS-1 cells.

Several studies suggest that the inflammation plays a role in the pathogenesis of some glucose disorders in adults. Exposure of pancreatic ß-cells to cytokines, such as interleukin-1ß (IL-1ß), is thought to contribute to ß-cell apoptosis. One important event triggered by IL-1ß is induction of nitric oxide synthase (iNOS), an enzyme that catalyzes intracellular generation of the cytotoxic free radical NO. Recent work have suggested that formononetin, as an O-methylated isoflavone found in a number of plants and herbs like Astragalus membranaceus, inhibited some pro-inflammatory cytokine production in macrophages. However, the roles of formononetin in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of formononetin on cell apoptosis induced by IL-1ß in the rat insulinoma cell line, INS-1. Our results demonstrate that formononetin significantly prevents IL-1ß-increased INS-1 cell death and blocks cytokine-induced apoptotic signaling (the reduction of Bax/Bcl-2 ratio and caspase-3 activity). Formononetin also inhibited the activation of nuclear factor-kappaB (NF-κB), which is a significant transcription factor for iNOS, so as to decease nitric oxide (NO) formation in a dose dependent manner in vitro. Our observations indicated that formononetin could protect against pancreatic ß-cell apoptosis caused by IL-1ß and therefore could be used in the future as a new drug improving diabetes mellitus.

Carotid stiffening predicts cardiovascular risk stratification in mid-life: non-invasive quantification with ultrafast ultrasound imaging.

PURPOSE: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV). METHODS: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs. RESULTS: cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P<0.05), but only PWV-ES increased gradually in age and SCORE-estimated risk subgroups (all P<0.05). Compared with cIMT (r=0.388, P<0.001) and PWV-BS (r=0.159, P<0.001), PWV-ES was more strongly correlated with SCORE categories (r=0.405, P<0.001). Higher PWV-ES values were associated with SCORE categories independently of sex, SBP, TC, and smoking in moderate-risk and high-risk subgroups (OR, 1.63; P<0.001 and OR, 2.12; P=0.024, respectively), but were not independent of age in all risk subgroups (all P>0.05). CONCLUSION: Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.

Individualized References of Carotid Stiffening Quantified With Ultrafast Ultrasound Imaging: Model Construction and Preliminary Validation.

To establish and preliminarily validate an individualized reference of carotid stiffness quantified by ultrafast pulse wave velocity (ufPWV), our study included 225 healthy individuals in the modeling cohort and 628 individuals in the validation cohort. All participants underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole and pulse wave velocity-end of systole (PWV-ES). A threshold equation of estimated PWV-ES was obtained by multiple linear regression analysis in the modeling cohort as follows: estimated PWV-ES (m/s) = 0.080 × age (y) + 0.767 × low-density lipoprotein (mmol/L) + 0.040 × systolic blood pressure (mm Hg) + 0.372 × sex (male = 1, female = 0) - 2.803. With this equation, the validation cohort was divided into the low PWV-ES (actual PWV-ES ≤ estimated PWV-ES) and high PWV-ES (actual PWV-ES > estimated PWV-ES) groups. A clear boundary was found to be present between the low PWV-ES and high PWV-ES groups in the validation cohort. Participants with increasing PWV-ES increased with age gradually. We further subdivided participants into cIMT subgroups using a cutoff thickness of 0.050 cm. Diagnostic performance analysis revealed that the sensitivity and specificity of the threshold equation were 78.9% and 73.9%, respectively. We established and validated a novel individualized reference equation for estimated PWV-ES, which can likely expand the application of prospective ufPWV assessment.

Strategy evaluation and optimization with an artificial society toward a Pareto optimum.

Strategy evaluation and optimization in response to troubling urban issues has become a challenging issue due to increasing social uncertainty, unreliable predictions, and poor decision-making. To address this problem, we propose a universal computational experiment framework with a fine-grained artificial society that is integrated with data-based models. The purpose of the framework is to evaluate the consequences of various combinations of strategies geared towards reaching a Pareto optimum with regards to efficacy versus costs. As an example, by modeling coronavirus 2019 mitigation, we show that Pareto frontier nations could achieve better economic growth and more effective epidemic control through the analysis of real-world data. Our work suggests that a nation's intervention strategy could be optimized based on the measures adopted by Pareto frontier nations through large-scale computational experiments. Our solution has been validated for epidemic control, and it can be generalized to other urban issues as well.