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Background: Abnormal stromal-epithelial cell communication is a pathogenic mechanism in endometriosis, and metformin can modulate it. Insulin-like growth factor binding protein-1 (IGFBP1) plays a role in endometriosis, but the exact mechanism is unknown. IGFBP1 is reportedly a downstream target of metformin in some diseases. We aimed to investigate the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression., Methods: Patients who underwent surgical treatment for endometriosis or other diseases were enrolled. Ten patients with ovarian-type endometriosis and eight patients each who underwent surgical treatment for other lesions with or without endometriosis were selected, and their tissues taken for cell proliferation, western blotting, polymerase chain reaction, and knockdown experiments., Results: Ectopic and eutopic stromal cells (EcSCs and EuSCs) lost their ability to inhibit epithelial cell proliferation, and IGFBP1 expression was downregulated in both groups of stromal cells compared to that in normal stromal cells (NSCs; 1.09 vs. 0.25, p  = .0002 1.09 vs. 0.57, p  = .0029). In an EcSC IGFBP1 overexpression model, the ability of EcSCs to inhibit epithelial cell proliferation was enhanced (EdU positivity decreased from 38% to 25%, p  = .0001). Furthermore, adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation was downregulated in EcSCs and EuSCs compared to that in NSCs (0.99 vs. 0.42, p  = .0006/0.99 vs. 0.57, p  = 0.0032). Treatment of EcSCs with metformin increased AMPK phosphorylation (0.47 vs. 1.04, p  = .0107) while upregulating IGFBP1 expression (0.69 vs. 1.01, p  = .0164), whereas pre-treatment with an AMPK phosphorylation inhibitor abrogated metformin-induced IGFBP1 upregulation., Conclusions: IGFBP1 mediates aberrant stromal-epithelial communication in endometriosis. Metformin can upregulate IGFBP1 expression in EcSCs by activating AMPK, and upregulated IGFBP1 enhances the inhibition of epithelial cell proliferation. IGFBP1 is expected to be a therapeutic target for endometriosis.

Introduction: Luteolin, a naturally occurring flavonoid compound, demonstrates promising anti-cancer properties. However, its mechanism against non-small-cell lung cancer (NSCLC) remains unknown. This study employed network pharmacology, molecular docking, molecular dynamics simulation (MDS), and in vitro experiments to investigate the potential mechanisms by which luteolin against NSCLC., Methods: Initially, the potential targets of luteolin and NSCLC-related targets were identified from public databases such as TCMSP, GeneCards, OMIM, DrugBank, and TTD. Subsequently, the protein-protein interaction (PPI) network screening and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The binding affinity and stability of luteolin with the core targets were assessed using molecular docking and MDS. Finally, the results were validated by in vitro experiments., Results: A total of 56 luteolin targets and 2145 NSCLC-related targets were identified. Six core targets, TP53, EGFR, AKT1, TNF, JUN, and CASP3, were screened via the PPI network. The GO and KEGG analyses indicated that luteolin's activity against NSCLC potentially involves PI3K-Akt, NF-kappa B, and other signaling pathways. Molecular docking revealed that luteolin had high binding affinity with the core targets. MDS confirmed the stable interaction between luteolin and key proteins TP53 and AKT1. in vitro , luteolin significantly inhibited the proliferation and migration of A549 cells, while also inducing apoptosis. In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002., Conclusion: Luteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Li, Shi, Liu, Zhou, Tang, Ren, Qiao and Liu.)

Mesenchymal stem cells (MSCs) have attracted more and more attention because of their multidirectional differentiation potential, immune regulatory abilities and self-renewal capacity. In recent years, their use has become prominent in the domains of regenerative medicine and tissue engineering. MSCs have shown promise in therapeutic studies for a variety of diseases and have become a new source of innovative solutions for the treatment of some obstetric and gynecological diseases. This review systematically presents the latest research on the use of MSCs in the treatment of obstetrics- and gynecology-related diseases. Specifically, this review encompasses the latest findings related to the role of MSCs in premature ovarian failure, polycystic ovary syndrome, ovarian cancer, fallopian tube-related diseases, uterine adhesions, endometriosis, cesarean scar defects, postmenopausal osteoporosis, and pelvic floor dysfunction. The shortcomings and challenges of the future use of MSCs in disease treatment are also discussed, with the intent to motivate improvements in MSC applications in clinical therapy. It is believed that with further research, MSCs will play a more important role in the treatment of obstetrics- and gynecology-related diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Enhancing microalgal growth and bioactive compound production is becoming a duty for improving photosynthetic microorganisms. In this study, the growth, carotenoid, and fatty acid profiles of Conticribra weissflogii were studied under four different silicate concentrations and silicate-deficient conditions in an f/2 medium with continuous aeration, light intensity (30 ± 2 µmol m -2 s -1 ), salinity (25 ± 2‱), pH (8), and temperature (25 ± 2 °C). At the end of the experiment, we observed that a silicate concentration of 120 mg L -1 produced the maximum biomass dry weight (0.86 g L -1 ), carotenoid content (1.63 µg mL -1 ), and fucoxanthin content (1.23 mg g -1 ) in C. weissflogii . The eicosapentaenoic acid (EPA) (11,354.37 µg g -1 ), docosahexaenoic acid (DHA) (2516.16 µg g -1 ), gamma-linolenic acid (C18:3n6) (533.51 µg g -1 ), and arachidonic acid (C20:4n6) (1261.83 µg g -1 ) contents were significantly higher at Si 120 mg L -1 . The results further showed the maximum fatty acid content in C. weissflogii at Si 120 mg L -1 . However, the silicate-deficient conditions (Si 0 mg L -1 ) resulted in higher levels of saturated fatty acids (38,038.62 µg g -1 ). This study presents a practical approach for the large-scale optimization of biomass, carotenoid, fucoxanthin, and fatty acid production in C. weissflogii for commercial purposes.

Background and Objective: Systemic treatments involving immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations and TKI monotherapy have significantly improved outcomes for patients with metastatic clear-cell renal cell carcinoma (mccRCC). However, there are no biomarkers for predicting the efficacy of these treatments. Our aim was to investigate the prognostic and therapeutic significance of serum immunoglobulin G (IgG) in patients with mccRCC patients receiving systemic therapy., Methods: We included 318 patients with mccRCC who received TKI or IO-TKI therapy. Patients were classified into groups according to whether they had an increase or decrease in serum IgG after systemic treatment. The association between baseline serum IgG and the objective response rate (ORR) was compared between the groups using a t test. The association of the change in serum IgG with progression-free survival (PFS) and overall survival (OS) was evaluated via Cox proportional-hazards regression, and survival curves were generated using the Kaplan-Meier method., Key Findings and Limitations: Baseline serum IgG was not significantly associated with ORR ( p  = 0.055). After 3-mo systemic therapy, 133 patients (42%) exhibited an increase in serum IgG. The group with an IgG increase had significantly poorer median PFS (5.6 vs 16.2 mo; hazard ratio [HR] 3.36, 95% confidence interval [CI] 2.58-4.36; p  < 0.001) and OS (26.0 vs 52.2 mo; HR 2.26, 95% CI 1.66-3.08; p  < 0.001) than the group with an IgG decrease. Multivariable analysis revealed that an increase in serum IgG after 3-mo systemic therapy was an independent risk factor for both PFS (HR 3.28, 95% CI 2.51-4.30; p  < 0.001) and OS (HR 1.94, 95% CI 1.41-2.68; p  < 0.001). An increase in serum IgG after 1-mo treatment ( n  = 160) was also significantly associated with poorer median PFS (7.9 vs 13.7 mo; HR 1.62, 95% CI 1.13-2.32; p  = 0.008) and OS (32.6 vs 50.5 mo; HR 1.68, 95% CI 1.09-2.59; p  = 0.017)., Conclusions and Clinical Implications: The change in serum IgG after 3-mo systemic therapy can predict the therapeutic effect and prognosis for patients with mccRCC. This predictive value was observed as early as 1 mo after treatment initiation. Our findings highlight the potential of serum IgG as a predictive biomarker in this setting. Further validation is required in large prospective studies., Patient Summary: We found that for patients with metastatic kidney cancer, changes in the level of an antibody called immunoglobulin G (IgG) in blood during systemic treatment can predict their overall response. Early measurement of IgG could help doctors in personalizing treatment plans and might possibly improve the effectiveness of treatment for these patients., (© 2024 The Author(s).)

Background: AccuFFRct (ArteryFlow Technology) is a novel noninvasive method for calculating fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA). The accuracy of AccuFFRct has not been adequately assessed., Objectives: This study sought to evaluate the diagnostic performance of AccuFFRct in detecting lesion-specific ischemia., Methods: This prospective study enrolled 339 patients with 404 vessels. CCTA-derived FFR was calculated using an on-site computational fluid dynamics-based method and compared with invasive FFR. The performance of AccuFFRct was comprehensively analyzed in all lesions and subgroups, including "gray zone" lesions, various lesion classifications, clinical presentations, stenosis severities, and lesion locations., Results: Using FFR ≤0.80 as a reference standard, the overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for AccuFFRct were 90.6% (95% CI: 87.3%-93.3%), 90.9% (95% CI: 85.1%-94.9%), 90.4% (95% CI: 86.1%-93.8%), 85.3% (95% CI: 79.8%-89.5%), and 94.2% (95% CI: 90.8%-96.4%), respectively. Good correlation and agreement were found between the computed AccuFFRct and measured FFR. AccuFFRct showed superior discrimination ability to CCTA (AUC: 0.93 [95% CI: 0.89-0.95] vs 0.77 [95% CI: 0.72-0.81]; P < 0.001) and quantitative coronary angiography (AUC: 0.93 [95% CI: 0.89-0.95] vs 0.89 [95% CI: 0.85-0.92]; P = 0.048) for identifying functionally significant stenosis. Notably, AccuFFRct maintained high diagnostic accuracy across the spectrum of lesion classifications, clinical presentations, stenosis severities, lesion locations, and in the "gray zone". Furthermore, in the cohort with ≥70% stenosis, AccuFFRct could significantly reduce the rate of un-necessary invasive tests (33.1% vs 6.6%; P < 0.001)., Conclusions: The study confirms the potential of AccuFFRct as a noninvasive alternative to invasive FFR for detecting ischemia in coronary artery disease and to risk stratify patients. The results highlight AccuFFRct's robust diagnostic ability across a wide range of lesion classifications, clinical presentations, stenosis severities, lesion locations, and in the "gray zone". (Diagnostic Performance of Fractional Flow Reserve Derived From Coronary CT Angiography [ACCURATE-CT]; NCT04426396)., Competing Interests: Funding Support and Author Disclosures This work was supported by Zhejiang Provincial Public Welfare Technology Research Project (grant LGF20H020012), National Natural Science Foundation of China (grant 82170332), Zhejiang Provincial Key Research and Development Plan (grants 2020C03016 and 2024C03095), and Hangzhou Leading Innovation and Entrepreneurship Team Project (grant TD2022007). Dr Koo has received institutional research grants from HeartFlow and AiMEDIC. Dr Wang serves as Editor-in-Chief for JACC: Asia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac ultrasound is one of the most important examinations in cardiovascular medicine, but the technical requirements for the operator are relatively high, which to some extent affects the scope of its use. This study was dedicated to investigating the agreement of ejection fraction between coronary computed tomography (CT) and cardiac ultrasound and diagnostic performance in evaluating the clinical diagnosis of patients with chronic heart failure., Methods: We conducted a single-center-based retrospective study including 343 consecutive patients enrolled between January 2019 to April 2020, all of whom presented with suspected symptoms of heart failure within one month. All enrolled cases performed cardiac ultrasound and coronary CT scans. The CT images were analyzed using accurate left ventricle (AccuLV) artificial intelligence (AI) software to calculate the ejection fraction-computed tomography (EF-CT) and it was compared with the ejection fraction (EF) obtained based on ultrasound. Cardiac insufficiency was determined if the EF measured by ultrasound was below 50%. Diagnostic performance analysis, correlation analysis and Bland-Altman plot were used to compare agreement between EF-CT and CT., Results: Of the 319 successfully performed patients, 220 (69%) were identified as cardiac insufficiency. Quantitative consistency analysis showed a good correlation between EF-CT and EF values in all cases (R square =0.704, r=0.837). Bland-Altman analysis showed mean bias of 6.6%, mean percentage error of 27.5% and 95% limit of agreement of -17% to 30% between EF and EF-CT. The results of the qualitative diagnostic study showed that the sensitivity and specificity of EF measured by coronary CT reached a high level of 91% [95% confidence interval (CI): 86-94%], and the positive diagnostic value was up to 96% (95% CI: 92-98%)., Conclusions: The EF-CT and EF have excellent agreement, and AccuLV-based AI left ventricular function analysis software perhaps can be used as a clinical diagnostic reference., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1864/coif). W.L., X.L. and J.X. are employees of ArteryFlow Technology company. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The production of fucoxanthin and fatty acids in Conticribra weissflogii has been examined, but there is still a lack of understanding regarding the impact of trace elements, including iron, on their co-production. To address this knowledge gap, this study investigated the effects of FeCl 3 ·6H 2 O on the growth, fucoxanthin, and fatty acids of C. weissflogii . The findings revealed that the highest cell density (1.9 × 10 6 cells mL -1 ), cell dry weight (0.89 ± 0.15 g L -1 ), and total fatty acid concentration (83,318.13 µg g -1 ) were achieved at an iron concentration of 15.75 mg L -1 , while the maximum carotenoid and fucoxanthin contents were obtained at an iron concentration of 3.15 mg L -1 . The study demonstrated that the content of the active substance in C. weissflogii could be increased by adjusting the iron concentration, providing new information as to the more efficient co-production of fucoxanthin and fatty acids and offering experimental support for large-scale production.

Background: This study aimed to introduce a novel optical coherence tomography-derived fractional flow reserve (FFR) computational approach and assess the diagnostic performance of the algorithm for assessing physiological function., Methods: The fusion of coronary optical coherence tomography and angiography was used to generate a novel FFR algorithm (AccuFFRoct) to evaluate functional ischemia of coronary stenosis. In the current study, a total of 34 consecutive patients were included, and AccuFFRoct was used to calculate the FFR for these patients. With the wire-measured FFR as the reference standard, we evaluated the performance of our approach by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: Per vessel accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRoct in identifying hemodynamically significant coronary stenosis were 93.8%, 94.7%, 92.3%, 94.7%, and 92.3%, respectively, were found. Good correlation (Pearson's correlation coefficient r = 0.80, p < 0.001) between AccuFFRoct and FFR was observed. The Bland-Altman analysis showed a mean difference value of -0.037 (limits of agreement: -0.189 to 0.115). The area under the receiver-operating characteristic curve (AUC) of AccuFFRoct in identifying physiologically significant stenosis was 0.94, which was higher than the minimum lumen area (MLA, AUC = 0.91) and significantly higher than the diameter stenosis (%DS, AUC = 0.78)., Conclusions: This clinical study shows the efficiency and accuracy of AccuFFRoct for clinical implementation when using invasive FFR measurement as a reference. It could provide important insights into coronary imaging superior to current methods based on the degree of coronary artery stenosis.

Background: The efficacy of systemic therapy regimens, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (IO-TKI) and targeted therapy, for metastatic clear cell renal cell carcinoma (ccRCC) remains unpredictable due to the lack of effective biomarkers. Neutrophil extracellular trap (NET) plays an important role in promoting ccRCC. This study explores the NET predictive value of the efficacy in metastatic ccRCC., Methods: In this retrospective study, patients with metastatic ccRCC who received targeted drugs and IO-TKI were included. Immunofluorescence staining was utilized to quantify the levels of tissue NETs through cell counts of H3Cit(+) and MPO(+) cells., Results: A total of 183 patients with metastatic ccRCC were enrolled, including 150 patients who received TKIs and 33 patients who received IO-TKI. The levels of NETs in tumor tissue were significantly higher than in para-tumor tissue (p < 0.001). In terms of predicting drug efficacy, a correlation between NET levels and progression-free survival (PFS) was observed in the TKI with metachronous metastasis group (HR 1.73 [95% CI 1.02-2.91], log-rank p = 0.037), while no correlation was observed in the TKI with synchronous metastasis group and IO-TKI group. Regarding overall survival (OS), activated NET levels were associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p  = 0.017) and IO-TKI group (HR 4.35 [95% CI 1.06-17.82], log-rank p =0.047). IMDC score (HR 1.462 [95% CI 1.030-2.075], p = 0.033) and tumor tissue NET levels (HR 1.733 [95% CI 1.165-2.579], p = 0.007) were independent prognostic risk factors for OS in patients with metastatic ccRCC.NET level was associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p  = 0.017)., Conclusions: The active NET levels in tumor tissue can predict drug efficacy in patients with metastatic ccRCC who received systemic therapy. Elevated levels of NETs in tumor tissue were also associated with poor efficacy in OS., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Migraine is a highly prevalent headache disorder, and intake of various nutrients and special diets may improve migraine symptoms. We aimed to clarify the association between nutritional status and migraine., Patients and Methods: We collected the data of 1838/8953 (migraineurs/all participants) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 cycle. We used weighted multivariable linear or logistic regression analyses to study the association between the prognostic nutritional index (PNI) and the occurrence of severe headache or migraine., Results: After adjusting for confounding variables, we found that mild (PNI 45-50) or moderate to severe (PNI <45) malnutrition were associated with higher prevalence of severe headache or migraine (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.12, P  = 0.004; OR 1.07, 95% CI 1.03-1.12, P  < 0.001). In addition, we found that those with severe headache or migraine consumed less alcohol, dietary fiber, cholesterol, total folate, vitamin A, riboflavin, vitamin B6, vitamin B12, vitamin C, vitamin K, selenium, potassium, magnesium, and copper, and consumed more caffeine and theobromine than did those without severe headache or migraine., Conclusion: The PNI is associated with migraine prevalence, and may thus serve as a predictor of migraine risk and highlights the potential of nutrition-based strategies for migraine prevention and treatment.

Objectives: The aim of this study was to investigate the generalization performance of deep learning segmentation models on a large cohort intravascular ultrasound (IVUS) image dataset over the lumen and external elastic membrane (EEM), and to assess the consistency and accuracy of automated IVUS quantitative measurement parameters., Methods: A total of 11,070 IVUS images from 113 patients and pullbacks were collected and annotated by cardiologists to train and test deep learning segmentation models. A comparison of five state of the art medical image segmentation models was performed by evaluating the segmentation of the lumen and EEM. Dice similarity coefficient (DSC), intersection over union (IoU) and Hausdorff distance (HD) were calculated for the overall and for subsets of different IVUS image categories. Further, the agreement between the IVUS quantitative measurement parameters calculated by automatic segmentation and those calculated by manual segmentation was evaluated. Finally, the segmentation performance of our model was also compared with previous studies., Results: CENet achieved the best performance in DSC (0.958 for lumen, 0.921 for EEM) and IoU (0.975 for lumen, 0.951 for EEM) among all models, while Res-UNet was the best performer in HD (0.219 for lumen, 0.178 for EEM). The mean intraclass correlation coefficient (ICC) and Bland-Altman plot demonstrated the extremely strong agreement (0.855, 95% CI 0.822-0.887) between model's automatic prediction and manual measurements., Conclusions: Deep learning models based on large cohort image datasets were capable of achieving state of the art (SOTA) results in lumen and EEM segmentation. It can be used for IVUS clinical evaluation and achieve excellent agreement with clinicians on quantitative parameter measurements., (© 2023. The Author(s).)

Oocystis borgei , a microalgae species employed for regulating the quality of aquaculture water, demonstrates the capacity to adsorb noxious substances, curtail the growth of detrimental bacteria, and outcompete blooming cyanobacteria. It can be concentrated by natural sedimentation and stored at room temperature, making it costless and simple to transport and use. To study the mechanism of adaptation to room temperature preservation, O. borgei was concentrated (1.19 × 10 7 -1.21 × 10 7 cell/mL) and stored for 50 days at low (5 °C, LT), normal (25 °C, NT), and high (35 °C, HT) temperatures, respectively. Polysaccharide content, lipid content, cell survival, and resuscitation were evaluated. RNA-Seq was also used to examine how concentrated O. borgei responded to temperature. During storage, there was an increase in polysaccharide content and a decrease in lipid content, with both being significantly upregulated in the LT and HT groups. Survival and cell density were highest in the NT group. The RNA-Seq analysis revealed extensive differences in transcript levels. ATP synthesis was inhibited in the LT group due to the reduced expression of PsaD , PsaE , PsaF , PsaK , and PsaL . Under HT, the formation of reactive oxygen species (ROS) was facilitated by low levels of redox-related genes ( nirA ) and high levels of oxidative genes ( gdhA , glna , and glts) . The findings suggest that storing concentrated O. borgei at room temperature is optimal for microalgae preservation, enhancing theoretical research in this field. Our study provides further theoretical and practical support for the development of O. borgei as a live ecological preparation for aquaculture microalgae ecology management.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: A recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations., Objectives: This study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies., Methods: In this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization., Results: Of 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies., Conclusions: In cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men., Competing Interests: Funding Support and Author Disclosures The FLAVOUR trial was funded by Boston Scientific. Dr Hahn has received research grants from Abbott Korea, Biosensors International Group, Biotronik, Boston Scientific Corporation, and Medtronic. Dr Koo received institutional research grants from Abbott Vascular, Boston Scientific Corporation, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Fucoxanthin is a natural active substance derived from diatoms that is beneficial to the growth and immunity of humans and aquatic animals. Temperature, light and salinity are important environmental factors affecting the accumulation of diatom actives; however, their effects on the production of fucoxanthin in C. weissflogii are unclear. In this study, single-factor experiments are designed and followed by an orthogonal experiment to determine the optimal combination of fucoxanthin production conditions in C. weissflogii. The results showed that the optimum conditions for fucoxanthin production were a temperature of 30 °C, a light intensity of 30 umol m -2 s -1 and a salinity of 25. Under these conditions, the cell density, biomass, carotenoid content and fucoxanthin content of C. weissflogii reached 1.97 × 10 6 cell mL -1 , 0.76 g L -1 , 2.209 mg L -1 and 1.372 mg g -1 , respectively, which were increased to 1.53, 1.71, 2.50 and 1.48 times higher than their initial content. The work sought to give useful information that will lead to an improved understanding of the effective method of cultivation of C. weissflogii for natural fucoxanthin production.

This study was designed to compare the diagnostic performance of angio-FFR and CT-FFR for detecting hemodynamically significant coronary stenosis. Angio-FFR and CT-FFR were measured in 110 patients (139 vessels) with stable coronary disease using invasive FFR as the reference standard. On per-patient basis, angio-FFR was highly correlated with FFR (r =0.78, p <0.001), while the correlation was moderate between CT-FFR and FFR (r =0.68, p <0.001). Diagnostic accuracy, sensitivity, and specificity for angio-FFR were 94.6%, 91.4%, and 96.0%, respectively; and those of CT-FFR were 91.8%, 91.4%, and 92%, respectively. Bland-Altman analysis showed that angio-FFR had a larger average difference and a smaller root mean squared deviation than CT-FFR compared with FFR (-0.014±0.056 vs. 0.0003±0.072). Angio-FFR had a slightly higher AUC than that of CT-FFR (0.946 vs. 0.935, p =0.750). Angio-FFR and CT-FFR computed from coronary images could be accurate and efficient computational tools for detecting lesion-specific ischemia of coronary artery stenosis. Angio-FFR and CT-FFR calculated based on the two types of images can both accurately diagnose functional ischemia of coronary stenosis. CT-FFR can act as a gatekeeper to the catheter room, assisting doctors in determining whether patients need to be screened by coronary angiography. Angio-FFR can be used in the catheter room to determine the functional significant stenosis for helping decision-making in revascularization., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario., Hypothesis: A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation., Methods: ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA 2 DS 2 -VASc score ≥ 2) will be recruited after implantation of new-generation DES. A total of 1472 eligible patients will be randomly assigned to receive a 12-month dual antithrombotic treatment of either clopidogrel 75 mg daily or ticagrelor 90 mg twice daily in combination with dabigatran 110 mg twice daily. Participants will be followed up for 12 months after randomization. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, unplanned revascularization, ischemic stroke, and systemic thromboembolism. The primary safety endpoint is set as major bleeding or clinically relevant nonmajor bleeding defined by the International Society of Thrombosis and Hemostasis. The enrollment and follow-up have been launched., Results: The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024., Conclusions: The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis., Methods: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures., Results: A total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 ( CI : 2.18-4.10, I 2  =  42.7%, P <0.05); Visual acuity MD=0.10( CI : 0.06-0.13, I 2  =  0%, P <0.05); Fundus efficacy OR=5.47 ( CI : 1.33-22.51, I 2  =  71.4%, P <0.05); Neovascularisation regression rate OR=8 ( CI : 3.83-16.71, I 2  =  30.1%, P <0.05); Macular foveal thickness MD=-44.24 ( CI : -84.55-3.93, I 2  =  95.6%, P <0.05); Absorption of vitreous hemorrhage OR=4.7 ( CI : 2.26-9.77, I 2  =  0%, P <0.05); Fasting blood glucose MD=-0.23, ( CI : -0.38-0.07, I 2  =  0%, P <0.05); 2h postprandial blood glucose MD=-0.19 ( CI : -0.52-0.14, I 2  =  0%, P =0.25). From the results, the combined Chinese medicine adjuvant therapy showed better efficacy than the control group. A total of 69 kinds of traditional Chinese medicine were involved in 18 studies, among which the top four applied frequencies were Panax notoginseng, Rehmannia rehmannii, Astragalus membranaceus and Poria cocos. Most of the medicines were sweet and bitter in taste, the qi tended to be slight cold and cold, and the meridian tropism belongs to the liver meridian., Conclusion: The combination of traditional Chinese medicine adjuvant therapy has a good curative effect on PDR patients. However, the relevant clinical trials are few and more high-quality clinical trials are still needed, what's more the attention should be paid to the exploration of its safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huai, Huai, Su, Song, Li, Cao, Xin and Liu.)

Background: A computational method (AccuFFrangio) based on invasive coronary angiography (ICA) and computational fluid dynamics (CFD) to calculate fractional flow reserve (FFR) without a pressure wire has been devised to clarify the physiological significance of coronary stenosis. This study aimed to evaluate the diagnostic performance of AccuFFRangio computation under different boundary conditions and vessel reconstruction approaches., Methods: Consecutive patients with stable angina pectoris who underwent ICA and FFR assessment from 2 centers were analyzed retrospectively. Using wire-based FFR as the reference standard, the diagnostic performances of AccuFFRangio and its variations were evaluated and compared. The calculation of AccuFFRangio involves several key boundary conditions, including patient-specific aortic pressure, contrast flow velocity derived from the thrombolysis in myocardial infarction (TIMI) frame count method, and vessel reconstruction based on 2 angiographic views. We considered the following 3 variations: (I) a fixed aortic pressure [fixed pressure AccuFFRangio (pAccuFFRangio)], (II) an empirical hyperemic velocity [fixed velocity AccuFFRangio (vAccuFFRangio)], and (III) vessel reconstruction using a single angiographic view [single view AccuFFRangio (sAccuFFRangio)]., Results: A total of 230 patients with 230 vessels were included in the final analysis. The accuracy for standard AccuFFRangio, pAccuFFRangio, vAccuFFRangio, and sAccuFFRangio was 93.91%, 86.52%, 81.74%, and 83.48%, respectively; the sensitivity was 90.74%, 51.85%, 83.33%, and 46.30%, respectively; the specificity was 94.89%, 97.16%, 81.25%, and 94.89%, respectively; and the area under the receiver operating characteristic curve was 0.971, 0.928, 0.892, and 0.870, respectively., Conclusions: The comparison suggested that the overall performance of the standard AccuFFRangio was superior to other variations and had the highest accuracy among all the cases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-893/coif). XS received grants from the Major Project of Social Development of Jinhua Science and Technology Project (No. 2021-3-028). LD received grants from the National Natural Science Foundation of China (No. 82170329). CL received grants from the Zhejiang Provincial Public Welfare Technology Research Project (No. LGF20H020012). JJ received grants from the National Natural Science Foundation of China (No. 81100141, 81570322, and 82170332) and grants from the Zhejiang Provincial Key Research and Development Plan (No. 2020C03016). YH and XY are the employees of ArteryFlow. Xiaochang Leng is a cofounder of ArteryFlow. JX is the chief executive officer of ArteryFlow. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Migraine and breast cancer are 2 prevalent diseases with high morbidity and mortality rates world-wide. There have been inconsistent reports regarding the association between migraine and risk of breast cancer. This systematic review and meta-analysis aimed to assess the risk of breast cancer in patients with migraine. By December, 1, 2022, we searched PubMed, Web of Science, Scopus, and Cochrane Library databases. Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CIs) were extracted or assessed to determine the pooled risk estimate using a random-effects model. We use the Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies. We included 9 studies involving 393,282 participants. The pooled analysis showed that patients with migraine had a slightly low risk of breast cancer (OR 0.82, 95% CI, 0.72-0.94; P = .003), especially in case-control studies (OR 0.69, CI: 0.60-0.81, I 2  = 74.1%, p < .001), and hormone receptor-positive breast cancer (OR 0.76, CI: 0.63-0.91; I 2  = 88.6%; p = .003). Our findings demonstrate a slightly low risk of breast cancer, especially hormone receptor-positive breast cancer, in patients with migraine., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Fractional flow reserve (FFR) is the gatekeeper for lesion-specific revascularization decision-making in patients with stable coronary artery disease (CAD). The potential of noninvasive calculation of FFR from coronary computed tomographic angiography (CCTA) to identify ischemia-causing lesions has not been sufficiently assessed. The objective of this study was to evaluate the feasibility and diagnostic accuracy of a novel computational fluid dynamics (CFD)-based technology, termed as AccuFFRct, for the diagnosis of functionally significant lesions from CCTA, using wire-based FFR as a reference standard., Methods: A total of 191 consecutive patients who underwent CCTA and FFR measurement for suspected or known CAD were retrospectively enrolled at 2 medical centers. Three-dimensional anatomic model of coronary tree was extracted from CCTA data, CFD was applied subsequently with a novel strategy for the computation of FFR in a blinded fashion by professionals. Results were compared to invasive FFR, a threshold of ≤0.80 was used to indicate the hemodynamically relevant stenosis., Results: On a per-patient basis, the overall accuracy, sensitivity, specificity of AccuFFRct for detecting ischemia were 91.78% (95% CI: 86.08% to 95.68%), 92.31% (95% CI: 81.46% to 97.86%) and 91.49% (95% CI: 83.92% to 96.25%), respectively; those for per-vessel basis were 91.05% (95% CI: 86.06% to 94.70%), 92.73% (95% CI: 82.41% to 97.98%) and 90.37% (95% CI: 84.10% to 94.77%), respectively. The AccuFFRct and FFR was well correlated on per-patient ( r =0.709, P<0.001) and per-vessel basis ( r =0.655, P<0.001). The AUC of AccuFFRct determination was 0.935 (95% CI: 0.881 to 0.969) and 0.927 (95% CI: 0.880 to 0.960) on per-patient and per-vessel basis., Conclusions: This novel CFD-based CCTA-derived FFR shows good diagnostic performance for detecting hemodynamic significance of coronary stenoses and may potentially become a new gatekeeper for invasive coronary angiography (ICA)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-521/coif). J Jiang received grants form National Natural Science Foundation of China (Nos. 81100141, 81570322, 82170332) and Zhejiang Provincial Key Research and Development Plan (No. 2020C03016); CD received grant from Major Medical and Health Science and Technology Plan of Zhejiang Province (No. WKJ-ZJ-1913); YH is an employee of ArteryFlow; YP received grants from Zhejiang Provincial Public Welfare Technology Research Project (No. LGF21H020003) and Major Project of Social Development of Jinhua Science and Technology Project (No. 2020-3-027); LB received grant from Key Project of Social Development of Jinhua Science and Technology Project (No. 2020-3-047); LD received grant from National Natural Science Foundation of China (No. 82170329); CL received grant from Zhejiang Provincial Public Welfare Technology Research Project (No. LGF20H020012); XL is a co-founder of ArteryFlow; JX is the CEO of ArteryFlow; JAW received grant from National Natural Science Foundation of China (Nos. 81320108003, 31371498). The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Fucoxanthin and fatty acids are active substances that are beneficial to the growth and immunity of humans and aquatic animals. However, relatively few species have been exploited for fucoxanthin and fatty acids in the industry. At the same time, due to its low extract content, poor stability, high production cost, and serious seasonal and regional limitations, the industry cannot normally meet the greater demand of the international market. Therefore, this experiment seeks to improve the fucoxanthin and fatty acid content of C. weissflogii by adjusting the nitrogen concentration in the culture medium. It was found that when the nitrogen concentration was 150 mg L -1 , the cell number was 1.5 × 10 6 cell mL -1 , and the average biomass was 0.75 g L -1 . The mean value of carotenoid concentration was 2.179 mg L -1 . The average concentration of fucoxanthin was 1.547 mg g -1 . When the nitrogen concentration was 75 mg L -1 , the fatty acid content reached its highest. By adjusting the concentration of nitrogen, the contents of fucoxanthin and fatty acids were increased. The results provided a theoretical basis for commercial extraction of fucoxanthin and fatty acids and further promoted the industrialization of fucoxanthin and fatty acids.

Background: Anaphylaxis is a life-threatening systemic allergic reaction. Omalizumab (OMA) is an established treatment in chronic urticaria (CU), but experience in anaphylaxis is limited., Objectives: The objective was to evaluate the efficacy and safety of OMA on anaphylaxis in patients with CU who are resistant to antihistamine therapy and have a history of anaphylaxis., Method: Patients with antihistamine-resistant CU and a history of anaphylaxis were eligible. OMA was given 300 mg/150 mg every 4 weeks. Urticaria control test (UCT) scores, the episodes of anaphylaxis, and adverse events were recorded during the OMA treatment., Results: A total of 7 adults were included. After starting OMA, all of them achieved a complete control (UCT = 16) after 3 months of OMA treatment; 6 of them did not suffer any attack of anaphylaxis in the follow-up periods (5 patients for more than 12 months and 1 patient for 4 months). No adverse events were observed., Conclusion: The study indicated the efficacy and safety of OMA for antihistamine-resistant CU patients with a history of anaphylaxis and its potential as a prevention option for anaphylaxis., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Hypothesis: Nomogram can be built to predict the pathological T3a upstaging from clinical T1a in patients with localized renal cell carcinoma before surgery., Purpose: Renal cell carcinoma (RCC) patients with clinical T1a (cT1a) disease who are upstaged to pathological T3a (pT3a) have reduced survivals after partial nephrectomy. We aimed to develop a nomogram-based model predicting pT3a upstaging in RCC patients with preoperative cT1a based on multiple preoperative blood indexes and oncological characteristics., Materials and Methods: Between 2010 and 2019, 510 patients with cT1a RCC were individually matched according to pT3a upstaging and pathological T1a (pT1a) at a 1:4 ratio using clinicopathologic features. Least absolute shrinkage and selection operator regression analysis was used to identify the most important risk factor from 40 peripheral blood indicators, and a predictive model was established. Multivariate logistic regression analysis was performed with the screened blood parameters and clinical data to identify significant variables. Harrell's concordance index (C-index) was applied to evaluate the accuracy of the model for predicting pT3a upstaging in patients with cT1a RCC., Results: Out of 40 blood indexes, the top ranked predictor was fibrinogen (FIB). Age, the ratio of the tumor maximum and minimum diameter (ROD), FIB, and tumor size were all independent risk factors for pT3a upstaging in multivariate analysis. A predictive ARFS model (Age, ROD, FIB, tumor Size) was established, and the C-index was 0.756 (95% CI, 0.681-0.831) and 0.712 (95% CI, 0.638-0.785) in the training and validation cohorts, respectively., Conclusions: Older age, higher ROD, increased FIB level, and larger tumor size were independent risk factors for upstaging. The ARFS model has a high prediction efficiency for pT3a upstaging in patients with cT1a RCC., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: To investigate the efficacy and complications of surgical treatment in patients with renal cell carcinoma aged ≥ 75 years., Methods: From January 2009 to May 2019, we assessed 166 patients aged 75 years and older, who either had radical nephrectomy (RN) or partial nephrectomy (PN) as treatments for diagnosed renal cell carcinoma. Patients were divided into one group of patients aged 75-79 years and the second group of patients ≥ 80 years. The complications and survival were compared between the two groups., Results: All 166 patients were successfully operated on. Differences between the two groups were statistically significant in intraoperative and postoperative complications and Clavien-Dindo score of ≥ 1 (P = 0.02, P < 0.001, P = 0.001). Univariate analysis revealed no significant correlation between a Clavien-Dindo score ≥ 1 versus gender, body mass index (BMI), lack of symptoms, KPS, baseline GFR, postoperative GFR, tumor size, tumor location, surgical method, and transfusion or no transfusion (ALL P > 0.05). Multifactor analysis showed that age ≥ 80 years, partial nephrectomy, and operation time were independent predictors of a Clavien-Dindo score ≥ 1. No significant difference was found in OS between the two groups, (P < 0.0001), and no significant difference in CSS (P = 0.056). There was no significant difference in OS and CSS between the RN and PN groups (P = 0.143, P = 0.281, respectively)., Conclusions: According to our findings, the overall safety of surgical therapy for elderly patients with renal cell carcinoma is adequate. PN should be carefully examined, especially over the age of 80. To select suitable patients based on an assessment of the tumor's complexity and patients' physical condition, such as age, underlying diseases and other conditions, technical feasibility, balance of benefits and a case-by-case., (© 2022. The Author(s).)

It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality and ecological environment and causes huge economic losses. Algicidal bacteria have a promising application prospect in controlling cyanobacterial blooms in aquaculture water. Here, the process of the algicidal bacterium Brevibacillus laterosporus strain Bl-zj acting on Microcystis aeruginosa was explored using transcriptome analysis to elucidate the algicidal mechanism. The results of the co-culture of bacterium and alga showed a strong alga-lysing effect of B. laterosporus against M. aeruginosa with an extreme morphology deformation of the algal cells. A total of 2744 differentially expressed genes of B. laterosporus were identified, which were mainly involved in the metabolism of amino acid, carbohydrate, and lipid. In the co-cultured group, the expression of genes mainly enriched in valine, leucine and isoleucine degradation, and fatty acid degradation were significantly increased. However, the expression of the genes related to ribosome were mainly inhibited. Transcriptome analysis showed that B. laterosporus obtained ATP and energy by the degradation of valine, leucine, isoleucine, and fatty acids, and destroyed algal cells by efflux pump transporters, secretion of hydrolytic enzymes, antibiotics, proteases, and other secondary metabolites, resulting in algal death and achieving the algicidal effect.

Background: Several models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC)., Methods: Patients with mccRCC (n = 213) treated with sunitinib from January 2008 to December 2018 were identified. Cutoff value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan-Meier method., Results: The optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD ≥ 1.34 group had shorter PFS (9.6 versus 17.7 months, p < 0.001) and OS (25.5 versus 32.6 months, p < 0.001) than patients in ROD < 1.34 group. After adjustment for other factors, multivariate analysis showed ROD ≥ 1.34 was an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.006). Patients in ROD ≥ 1.34 group presented higher proportions of pT3/4 stage (89.2% versus 10.8%, p = 0.021), WHO/ISUP grade III/IV (72.0% versus 28.0%, p = 0.010), tumor necrosis (71.0% versus 29.0%, p = 0.039), sarcomatoid differentiation (79.1% versus 20.9%, p = 0.007), poor MSKCC risk score (78.4% versus 21.6%, p < 0.001) and poor IMDC risk score (74.4% versus 25.6%, p < 0.001) than ROD < 1.34 group., Conclusion: Primary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high pT stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score., (© 2022. The Author(s).)

Objectives: This study sought to present a novel approach for computation of the index of microcirculatory resistance (IMR) and to evaluate its diagnostic performance., Background: IMR is a quantitative assessment to identify coronary microvascular dysfunction. However, its clinical use remains extremely limited. Calculation of IMR from coronary angiography images may increase the utility of coronary microvasculature assessment., Methods: 203 patients with 203 vessels were included in this study. Physiology measurements were obtained with pressure-wire in the whole cohort. The computational fluid dynamics (CFD)-based AccuIMR was computed and evaluated in a blinded fashion using wire-based IMR as the reference standard., Results: The overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AccuIMR for detecting coronary microvascular disease were 91.1% (95% CI: 86.4% to 94.7%), 89.4% (95% CI: 80.9% to 95.0%), 92.4% (95% CI: 86.0% to 96.5%), 89.4% (95% CI: 81.8% to 94.1%), and 92.2% (95% CI: 86.7% to 95.8%), respectively. The correlation coefficient equaled to 0.81 (p < 0.001) between AccuIMR and wire-based IMR with the receiver-operating curve had area under the curve of 0.924 (95% CI: 0.878 to 0.956)., Conclusions: AccuIMR is a novel pressure-wire free approach to assess coronary microvascular disease with great diagnostic performance, which can be a valid, efficient, and cost-reducing tool to provide an easier routine assessment of coronary microcirculation., Competing Interests: Conflict of Interest The authors have no conflict of interest to declare that are relevant to the content of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa., Methods: We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether., Results: In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7-95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83-0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1-99.5%) high grade tumors and 60.0% (95% CI 17.0-92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history., Conclusions: Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors., (© 2022. The Author(s).)

This study evaluated the possibility of using Oocystis borgei to prevent and control harmful algae blooms. Firstly, Microcystis aeruginosa and O. borgei were co-cultured to assess the competition for nutrients between them. Different physiological and biochemical parameters, such as growth, cell membrane permeability and esterase activities were determined in exudate culture experiment to investigate allelopathic effects of O. borgei culture and mixed cultures ( O. borgei and M. aeruginosa ) at different growth phase on harmful microalgae ( M. aeruginosa ). Results showed that O. borgei could significantly inhibited M. aeruginosa when volume ratios were 4:1 and 1:1 ( M. aeruginosa: O. borgei ) in co-culture experiment. Further, it was found that the membrane system of M. aeruginosa was disintegrated by the culture filtrate of O. borgei at exponential phase. In addition, esterase activities and photorespiration were significantly inhibited. In conclusion, O. borgei exhibited different allelopathic effects at different growth phase. Its exponential phase showed a significant inhibitory effect, while no inhibitory effect was observed at the decline phase.

Objectives: Metastatic renal cell carcinoma can occur synchronously or metachronously. We characterized the time from diagnosis to systematic therapy as a categorical variable to analyze its effect on the overall survival and first-line treatment efficacy of metastatic renal cell carcinoma patients., Methods: We initially enrolled 949 consecutive metastatic renal cell carcinoma patients treated with targeted therapies retrospectively from December 2005 to December 2019. X-tile analysis was used to determine cut-off values of time from diagnosis to systematic therapy referring to overall survival. Patients were divided into different groups based on the time from diagnosis to systematic therapy and then analyzed for survival., Results: Of 358 eligible patients with metastatic renal cell carcinoma, 125 (34.9%) had synchronous metastases followed by cytoreductive nephrectomy, and 233 (65.1%) had metachronous metastases. A total of 28 patients received complete metastasectomy. Three optimal cut-off values for the time from diagnosis to systematic therapy (months) - 1.1, 7.0 and 35.9 - were applied to divide the population into four groups: the synchro group (time from diagnosis to systematic therapy ≤1.0), early group (1.0 < time from diagnosis to systematic therapy ≤ 7.0), intermediate group (7.0 < time from diagnosis to systematic therapy < 36.0) and late group (time from diagnosis to systematic therapy ≥36.0). The targeted therapy-related overall survival (P < 0.001) and progression-free survival (P < 0.001) values were significantly different among the four groups. Patients with longer time from diagnosis to systematic therapy had better prognoses and promising efficacy of targeted therapy. With the prolongation of time from diagnosis to systematic therapy, complete metastasectomy was more likely to achieve and bring a better prognosis., Conclusions: The time from diagnosis to systematic therapy impacts the survival of metastatic renal cell carcinoma patients treated with targeted therapy. The cutoff points of 1, 7 and 36 months were statistically significant. The statistical boundaries might be valuable in future model establishment., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: Non-invasive fractional flow reserve (FFR) has been increasingly used in the clinical workflow to assist clinical decision-making for percutaneous coronary intervention (PCI). This clinical study evaluates the diagnostic accuracy of coronary stenosis assessed by a non-invasive FFR analysis method (termed AccuFFRangio) based on invasive coronary angiography (ICA). It is a blinded, self-controlled, retrospective, and dual-center clinical investigation study., Methods: Coronary angiography data and the related information of 320 patients with 320 vessels were collected, and AccuFFRangio was used to assess the FFR for these patients. Compared with the wire-measured FFR values, we evaluated AccuFFRangio performance by its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: The diagnostic accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRangio in identifying hemodynamically significant coronary stenosis were 93.3%, 92.6%, 93.5%, 84.3%, and 97.1%, respectively. The direct correlation between computed AccuFFRangio and measured FFR was 0.812 (P<0.001), and the area under the receiver operating characteristic curve (AUC) value of AccuFFRangio was 0.96., Conclusions: This clinical study demonstrates the efficiency and accuracy of AccuFFRangio for clinical implementation when using invasive wire-measured FFR as a reference. Further validation is required in a large prospective multicenter study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-463). JJ receives research grants from National Natural Science Foundation of China (81570322) and Zhejiang Provincial Key Research and Development Plan (2020C03016). LT receives research grant from Zhejiang Provincial Key Research and Development Plan (2017C03034). CD receives research grant from Major Medical and Health Science and Technology Plan of Zhejiang Province (WKJ-ZJ-1913). XL receives research grant from National Natural Science Foundation of China (11802113). CL reeives research grants from Zhejiang Provincial Public Welfare Technology Research Project (LGF20H020012) and Scientific Research Project of Zhejiang Education Department (Y201330290). JX receives research grant from National Natural Science Foundation of China (81771242) and Stock/Stock Options of ArteryFlow Technology., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Testicular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy., Methods: We retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed., Results: Among the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months., Conclusions: TSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shang, Cao, Jiang, Shi, Bi, Cui, Shou, Zheng, Zhang, Zhou, Li and Ma.)

Background: Retinal artery occlusion (RAO) is an emergency condition in both neurology and ophthalmology departments. However, RAO's management and visual outcome in different initial departments remain unclear. Therefore, we aimed to investigate the impact of the initial department on the management and prognosis of RAO., Methods: Consecutive cases of RAO between January 2011 and December 2021 were retrospectively analyzed. The neurology and ophthalmology departments compared the baseline characteristics, relevant evaluation, and treatment. The primary outcome was the visual recovery rate. The secondary outcomes were newly diagnosed cardiovascular factors, concurrent stroke and new-onset cardiovascular events., Results: A total of 74 RAO patients were included. The median age was 54 years, and 67.6% were male. 42 (56.8%) patients were admitted to the neurology department and 32 (43.2%) to the ophthalmology department. The visual recovery rate was higher in the neurology department than in the ophthalmology department, although the difference did not reach statistical significance (27.8 vs. 12.5%, p = 0.120). Risk factor evaluation and secondary prevention were taken more frequently in the neurology department (p < 0.001). Cardiovascular risk factors and concurrent stroke were all discovered in the neurology department. However, the incidence of new-onset cardiovascular events was similar between the two departments., Conclusion: The study demonstrated that the visual prognosis of RAO was devastating regardless of the neurology and ophthalmology department. Given the admission delay, inadequate management, and high risk of cardiovascular risk factors and stroke, stroke centers should be recommended as initial admission departments for RAO patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Non-metastatic renal cell carcinoma (RCC) with tumor thrombus showed a greater tendency for developing metastases after surgery. Early identification of patients with high risk of poor prognosis is especially important to explore adjuvant treatment of improving outcomes. Neutrophil-to-lymphocyte ratio (NLR) was a systemic inflammation marker and outcome predictor in RCC, reflecting the chaos in systemic immune status in cancer as myeloid cell expansion and lymphatic cell suppression. Neutrophil extracellular traps (NET) formation (NETosis) is the process of neutrophils generating an extracellular DNA net-like structure. NETosis in tumor was demonstrated to conduce to the subsequent metastases of tumor. However, the role of NLR for systemic immune status and tumor local immune infiltration, especially for neutrophil-associated NETs, in non-metastatic RCC with thrombus remains unclear., Patients and Methods: In our clinical cohort, we enrolled the clinical, pathologic, and preoperative laboratory parameters of 214 RCC patients with tumor thrombus who were treated surgically. The clinical endpoint was defined as cancer-specific survival (CSS). In our basic research cohort, RNA-seq, TCR-seq, and scRNA-seq data were analyzed. Patients who reached the endpoint as recurrence-free survival (RFS) were defined as the "High-risk" group. Otherwise, they were separated into the "Low-risk" group., Results: In the clinical cohort, NLR≥4 was an independent risk factor for 203 localized RCC with tumor thrombus. In the basic research cohort, tumor thrombi were separated into NETosis-thrombi belonging to the "High-risk" group and non-NETosis-thrombi to the "Low-risk" group. NETs induced by tumor-derived G-CSF in tumor thrombus has a mechanistic role in unfavorable prognosis. Besides, NETs-score from single sample GSEA (ssGSEA) algorithm was an independent prognostic factor validated in the TCGA data. Apart from the neutrophils-associated NETosis, systemic immune perturbations of lymphocytes occurred in the "High-risk" group, represented with decreased TCR diversity and increasingly high proportion of CD4-positive effector memory T (Tem) cells, which indirectly represented the state of lymphopenia., Conclusions: Our findings firstly demonstrated that neutrophils-associated NETosis and systemic lymphocytes perturbations were considered as tumor progression in patients of localized RCC with tumor thrombus, which reflected NLR≥4 as an independent risk factor for patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shang, Guo, Shen, Cao, Xie, Jiang, Wen, Bi, Shi, Zheng, Li, Ma, Zhang, Feng and Shou.)

With the improvement of living standards, people have more and more physical health problems. Among them, high-risk cardiovascular diseases such as hypertension, diabetes, and coronary heart disease are the most prominent. The number of cardiology patients is increasing year by year. Effectively improving the treatment of cardiology patients and speeding up the recovery of cardiology patients have become a social problem. This article aims to explore the impact of diverse nursing care on patients in cardiology treatment. This article first gives a detailed introduction to the treatment of diverse nursing and cardiology diseases, then takes 300 cardiology patients in our hospital as experimental subjects, and conducts a controlled experiment of nursing intervention, which is categorized into an experimental group of 150 cases (including 35 cases of hypertension, 46 cases of diabetes, 28 cases of coronary heart disease, 24 cases of angina pectoris, and 17 cases of multiple complications) and a control group of 150 cases (including 30 cases of hypertension, 47 cases of diabetes, 39 cases of coronary heart disease, 21 cases of angina pectoris, and 13 cases of multiple complications). The experimental results showed the following: the general information of the two groups of patients was not statistically different ( P > 0.05); after the nursing intervention, the blood glucose levels of the two groups of patients decreased, but the experimental group decreased more significantly and the blood glucose control effect was more obvious; after the intervention, in the experimental group that implemented diversified nursing interventions, the patient's condition management effect was better and their scores were between 8 and 10; the mental state self-evaluation of the two groups of patients was significantly different from the domestic reference value ( P < 0.05), and there is a very significant statistical difference between the two groups after nursing intervention ( P < 0.01); after nursing intervention, compared with the control group, the quality of life of the experimental group improved more significantly and the highest score reached about 70; the overall satisfaction of the experimental group with nursing work reached 92%, while the satisfaction of the control group with nursing work was only 44.67%. Studies have shown that diversified care has a positive impact on the rehabilitation of patients in cardiology treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Changling Li and Aijie He.)

The installed wind energy generation capacity has been increasing dramatically all over the world. However, most wind turbines are installed in hostile environments, where regular operation needs to be ensured by effective fault tolerant control methods. An adaptive observer-based fault tolerant control scheme is proposed in this article to address the sensor and actuator faults that usually occur on the core subsystems of wind turbines. The fast adaptive fault estimation (FAFE) algorithm is adopted in the adaptive observers to accurately and rapidly located the faults. Based on the states and faults estimated by the adaptive observers, the state feedback fault tolerant controllers are designed to stabilize the system and compensate for the faults. The gain matrices of the controllers are calculated by the pole placement method. Simulation results illustrate that the proposed fault tolerant control scheme with the FAFE algorithm stabilizes the faulty system effectively and performs better than the baseline on the benchmark model of wind turbines.

Background: The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Therefore, a convenient diagnostic nomogram for neurosyphilis is warranted. This study aimed to construct diagnostic models for diagnosing neurosyphilis., Methods: This cross-sectional study included data of two patient cohorts from Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin Hospital between September 2019 and April 2021 as the development cohort and the external validation cohort, respectively. A diagnostic model using logistic regression analysis was constructed to readily provide the probability of diagnosis at point of care and presented as a nomogram. The clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) and Harrell concordance (Harrell C) index for discrimination and calibration plots for accuracy, which adopted bootstrap resampling 500 times., Results: One hundred forty-eight and 67 patients were included in the development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive neurosyphilis under the criteria of positive results in both CSF treponemal and non-treponemal tests. In the development cohort, male, psychiatric behaviour disorders, and serum toluidine red unheated serum test were selected as diagnostic indicators applying a stepwise procedure in multivariable logistic model. The model reached 80% specificity, 79% sensitivity, and 0·85 area under the curves (AUC) (95% confidence interval, 0·76-0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive neurosyphilis was 0·71., Conclusions: A convenient model using gender, presence of psychiatric behaviour disorders, and serum TRUST titre was developed and validated to indicate diagnostic results in patients suspected of neurosyphilis. Checking the model value of factors on nomogram is a feasible way to assist clinicians and primary health servers in updating patients' medical charts and making a quantitatively informed decision on neurosyphilis diagnosis., Trial Registration: This research was retrospectively registered in the Ethics committee on biomedical research, West China Hospital of Sichuan University. The research registration and committee's reference number was 1163 in 2020 approval., (© 2021. The Author(s).)

Background: Intravascular ultrasound (IVUS) provides good insight into lumen boundary and plaques; however, it is still difficult to detect functionally significant stenosis from IVUS images for the guidance of coronary percutaneous intervention (PCI). This study aimed to develop a novel method to estimate fractional flow reserve (FFR) value for determining the functional significance of coronary artery disease through the fusion of IVUS and X-ray angiographic images., Methods: We developed a novel approach to 3D vessel reconstruction by integrating IVUS with X-ray angiographic images. Based on the reconstructed geometry and the inlet flow derived from the thrombolysis in myocardial infarction (TIMI) frame count, a simplified fluid dynamics equation was established to compute the pressure drop and IVUS-derived FFR (AccuFFRivus) was subsequently obtained. To validate the feasibility and performance of this IVUS-based FFR method, we performed AccuFFRivus calculations on 32 coronary vessels with invasive FFR as the reference standard., Results: Great correlation (r=0.86, P<0.001) was observed between AccuFFRivus and FFR. The area under the receiver-operating characteristic curve (AUC) was higher for AccuFFRivus than minimal lumen area (MLA, <4 mm 2 ) and diameter stenosis rate (DS% ≥50%) [0.98 (95% CI: 0.86 to 1.0) vs. 0.78 (95% CI: 0.60 to 0.91) and 0.66 (95% CI: 0.47 to 0.82)]. Bland-Altman plot showed a mean difference value of -0.011 (limits of agreement: -0.156 to 0.134)., Conclusions: AccuFFRivus is a novel method for hybridizing IVUS and X-ray angiographic images to identify functionally significant stenosis with FFR ≤0.80. The good diagnostic performance from the initial validation study demonstrates the potential for clinical utilization of physiologically guided decision-making. Further validation is required in future studies with a large number of cases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-20-1324). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: A new method for calculating fraction flow reserve (FFR) without pressure-wire (angiography-derived FFR) based on invasive coronary angiography (ICA) images can be used to evaluate the functional problems of coronary stenosis. Objective: The aim of this study was to assess the diagnostic performance of a novel method of calculating the FFR compared to wire-based FFR using retrospectively collected data from patients with stable angina. Methods: Three hundred patients with stable angina pectoris who underwent ICA and FFR measurement were included in this study. Two ICA images with projections >25° apart at the end-diastolic frame were selected for 3D reconstruction. Then, the contrast frame count was performed in an angiographic run to calculate the flow velocity. Based on the segmented vessel, calculated velocity, and aortic pressure, AccuFFRangio distribution was calculated through the pressure drop equation. Results: Using FFR ≤ 0.8 as a reference, we evaluated AccuFFRangio performance for 300 patients with its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Comparison of AccuFFRangio with wire-measured FFR resulted in an area under the curve (AUC) of 0.954 (per-vessel, p < 0.0001). Accuracy for AccuFFRangio was 93.7% for Pa set from measurement and 87% for Pa = 100 mmHg in this clinical study. Overall sensitivity, specificity, PPV, and NPV for per-vessel were 90, 95, 86.7, 96.3, and 57.5, 97.7, 90.2, 86.3%, respectively. Overall accuracy, sensitivity, specificity, PPV, and NPV for 2-dimensional (2D) quantitative coronary angiography (QCA) were 63.3, 42.5, 70.9, 34.7, and 77.2%, respectively. The average processing time of AccuFFRangio was 4.30 ± 1.87 min. Conclusions: AccuFFRangio computed from coronary ICA images can be an accurate and time-efficient computational tool for detecting lesion-specific ischemia of coronary artery stenosis., Competing Interests: XL is employed by ArteryFlow Technology and receives grants from National Natural Science Foundation of China (No. 11802113). JH and YX was employed by ArteryFlow Technology. JX is the CEO of ArteryFlow Technology and receives grants from National Natural Science Foundation of China (No. 81771242). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Leng, He, Xia, Jiang, Pan, Dong, Sun, Hu, Wang, Xiang and Jiang.)

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy., Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate., Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory., Conclusion: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Harmful algal blooms caused huge ecological damage and economic losses around the world. Controlling algal blooms by algicidal bacteria is expected to be an effective biological control method. The current study investigated the molecular mechanism of harmful cyanobacteria disrupted by algicidal bacteria. Microcystis aeruginosa was co-cultured with Brevibacillus laterosporus Bl-zj, and RNA-seq based transcriptomic analysis was performed compared to M. aeruginosa , which was cultivated separately. A total of 1706 differentially expressed genes were identified, which were mainly involved in carbohydrate metabolism, energy metabolism and amino acid metabolism. In the co-cultured group, the expression of genes mainly enriched in photosynthesis and oxidative phosphorylation were significantly inhibited. However, the expression of the genes related to fatty acid synthesis increased. In addition, the expression of the antioxidant enzymes, such as 2-Cys peroxiredoxin, was increased. These results suggested that B. laterosporus could block the electron transport by attacking the PSI system and complex I of M. aeruginosa , affecting the energy acquisition and causing oxidative damage. This further led to the lipid peroxidation of the microalgal cell membrane, resulting in algal death. The transcriptional analysis of algicidal bacteria in the interaction process can be combined to explain the algicidal mechanism in the future.

Background: Fractional flow reserve (FFR) is a widely used gold standard to evaluate ischemia-causing lesions. A new method of non-invasive approach, termed as AccuFFRct, for calculating FFR based on coronary computed tomography angiography (CCTA) and computational fluid dynamics (CFD) has been proposed. However, its diagnostic accuracy has not been validated., Objectives: This study sought to present a novel approach for non-invasive computation of FFR and evaluate its diagnostic performance in patients with coronary stenosis., Methods: A total of 54 consecutive patients with 78 vessels from a single center who underwent CCTA and invasive FFR measurement were retrospectively analyzed. The CT-derived FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of AccuFFRct and CCTA in detecting hemodynamically significant coronary artery disease (CAD) was evaluated using the invasive FFR as a reference standard., Results: Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for AccuFFRct in detecting FFR ≤ 0.8 on per-patient basis were 90.7, 89.5, 91.4, 85.0 and 94.1%, respectively, while those of CCTA were 38.9, 100.0, 5.71, 36.5 and 100.0%, respectively. The correlation between AccuFFRct and FFR was good (r = 0.76 and r = 0.65 on per-patient and per-vessel basis, respectively, both p < 0.0001). Area under the curve (AUC) values of AccuFFRct for identifying ischemia per-patient and per-vessel basis were 0.945 and 0.925, respectively. There was much higher accuracy, specificity and AUC for AccuFFRct compared with CCTA., Conclusions: AccuFFRct computed from CCTA images alone demonstrated high diagnostic performance for detecting lesion-specific ischemia, it showed superior diagnostic power than CCTA and eliminated the risk of invasive tests, which could be an accurate and time-efficient computational tool for diagnosing ischemia and assisting clinical decision-making., (© 2021. The Author(s).)

Objectives: This multicenter, prospective clinical study investigates whether the microelectromechanical-systems-(MEMS)-sensor pressure microcatheter (MEMS-PMC) is comparable to a conventional pressure wire in fractional flow reserve (FFR) measurement., Background: As a conventional tool for FFR measurement, pressure wires (PWs) still have some limitations such as suboptimal handling characteristics and unable to maintain the wire position during pullback assessment. Recently, a MEMS-PMC compatible with any 0.014″ guidewire is developed. Compared with the existing optical-sensor PMC, this MEMS-PMC has smaller profiles at both the lesion crossing and sensor packaging areas., Methods: Two hundred and forty-two patients with visually 30-70% coronary stenosis were enrolled at four centers. FFR was measured first with the MEMS-PMC, and then with the PW. The primary endpoint was the Bland-Altman mean bias between the MEMS-PMC and PW FFR., Results: From the 224-patient per-protocol data, quantitative coronary angiography showed 17.9% and 55.9% vessels had diameter < 2.5 mm and stenosis >50%, respectively. The two systems' mean bias was -0.01 with [-0.08, 0.06] 95% limits-of-agreement. Using PW FFR≤0.80 as cutoff, the MEMS-PMC per-vessel diagnostic accuracy was 93.4% [95% confidence interval: 89.4-96.3%]. The MEMS-PMC's success rate was similar to that of PW (97.5 vs. 96.3%, p = .43) with no serious adverse event, and its clinically-significant (>0.03) drift rate was 43% less (9.5 vs. 16.7%, p = .014)., Conclusions: Our study showed the MEMS-PMC is safe to use and has a minimal bias equal to the resolution of current FFR systems. Given the MEMS-PMC's high measurement accuracy and rapid-exchange nature, it may become an attractive new tool facilitating routine coronary physiology assessment., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Natural astaxanthin helps reduce the negative effects caused by oxidative stress and other related factors, thereby minimizing oxidative damage. Therefore, it has considerable potential and broad application prospects in human health and animal nutrition. Haematococcus pluvialis is considered to be the most promising cell factory for the production of natural astaxanthin. Previous studies have confirmed that nonmotile cells of H. pluvialis are more tolerant to high intensity of light than motile cells. Cultivating nonmotile cells as the dominant cell type in the red stage can significantly increase the overall astaxanthin productivity. However, we know very little about how to induce nonmotile cell formation. In this work, we first investigated the effect of phosphorus deficiency on the formation of nonmotile cells of H. pluvialis , and then investigated the effect of NaCl on the formation of nonmotile cells under the conditions of phosphorus deficiency. The results showed that, after three days of treatment with 0.1% NaCl under phosphorus deficiency, more than 80% of motile cells had been transformed into nonmotile cells. The work provides the most efficient method for the cultivation of H. pluvialis nonmotile cells so far, and it significantly improves the production of H. pluvialis astaxanthin.

Background: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study., Methods: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal., Results: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011)., Conclusions: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.

We analyzed the complete genome of the bacteria Brevibacillus laterosporus Bl-zj. Its genome has a total length of 5,202,546 bp with 4594 annotated genes. The functional groups included transporters, pathogen-host interaction factors, antibiotic resistance genes, virulence factor, and secreted proteins were predicted, and carbon and nitrogen metabolism and transporters were mapped. A total of 34 genes possibly involved in algae-lysing processes were further screened, including 8 virulence factors, 18 secreted proteases, and 8 antibiotic-resistant genes, which could be playing important roles in host identification, invasion, and the destruction of algal cells. This study will provide a theoretical framework for the algicidal mechanism of algae-lysing bacteria and possible application to algal control.

Background and Objectives: Accurate segmentation of left ventricle (LV) is a fundamental step in evaluation of cardiac function. Cardiac CT angiography (CCTA) has become an important clinical diagnostic method for cardio-vascular disease (CVD) due to its non-invasive, short exam time, and low cost. To obtain the segmentation of the LV in CCTA scans, we present a deep learning method based on an 8-layer residual U-Net with deep supervision., Methods: Based on the original 4-layer U-Net, our method deepened the network to eight layers, which increased the fitting capacity of the network, thus greatly improved its LV recognition capability. Residual blocks were incorporated to optimize the network from the increased depth. Auxiliary paths as deep supervision were introduced to supervise the intermediate information to improve the segmentation quality. In this study, we collected CCTA scans of 100 patients. Eighty patients with 1600 discrete slices were used to train the LV segmentation and the remaining 20 patients with 400 discrete slices were used for testing our method. An interactive graph cut algorithm was utilized reliably to annotate the LV reference standard that was further confirmed by cardiologists. Online data augmentation was performed in the training process to improve the generalization and robustness of our method., Results: Compared with the segmentation results from the original U-Net and FC-DenseNet56 with Dice similarity coefficient (DSC) of 0.878±0.230 and 0.897±0.189, respectively, our method demonstrated higher segmentation accuracy and robustness for varying LV shape, size, and contrast, achieving DSC of 0.927±0.139. Without online data augmentation, our method resulted in inferior performance with DSC of 0.911±0.170. In addition, compared with the provided results from other existing studies in the LV segmentation of cardiac CT images, our method achieved a competitive performance for the LV segmentation., Conclusions: The proposed 8-layer residual U-Net with deep supervision accurately and efficiently segments the LV in CCTA scans. This method has potential advantages to be a reliable segmentation method and useful for the evaluation of cardiac function in the future study., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this article., (Copyright © 2020. Published by Elsevier B.V.)