Theoretical Study on the Reaction between Carcinogenic 2,5-Dichloro-1,4-benzoquinone and tert-Butyl Hydroperoxide: Self-Catalysis and Water Catalysis.

The potentially carcinogenic halobenzoquinones (HBQs) have been recently identified in drinking water as disinfection byproducts. Several radical intermediates in the reaction of 2,5-dichloro-1,4-benzoquinone (DCBQ) and t-butyl hydroperoxide (t-BuOOH), which may induce DNA damage, were detected experimentally, and metal-independent decomposition reactions of t-BuOOH by DCBQ were proposed. It has not yet been confirmed by theoretical calculations. The theoretical study in this work provides insights into the details of the reaction. An unprecedented self-catalysis mechanism of organic hydroperoxides, that is, the reactant t-BuOOH also has a catalytic effect, was uncovered at the molecular level. Moreover, as the solvent, water molecules also clearly have an efficient catalytic effect. Due to the catalysis of t-BuOOH and water, the metal-independent reaction of t-BuOOH and DCBQ can occur under moderate conditions. Our findings about the novel catalytic effect of organic hydroperoxides t-BuOOH could offer a unique perspective into the design of new catalysts and an understanding of the catalytic biological, environmental, and air pollution reactions. Furthermore, organic hydroperoxide t-BuOOH could serve as a proton shuttle, where the proton transfer process is accompanied by simultaneous charge transfer. Therefore, organic hydroperoxides may disrupt the vital proton transfer process in biological systems and may give rise to unexpected toxicity.

Pan-cancer analyses of immunogenic cell death-derived gene signatures: Potential biomarkers for prognosis and immunotherapy.

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. AIMS: The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database. METHODS AND RESULTS: We identified key genes that had strong relationships with survival and the tumor microenvironment, contributing to a better understanding of the role of ICD genes in cancer therapy. In addition, we predicted therapeutic agents that target ICD genes and explored the potential mechanisms by which gemcitabine induce ICD. Moreover, we developed an ICD score based on the ICD genes and found it to be associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. A high ICD score was linked to the immune-hot phenotype, while a low ICD score was linked to the immune-cold phenotype. CONCLUSION: We uncovered the potential of ICD gene signatures as comprehensive biomarkers for ICD in pan-cancer. Our research provides novel insights into immuno-phenotypic assessment and cancer therapeutic strategies, which could help to broaden the application of immunotherapy to benefit more patients.

The association between mammographic density and breast cancer risk in Chinese women: a systematic review and meta-analysis.

PURPOSE: Breast density has consistently been shown to be an independent risk factor for breast cancer in Western populations; however, few studies have evaluated this topic in Chinese women and there is not yet a unified view. This study investigated the association between mammographic density (MD) and breast cancer risk in Chinese women. METHODS: The PubMed, Cochrane Library, Embase, and Wanfang databases were systematically searched in June 2023 to include all studies on the association between MD and breast cancer risk in Chinese women. A total of 13,977 breast cancer cases from 14 studies were chosen, including 10 case-control/cross-sectional studies, and 4 case-only studies. For case-control/cross-sectional studies, the odds ratios (ORs) of MD were combined using random effects models, and for case-only studies, relative odds ratios (RORs) were combinations of premenopausal versus postmenopausal breast cancer cases. RESULTS: Women with BI-RADS density category II-IV in case-control/cross-sectional studies had a 0.93-fold (95% confidence interval [CI] 0.55, 1.57), 1.08-fold (95% CI 0.40, 2.94), and 1.24-fold (95% CI 0.42, 3.69) higher risk compared to women with the lowest density category. Combined RORs for premenopausal versus postmenopausal women in case-only studies were 3.84 (95% CI 2.92, 5.05), 22.65 (95% CI 7.21, 71.13), and 42.06 (95% CI 4.22, 419.52), respectively, for BI-RADS density category II-IV versus I. CONCLUSIONS: For Chinese women, breast cancer risk is weakly associated with MD; however, breast cancer risk is more strongly correlated with mammographic density in premenopausal women than postmenopausal women. Further research on the factors influencing MD in premenopausal women may provide meaningful insights into breast cancer prevention in China.

Cost-utility analysis of treating mild stage normal tension glaucoma by surgery in China: a decision-analytic Markov model.

BACKGROUND: Many individuals suffer from normal tension glaucoma (NTG) in China. This study utilized Markov models to evaluate the cost-utility of applying many medications and surgery for mild-stage NTG when disease progression occurred at a mild stage. METHODS: A 10-year decision-analytic Markov model was developed for the cost-utility analysis of treating mild-stage NTG with surgery and increased application of medication. We hypothesized that all 100,000 samples with a mean age of 64 were in mild stages of NTG. Transitional probabilities from the mild to moderate to severe stages and the basic parameters acquired from the CNTGS were calculated. Incremental cost-utility ratios (ICUR) were calculated for treating all patients with NTG by probabilistic sensitivity analysis (PSA) and Monte Carlo simulation. One-way sensitivity analysis were conducted by adjusting the progression rate, cost of medications or trabeculectomy, cost of follow-up, and surgical acceptance rate. RESULTS: The ICUR of treating mild stage NTG with medication over 10 years was $12743.93 per quality-adjusted life years (QALYs). The ICUR for treating mild stage NTG patients with a 25% and 50% surgery rate with medication were $8798.93 and $4851.93 per QALYs, respectively. In this model, the cost-utility of treating NTG was sensitive to disease progression rate, surgical treatment rate, and medication costs. CONCLUSIONS: According to the results of the cost-utility analysis, it was a reasonable and advantageous strategy to administer a lot of medication and surgery for NTG in the mild stages of the disease. In the model, the greater the probability of patients undergoing surgery, the strategy becomes more valuable.

The effect of image resolution on convolutional neural networks in breast ultrasound.

Purpose: The objective of this research was to investigate the efficacy of various parameter combinations of Convolutional Neural Networks (CNNs) models, namely MobileNet and DenseNet121, and different input image resolutions (REZs) ranging from 64×64 to 512×512 pixels, for diagnosing breast cancer. Materials and methods: During the period of June 2015 to November 2020, two hospitals were involved in the collection of two-dimensional ultrasound breast images for this retrospective multicenter study. The diagnostic performance of the computer models MobileNet and DenseNet 121 was compared at different resolutions. Results: The results showed that MobileNet had the best breast cancer diagnosis performance at 320×320pixel REZ and DenseNet121 had the best breast cancer diagnosis performance at 448×448pixel REZ. Conclusion: Our study reveals a significant correlation between image resolution and breast cancer diagnosis accuracy. Through the comparison of MobileNet and DenseNet121, it is highlighted that lightweight neural networks (LW-CNNs) can achieve model performance similar to or even slightly better than large neural networks models (HW-CNNs) in ultrasound images, and LW-CNNs' prediction time per image is lower.

A new xAI framework with feature explainability for tumors decision-making in Ultrasound data: comparing with Grad-CAM.

BACKGROUND AND OBJECTIVE: The value of implementing artificial intelligence (AI) on ultrasound screening for thyroid cancer has been acknowledged, with numerous early studies confirming AI might help physicians acquire more accurate diagnoses. However, the black box nature of AI's decision-making process makes it difficult for users to grasp the foundation of AI's predictions. Furthermore, explainability is not only related to AI performance, but also responsibility and risk in medical diagnosis. In this paper, we offer Explainer, an intrinsically explainable framework that can categorize images and create heatmaps highlighting the regions on which its prediction is based. METHODS: A dataset of 19341 thyroid ultrasound images with pathological results and physician-annotated TI-RADS features is used to train and test the robustness of the proposed framework. Then we conducted a benign-malignant classification study to determine whether physicians perform better with the assistance of an explainer than they do alone or with Gradient-weighted Class Activation Mapping (Grad-CAM). RESULTS: Reader studies show that the Explainer can achieve a more accurate diagnosis while explaining heatmaps, and that physicians' performances are improved when assisted by the Explainer. Case study results confirm that the Explainer is capable of locating more reasonable and feature-related regions than the Grad-CAM. CONCLUSIONS: The Explainer offers physicians a tool to understand the basis of AI predictions and evaluate their reliability, which has the potential to unbox the "black box" of medical imaging AI.

Identifying greenhouse gas emission reduction potentials through large-scale photovoltaic-driven seawater desalination.

To widely promote freshwater production through seawater desalination, renewable energy is expected to replace traditional fossil energy to drive seawater desalination. Based on the input list of components and materials, this study attempts to quantify greenhouse gas (GHG) emissions of photovoltaic-driven seawater desalination projects through replacing traditional thermal power plants and evaluate GHG emission reduction potentials by comparing the thermal- and photovoltaic-driven seawater desalination projects. The GHG emission of photovoltaic-driven seawater desalination project could be reduced by 94.97 % compared with the thermal-driven seawater desalination project, and the GHG emission per unit water production is reduced by 9.8 kg CO2-eq/ton, which could greatly reduce GHG emissions in the whole life cycle. In addition, it is estimated that the large-scale implementation of photovoltaic power stations in LT-MED seawater desalination project can reduce GHG emissions from 1.61E+05 to 3.86E+06 t CO2-eq per year. Through the payback period assessment, the combination of photovoltaic power stations and thermal power plants to drive the seawater desalination project can offset the GHG emission of 7.94E+03 t CO2-eq, and the payback period of photovoltaic-driven seawater desalination project is estimated to be 0.33 years. Using renewable energy instead of traditional thermal energy can reduce the fossil fuel combustion and GHG emissions during the water desalination process, which provides essential references for the low-carbon transition and energy saving in seawater desalination projects in China's coastal areas.

Feasibility of using AI to auto-catch responsible frames in ultrasound screening for breast cancer diagnosis.

The research of AI-assisted breast diagnosis has primarily been based on static images. It is unclear whether it represents the best diagnosis image.To explore the method of capturing complementary responsible frames from breast ultrasound screening by using artificial intelligence. We used feature entropy breast network (FEBrNet) to select responsible frames from breast ultrasound screenings and compared the diagnostic performance of AI models based on FEBrNet-recommended frames, physician-selected frames, 5-frame interval-selected frames, all frames of video, as well as that of ultrasound and mammography specialists. The AUROC of AI model based on FEBrNet-recommended frames outperformed other frame set based AI models, as well as ultrasound and mammography physicians, indicating that FEBrNet can reach level of medical specialists in frame selection.FEBrNet model can extract video responsible frames for breast nodule diagnosis, whose performance is equivalent to the doctors selected responsible frames.

Assessment of elastographic Q-analysis score combined with Prostate Imaging-Reporting and Data System (PI-RADS) based on transrectal ultrasound (TRUS)/multi-parameter magnetic resonance imaging (MP-MRI) fusion-guided biopsy in differentiating benign and malignant prostate.

Background: Magnetic resonance imaging (MRI) has advantages in the diagnosis of prostate diseases, but there is also overdiagnosis. We compensate for this with fusion imaging and elastography. In this study, we want to evaluate Elastographic Q-analysis score (EQS) combined with Prostate Imaging Reporting and Data System (PI-RADS), based on transrectal ultrasound (TRUS)/multi-parameter magnetic resonance imaging (MP-MRI) fusion biopsy in differentiating benign and malignant prostate lesions. Methods: A total of 296 patients with 318 prostate lesions who underwent TRUS/MP-MRI fusion biopsy between October 2017 and October 2019 were retrospectively analysed. The performance of the EQS was evaluated on the sites of the suspicious areas of MP-MRI. The cut-off value of EQS was obtained according to receiver operating characteristic (ROC) curve, which was used to upgrade and downgrade the PI-RADS scores. The area under the curve (AUC), integrated discrimination improvement, and decision curve analysis were used to assess the new PI-RADS performance. Results: In total, 318 MP-MRI suspicious prostate lesions (94 malignant vs. 224 benign lesions). The EQS optimal threshold was 1.85, and the AUC was 0.816. All cases were constructed three models by using 1.85 as the cut-off value: upgrade-PI-RADS, downgrade-PI-RADS and complex-PI-RADS. The AUC of PI-RADS, upgrade-PI-RADS, downgrade-PI-RADS and complex-PI-RADS were 0.869, 0.867, 0.872 and 0.873 respectively. The diagnostic coincidence rate of PI-RADS was increased from 0.667 to 0.874 by using strain elastography, among which the diagnostic rate of prostate cancer was increased from 0.557 to 0.806, and the diagnostic rate of non-prostate cancer was increased from 0.775 to 0.967. The integrated discrimination improvement indicated that downgrade-PI-RADS had a better diagnostic capability (P<0.05). The net benefit of all models, which downgrade-PI-RADS can maximize the net benefit value of patients by decision curve analysis. Conclusions: The combination of PI-RADS and EQS with TRUS/MP-MRI fusion, particularly downgrade-PI-RADS, can reduce unnecessary biopsy procedures and prevent overdiagnosis.

Erythrocyte Membrane-Coated Invisible Acoustic-Sensitive Nanoparticle for Inducing Tumor Thrombotic Infarction by Precisely Damaging Tumor Vascular Endothelium.

Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.

Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity.

Endometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes of EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload occurs in ovarian follicular fluid (FF) of patients with EMs, and this condition is associated with oocyte maturation disorder. However, the underlying molecular mechanism remains largely unknown. In the present study, we identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs based on a retrospective review of in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes in infertile patients with EMs. Mouse granulosa cells were treated with EMs-related infertile patients' follicular fluid (EMFF) in vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, and transmission electron microscopy were used to assess granulosa cells ferroptosis. The effects of exosomes were examined by nanoparticle tracking analysis, RNA-seq, and Western blot analysis. Finally, the therapeutic values of vitamin E and iron chelator (deferoxamine mesylate) in vivo were evaluated in an EMs-related infertility model. Patients with ovarian EMs experienced poorer oocyte fertility than patients with non-ovarian EMs. We observed that EMFF with iron overload-induced granulosa cell ferroptosis in vitro and in vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved in this process. Notably, granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes from granulosa cells. In therapeutic studies, vitamin E and iron chelators effectively alleviated EMs-related infertility models. Our study indicates a novel mechanism through which EMFF with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity in EMs-related infertility, providing a potential therapeutic strategy for EMs-related infertility.

Knockdown of ARL5B Induces Mitochondrial-mediated Apoptosis and Inhibits Glycolysis in Breast Cancer Cells by Activating MDA5 Signaling.

AIM: Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells. BACKGROUND: ADP-ribosylation factor-like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and breast cancer (BC) progression, but the underlying mechanism needs to be further understood. OBJECTIVE: We investigated the effects of ARL5B on the apoptosis and glycolysis of breast cancer cells and its underlying mechanisms. METHODS: Quantitative reverse transcription-PCR (qRT-PCR) and western blot assays were used to detect the expression of ARL5B in breast cancer tissues and cells. An ARL5B loss-of-function assay was performed to verify its role in BC development. RESULTS: ARL5B was upregulated in breast cancer tissues and cell lines. ARL5B knockdown induced apoptosis and activated the mitochondrial pathway in breast cancer cells. Interestingly, the inhibition of ARL5B repressed the aerobic glycolysis of breast cancer cells. The role of ARL5B in breast cancer cells was exerted by mediating the activation of viral RNA sensor MDA5-evoked signaling. Silencing ARL5B triggered MDA5 signaling by upregulating the key proteins involved in the MDA5 pathway. Importantly, MDA5 silencing reversed the effects of ARL5B knockdown on mitochondrial-mediated apoptosis and glycolysis, whereas poly (I:C), as a ligand for MDA5, further enhanced ARL5B knockdown- facilitated mitochondrial apoptosis and the inhibition of glycolysis. CONCLUSION: The knockdown of ARL5B activated MDA5 signaling and thus led to the enhanced mitochondrial- mediated apoptosis and glycolysis inhibition in breast cancer cells. Our study suggested that ARL5B might be a potential therapy target for BC.

Clinical correlation between serum cytokines and the susceptibility to Polygonum multiflorum-induced liver injury and an experimental study.

Polygonum multiflorum (PM), a popular functional food, and a herbal and dietary supplement, is widely used as a tonic in China and East Asia. In recent years, it has attracted great concern for its ability to cause idiosyncratic drug-induced liver injury (IDILI). However, identifying individuals susceptible to IDILI remains challenging. This is a prospective study. For 6 patients whose serum alanine aminotransferase (ALT) levels after consuming PM were abnormally elevated (susceptible group), 15 patients with normal levels of liver injury markers were matched (tolerant group) based on similar baseline characteristics. ProcartaPlex immunoassays were adopted to quantitatively detect 33 serum cytokines in the two groups of patients before consuming PM, to characterize the cytokine profile and screen differential cytokines. Subsequently, the susceptibility of a potential biomarker to regulate PM-induced liver injury was validated in animal models. There were significant differences in the cytokine profiles between the susceptible and tolerant groups, wherein the susceptible patients showed immune perturbation characterized by high expression of multiple inflammatory cytokines, especially the proinflammatory cytokine TNF-α (P = 0.006). Among them, the cytokine TNF-α had the strongest correlation with ALT, where the correlation coefficient was greater than 0.6, and the area under the receiver operating characteristic curve was more than 0.8. Animal experiments revealed that both PM water extract and its susceptibility component of liver injury, cis-stilbene glucoside, could cause liver injury in the mice pre-stimulated using TNF-α. Conversely, administration of the same dose of drugs on control mice did not show any hepatotoxicity. In conclusion, immune perturbation mainly mediated by TNF-α may regulate the susceptibility to PM-induced liver injury. This provides a new perspective for the study of susceptibility to IDILI.

Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. METHODS: Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. RESULTS: Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization. CONCLUSION: The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization.

Pedicle Subtraction Osteotomy in Lateral Position: A New Strategy for Correcting Severe Thoracolumbar Kyphosis Combined with Hip Flexion Contracture in Ankylosing Spondylitis.

OBJECTIVE: To describe spinal osteotomy in lateral position, which might be a new strategy for correcting thoracolumbar kyphotic deformity combined with severe hip flexion contracture, and to present two cases in which this method was successfully performed. METHODS: Spinal osteotomies in lateral position were performed in two patients with severe thoracolumbar kyphosis combined with hip flexion contracture, which was not suitable for operation in the prone position. Case 1: a 33-year-old female AS patient still had severe hip flexion contracture due to poor rehabilitation after total hip replacement (THR). The range of movement of the hip was only about 15° in right and 10° in left. Pre-operativethoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), and sagittal vertical axis (SVA) were 52.4°, 49.1°, 42.7°, and 315 mm, respectively. Pedicle subtraction osteotomy (PSO) at L3 was performed in the lateral position. The eggshell procedure was used during osteotomy. Case 2: a 45-year-old male AS patient presented coexisting rigid thoracolumbar kyphosis and hip flexion contracture. The range of movement of the hip was only about 20° in right and 25° in left. Pre-operativeTK, TLK, LL and SVA were 34.9°, 66.8°, 58.8° and 290.8 mm, respectively. PSO at L2 was performed in lateral position. The eggshell procedure was also used. RESULTS: Sagittal malalignments of both patients were greatly improved. For case 1, the total operation time was 5.5 h. The blood loss was 1500 mL and the amount of allogeneic blood transfusion was 1580 mL during the operation. SVA was reduced to 127 mm and LL decreased from preoperative 42.7° to -28.4°. The correction angle through L3 was 34.7° and the correction angle through the osteotomy segment was 62.9°. For case 2, the duration of surgery was 6.5 h. The operative blood loss was 2000 mL and the total amount of blood transfusion was 2020 mL. SVA was reduced to 209.8 mm and LL decreased from preoperative 58.8° to 9.2°.The correction angle through L2 was 37.1° and the correction angle through the osteotomy segment was 55°. No intra-operative or post-operative complications were observed. Six months after PSO, case 1 had good posture for standing and sitting. The case 2 underwent bilateral THRs nine months after PSO. CONCLUSION: PSO could be performed in the lateral position successfully. For AS patients who cannot be placed in the prone position due to coexisting severe thoracolumbar kyphosis and hip flexion contracture, performing spinal osteotomy in the lateral position as the first step is an alternative.

Diagnostic performance of elastography for breast non-mass lesions: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the diagnostic performance of ultrasound elastography in the differentiation of benign and malignant breast non-mass lesions (NMLs). METHODS: PubMed, Cochrane Library, and Embase databases were searched for eligible studies up to end of June 2021. The diagnostic performance of elastography for NMLs was investigated using pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio (DOR), post-test probability, and the area under hierarchical summary receiver operating characteristic curve (HSROC). RESULTS: Eleven studies involving 812 NMLs (malignant 414) were included. The pooled sensitivity, specificity, DOR, positive likelihood ratio, and negative likelihood of elastography for the differentiation of benign and malignant breast NMLs were 79% (95 %CI: 71-85), 86% (95 %CI: 79-91), 23.32 (95 %CI: 13.38-40.66), 5.67 (95 %CI: 3.79-8.47), and 0.24 (95 %CI: 0.17-0.34), respectively. No significant publication bias existed. The area under the HSROC curve was 90% (95 %CI: 87-92). Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed. Country, measurement index, and number of lesions served as potential sources of heterogeneity. CONCLUSIONS: The results of this study suggest that elastography has high diagnostic accuracy in differentiating between malignant and benign NMLs. Elastography can be a feasible and non-invasive tool for breast NMLs.

Development and validation of a nomogram based on multiparametric magnetic resonance imaging and elastography-derived data for the stratification of patients with prostate cancer.

BACKGROUND: This study sought to develop and validate a nomogram combining the elastographic Q-analysis score (EQS), the Prostate Imaging Reporting and Data System (PI-RADS) score, and clinical parameters for the stratification of patients with prostate cancer (PCa). METHODS: A retrospective study was conducted of 375 patients with 375 lesions who underwent volume-navigation transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (MP-MRI)-fusion targeted biopsies between April 2017 and January 2020. Based on a multivariate logistic regression model, a nomogram was created to assess any PCa and high-risk PCa [Gleason score (GS) ≥4+3] using data from patients diagnosed between April 2017 and June 2019 (n=271), and was validated in patients diagnosed after July 2019 (n=104). The nomogram's performance was evaluated based on its discrimination, calibration, and clinical usefulness. RESULTS: The areas under the curve (AUCs) of the nomogram for predicting any PCa and high-risk PCa were 0.949 [95% confidence interval (CI), 0.921 to 0.978] and 0.936 (95% CI, 0.906 to 0.965), respectively, in the training cohort, and 0.946 (95% CI, 0.894 to 0.997) and 0.971 (95% CI, 0.9331 to 1), respectively, in the validation cohort. The nomogram was well calibrated, and no significant difference was found between the predicted and observed probabilities. A decision curve analysis (DCA) for the nomogram with and without the EQS showed that the threshold probability of for any PCa was <67%. CONCLUSIONS: The nomogram that combined elastography-derived and MP-MRI data was more clinically useful than the model based on PI-RADS and clinical parameters alone. Our nomogram could aid urologists to make decisions and avoid unnecessary biopsies.

Design, synthesis and structure-activity relationships of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives against various resistant bacteria.

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.

The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients.

BACKGROUND: At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients. OBJECTIVE: To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients. METHODS: Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC. RESULTS: In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. "AFP + PIVKA-II" yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. "AFP + PIVKA-II" achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR = 4.890, P = 0.020). CONCLUSION: PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy.

Development of a Nomogram Model for Treatment of Nonmetastatic Nasopharyngeal Carcinoma.

Importance: Because of tumor heterogeneity, overall survival (OS) differs significantly among individuals with nasopharyngeal carcinoma (NPC), even among those with the same clinical stage. Relying solely on TNM staging to guide treatment remains imperfect. Objectives: To establish a comprehensive nomogram to estimate individualized OS and to explore stratified treatment regimens for risk subgroups in nonmetastatic NPC. Design, Setting, and Participants: This cohort study included 8093 patients diagnosed with NPC at a single center in China from April 2009 to December 2015. The sample was split into a training cohort (5398 participants [66.7%]) and validation cohort (2695 [33.3%]). Data were analyzed in May 2020. Exposures: Age, T stage, N stage, Epstein-Barr virus (EBV) DNA level, serum lactate dehydrogenase (LDH) levels, and albumin (ALB) levels. Main Outcomes and Measures: The primary end point was OS. The nomogram for estimating OS was generated based on multivariate Cox proportional hazards regression. The performance of the nomogram was quantified using Harrell concordance index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, and a calibration curve. OS rates were established using the Kaplan-Meier method, and intersubgroup differences were examined by the log-rank test. Results: Among the 8093 participants, 5688 (70.3%) were men, and the median age at diagnosis was 45 years (range, 7-85 years). Six variables (age, T stage, N stage, EBV DNA levels, LDH levels, and ALB levels) were identified through multivariate Cox regression and incorporated into a nomogram to estimate OS. The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating OS (C index, 0.716 [95% CI, 0.698-0.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; AUC, 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates. The validation cohort confirmed the results. Patients were stratified into 4 risk groups based on the 25th, 50th, and 75th percentile score values estimated from the nomogram. The 4 nomogram-defined risk groups demonstrated significantly different intergroup OS (3-year OS rates: risk group 1, 1328 of 1345 [98.7%]; risk group 2, 1289 of 1341 [96.1%]; risk group 3, 1222 of 1321 [92.5%]; risk group 4, 1173 of 1391 [84.3%]; P < .001). These risk groups were associated with the efficacy of different treatment regimens. For example, for risk group 4, induction chemotherapy with concurrent chemoradiotherapy was associated with a significantly better OS than concurrent chemoradiotherapy (log-rank P = .008) and intensity-modulated radiotherapy alone (log-rank P < .001). Conclusions and Relevance: In this study, the proposed nomogram model enabled individualized prognostication of OS and could help to guide risk-adapted treatment for patients with nonmetastatic NPC.