Cuproptosis: Mechanism, role, and advances in urological malignancies.

Prostate, bladder, and kidney cancers are the most common malignancies of the urinary system. Chemotherapeutic drugs are generally used as adjuvant treatment in the middle, late, or recurrence stages after surgery for urologic cancers. However, traditional chemotherapy is plagued by problems such as poor efficacy, severe side effects, and complications. Copper-containing nanomedicines are promising novel cancer treatment modalities that can potentially overcome these disadvantages. Copper homeostasis and cuproptosis play crucial roles in the development, adaptability, and therapeutic sensitivity of urological malignancies. Cuproptosis refers to the direct binding of copper ions to lipoylated components of the tricarboxylic acid cycle, leading to protein oligomerization, loss of iron-sulfur proteins, proteotoxic stress, and cell death. This review focuses on copper homeostasis and cuproptosis as well as recent findings on copper and cuproptosis in urological malignancies. Furthermore, we highlight the potential therapeutic applications of copper- and cuproptosis-targeted therapies to better understand cuproptosis-based drugs for the treatment of urological tumors in the future.

Synthesis of Mono- and Dinuclear Aluminum Complexes Bearing Aromatic Amino-Phenolato Ligands: A Comparative Study in the Ring-Opening Polymerization of Cyclohexene Oxide.

Dinuclear aluminum methyl complexes bearing aromatic diamine-bridged tetra(phenolato) ligands and the mononuclear aluminum methyl complex with the phenylamine-bridged bis(phenolato) ligand have been synthesized and characterized. Structure determination revealed that the Al-Al distances in these dinuclear aluminum complexes are tunable by the choice of the suitable aromatic backbone of the diamine-bridged tetra(phenolato) ligands. The catalytic behaviors of these mono- and dinuclear aluminum complexes for cyclohexene oxide (CHO) polymerization were investigated. The activities of these dinuclear Al complexes were observed to increase with the decrease of Al-Al distances, and the dinuclear Al complexes appeared to have better catalytic activity than the mononuclear Al complex, even if the Al-Al distance is as long as 9.401 Å. Dinuclear aluminum complex 2, with the shortest Al-Al distance (7.236 Å), showed the highest activity toward CHO polymerization with TOFs up to 6460 h-1 in neat CHO at 30 °C. Furthermore, comparative kinetic studies revealed that the polymerization is first-order for CHO concentration, and the reaction orders for initiator concentration are different for the mono- and dinuclear Al complexes. The polymerization mechanism study revealed that both the methyl and phenolate groups were involved in the initiation process.

Urban residents' self-rescue in response to public health emergencies in China: a qualitative study.

BACKGROUND: The abject uncertainty and unpredictability of public health emergencies have plagued various countries. Global health governance and international communities are facing long-term and arduous challenges. The self-rescue ability of individuals in a public emergency may be the most powerful trait to improve the survival rate outside the hospital. The study explores the cognitive ability and attitudes of urban residents in China towards self-rescue in response to public health emergencies. It provides appropriate evidence for improving the self-rescue ability of urban residents in China. METHODS: Sixteen urban residents were selected using the purposive sampling method for semi-structured interviews. Theme analysis was used to collate and analyse the interview data. RESULTS: Two themes and five sub-themes were analysed. The two themes included cognition and attitude of Chinese urban residents for self-rescue in an emergency. Urban residents believed that their knowledge and skills for self-rescue in an emergency were low. The ability for emergency self-rescue is affected by multiple factors, with relatively limited options for improvement. Nonetheless, the respondents expressed a desire to accept interventions under psychological crisis and a strong willingness to acquire knowledge and skills required for emergency self-rescue. CONCLUSION: This study investigated the perceptions and attitudes of Chinese urban residents towards emergency self-rescue. The results support enhanced ability of urban residents to respond to public health emergencies, thereby diminishing the negative outcomes. The findings suggest the need for strategies to address the factors affecting emergency self-rescue.

A self-supervised classification model for endometrial diseases.

PURPOSE: Ultrasound imaging is the preferred method for the early diagnosis of endometrial diseases because of its non-invasive nature, low cost, and real-time imaging features. However, the accurate evaluation of ultrasound images relies heavily on the experience of radiologist. Therefore, a stable and objective computer-aided diagnostic model is crucial to assist radiologists in diagnosing endometrial lesions. METHODS: Transvaginal ultrasound images were collected from multiple hospitals in Quzhou city, Zhejiang province. The dataset comprised 1875 images from 734 patients, including cases of endometrial polyps, hyperplasia, and cancer. Here, we proposed a based self-supervised endometrial disease classification model (BSEM) that learns a joint unified task (raw and self-supervised tasks) and applies self-distillation techniques and ensemble strategies to aid doctors in diagnosing endometrial diseases. RESULTS: The performance of BSEM was evaluated using fivefold cross-validation. The experimental results indicated that the BSEM model achieved satisfactory performance across indicators, with scores of 75.1%, 87.3%, 76.5%, 73.4%, and 74.1% for accuracy, area under the curve, precision, recall, and F1 score, respectively. Furthermore, compared to the baseline models ResNet, DenseNet, VGGNet, ConvNeXt, VIT, and CMT, the BSEM model enhanced accuracy, area under the curve, precision, recall, and F1 score in 3.3-7.9%, 3.2-7.3%, 3.9-8.5%, 3.1-8.5%, and 3.3-9.0%, respectively. CONCLUSION: The BSEM model is an auxiliary diagnostic tool for the early detection of endometrial diseases revealed by ultrasound and helps radiologists to be accurate and efficient while screening for precancerous endometrial lesions.

Rare Earth Amide-Catalyzed Direct Thioesterification of Aldehydes with Thiols under Mild Conditions.

Direct thioesterification of aldehydes with thiols catalyzed by readily accessible rare earth/lithium amide RE[N(SiMe3)2]3(µ-Cl)Li(THF)3 is developed, which enables the preparation of a range of thioesters (31 examples) under room temperature and solvent-free conditions, without using any additive or external oxidant. This method provides a straightforward and atom-efficient approach for the thioester synthesis.

Research on the learning experience of virtual simulation class experimental teaching and learning based on the perspective of nursing students.

BACKGROUND: The enrichment of information technology has impacted traditional teaching modes. The emergence of virtual simulation class experimental teaching software has effectively improved the quality of nursing experiment teaching. The learning experience of virtual simulation class experiment teaching and learning based on the perspective of nursing students is explored to provide a basis for improving related learning effects in the future. METHODS: Fourteen undergraduate nursing students were selected using the purposive sampling method for semi-structured interviews. The Colaizzi seven-step analysis method was used to collate and analyse the interview data. RESULTS: Two themes and six sub-themes were considered during the data analysis. The two themes were positive experiences and negative experiences. In the positive learning experience, undergraduate nursing students showed a deep memory of authentic and diverse scenes, which presented knowledge in a clearly logical, visualised and stereoscopic manner. Negative experiences are manifested as significantly different learning efficiencies in different grades and subjects, and timing the delivery of teaching feedback is difficult. CONCLUSION: Virtual simulation experimental teaching can promote the subjective initiative of nursing students' learning and promote better coordination and unity in their image and theoretical thinking. Some advantages can be augmented by following the national educational policy, strengthening the information construction, combining the construction of virtual simulation experiments with the discipline's characteristics and optimising the resources. This paper provides a reference for the future exploration of nursing education and further improving the construction of virtual simulation experimental teaching tools and resources.

Knockdown of KIF15 suppresses proliferation of prostate cancer cells and induces apoptosis through PI3K/Akt signaling pathway.

Prostate cancer is one of the most common malignancies in men, which has been considered a public health threat. KIF15 is a kind of driver protein, and its abnormal expression is closely related to the occurrence and development of malignant tumors. The purpose of the study was to explore the significance and role of KIF15 in prostate cancer and to show some potential value for prostate cancer. Immunohistochemistry analysis showed that KIF15 was highly expressed in prostate cancer tissues, which was also positively correlated with T Infiltrate. The loss-of-function and gain-of-function assays based on prostate cancer cells indicated that the change in KIF15 expression could significantly affect cell proliferation, tumorigenesis, migration, and cell apoptosis. The inhibition of prostate cancer development by KIF15 knockdown was also assured in vivo. The Human Apoptosis Antibody Array showed that CD40L, cytoC, DR6, and p21 were up-regulated upon KIF15 knockdown, while IGF-I and Survivin were down-regulated. Moreover, the involvement of the PI3K/Akt pathway in the KIF15-mediated regulation of prostate cancer was preliminarily proved. In summary, KIF15 was identified to play an important role in the development or biological progress of prostate cancer and is considered to possess the potential to be used as a therapeutic target.

Efficacy of photorejuvenation combined with tranexamic acid and hydroquinone cream in the treatment of complex facial pigmentation.

The aim of this study was to assess the effectiveness of photo rejuvenation combined with tranexamic acid and hydroquinone cream in the treatment of complex facial pigmentation. A total of 108 patients with complex facial pigmentation between October 2019 and October 2021 were included in this retrospective study and divided into 2 groups according to the treatment that they received, with 54 cases in each group. The control group received treatment with tranexamic acid and hydroquinone cream. On the basis of the control group, the observation group was treated with photo rejuvenation combined with tranexamic acid and hydroquinone cream. The effectiveness of the treatments in both groups was determined through photographs and melasma area severity index score. The skin conditions were also compared before and after treatment. The effective rate of the observation group was significantly higher than that of the control group (98.15% vs 83.33%, P = .025). The melasma area and severity index score in the observation group was significantly lower than that in the control group after treatment (1.58 ±â€…0.14 vs 2.96 ±â€…0.13, P < .001). Before treatment, there was no significant difference in the skin elasticity and skin water content between the observation group and control group (P > .05). After treatment, the skin elasticity and skin water content were significantly higher than that in the control group (P < .05). Photo rejuvenation combined with tranexamic acid and hydroquinone cream has a significant curative effect on patients with complex facial pigmentation, which can significantly improve skin elasticity, increase skin water content, and reduce the degree of skin lesions.

MRI-derived radiomics models for diagnosis, aggressiveness, and prognosis evaluation in prostate cancer. / MRIç›¸å ³å½±åƒç»„å­¦æ¨¡åž‹ç”¨äºŽå‰åˆ—è ºç™Œè¯Šæ–­ã€ä¾µè¢­æ€§å’Œé¢„åŽè¯„ä¼°.

Prostate cancer (PCa) is a pernicious tumor with high heterogeneity, which creates a conundrum for making a precise diagnosis and choosing an optimal treatment approach. Multiparametric magnetic resonance imaging (mp-MRI) with anatomical and functional sequences has evolved as a routine and significant paradigm for the detection and characterization of PCa. Moreover, using radiomics to extract quantitative data has emerged as a promising field due to the rapid growth of artificial intelligence (AI) and image data processing. Radiomics acquires novel imaging biomarkers by extracting imaging signatures and establishes models for precise evaluation. Radiomics models provide a reliable and noninvasive alternative to aid in precision medicine, demonstrating advantages over traditional models based on clinicopathological parameters. The purpose of this review is to provide an overview of related studies of radiomics in PCa, specifically around the development and validation of radiomics models using MRI-derived image features. The current landscape of the literature, focusing mainly on PCa detection, aggressiveness, and prognosis evaluation, is reviewed and summarized. Rather than studies that exclusively focus on image biomarker identification and method optimization, models with high potential for universal clinical implementation are identified. Furthermore, we delve deeper into the critical concerns that can be addressed by different models and the obstacles that may arise in a clinical scenario. This review will encourage researchers to design models based on actual clinical needs, as well as assist urologists in gaining a better understanding of the promising results yielded by radiomics.

Outcome comparison of radical prostatectomy versus seed brachytherapy for clinically localized prostate cancer using two biochemical recurrence definitions.

OBJECTIVE: We compared the outcome of radical prostatectomy (RP) with seed brachytherapy (BT) in clinically localized prostate cancer (LPCa) using two different biochemical recurrence (BCR) definitions. METHODS: Clinical data of 1117 patients with non-metastatic prostate cancer (PCa) treated with either RP or BT as the basis of the multimodal therapy from a single tertiary hospital between 2007 and 2021 were retrospectively analyzed. 843 LPCa patients (RP = 737, BT = 106) with at least one prostate-specific antigen (PSA) test after treatment were finally included. The BCR survival was evaluated by direct comparison and one-to-one propensity score matching (PSM) analysis using surgical definition (PSA ≥ 0.2ng/ml) for RP and surgical/Phoenix definition (PSA nadir + 2ng/ml ) for BT. The propensity score (PS) was calculated by multivariable logistic regression based on the clinicopathological parameters. RESULTS: Median follow-up was 43 months for RP patients and 45 months for BT patients. Kaplan-Meier analysis did not show any statistically significant differences in terms of BCR-free survival (BFS) between the two groups when using Phoenix definition for BT (P > 0.05). Similar results were obtained in all D'Amico risk groups when stratified analyses were conducted. However, RP achieved improved BFS compared to BT in the whole cohort and all risk groups with the surgical definition for BT(P < 0.05). After adjusting PS, 192 patients were divided into RP and BT groups (96 each). RP presented a better BFS than BT when using the surgical definition (P < 0.001), but no significant difference was found when using the Phoenix definition (P = 0.609). CONCLUSION: Inconsistent BCR-free survival outcomes were acquired using two different BCR definitions for BT patients. RP provided comparable BFS with BT using the Phoenix definition but better BFS using the surgical definition, regardless of whether the PSM was performed. Our findings indicated that an exact BCR definition was critical for prognostic assessment. The corresponding results will assist physicians in pretreatment consultation and treatment selection.

MRI-Derived Radiomics Model to Predict the Biochemical Recurrence of Prostate Cancer Following Seed Brachytherapy.

OBJECTIVE: We aimed to investigate the predictive value of imaging features derived from magnetic resonance imaging (MRI) and develop a radiomics model predicting the biochemical recurrence-free survival (BFS) in prostate cancer (PCa) patients treated with seed brachytherapy (seed-BT). METHODS: The data of 272 patients with PCa treated with seed-BT at Peking University Third Hospital from 2007 to 2019 was retrospectively investigated. Based on the eligibility criteria, 83 patients were finally included in our study. The cohort was divided into two groups in a ratio of 8:2 (training set: n = 67, test set: n = 16). The Cox survival model combined with the least absolute shrinkage and selection operator (LASSO) algorithm was applied to select the radiomics features from T2WI of pretreatment MRI. A radiomics model with selected features was established to predict the BFS. RESULTS: Nineteen patients experienced biochemical recurrence (BCR) during a median follow-up period of 46 months. Three features with non-zero coefficients were selected from 1598 features and used to construct a radiomics model for BCR prediction. The model accurately predicted the BCR in both the training and test groups, for which the concordance index (C-index) were 0.83 and 0.78, respectively. Receiver operating characteristic (ROC) analysis of the test set was conducted to assess the prediction accuracy. The model achieved a high area under the operator curve (AUC) performance for BCR prediction in the test cohort. CONCLUSIONS: Our study revealed the considerable potential of a radiomics model based on MRI-derived imaging features in BCR prediction of PCa patients after seed-BT. Radiomics provides a new perspective to clinicians assessing the outcome of radiotherapy, facilitating accurate prognostic evaluation and preoperative consultation for PCa patients followed by seed-BT.

MRI-Derived Radiomics Model to Predict the Biochemical Recurrence of Prostate Cancer Following Seed Brachytherapy

Objective: We aimed to investigate the predictive value of imaging features derived from magnetic resonance imaging (MRI) and develop a radiomics model predicting the biochemical recurrence-free survival (BFS) in prostate cancer (PCa) patients treated with seed brachytherapy (seed-BT). Methods: The data of 272 patients with PCa treated with seed-BT at Peking University Third Hospital from 2007 to 2019 was retrospectively investigated. Based on the eligibility criteria, 83 patients were finally included in our study. The cohort was divided into two groups in a ratio of 8:2 (training set: n = 67, test set: n = 16). The Cox survival model combined with the least absolute shrinkage and selection operator (LASSO) algorithm was applied to select the radiomics features from T2WI of pretreatment MRI. A radiomics model with selected features was established to predict the BFS. Results: Nineteen patients experienced biochemical recurrence (BCR) during a median follow-up period of 46 months. Three features with non-zero coefficients were selected from 1598 features and used to construct a radiomics model for BCR prediction. The model accurately predicted the BCR in both the training and test groups, for which the concordance index (C-index) were 0.83 and 0.78, respectively. Receiver operating characteristic (ROC) analysis of the test set was conducted to assess the prediction accuracy. The model achieved a high area under the operator curve (AUC) performance for BCR prediction in the test cohort. Conclusions: Our study revealed the considerable potential of a radiomics model based on MRI-derived imaging features in BCR prediction of PCa patients after seed-BT. Radiomics provides a new perspective to clinicians assessing the outcome of radiotherapy, facilitating accurate prognostic evaluation and preoperative consultation for PCa patients followed by seed-BT (AU)

MRI-derived tumor volume as a predictor of biochemical recurrence and adverse pathology in patients after radical prostatectomy: a propensity score matching study.

PURPOSE: To investigate the predictive value of MRI-derived tumor volume (TV) of biochemical recurrence (BCR) and adverse pathology (AP) in patients following radical prostatectomy (RP). METHODS: The data of 565 patients receiving RP in a single institution between 2010 and 2021 were retrospectively analyzed. All suspicious tumor foci were delineated manually using ITK-SNAP software as the regions of interest (ROIs). The sum of the TV of all lesions was calculated automatically based on the voxel in the ROIs to acquire the final TV parameter. TV was categorized as low-volume (≤ 6.5 cm3) and high-volume (> 6.5 cm3) based on the cut-off value. Univariate and multivariate Cox and logistic regression analyses were performed to identify independent predictors of BCR and AP. The Kaplan-Meier with the log-rank test was conducted to compare the BCR-free survival (BFS) between the low and high-volume groups. RESULTS: All the included patients were divided into the low-volume group (n = 337) and the high-volume group (n = 228). The TV was an independent predictor of BFS in the multivariate Cox regression analysis (Hazard Ratio (HR) [95% CI]: 1.550 [1.066-2.256], P = 0.022). The Kaplan-Meier analysis demonstrated that low volume was associated with a better BFS than high volume before propensity score matching (PSM) (P < 0.001). One hundred and fifty-eight pairs were obtained by 1:1 PSM to balance the baseline parameters between the two groups. After the PSM, low-volume remained to be associated with a better BFS than high-volume (P = 0.006). TV as a categorical variable was an independent factor of AP in multivariate logistic regression analysis (Odd ratio (OR) [95% CI]: 1.821 [1.064-3.115], P = 0.029). After balancing the potential factors influencing AP by 1:1 PSM, 162 new pairs were identified. The high-volume group had a higher AP rate than the low-volume group after PSM (75.9 vs. 64.8%, P = 0.029). CONCLUSION: We adopted a novel approach to acquiring the TV on preoperative MRI. TV was significantly associated with BFS and AP of patients undergoing RP, which was further illustrated by PSM analysis. MRI-derived TV may serve as a predictive marker for assessing BFS and AP in further studies, which will facilitate clinical decision-making and patient counseling.

Random copolymerization of trimethylene carbonate with L-lactide initiated by amine-bridged bis(phenolate) neodymium alkoxides.

Random copolymerization of trimethylene carbonate (TMC) with L-lactide (LA) under mild conditions is a challenging task in polymer synthesis. Two amino-bridged bis(phenolate) neodymium complexes were synthesized and employed as efficient initiators for the copolymerization of TMC and L-LA under mild conditions to give random copolymers. NMR monitoring experiments of the chain microstructure versus polymerization time confirmed that a TMC/LA random copolymer was generated by a random copolymerization.

Characterization of an orally available respiratory syncytial virus L protein polymerase inhibitor DZ7487.

OBJECTIVES: Respiratory Syncytial Virus (RSV) is a leading cause of death and hospitalization among infants and young children. People with an immunocompromised status are also at risk for severe RSV infection. There is no specific treatment for RSV infection available. Ribavirin, an antiviral drug approved for severe lung infection by RSV, has shown limited clinical efficacies with severe side effects. Additionally, given the genetic variability of RSV genomes and seasonal change of different strains, a broad-spectrum antiviral drug is highly desirable. The RNA-dependent RNA polymerase (RdRp) domain is relatively conserved and indispensable for the replication of the virus genome and therefore serves as a potential therapeutic target. Previous attempts to identify an RdRp inhibitor have not been successful due to lack of potency or high enough blood exposure. DZ7487 is a novel orally available small molecule inhibitor specifically designed to target the RSV RdRp. Here we present our data showing that DZ7487 can potently inhibited all clinical viral isolates tested, with large safety margin predicted for human. METHODS: HEp-2 cells were infected by RSV A and B. Antiviral activities were assessed by in vitro cytopathic effect assay (CPE) and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). DZ7487 antiviral effects in lower airway cells were evaluated in A549 and human small airway epithelial cells (SAEC) cells. DZ7487 induced RSV A2 escape mutations were selected through continuous culture with increasing DZ7487 concentrations in the culture medium. Resistant mutations were identified by next generation sequencing and confirmed by recombinant RSV CPE assays. RSV infection models in both BALB/c mice and cotton rats were used to evaluate DZ7487 in vivo antiviral effects. RESULTS: DZ7487 potently inhibited viral replication of all clinical isolates of both RSVA and B subtypes. In lower airway cells, DZ7487 showed superior efficacy than the nucleoside analog ALS-8112. Acquired resistant mutation was predominantly restricted at the RdRp domain resulting asparagine to threonine mutation (N363T) of the L protein. This finding is consistent with DZ7487's presumed binding mode. DZ7487 was well tolerated in animal models. Unlike fusion inhibitors, which can only prevent viral infection, DZ7487 potently inhibited RSV replication before and after RSV infection in vitro and in vivo. CONCLUSIONS: DZ7487 demonstrated potent anti-RSV replication effect both in vitro and in vivo assays. It has the desired drug-like physical properties to be an effective orally available anti-RSV replication drug with broad spectrum.

Design of improved four-coil structure with high uniformity and effective coverage rate.

Helmholtz coils have extensive applications in biological medicine, aerospace, and other industries depending on the simple structure and miraculous magnetic field characteristics. However, the uniform zone generated by them is not appropriate for scientific experiments with large devices. Due to the limitations of Helmholtz coils in application, a novel design technique is proposed to improve the homogeneity and region of magnetic field. The main approach is to add an auxiliary coil on each side of Helmholtz coils to compensate for the magnetic field that exists farther out from the center point. To analyze the size relationship between the auxiliary coil and the main coil to obtain the best magnetic field distribution, the traditional Maclaurin expansion method and particle swarm optimization (PSO) algorithm are used to research and discuss. The magnetic field distribution and the corresponding effective coverage rate (ECR) of the improved schemes with different structural parameters are calculated under the relative deviations of 0.1%, 0.5% and 1%, respectively. The results obtained by the above optimization methods are verified by the finite element software COMSOL and specific experiments. Both optimization methods manifest that the maximum effective coverage rate can be achieved when the size of the auxiliary coil is consistent with that of the main coil. In addition, we compare the improved four-coil structure proposed in this paper with the existing four-coil square structure under the same volume. The data show that the improved structure has certain advantages in the spatial magnetic field distribution. The corresponding tri-axial coil system is established by adopting the parameters on the single axis, which can achieve a constant magnetic field in arbitrary directions by controlling the magnitude and direction of current on each axis. This provides a theoretical basis for the application of magnetic navigation technology.

Development of Prognostic Biomarkers by TMB-Guided WSI Analysis: A Two-Step Approach.

The rapid development of computational pathology has brought new opportunities for prognosis prediction using histopathological images. However, the existing deep learning frameworks lack exploration of the relationship between images and other prognostic information, resulting in poor interpretability. Tumor mutation burden (TMB) is a promising biomarker for predicting the survival outcomes of cancer patients, but its measurement is costly. Its heterogeneity may be reflected in histopathological images. Here, we report a two-step framework for prognostic prediction using whole-slide images (WSIs). First, the framework adopts a deep residual network to encode the phenotype of WSIs and classifies patient-level TMB by the deep features after aggregation and dimensionality reduction. Then, the patients' prognosis is stratified by the TMB-related information obtained during the classification model development. Deep learning feature extraction and TMB classification model construction are performed on an in-house dataset of 295 Haematoxylin & Eosin stained WSIs of clear cell renal cell carcinoma (ccRCC). The development and evaluation of prognostic biomarkers are performed on The Cancer Genome Atlas-Kidney ccRCC (TCGA-KIRC) project with 304 WSIs. Our framework achieves good performance for TMB classification with an area under the receiver operating characteristic curve (AUC) of 0.813 on the validation set. Through survival analysis, our proposed prognostic biomarkers can achieve significant stratification of patients' overall survival (P 0.05) and outperform the original TMB signature in risk stratification of patients with advanced disease. The results indicate the feasibility of mining TMB-related information from WSI to achieve stepwise prognosis prediction.

Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study.

BACKGROUND: To investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan-Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM). RESULTS: Enrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan-Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses. CONCLUSIONS: Hyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.

Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy.

Chemotherapy has an essential role not only in advanced solid tumor therapy intervention but also in society's health at large. Chemoresistance, however, seriously restricts the efficiency and sensitivity of chemotherapeutic agents, representing a significant threat to patients' quality of life and life expectancy. How to reverse chemoresistance, improve efficacy sensitization response, and reduce adverse side effects need to be tackled urgently. Recently, studies on the effect of ultrasonic microbubble cavitation on enhanced tissue permeability and retention (EPR) have attracted the attention of researchers. Compared with the traditional targeted drug delivery regimen, the microbubble cavitation effect, which can be used to enhance the EPR effect, has the advantages of less trauma, low cost, and good sensitization effect, and has significant application prospects. This article reviews the research progress of ultrasound-mediated microbubble cavitation in the treatment of solid tumors and discusses its mechanism of action to provide new ideas for better treatment strategies.

Prognostic Value of Tumor Size in Patients with Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-analysis.

Context: The role of tumor size in predicting prognosis in upper tract urothelial carcinoma (UTUC) patients remains poorly defined. Objective: To assess the prognostic value of tumor size in patients with UTUC through a systematic review and meta-analysis. Evidence acquisition: A comprehensive literature search of the PubMed and Embase databases were performed to identify all relevant articles published up to December 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Available hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the association between tumor size and survival outcomes. Evidence synthesis: A total of 35 articles representing 32 292 patients met the eligibility criteria and were finally included for the meta-analysis. Tumor size was significantly associated with poor outcomes in terms of overall survival (HR = 1.42, 95% CI = 1.28-1.58), cancer-specific survival (HR = 1.66, 95% CI = 1.47-1.88), recurrence-free survival (HR = 1.25, 95% CI = 1.13-1.38), and intravesical recurrence (HR = 1.12, 95% CI = 1.04-1.20). There was between-study heterogeneity in the effect of tumor size on all these meta-analyses, with p < 0.10 and I2 generally >50%. Subgroup analyses illustrated that the association of tumor size with adverse prognosis in UTUC patients is not affected by treatment modalities. Segmental resection of ureter, whether receiving lymph node dissection, cutoff of tumor size, and region of population were potential sources of heterogeneity. The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes. Conclusions: This study shows that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in UTUC. Integration of tumor size with other prognostic indicators may help in risk stratification and individualized treatment of UTUC. Patient summary: Through a systematic review and meta-analysis, this study found that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in patients with upper tract urothelial carcinoma.