The application of "S.I.S" technique improves long-term continence after robotic radical prostatectomy.

AIMS: To propose a novel S.I.S technique during the robotic-assisted radical prostatectomy (RARP), encompassing pubourethral suspension, posterior wall intensification, and bladder neck stripping, and to present functional and oncological outcomes with a special focus on long-term continence. METHODS: From January 1, 2018, to December 31, 2019, consecutive patients who underwent RARP were retrospectively investigated and separated into the S.I.S group and the conventional group. Preoperative patient characteristics, tumor status, and perioperative parameters were collected, followed by the assessment of self-reported status on continence, using an International Consultation on Incontinence Modular Questionnaire-urinary incontinence short form (ICIQ-UI-SF). Statistical comparisons were performed on variables between the two surgery groups, and multivariate logistic regression analysis was used to determine predictive factors for postoperative incontinence severity. RESULTS: A total of 602 subjects were analyzed with a median follow-up of 24 months. There was no significant difference regarding baseline characteristics and perioperative parameters, except for a more advanced tumor stage in the S.I.S group. The application of the S.I.S technique did not jeopardize the positive surgical margin rate at the bladder neck or long-term tumor control. Notably, the patient-reported degree of incontinence was significantly reduced with the assistance of S.I.S technique, as evidenced by the diminished severe-to-very severe cases. On multivariate analysis, both preoperative body mass index and use of S.I.S modification were independent predictive factors for the long-term incontinence severity. CONCLUSIONS: The application of S.I.S technique during RARP is feasible and superior compare with the conventional approach, with a significantly alleviated long-term incontinence severity, without compromising cancer control.

Design of BRC analogous peptides based on the complex BRC8-RAD51 and the preliminary study on the peptide structures.

BRCA2 is an important tumor suppressor gene that plays a critical role in preserving the stability of cellular genetic information, participating in DNA repair by engaging in binding interactions with RAD51 proteins. However, the lack of structural data on BRCA2 and RAD51 makes the study of their interaction mechanism still a great challenge. We characterize the structure of the BRC8-RAD51 complex using ZDOCK protein docking software and identify the potential non-conserved active site of BRC8 via virtual alanine scanning, utilizing the obtained results to synthesize BRC8, its six analogous peptides (BRC8-1 to BRC8-6), and critical peptide fragment of RAD51 (RAD51(231-260)) by Fmoc solid-phase synthesis. The analogous peptides are found to exhibit a secondary structure significantly different from that of BRC8 by circular dichroism spectroscopy, which indicates that mutation sites determined by computer-aided simulation correspond to key amino acid residues substantially affecting polypeptide structure. On the other hand, the secondary structure of RAD51(231-260) was also considerably influenced by its interaction with BRC8 and analogs, e.g., the fraction of the α-helical structure in RAD51(231-260) increased to 23.6, 15.1, and 13.5% upon interaction with BRC8-1, BRC8-3, and BRC8-6, respectively. The results show that the properties of C-terminal amino acid residues significantly influence peptide-peptide interactions, in agreement with the results of virtual alanine scanning. Therefore, computer-aided simulation was confirmed to be a technique that is useful for narrowing down the range of sites responsible for interactions between peptides or proteins, and provides new inspirations for the design of peptides with strong interactions.

Mobile-based ecological momentary assessment and intervention: bibliometric analysis.

Objective: The aim of this article was to review existing documents in the field of mobile-based EMA and EMI, provide an overview of current hot topics, and predict future development trends. Methods: We conducted a bibliometric study on mobile-based EMA and EMI publications that were collected from the Web of Science Core Collection database. Biblioshiny and CiteSpace were utilized to analyze scientific productions, leading sources, authors, affiliations, documents, research hot topics, keywords, and trend topics. Results: A total of 2222 documents related to EMA and EMI published between 1992 and 2023 were retrieved. In recent years, scholarly publications have generally increased in mobile-based EMA and EMI research, particularly in the last decade. JMIR mHealth and uHealth (n=86), as well as JMIR (n=73), showed the highest number of publications. The United States (n=1038), Germany (n=218) and Netherlands (n=175) were leading countries. Regarding keyword co-occurrence and trend topics analysis, mental health, health behaviors, and feasibility were hot topics in mobile-based EMA and EMI research. Future research trends included using EMA for tailoring EMI, just-in-time adaptive interventions (JITAI), and digital phenotyping. Conclusion: This bibliometric study on mobile-based EMA and EMI is a valuable resource for understanding the field's evolution and future trends. Our analysis indicates that EMA and EMI have great potential in health behaviors and mental health, but implementation should consider feasibility and reactivity issues carefully. Emerging trends include EMA-tailored EMI, JITAI, and digital phenotyping. In the future, strengthening multidisciplinary cooperation will be necessary to promote the continued development of the field.

Effectiveness of identity-building interventions on recovery identity and patient-reported health outcomes in chronic diseases: A meta-analysis.

This meta-analysis aimed to assess the impact of identity-building interventions on recovery identity and patient-reported health outcomes in chronic disease patients. We identified 15 relevant empirical studies (comprising 2261 patients) from 989 records through extensive keyword searches and manual screening conducted between March 2nd and March 13th, 2023. Utilizing the Cochrane tool, meta-regression, and the GRADE approach, we evaluated these studies for their characteristics, findings, and quality. The analysis revealed that identity-building interventions, encompassing recovery-oriented group, interest group, and linguistic approaches, positively influenced identity synthesis and had varying effects on health outcomes. Notably, multiple regression analysis demonstrated that identity synthesis significantly predicted health outcomes. However, the study identified mild heterogeneity, a high attrition bias risk, and insufficient data on selection and detection bias as limitations. Overall, identity-building interventions proved influential in enhancing recovery identity, a vital predictor of patient-reported health outcomes in chronic disease patients.

Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits.

Background: Patients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy. Methods: The whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to identify predictive biomarkers for guiding treatment selection. Results: Comparing the transcriptome profiling of pre- and post-treatment LAPCa specimens, NHT and NCHT shared 1917 up- and 670 down-regulated DEGs at least 2-fold. Pathway enrichment analysis showed up-regulated pathways in response to NHT and NCHT were both enriched in cytokine receptor interaction pathways, and down-regulated pathways in response to NCHT were enriched in cell cycle pathways. By comprehensive transcriptome profiling of 64 baseline specimens, ten predictive markers were identified. We integrated them into the signature to evaluate the relative benefits of neoadjuvant therapy, which categorizes patients into two subgroups with relative bPFS benefits from either NHCT or NHT. In the high-score (≥ -95.798) group (n = 37), NCHT treatment led to significantly longer bPFS (P< 0.0001), with a clear and early separation of the Kaplan-Meier curves. In the low-score (< -95.798) group (n = 27), NHT also led to significantly longer bPFS (P=0.0025). Conclusions: In this study, we proposed the first predictive transcriptomic signature might potentially guide the effective selection of neoadjuvant therapy in LAPCa and might provide precise guidance toward future personalized adjuvant therapy. Trial registration: The study was approved by the Ethics Committee of Renji Hospital affiliated to Shanghai Jiao Tong University (Ky2019-087).

Early serial circulating tumor DNA sequencing predicts the efficacy of chemohormonal therapy in patients with metastatic hormone-sensitive prostate cancer.

Chemohormonal therapy is a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC); however, there are no biomarkers to guide clinical decisions regarding therapeutic options. We aimed to evaluate the clinical utility of serial circulating tumor DNA (ctDNA) sequencing in early prediction of the efficacy of chemohormonal therapy in patients with mHSPC. We conducted a retrospective observational study of 66 patients with mHSPC receiving chemohormonal therapy who underwent serial targeted gene-panel ctDNA sequencing. Peripheral blood samples were collected before treatment and after one cycle of chemotherapy. Kaplan-Meier and log-rank analyses were used to analyze the association between ctDNA status and disease progression-free survival. Serial changes in the ctDNA fraction and genetic alterations were also observed. After one cycle of chemotherapy, 23 (34.8%) patients displayed elevated ctDNA levels, whereas the other patients (65.2%, n = 43) did not. The median time to castration resistance in the group with reduced ctDNA levels was significantly longer than that in the group with increased ctDNA levels (17.70 vs. 8.43 months [mo], p < 0.001). Interestingly, patients with de novo alterations in homologous recombination pathway genes after treatment experienced a shorter time to castration resistance than that experienced by the remaining patients (8.02 vs. 13.20 mo, p = 0.011). The increased ctDNA levels or de novo alterations detected in homologous recombination pathway genes are a harbinger of disease progression. Early serial ctDNA sequencing could aid clinicians in making accurate treatment decisions.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Head and neck squamous cell carcinoma targeted chemosensitization.

OBJECTIVE: The current treatment for advanced head and neck squamous cell carcinoma continues to result in poor outcomes. The purpose of this study is to investigate the benefit of fibroblast growth factor 2-targeted adenovirus-mediated mutant-Rad50 (FGF2-Ad-Rad50) gene transfer in enhancing chemosensitization for head and neck squamous cell carcinoma and reducing chemotoxicity. STUDY DESIGN: Randomized controlled laboratory study. SETTING: University of Pennsylvania, Philadelphia, PA. SUBJECTS AND METHODS: Human head and neck squamous cell carcinoma tumor cells and a mouse model with human head and neck squamous cell carcinoma were used for this study. There were five mice in each study group. FGF2-fab' molecule was conjugated with an adenoviral mutant-Rad50 construct. FGF2-targeted transgene expression efficiency was evaluated in vitro. Tumor cytotoxicity and growth inhibition were examined after combined FGF2-Ad-Rad50 with cisplatin treatment in vitro and in vivo. Anti-tumor mechanisms were investigated. RESULTS: FGF2-targeted gene transfer approach significantly improved transgene expression in head and neck squamous cell carcinoma tumor cells over a nontargeted approach (207.51+/-33.62 vs 51.44+/-8.28, respectively). FGF2-Ad-Rad50 with cisplatin demonstrated a superior tumor suppression effect (264.5+/-124.1 mm3 vs 567.1+/-267.6 mm3), increased DNA double-strand breaks (1349+/-51.67 vs 774+/-28.56), and anti-angiogenesis (%ROI: 0.76%+/-0.38% vs 2.10%+/-1.66%) in tumor cells over nontargeted adenovirus. CONCLUSION: Combination of FGF2-Ad-Rad50 with cisplatin significantly improves anti-tumor effect by targeting DNA repair systems and tumor angiogenesis. The great benefit of this strategy supports clinical trial for novel treatment of head and neck squamous cell carcinoma.

Design and synthesis of BRC analogous peptides and their interactions with a key p53 peptide.

Mutations in breast cancer susceptibility gene 2 (BRCA2) can lead to chromosomal instability and result in breast cancer, which is strongly associated with p53 mutations. Here, based on the crystal structure of BRC4 and p53, the spatial structure of BRC2 and p53 (171-192) was simulated, providing structural basis for the site-specific mutation of BRC2. The BRC analogous peptides and p53 (171-192) were synthesized, and the interaction between the mutant peptide and p53 (171-192) was studied using circular diachronic spectroscopy and fluorescence spectroscopy. The results show that the mutations of amino acid residues constituting the BRC2 α-helix significantly affect the structure and interaction of BRC analogs and p53 (171-192), which provides support for understanding the structure of the BRC repeat motifs and its interaction pattern with p53.