Freeform robotic optical coherence tomography beyond the optical field-of-view limit.

Imaging complex, non-planar anatomies with optical coherence tomography (OCT) is limited by the optical field of view (FOV) in a single volumetric acquisition. Combining linear mechanical translation with OCT extends the FOV but suffers from inflexibility in imaging non-planar anatomies. We report the freeform robotic OCT to fill this gap. To address challenges in volumetric reconstruction associated with the robotic movement accuracy being two orders of magnitudes worse than OCT imaging resolution, we developed a volumetric registration algorithm based on simultaneous localization and mapping (SLAM) to overcome this limitation. We imaged the entire aqueous humor outflow pathway, whose imaging has the potential to customize glaucoma surgeries but is typically constrained by the FOV, circumferentially in mice as a test. We acquired volumetric OCT data at different robotic poses and reconstructed the entire anterior segment of the eye. The reconstructed volumes showed heterogeneous Schlemm's canal (SC) morphology in the reconstructed anterior segment and revealed a segmental nature in the circumferential distribution of collector channels (CC) with spatial features as small as a few micrometers.

Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.

BACKGROUND: The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state. METHODS: CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023. DISCUSSION: The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases. TRIAL REGISTRATION: The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.

Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis.

Smoking continues to pose a global threat to morbidity and mortality in populations. The detrimental impact of smoking on health and disease includes bone destruction and immune disruption in various diseases. Osteoimmunology, which explores the communication between bone metabolism and immune homeostasis, aims to reveal the interaction between the osteoimmune systems in disease development. Smoking impairs the differentiation of mesenchymal stem cells and osteoblasts in bone formation while promoting osteoclast differentiation in bone resorption. Furthermore, smoking stimulates the Th17 response to increase inflammatory and osteoclastogenic cytokines that promote the receptor activator of NF-κB ligand (RANKL) signaling in osteoclasts, thus exacerbating bone destruction in periodontitis and rheumatoid arthritis. The pro-inflammatory role of smoking is also evident in delayed bone fracture healing and osteoarthritis development. The osteoimmunological therapies are promising in treating periodontitis and rheumatoid arthritis, but further research is still required to block the smoking-induced aggravation in these diseases. Translational potential: This review summarizes the adverse effect of smoking on mesenchymal stem cells, osteoblasts, and osteoclasts and elucidates the smoking-induced exacerbation of periodontitis, rheumatoid arthritis, bone fracture healing, and osteoarthritis from an osteoimmune perspective. We also propose the therapeutic potential of osteoimmunological therapies for bone destruction aggravated by smoking.

IRE1α regulates macrophage polarization in type 2 diabetic periodontitis through promoting endoplasmic reticulum stress.

OBJECTIVES: The aim of this study was to investigate the effect of 4µ8c, an inhibitor targeting the endoplasmic reticulum stress-associated factor IRE1α, on macrophage polarization in an experimental model of diabetic periodontitis through ex vivo experiments. MATERIALS AND METHODS: Local alveolar bone parameters were evaluated using Micro-CT following intraperitoneal administration of 4µ8c in mice with experimental diabetic periodontitis. Surface markers indicating macrophage polarization were identified using immunofluorescence. In vitro experiments were performed employing bone marrow-derived macrophages and gingival fibroblasts. Macrophage polarization was determined using flow cytometry. Principal impacted signaling pathways were identified through Western blot analysis. RESULTS: Results from both in vitro and in vivo experiments demonstrated that 4µ8c mitigated alveolar bone resorption and inflammation in mice with diabetic periodontitis. Furthermore, it modulated macrophage polarization towards the M2 phenotype and augmented M2 macrophage polarization through the MAPK signaling pathway. CONCLUSIONS: These findings suggest that inhibiting IRE1α can modulate macrophage polarization and alleviate ligature-induced diabetic periodontitis via the MAPK signaling pathway. This unveils a novel mechanism, offering a scientific foundation for the treatment of experimental diabetic periodontitis.

Knowledge, Attitudes and Practices Towards Psoriasis Among Patients and Their Family Members.

Purpose: KAP studies serve to enhance health consciousness and furnish foundational data for appraising, strategizing, and enacting disease management and prejudice eradication initiatives. There remains a dearth of published studies elucidating the dimensions of knowledge, attitudes, and practices among psoriasis patients in China. To investigate the knowledge, attitudes and practices (KAP) towards psoriasis among patients and their family members in Northern China. Methods: This web-based, cross-sectional study was conducted among psoriasis patients and their family members through a self-administered questionnaire. Results: Among patients (n=260), their mean KAP scores were 9.76±5.69 (range: 0-19), 35.64±11.48 (range: 14-70), and 56.73±10.98 (range: 16-80), respectively. Among family members (n=237), their mean KAP scores were 11.93±5.34 (range: 0-19), 35.80±4.34 (range: 8-40), and 37.04±4.38 (range: 8-40), respectively. Structural equation modeling (SEM) analysis for patients indicated significant and negative path relations between knowledge and attitudes (ß=-2.271, P<0.001), and between knowledge and practice (ß=-0.398, P<0.001). Extended SEM analysis, which divides knowledge into K1, K2, and K3 parts, showed negative path relations between K3 and attitude (ß=-1.300, P=0.002), between attitude and practice (ß=-0.634, P<0.001). Moreover, SEM for family members showed positive path relations between knowledge and attitude (ß=1.536, P<0.001), between attitude and practice (ß=0.682, P<0.001). Conclusion: Patients in Northern China demonstrated insufficient knowledge, negative attitude, and proactive practice, while their family members had insufficient knowledge, positive attitude, and proactive practice toward psoriasis. It is recommended to implement educational interventions addressing knowledge gaps among patients and families.

From biology to the clinic - exploring liver metastasis in prostate cancer.

Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3-10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20-30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET-CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negative results, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group.

Recent Advances of Chiral Isolated and Small Organic Molecules: Structure and Properties for Circularly Polarized Luminescence.

This paper explores recent advancements in the field of circularly polarized luminescence (CPL) exhibited by small and isolated organic molecules. The development and application of small CPL molecule are systematically reviewed through eight different chiral skeleton sections. Investigating the intricate interplay between molecular structure and CPL properties, the paper aims at providing and enlighting novel strategies for CPL-based applications.

One-step carbonization/activation synthesis of chitosan-based porous sheet-like carbon and studies of adsorptive removal for Rhodamine B.

In this work, new N, O-codoped chitosan-derived carbon adsorbents (CKC-x, x refer to the calcination temperature) were synthesized over a simple process of chitosan-KOH aerogel production and simultaneous carbonization/activation of the aerogel. CKC-700 was characterized by sheet-like morphology (even containing a portion of carbon nano-sheet of 3 nm thickness), high porosity and specific surface area (1702.1 m2/g), and pyridinic/pyrrolic/graphitic N groups. The simultaneous carbonization/activation of chitosan-KOH aerogel prepared by top-down coagulation of chitosan aqueous solution by KOH aqueous solution rendered these beneficial characteristics. CKC-700 exhibited a superior adsorption capacity for Rhodamine B (RhB) to other chitosan-derived carbon adsorbents, and the maximum adsorption capacity for RhB of 594 mg/g was achieved at 55 °C. CKC-700 also possessed reasonable reusability for the removal of RhB, and the removal efficiency was still above 95 % in the fifth cycle. The effects of adsorption temperature and time, adsorbent dose, organic dye concentration, and solution pH on the adsorption capacity of CKC-700 were studied. Moreover, the adsorption isotherm, kinetics, thermodynamics, and the adsorption mechanism of RhB on CKC-700 were discussed. In addition, CKC-700 also showed favorable adsorption performance for methylene blue (441 mg/g), methyl orange (457 mg/g), and congo red (500 mg/g) at around 25 °C.

Nomogram to predict the presence of PSMA-negative but FDG-positive lesion in castration-resistant prostate cancer: a multicenter cohort study.

Background: PSMA-negative but FDG-positive (PSMA-/FDG+) lesion in dual-tracer (68Ga-PSMA and 18F-FDG) positron emission tomography/computed tomography (PET/CT) is associated with an unfavorable response to Lutetium-177 (177Lu)-PSMA-617. This study sought to develop both radiomics and clinical models for the precise prediction of the presence of PSMA-/FDG+ lesions in patients with castration-resistant prostate cancer (CPRC). Methods: A cohort of 298 patients who underwent dual-tracer PET/CT with a less than 5-day interval was included. The evaluation of the prognostic performance of the radiomics model drew upon the survival data derived from 40 patients with CRPC treated with 177Lu-PSMA-617 in an external cohort. Two endpoints were evaluated: (a) prostate-specific antigen (PSA) response rate, defined as a reduction exceeding 50% from baseline and (b) overall survival (OS), measured from the initiation of 177Lu-PSMA-617 to death from any cause. Results: PSMA-/FDG+ lesions were identified in 56 (18.8%) CRPC patients. Both radiomics (area under the curve [AUC], 0.83) and clinical models (AUC, 0.78) demonstrated robust performance in PSMA-/FDG+ lesion prediction. Decision curve analysis revealed that the radiomics model yielded a net benefit over the 'screen all' strategy at a threshold probability of ⩾4%. At a 5% probability threshold, the radiomics model facilitated a 21% reduction in 18F-FDG PET/CT scans while only missing 2% of PSMA-/FDG+ cases. Patients with a low estimated score exhibited significantly prolonged OS (hazard ratio = 0.49, p = 0.029) and a higher PSA response rate (75% versus 35%, p = 0.011) compared to those with a high estimated score. Conclusion: This study successfully developed two models with accurate estimations of the risk associated with PSMA-/FDG+ lesions in CRPC patients. These models held potential utility in aiding the selection of candidates for 177Lu-PSMA-617 treatment and guiding 68Ga-PSMA PET/CT-directed radiotherapy.

Predictive nomogram for PSMA-/FDG+ lesion This study developed two models with accurate estimations of the risk associated with specific lesions in prostate cancer.

Temporal and spatial effects on C-reactive protein's regulation of inducible nitric oxide synthase production in periodontal disease.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is associated with inflammation and osteoclastic differentiation in periodontal disease. This study was conducted to compare the time-dependent variation in iNOS production between the gingiva and other periodontal tissues and to explore the potential association with C-reactive protein (CRP) in early periodontal disease. METHODS: Ligature-induced periodontal disease models (0-14 days) were established in wild-type and CRP knockout rats. Changes in CRP, iNOS, and autophagy levels were examined in the gingiva and other periodontal tissues. Macrophages were treated with lipopolysaccharide and chloroquine to explore the role of autophagy in iNOS production. iNOS, CRP, and autophagy-related proteins were analyzed using Western blotting, immunostaining, and enzyme-linked immunosorbent assays. mRNA expression was detected by quantitative real-time polymerase chain reaction. Hematoxylin and eosin staining was used for histological analysis. Cathepsin K immunostaining and microcomputed tomography of the maxillae were performed to compare alveolar bone resorption. RESULTS: iNOS and CRP levels increased rapidly in periodontal tissues, as observed on Day 2 of ligature, then decreased more rapidly in the gingiva than in other periodontal tissues. CRP deficiency did not prevent iNOS generation, but effectively accelerated iNOS reduction and delayed alveolar bone loss. The CRP effect on iNOS was accompanied by a change in autophagy, which was reduced by CRP knockout. CONCLUSIONS: The regulation of iNOS by CRP shows temporospatial variation in early periodontal disease and is potentially associated with autophagy. These findings may contribute to the early detection and targeted treatment of periodontal disease.

Proteomic analysis reveals the aging-related pathways contribute to pulmonary fibrogenesis.

Aging usually causes lung-function decline and susceptibility to chronic lung diseases, such as pulmonary fibrosis. However, how aging affects the lung-fibrosis pathways and leads to the occurrence of pulmonary fibrosis is not completely understood. Here, mass spectrometry-based proteomics was used to chart the lung proteome of young and old mice. Micro computed tomography imaging, RNA immunoprecipitation, dual-fluorescence mRFP-GFP-LC3 adenovirus monitoring, transmission electron microscopy, and other experiments were performed to explore the screened differentially expressed proteins related to abnormal ferroptosis, autophagy, mitochondria, and mechanical force in vivo, in vitro, and in healthy people. Combined with our previous studies on pulmonary fibrosis, we further demonstrated that these biological processes and underlying molecular players were also involved in the aging process. Our work depicted a comprehensive cellular and molecular atlas of the aging lung and attempted to explain why aging is a risk factor for pulmonary fibrosis and the role that aging plays in the progression of pulmonary fibrosis. The abnormalities of aging triggered an increase in mechanical force and ferroptosis, autophagy blockade, and mitochondrial dysfunction, which often appear during pulmonary fibrogenesis. We hope that the elucidation of these anomalies will help to enhance our understanding of senescence-inducing pulmonary fibrosis, thereby guiding the use of anti-senescence as an entry point for early intervention in pulmonary fibrosis and age-related diseases.

A 37-Year-Old Man with Myofibroblast Sarcoma Combined with Pleural Maculopathy: Case Report.

Myofibroblastic sarcoma (MS) is a malignant tumor of soft tissue or bone that can occur in children or adults, with a high rate of recurrence and metastasis. We report a case of low-grade malignant MS of the left shoulder, diagnosed based on pathological examination and immunohistochemical staining. However, the patient had unexplained pleural maculopathy. The patient passed away 6 months after the diagnosis of myofibroblast sarcoma due to multiple metastases throughout the sarcoma. Combined with the patient's history, ancillary findings, and after MDT discussion, the patient was ultimately considered to have a high probability of myofibroblast sarcoma combined with pleural maculopathy. In conclusion, when a patient is diagnosed with myofibroblast sarcoma in combination with pleural macula, in the absence of other causative factors, a deep tissue biopsy of the pleura should be actively performed to confirm the diagnosis.

Inhibition of the lncRNA 585189 prevents podocyte injury and mitochondria dysfunction by promoting hnRNP A1 and SIRT1 in diabetic nephropathy.

Podocyte dysfunction has been identified as a crucial pathological characteristic of diabetic nephropathy (DN). However, the regulatory effects of long non-coding RNAs (lncRNAs) in this process have not been fully elucidated. Here, we performed an unbiased RNA-sequencing (RNA-seq) analysis of renal tissues and identified a significantly upregulated long non-coding RNA, ENST00000585189.1 (lncRNA 585189), in patients with DN. Furthermore, lncRNA 585189 was positively correlated with renal insufficiency and was upregulated in both DN patients and high-glucose-induced human podocytes. Gain- and loss-of-function experiments revealed that silencing lncRNA 585189 decreased the production of ROS, rescued aberrant mitochondrial morphology and membrane potential, and alleviated podocyte damage caused by high glucose. Mechanistically, bioinformatics analysis predicted an interaction between lncRNA 585189 and hnRNP A1, which was subsequently confirmed by RIP, pull-down, and EMSA assays. Further investigation revealed that lncRNA 585189 destabilizes the hnRNP A1 protein, leading to the downregulation of its expression. Conversely, hnRNP A1 promoted the expression of lncRNA 585189. Moreover, both RIP and pull-down assays demonstrated a direct interaction between hnRNP A1 and SIRT1, which enhanced SIRT1 mRNA stability. Our findings suggest that lncRNA 585189 suppresses SIRT1 through hnRNP A1, thereby hindering the recovery from mitochondrial abnormalities and podocyte damage. In summary, targeting lncRNA 585189 is a promising strategy for reversing mitochondrial dysfunction and treating DN.

Clostridium butyricum MIYAIRI 588 alleviates periodontal bone loss in mice with diabetes mellitus.

The gut microbiota is a bridge linking periodontitis and systemic diseases, such as diabetes mellitus (DM). The probiotic Clostridium butyricum MIYAIRI 588 (CBM588) is reportedly an effective therapeutic approach for gut dysbiosis. Here, in a mouse model, we explored the therapeutic effect of CBM588 on periodontal bone destruction in DM and DM-associated periodontitis (DMP), as well as the underlying mechanism. Micro-computed tomography revealed that DM and DMP both aggravated periodontal bone destruction, which was alleviated by intragastric supplementation with CBM588. Moreover, 16S rRNA sequencing and untargeted metabolite analysis indicated that CBM588 ameliorated DMP-triggered dysbiosis and led to reduced oxidative stress associated with elevated 4-hydroxybenzenemethanol (4-HBA) in serum. Furthermore, in vitro and in vivo experiments found that the metabolite 4-HBA promoted nuclear factor erythroid 2-related factor 2 (Nrf2) signaling activation and modulated the polarization of macrophages, thus ameliorating inflammatory bone destruction in DMP. Our study demonstrates the protective effects of CBM588 in DM-induced mice, with and without ligature-induced periodontitis. The mechanism involves regulation of the gut microbiota and restoration of the integrity of the gut barrier to alleviate oxidative damage by elevating serum 4-HBA. This study suggests the possibility of CBM588 as a therapeutic adjuvant for periodontal treatment in diabetes patients.

Increased serum α-tocopherol acetate mediated by gut microbiota ameliorates alveolar bone loss through the STAT3 signalling pathway in diabetic periodontitis.

AIM: To evaluate whether and how gut microbiota-meditated metabolites regulate alveolar bone homeostasis in diabetic periodontitis (DP). MATERIALS AND METHODS: Lactobacillus casei (L. casei) was employed as a positive modulator of gut microbiota in DP mice. The destruction of alveolar bone was evaluated. Untargeted metabolomics was conducted to screen out the pivotal metabolites. A co-housing experiment was conducted to determine the connection between the gut microbiota and alpha-tocopherol acetate (α-TA). α-TA was applied to DP mice to investigate its effect against alveolar bone loss. Human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (HGFs) were extracted for the in vitro experiment. Transcriptomic analysis and immunohistochemistry were performed to detect the major affected signalling pathways. RESULTS: Positive regulation of the gut microbiota significantly attenuated alveolar bone loss and increased the serum α-TA level. The alteration in gut microbiota composition could affect the serum α-T (the hydrolysates of α-TA) level. α-TA could alleviate alveolar bone destruction in DP mice and α-T exert beneficial effects on hPDLCs and HGFs. Mechanistically, the STAT3 signalling pathway was the pivotal pathway involved in the protective role of α-TA. CONCLUSIONS: The gut microbiota-α-TA-STAT3 axis plays an important role in the regulation of diabetic alveolar bone homeostasis.

Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity.

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.

Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis.

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a new mode of intercellular crosstalk and are responsible for many of the therapeutic effects of MSCs. To promote the application of MSC-EVs, recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities. The current paper details an optimization method using non-invasive low-intensity pulsed ultrasound (LIPUS) as the stimulation for improving oral MSC-EV production and effectiveness. Stem cells from apical papilla (SCAP), a type of oral mesenchymal stem cell, displayed intensity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis. The stimuli increased the secretion of EVs by promoting the expression of neutral sphingomyelinases in SCAP. In addition, EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of periodontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo. In addition, LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs. Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV production and efficacy.

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer.

BACKGROUND: Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. METHODS: This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. RESULTS: Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28-0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33-0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68-0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52-0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62-0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60-0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57-0.78; P<.001). CONCLUSIONS: Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

Mismatch repair gene germline mutations in patients with prostate cancer. / 855ä¾‹å‰åˆ—è ºç™Œæ‚£è€ é”™é ä¿®å¤åŸºå› èƒšç³»çªå˜ä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics. METHODS: Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR－ group) and patients without DDR gene germline pathogenic mutation (DDR－ group). RESULTS: Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR－ group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR－ group and DDR－ group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR－ group and DDR－ group (both P<0.01), while there was no significant difference between DDR+MMR－ group and DDR－ group (P>0.05). CONCLUSIONS: MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.