Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective To construct a risk prediction model for venous thromboembolism(VTE)in patients with acute stroke and analyze its predictive value with decision curve.Methods Clinical data of 265 patients with acute stroke admitted to Department of Neurology of Pingxiang People's Hospital between May 2022 and May 2024 were collected,and 185 of them(69.8％)were assigned to a training set and 80 cases(30.2％)into a validation set.Based on the results of color Doppler ultrasound examination,the patients in the training set were divided into the VTE group(72 cases)and the non-VTE group(113 cases).Multivariate logistic regression analysis was used to identify the risk factors for VTE occurrence in the patients.A prediction model was constructed and a nomegram was developed to visually present the logistic regression prediction model.ROC curve and decision curve analyses were applied to evaluate the predictive performance of the logis-tic regression model.Results The VTE group had significantly larger intracranial hemorrhage volume,higher fibrinogen(FIB),D-dimer and C-reactive protein(CRP)levels,and lower Glasgow Coma Scale(GCS)score than the non-VTE group(P＜0.01).Multivariate logistic regression analysis indicated that intracranial hemorrhage volume(OR=1.243,95％CI:1.015-1.522),FIB(OR=3.161,95％CI:1.711-5.841),CRP(OR=1.595,95％CI:1.283-1.981),and D-dimer(OR=6.234,95％CI:2.693-14.434)were independent risk factors for the occurrence of VTE in the patients with acute stroke,while GCS score(OR=0.587,95％CI:0.413-0.834,P=0.003)was an independent protective factor against the occurrence.A VTE prediction model based on these influencing factors obtained a consistency index of 0.978.The calibration curve results showed that the observed values were in good agreement with the predicted values.ROC curve analysis indicated that the AUC value of the prediction model was 0.978(95％CI:0.945-0.994)in the training set and 0.959(95％CI:0.890-0.991)in the validation set.Decision curve analysis revealed that the model achieved higher net benefit when the threshold probability was between 20％and 80％.Conclusion Intracranial bleeding volume,GCS score,CRP,Didimer and FIB are related influencing factors of VTE in patients with acute stroke,and the prediction model of deci-sion curve based on the above factors is of high prediction efficiency.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a chronic liver condition intricately linked to metabolic abnormalities such as obesity,type 2 diabetes,dyslipidemia,and hypertension.The global prevalence of MASLD continues to rise,posing a significant public health challenge.The pathogenesis of MASLD is multifactorial,with the"multiple-hit"hypothesis suggesting that hepatic lipid accumulation,insulin resistance,oxidative stress,gut microbiota dysbiosis,and genetic factors collectively drive disease progression.Currently,clinical management primarily relies on lifestyle interventions;however,there is a lack of targeted pharmacological interventions,and there is an urgent need to investigate novel adjunctive therapeutic strategies.In recent years,probiotics have demonstrated potential value in MASLD treatment due to their capacity to modulate gut microbiota,enhance insulin sensitivity,and reduce liver inflammation.This review systematically examines the pathogenesis of MASLD and the limitations of existing therapeutic approaches,synthesizing the latest evidence of probiotics-assisted therapy for MASLD from the perspectives of animal studies and clinical trials.By analyzing the target mechanisms and molecular pathways of different strains(e.g.,Bifidobacterium,Lactobacillus),this review explores the translational potential of probiotics in MASLD treatment,aiming to provide a theoretical foundation and future research directions.

Objective To construct a risk prediction model for venous thromboembolism(VTE)in patients with acute stroke and analyze its predictive value with decision curve.Methods Clinical data of 265 patients with acute stroke admitted to Department of Neurology of Pingxiang People's Hospital between May 2022 and May 2024 were collected,and 185 of them(69.8％)were assigned to a training set and 80 cases(30.2％)into a validation set.Based on the results of color Doppler ultrasound examination,the patients in the training set were divided into the VTE group(72 cases)and the non-VTE group(113 cases).Multivariate logistic regression analysis was used to identify the risk factors for VTE occurrence in the patients.A prediction model was constructed and a nomegram was developed to visually present the logistic regression prediction model.ROC curve and decision curve analyses were applied to evaluate the predictive performance of the logis-tic regression model.Results The VTE group had significantly larger intracranial hemorrhage volume,higher fibrinogen(FIB),D-dimer and C-reactive protein(CRP)levels,and lower Glasgow Coma Scale(GCS)score than the non-VTE group(P＜0.01).Multivariate logistic regression analysis indicated that intracranial hemorrhage volume(OR=1.243,95％CI:1.015-1.522),FIB(OR=3.161,95％CI:1.711-5.841),CRP(OR=1.595,95％CI:1.283-1.981),and D-dimer(OR=6.234,95％CI:2.693-14.434)were independent risk factors for the occurrence of VTE in the patients with acute stroke,while GCS score(OR=0.587,95％CI:0.413-0.834,P=0.003)was an independent protective factor against the occurrence.A VTE prediction model based on these influencing factors obtained a consistency index of 0.978.The calibration curve results showed that the observed values were in good agreement with the predicted values.ROC curve analysis indicated that the AUC value of the prediction model was 0.978(95％CI:0.945-0.994)in the training set and 0.959(95％CI:0.890-0.991)in the validation set.Decision curve analysis revealed that the model achieved higher net benefit when the threshold probability was between 20％and 80％.Conclusion Intracranial bleeding volume,GCS score,CRP,Didimer and FIB are related influencing factors of VTE in patients with acute stroke,and the prediction model of deci-sion curve based on the above factors is of high prediction efficiency.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Bladder cancer is a common malignancy in the genitourinary system and the current therapeutic approaches are unsatisfactory. Urinary cell-free DNA (ucf DNA) has the ability to give comprehensive and crucial information on cancer as it carries genetic messages from cells shedding directly into urine as well as transporting from circulation. The ucf DNA of patients with bladder cancer carries disease information, suggesting that ucf DNA may have the ability to detect, monitor, and prognosticate patients with bladder cancer. The ucf DNA analysis bridges the gap between current techniques and enhances diagnostic and detection capabilities, and has a very promising future in term of translation into clinical practice. This article reviewed the progress of clinical applications of ucf DNA in bladder cancer.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Suboptimal diet is one of the most important controllable risk factors for non-communicable diseases. However, randomized controlled trials make it difficult to quantify the causal association between specific dietary factors and health outcomes. In recent years, the rapid development of causal inference has provided a robust theoretical and methodological tool for making full use of observational research data and producing high-quality nutritional epidemiologic research evidence. The causal graph model visualizes the complex causal relationship system by integrating a large amount of prior knowledge and provides a basic framework for identifying confounding and determining causal effect estimation strategies. Different analysis strategies such as adjusting confounders, instrumental variables, or mediation analysis can be created based on other causal graphs. This paper introduces the idea of the causal graph model and the characteristics of various analysis strategies and their application in nutritional epidemiology research, aiming to promote the application of the causal graph model in nutrition and provide references and suggestions for the follow-up research.

OBJECTIVE: To investigate the effects of on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice. METHODS: Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (=20) and control group (=20) for intravenous injection of suspension (200 μL, 4 × 10 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining. RESULTS: In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (=0.01); the acoustic velocity (=0.001) and the acoustic attenuation (=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (=0.0006) and larger coagulative necrosis volume (=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (=0.0134). CONCLUSIONS can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.
Acoustics ; Animals ; Bifidobacterium ; pathogenicity ; Breast Neoplasms ; pathology ; Collagen ; Elasticity Imaging Techniques ; High-Intensity Focused Ultrasound Ablation ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation