Objective:To compare the clinical efficacy and adverse events of different postoperative radiotherapy strategies (adjuvant radiotherapy versus salvage radiotherapy) and different irradiation fields (prostate bed versus prostate bed + pelvic radiation) in patients after radical prostatectomy for prostate cancer.Methods:This retrospective analysis included clinical data from 115 patients with localized or locally advanced prostate cancer who received intensity-modulated radiotherapy (IMRT) after radical prostatectomy at Beijing Hospital between March 2014 and September 2023. Among them, 40 patients received adjuvant radiotherapy, and 75 received salvage radiotherapy. And 74 patients received irradiation to both the prostate bed and pelvic (prostate bed + pelvic radiation group), while 41 patients received irradiation to the prostate bed alone (prostate bed irradiation group). Comparison was made between the adjuvant radiotherapy group and salvage radiotherapy group, as well as between prostate bed + pelvic radiation group and prostate bed irradiation group, in terms of overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and the incidence of adverse events. Clinical characteristics were compared using the chi-square test. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors affecting survival were analyzed using Cox multivariate regression.Results:The median follow-up duration was 73.1 months. The 5-year OS, PFS and LRRFS rates for the entire cohort were 96.4%, 86.4%, and 93.2%, respectively. A total of 59 patients (51.3%) experienced grade 1-2 acute radiotherapy-related adverse events, while 43 patients (37.4%) experienced grade 1-2 late radiotherapy-related adverse events. No grade ≥ 3 late adverse events were observed. There were no statistically significant differences in OS, PFS, or LRRFS between the adjuvant and salvage radiotherapy groups ( P = 0.807, 0.996, and 0.976, respectively), or in the incidence of grade 1-2 acute or late adverse events ( P > 0.05). The OS rate in the prostate bed + pelvic radiation group was significantly lower than that in the prostate bed irradiation group ( P = 0.036), while no significant differences were found in PFS or LRRFS ( P = 0.109 and 0.190, respectively), or in the incidence of grade 1-2 acute or late adverse events ( P > 0.05). Multivariable analysis showed no statistically significant differences in OS, PFS, or LRRFS between the adjuvant and salvage radiotherapy groups, or between the prostate bed and prostate bed + pelvic irradiation groups ( P = 0.756, 0.341, 0.605; 0.938, 0.987, 0.605, respectively). Conclusions:In the era of modern IMRT, both adjuvant and salvage radiotherapy, as well as prostate bed and prostate bed + pelvic irradiation, demonstrate similar efficacy and safety profiles after radical prostatectomy for prostate cancer. Treatment outcomes were favorable, and adverse events were minimal.

Objective Through in vitro experiments,biomechanical data of the transtibial pullout suture(TPS),tendon reconstruction(TR),and tendon reconstruction with suture augmentation(TRS)were collected,so as to evaluate the biomechanical effectiveness of tendon reconstruction for repairing medial meniscus posterior root tear(MMPRT).Methods Eighteen porcine knee joint models were divided into TPS,TR,and TRS groups.Sutures were used to fix the meniscal root in TPS group.Tendons were passed through an incision at the meniscal root in TR group.Tendons were passed through an incision at the meniscal root and secured at tendon-meniscus contact area with additional sutures in TRS group.The sutures and tendons were pulled out through tibial tunnels and fixed at the anteromedial tibia.All groups underwent failure load tests,and ultimate failure load,displacement at failure load,load at clinical failure,stiffness,and failure modes of the samples were recorded.Results The maximum failure load in TPS group was significantly higher than that in TR group(P＜0.05),but there was no significant difference between TPS group and TRS group(P＞0.05).The maximum failure load in TRS group was significantly higher than that in TR group(P＜0.05).The displacement under failure load in TR group and TRS group was significantly lower than that in TPS group(P＜0.05),but there was no significant difference between TR group and TRS group(P＞0.05).There were no significant differences in the load under clinical failure among the 3 groups(P＞0.05).The stiffness of TRS group was significantly greater than that of TPS group(P＜0.05),but no significant difference was observed between TR group and TPS group,as well as between TR group and TRS group(P＞0.05).All failures were caused by suture or tendon cutting through the meniscus.Conclusions The tendon reconstruction techniques is superior to the TPS in terms of failure displacement and stiffness,while the TRS further enhances the stability of the repair.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Cancer is the main cause of death,and drug therapy has greatly improved the effectiveness of anti-tumor treatment.However,there are problems such as high adverse reactions and the risk of developing drug resistance after long-term use.There is an urgent need to seek new drug targets.Human antigen R(HuR),as an RNA binding protein,promotes the whole process of tumor occurrence,development and metastasis through post transcriptional regulation of mRNA stability,and HuR is general-ly highly expressed in tumor tissue,making it a new target for an-ti-tumor therapy and a standard for prognosis evaluation.Tradi-tional Chinese medicine formulas and their various chemical components can inhibit tumor proliferation,induce tumor cell ap-optosis,inhibit angiogenesis,suppress immune escape,and re-verse tumor drug resistance by regulating HuR activity.This re-view summarizes the importance of HuR in regulation of tumor progression,as well as analyzes the mechanisms of the antitumor effects through active ingredients of Chinese medicine with the regulation of HuR.It is expected to provide new ideas for tumor therapy and guidance for the development of HuR-targeted anti-tumor drugs.

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*