Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Diabetic cardiomyopathy （DCM） is a common chronic complication of diabetes， categorized as consumptive thirst in traditional Chinese medicine （TCM）， and it subsequently gives rise to chest impediment. DCM is characterized by a complex pathogenesis and exhibits long-term progression with poor prognosis in clinical practice. Astragali Radix， as a medicinal material with edible value， possesses diverse active components including saponins， polysaccharides， and flavonoids. It has the effects of tonifying Qi， elevating Yang， promoting fluid production， nourishing blood， expressing toxin， and expelling pus. Modern pharmacological studies have confirmed that Astragali Radix and its active components exert therapeutic effects in various aspects such as inhibition of inflammation， alleviation of stress injury， regulation of programmed cell death， modulation of glucose and lipid metabolism， inhibition of myocardial fibrosis， and regulation of gut microbiota and metabolites， treating DCM in a multi-component， multi-target， and multi-pathway manner. The compatibility of Astragali Radix exerts both synergistic and antagonistic effects. The compound preparations and extracts of Astragali Radix are widely used in clinical practice， and the development of novel nano and gel materials and extracellular vesicles helps to improve the oral bioavailability， providing more possibilities for the clinical application of Astragali Radix in DCM， though its potential for clinical translation requires ongoing exploration. This review summarizes the TCM theoretical basis of Astragali Radix in the treatment of DCM， and integrates modern pharmacological research results to delve into the effects and mechanisms of the herb combinations， compound preparations， extracts， and new composite materials of Astragali Radix in the treatment of DCM， aiming to provide a reference for in-depth research and new drug development of Astragali Radix for DCM.

Curcumin (Cur), a natural polyphenolic compound extracted from the rhizomes of plants belonging to the Zingiberaceae and Araceae families, has attracted considerable interest for its remarkable antioxidant, anti-inflammatory, antibacterial, and anticancer activities. Extensive studies have focused on its potential in treating various diseases, including cancers, neurodegenerative diseases, inflammation, and autoimmune disorders. However, its clinical application has been hampered by inherent physicochemical challenges, such as poor aqueous solubility, short half-life, and low bioavailability. To address these challenges, nanodrug delivery systems have been developed to improve the pharmacokinetic and pharmacodynamic profiles of curcumin, thereby enhancing its therapeutic efficacy. This review summarizes the pharmacological activities and underlying mechanisms of curcumin, encompassing its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial effects. Furthermore, it highlights the significant advancements achieved through the development of curcumin-based nanomedicines. By synthesizing current findings, this review aims to provide insights that may inspire innovative strategies for the future design and broader applications of curcumin nanomedicines.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Compared to traditional machine learning algorithms,which often suffer from low feature extraction efficiency,insufficient nonlinear pattern recognition capabilities and slow training speeds,the broad learning system(BLS)enhances the learning ability and efficiency by horizontally expanding the network structure.BLS offers advantages such as a simple structure,fast training speed,and strong generalization capabilities.While BLS has demonstrated potential in various fields,but its application in identification of complex samples has not been fully explored.This research investigated the feasibility of using BLS algorithm for identification of complex samples based on physicochemical indicators.Using the iris,wine,and breast cancer datasets,the length and width of petals and sepals of iris flowers,the physicochemical properties of wine,and the nuclear characteristics of breast cancer cells were used as input variables to establish BLS models for identifying iris species,wine varieties,and benign versus malignant nucleus.The model performance was evaluated by confusion matrices,accuracy,and runtime.Compared with partial least squares-discriminant analysis(PLS-DA),soft independent modeling of class analogies(SIMCA),and artificial neural networks(ANN),the results indicated that BLS demonstrated significant advantages in computational efficiency and recognition accuracy.Thus,BLS was an efficient and reliable method for identification of complex samples.

Objective:To establish a quality control method for the standard decoction of Polygoni Avicularis Herba.Methods:Totally 12 batches of decoction pieces from different origins were collected, the standard decoction was prepared and the quality evaluation method was established, the content of index components in the decoction pieces and the standard decoction was determined with HPLC, the index components, solution pH and other parameters were calculated, and the similarity analysis was carried out against the fingerprints.Results:The total content of myricetin in 12 batches of decoction pieces was >0.12%, and the content of myricetin in the standard decoction was >0.03%, which met the standard of the 2020 edition of the Chinese Pharmacopoeia. The pH value was 5.1-5.5, the transfer rate of myricetin components ranged from 50.0%-106.3%, and the fingerprint study showed that there were 7 common peaks. The similarity analysis results indicated that the standard decoction of 12 batches of decoction pieces of Polygoni Avicularis Herba had good consistency.Conclusion:The preparation process is stable and feasible in line with the traditional decoction preparation method, and can be used for the research and quality evaluation of the standard decoction.

This article highlights the limitations of traditional treatment methods for non-muscle-invasive bladder cancer and the multi-dimensional exploration of emerging strategies.It firsty reviews the history and challenges of BCG immunotherapy,pointing out its bottlenecks in efficacy,tolerance,and supply,and focuses on its chemicobiological modifications,such as the optimization of nanoparticle drug delivery systems and immune-active components.Subsequently,it summarizes the development of various new treatment approaches,including gene therapy,photodynamic/sonodynamic therapy,chemodynamic therapy,and proteolysis-targeting chimeras for targeted protein degradation strategies.It particularly emphasizes the enhancement of drug delivery efficiency and targeting in the bladder through nanotechnology,aptamer-mediated systems,and biomimetic carriers.The treatment of bladder cancer is gradually transforming from local and single-mode to precise,synergistic,and low-toxicity directions,with chemicobiological means playing a core role in driving this transformation.Interdisciplinary integration provides a broad space and new hope for the treatment of bladder cancer.

Objective:To analyze the morphologic changes and the extent of severity in end-stage heart disease; and to explore the correlation with their clinical features.Methods:Twelve cases of recipients who underwent pediatric cardiac allograft transplantation were collected from May 2022 to November 2023 at the Seventh Medical Center of People′s Liberation Army of China General Hospital. Gross pathologic examinations were performed and morphological changes were observed under a light microscope after HE, Masson′s trichrome, and reticulin staining. Semi-quantitative analysis of morphologic changes was performed. One case received DMD genetic testing, one received mtDNA variation testing for mitochondriopathy, and 1 received metagenomics next-generation sequencing. Clinical data and related literature were reviewed for comprehensive analysis.Results:There were 12 recipient hearts including 11 dilated cardiomyopathy (DCM) and 1 fulminant myocarditis (FM). The median age of DCM was 12 years (range, 3 to 15 years). DCM showed cardiomyocyte hypertrophy, cardiomyocyte disarray, nuclear morphological changes, interstitial fibrosis and fatty infiltration. One DCM was confirmed as Becker muscular dystrophy by DMD genetic testing. No pathogenic mutations were found in 1 patient that received mtDNA variation testing. H. influenzae was detected in the case of FM. FM showed diffuse and full-thickness inflammatory cell infiltration by large numbers of lymphocytes and plasma cells, scattered eosinophils, and few neutrophils.Conclusions:Cardiac transplantation is an excellent treatment for end-stage heart disease. The morphological features of DCM include cardiomyocyte hypertrophy, nuclear morphological changes, interstitial fibrosis and fatty infiltration. The severity of the lesion is influenced by multiple factors. FM predominantly presents diffuse infiltration of lymphocytes and plasma cells.

BACKGROUND:Numerous studies have indicated that pyroptosis plays a key role in the progression of cancer.In recent years,research has shown that pyroptosis is inextricably linked to the occurrence,development,and treatment of breast cancer.The development of effective pyroptosis-based therapeutic strategies has become a hot topic in the field of breast cancer treatment.OBJECTIVE:To comprehensively analyze the mechanisms of pyroptosis,explore the role of pyroptosis in the anti-tumor effects in breast cancer,and its potential application value in clinical treatment.METHODS:Using English search terms"pyroptosis,breast cancer,inflammasome,gasdermin,caspase,drug resistance,treatment",PubMed database was searched for articles published from inception to August 2024.Through the preliminary screening of reading titles and abstracts,literature with poor relevance to the research content,outdated information,repeated views,and lack of authority was excluded.Finally,121 articles were included for review.RESULTS AND CONCLUSION:Pyroptosis is a special form of programmed cell death that is carried out by the activation of the gasdermin family of proteins,showing potential application value in the treatment of breast cancer.Long-term or improper treatment can lead to drug resistance in cancer cells;research on the mechanism of pyroptosis helps to overcome resistance deficiencies.Pyroptosis can trigger immunogenic cell death,promoting the release of tumor-specific antigens,thereby activating the immune system and enhancing its ability to recognize and clear tumor cells.The expression levels of pyroptosis-related genes can serve as prognostic indicators for breast cancer,helping to assess patients'treatment responses and survival periods.Research on the mechanisms of pyroptosis can provide new strategies for the treatment of breast cancer,such as targeted drugs and therapeutic methods that induce pyroptosis,contributing to the realization of personalized treatment plans for breast cancer.

Objective To evaluate the clinical outcome of neurosurgical robot-assisted stereotactic puncture and drainage for brain abscess.Methods A retrospective analysis was conducted on the clinical data of 53 patients with brain abscess admitted to our hospital from January 2018 to December 2024.Among them,29 cases underwent craniotomy for abscess resection(craniotomy group),while 24 cases received neurosurgical robot-assisted stereotactic puncture and drainage(robot-assisted group).The operation time,intraoperative blood loss,decompressive craniectomy rate,proportion of postoperative antibiotic regimen adjustment,postoperative hospital stay,incidence of postoperative complications,mortality rate and Glasgow outcome scale(GOS)scores 6 months after surgery of patients were compared between the two groups.Results Compared with the craniotomy group,the robot-assisted group demonstrated significantly shorter operation time,less intraoperative blood loss,and lower incidence of postoperative complication,the differences were all statistically significant(P<0.05).However,there were no statistically significant differences in terms of decompressive craniectomy rate,postoperative hospital stay,mortality rate,GOS score,or proportion of the postoperative antibiotic regimen adjustment between the two groups(P>0.05).Conclusion As a precise and minimally invasive surgical method,neurosurgical robot-assisted stereotactic puncture and drainage for patients with brain abscess can effectively improve the operational efficiency,shorten the operation time,reduce intraoperative injury,and lower the risk of postoperative complications.It has high clinical application value and potential for widespread adoption.