In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Mitochondria, the primary energy-producing organelles of the cell, also serve as signaling hubs and participate in diverse physiological and pathological processes, including apoptosis, inflammation, oxidative stress, neurodegeneration, and tumorigenesis. As semi-autonomous organelles, mitochondrial functionality relies on nuclear support, with mitochondrial biogenesis and homeostasis being stringently regulated by the nuclear genome. This interdependency forms a bidirectional signaling network that coordinates cellular energy metabolism, gene expression, and functional states. During mitochondrial damage or dysfunction, retrograde signals are transmitted to the nucleus, activating adaptive transcriptional programs that modulate nuclear transcription factors, reshape nuclear gene expression, and reprogram cellular metabolism. This mitochondrion-to-nucleus communication, termed “mitochondrial retrograde signaling”, fundamentally represents a mitochondrial “request” to the nucleus to maintain organellar health, rooted in the semi-autonomous nature of mitochondria. Despite possessing their own genome, the “fragmented” mitochondrial genome necessitates reliance on nuclear regulation. This genomic incompleteness enables mitochondria to sense and respond to cellular and environmental stressors, generating signals that modulate the functions of other organelles, including the nucleus. Evolutionary transfer of mitochondrial genes to the nuclear genome has established mitochondrial control over nuclear activities via retrograde communication. When mitochondrial dysfunction or environmental stress compromises cellular demands, mitochondria issue retrograde signals to solicit nuclear support. Studies demonstrate that mitochondrial retrograde signaling pathways operate in pathological contexts such as oxidative stress, electron transport chain (ETC) impairment, apoptosis, autophagy, vascular tension, and inflammatory responses. Mitochondria-related diseases exhibit marked heterogeneity but invariably result in energy deficits, preferentially affecting high-energy-demand tissues like muscles and the nervous system. Consequently, mitochondrial dysfunction underlies myopathies, neurodegenerative disorders, metabolic diseases, and malignancies. Dysregulated retrograde signaling triggers proliferative and metabolic reprogramming, driving pathological cascades. Mitochondrial retrograde signaling critically influences tumorigenesis and progression. Tumor cells with mitochondrial dysfunction exhibit compensatory upregulation of mitochondrial biogenesis, excessive superoxide production, and ETC overload, collectively promoting metastatic tumor development. Recent studies reveal that mitochondrial retrograde signaling—mediated by altered metabolite levels or stress signals—induces epigenetic modifications and is intricately linked to tumor initiation, malignant progression, and therapeutic resistance. For instance, mitochondrial dysfunction promotes oncogenesis through mechanisms such as epigenetic dysregulation, accumulation of mitochondrial metabolic intermediates, and mitochondrial DNA (mtDNA) release, which activates the cytosolic cGAS-STING signaling pathway. In normal cells, miR-663 mediates mitochondrion-to-nucleus retrograde signaling under reactive oxygen species (ROS) regulation. Mitochondria modulate miR-663 promoter methylation, which governs the expression and supercomplex stability of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and assembly factors. However, dysfunctional mitochondria induce oxidative stress, elevate methyltransferase activity, and cause miR-663 promoter hypermethylation, suppressing miR-663 expression. Mitochondrial dysfunction also triggers retrograde signaling in primary mitochondrial diseases and contributes to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Current therapeutic strategies targeting mitochondria in neurological diseases focus on 5 main approaches: alleviating oxidative stress, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, mitochondrial protection, and insulin sensitization. In AD patients, mitochondrial morphological abnormalities and enzymatic defects, such as reduced pyruvate dehydrogenase and α-ketoglutarate dehydrogenase activity, are observed. Platelets and brains of AD patients exhibit diminished cytochrome c oxidase (COX) activity, correlating with mitochondrial dysfunction. To model AD-associated mitochondrial pathology, researchers employ cybrid technology, transferring mtDNA from AD patients into enucleated cells. These cybrids recapitulate AD-related mitochondrial phenotypes, including reduced COX activity, elevated ROS production, oxidative stress markers, disrupted calcium homeostasis, activated stress signaling pathways, diminished mitochondrial membrane potential, apoptotic pathway activation, and increased Aβ42 levels. Furthermore, studies indicate that Aβ aggregates in AD and α‑synuclein aggregates in PD trigger mtDNA release from damaged microglial mitochondria, activating the cGAS-STING pathway. This induces a reactive microglial transcriptional state, exacerbating neurodegeneration and cognitive decline. Targeting the cGAS-STING pathway may yield novel therapeutics for neurodegenerative diseases like AD, though translation from bench to bedside remains challenging. Such research not only deepens our understanding of disease mechanisms but also informs future therapeutic strategies. Investigating the triggers, core molecular pathways, and regulatory networks of mitochondrial retrograde signaling advances our comprehension of intracellular communication and unveils novel pathogenic mechanisms underlying malignancies, neurodegenerative diseases, and type 2 diabetes mellitus. This review summarizes established mitochondrial-nuclear retrograde signaling axes, their roles in interorganellar crosstalk, and pathological consequences of dysregulated communication. Targeted modulation of key molecules and proteins within these signaling networks may provide innovative therapeutic avenues for these diseases.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective To explore the relationship between the types of bicuspid aortic valves(BAV)and the outcome of functional mitral regurgitation(FMR)and the affecting factors of FMR.Methods From Jun 2018 to Sep 2022,patients with severe BAV aortic valve stenosis(AS)complicated with FMR underwent post transcatheter aortic valve replacement(TAVR)in Zhongshan Hospital,Fudan University were retrospectively analyzed.The baseline information and imaging data of different BAV patients were collected.Logistic regression was used to analyze the factors affecting the outcome of FMR(improvement and non-improvement).Result A total of 100 patients with TAVR were included,including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV.Compared with patients of type 1,patients of type 0 had younger age[(72.78±6.09)y vs.(77.00±8.35)y,P=0.050],lower male ratio(47%vs.73%,P= 0.009)higher BMI[(23.19±2.62)kg/m2 vs.(21.99±3.13)kg/m2,P=0.041],and lower incidence of aortic regurgitation(69%vs.92%,P=0.040).Compared with the non-improvement group,the improvement group had a lower incidence of coronary heart disease(5%vs.18%,P=0.042),higher incidence of pulmonary hypertension(20%vs.2%,P=0.007),larger left ventricular diastolic diameter[(51.98±6.74)mm vs.(48.04±7.72)mm,P=0.009]and higher maximum flow velocity[(4.86±0.95)cm/s vs.(4.47±0.75)cm/s,P= 0.023]of the aortic valve.The results of Logistic regression analysis showed that preoperative pulmonary hypertension,left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR.Conclusion No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR.For BAV patients with AS,preoperative pulmonary hypertension,larger left ventricular end-diastolic diameter,and faster aortic valve flow velocity were associated with higher FMR improvement rate.

Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L^-1, which provided reference for the research of their antioxidant activity.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.