Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective:To identify the main components of Huanglian Jiedu Decoction(HLJDD)using ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),and to explore the potential mechanism of action of HLJDD in the treatment of gouty arthritis(GA)using network pharmacology and molecular docking methods.Methods:We identi-fied the chemical components of HLJDD by combining UPLC-Q-TOF-MS data acquired in both positive and negative ion modes with reference standards,relevant literature,and database searches.We analyzed the potential therapeutic mechanism of HLJDD for GA by using network pharmacology to determine the intersection targets between the active ingredients of HLJDD and GA for further enrich-ment analysis and visual network mapping.The binding affinity of the active ingredients with the intersection targets was validated through molecular docking.Results:A total of 47 components were identified by UPLC-Q-TOF-MS;54 key components of HLJDD for GA treatment and 37 intersection targets were determined by net-work pharmacology;and the top 10 key targets by Degree value were obtained by protein-protein interaction analysis.The Gene On-tology functional enrichment analysis revealed 20 biological pro-cesses,7 cellular components,and 8 molecular functions.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated 96 GA-related intervention pathways,in which inflammatory signaling pathways such as interleukin-17(IL-17)and tu-mor necrosis factor(TNF)were involved.Molecular docking verified that the key components of HLJDD had high binding affinity with the core targets.Conclusion:The identified key components in HLJDD,such as phellodendrine,coptisine,wogonin,and β-sitosterol,may alleviate GA by regulating multiple core targets in the IL-17 and TNF pathways,such as PTSG2,which provides a theoretical ba-sis for future investigation into the mechanism of action of HLJDD.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Liver cirrhosis is the terminal stage of chronic liver disease. Minimizing complications of liver cirrhosis and the occurrence of liver cancer has become an important goal for liver cirrhosis treatment. The primary etiology leading to liver cirrhosis is chronic hepatitis B infection. "Dual-anti therapy" refers to the combination of anti-viral and anti-fibrosis treatment, which is the characteristic and advantage of the integration of Chinese and Western medicine. The article elaborates on the concept and strategies of "dual antibody therapy" based on evidence-based medicine and introduces the research progress in terms of representative anti-fibrotic Chinese patent medicines for reversing liver cirrhosis, reducing the occurrence of hepatocellular carcinoma, and loweri ng portal hypertension and its complications and others, revealing that dual antibody therapy can clinically facilitate dual reduction" (reducing both liver cancer and complications of cirrhosis). Additionally, it analyzes and summarizes the mechanism of action of anti-fibrotic Chinese patent medicines and prospects of a new model of liver cirrhosis treatment combining Chinese and Western medicine, thereby providing novel ideas for the prevention and treatment of clinical liver diseases.

Myocardial fibrosis(MF)is the leading cause of car-diac insufficiency.Its complex pathogenesis and lack of effective treatment are key issues to be addressed in the cardiovascular field.Mitochondrial quality control system(MQC)is an impor-tant mechanism for eukaryotic cells to maintain the stability of mitochondrial form,quantity and quality.MQC disorders,which are characterized by low level of mitochondrial biogenesis,exces-sive mitochondrial oxidative stress,mitochondrial autophagy de-fect and mitochondrial dynamics disorder,play a crucial role in mediating the pathophysiological process of MF.Consequently,this article reviews the role of MQC in MF pathogenesis and the latest research,in order to better understand the molecular mech-anism of MF and provide reference for the development of more natural drugs in the future.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.