ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by in-tegrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experi-mentation to validate its potential as a treatment for di-abetic gastroparesis.Methods The chemical constit-uents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key tar-gets.Subsequently,a compound-target-pathway net-work diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular doc-king was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Addi-tionally,Western blot was conducted to detect the ex-pression of AGEs,RAGE,and NF-κB in eggs.The re-sults revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carci-nogenesis,hepatitis B,and alcoholism signaling path-way among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histo-pathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improve-ment of DGP.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Aim To establish an animal model of diabetic kidney disease(DKD)integrating blood stasis syndrome and syndrome evaluation indicators.Methods Twenty-five SD rats were ran-domly divided according to body weight into a control group(8 rats)and a modeling group(17 rats).The modeling group was fed a high-sugar and high-fat diet for four weeks and induced to form diabetic rats by intraperitoneal injection of 30 mg·kg-1 streptozocin.The modeling rats were randomly divided into the DKD group and blood stasis syndrome combination group accord-ing to 24-hour urinary protein(24-hUP).The blood stasis syn-drome combination group was induced to replicate the DKD blood stasis syndrome model by injecting 10％high molecular weight D-glucoside three times at a dose of 0.05 mg·kg-1 via tail vein.The model was evaluated based on random blood glu-cose level,24-hUP level,syndrome assessment,pathological staining etc,and differential metabolites were selected using metabolomics.Results The comprehensive evaluation of syn-drome manifestations and pathological staining in the combined model of blood stasis syndrome in rats demonstrated successful replication.Utilizing the technique of liquid chromatography-mass spectrometry,22 differential metabolites were identified,with associated pathways showing a certain relevance to blood stasis syndrome in DKD.Conclusions The successful replica-tion of an animal model combining the syndrome of blood stasis in DKD has been achieved in this study.Evaluation of indicators and results from metabolomics studies consistently demonstrate a correlation with the syndrome of blood stasis in DKD.

Objective:Accurately grasping the disability levels and characteristics of the elderly population in China is of significant importance for responding effectively to the care service needs of this demographic.Methods:Based on multi-wave data(2011-2023)from three nationally representative aging-related surveys CLHLS,CHARLS and CALSS,this study assessed,compared,and predicted the disability levels and characteristics of China's elderly population.Results:Direct estimates from existing survey data showed low reliability.Integrated multi-source projections indicate that the disability rate among China's population aged 65 and older will follow a phased upward trend,ranging approximately between 12.27%and 15.05%from 2025 to 2050,with the disabled elderly population growing continuously from 25.9 million to 58.64 million.Bathing,toileting,and dressing were the three activities with the highest disability rates.Discussion and Suggestions:Future efforts should focus on improving the construction of an elderly capacity assessment system and addressing the shortage of high-quality disability data.Research should emphasize the evaluation process of item-specific disability among older adults.It is essential to grasp the phased characteristics of changes in disability levels and identify critical windows of opportunity for response.Based on the item-specific disability characteristics of older adults,the focus of elderly care services,facilities,and product supply should be accurately targeted.

Methods: This retrospective study analyzed 32 consecutive IDS patients who underwent UEDD surgery. Clinical features, laboratory data (erythrocyte sedimentation rate and C-reactive protein), and treatment outcomes were analyzed. Results: Definite microorganisms were identified in 27 patients (84.3%), with 24 (88.9%) meeting cure criteria. The cure rate was significantly higher in the detected pathogen group compared to the undetected pathogen group (88.9% vs. 80%; χ²=19.36, p<0.0001). Metagenomic next generation sequencing (mNGS) provided faster diagnosis (41.72±6.81 hours) compared to tissue culture (95.74±35.47 hours, p<0.05). The predominant causative pathogen was Mycobacterium tuberculosis, followed by Staphylococcus aureus. Significant improvements were observed in Visual Analog Scale pain scores, from a mean of 7.9 preoperatively to 1.06 at 1 year postoperatively. The Oswestry Disability Index revealed a similar trend, showing significant improvement (p<0.05). Conclusions UEDD is a viable alternative to traditional open surgery for managing IDS in high-risk patients. UEDD offers a dual therapeutic-diagnostic advantage during the initial admission phase, enabling simultaneous debridement, neurological decompression, and targeted biopsy in a single intervention. Compared with traditional tissue culture, mNGS enables rapid microbiological diagnosis and extensive pathogen coverage.

Objective:To systematically summarize the current status and effects of home-based palliative care for patients with advanced chronic heart failure, providing reference for the implementation and development of palliative care in China..Methods:A systematic search was conducted in multiple databases, including China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, EMBASE, CINAHL, and Cochrane Library, for relevant literature on home-based palliative care for patients with advanced chronic heart failure. Reference lists of included studies were also traced, and grey literature was supplemented by searching Baidu Scholar and Google Scholar. The search period was from the inception of each database to December 19, 2024. Two researchers independently evaluated the quality of the literature and extracted data.Results:A total of 11 studies were included. The interventions in home-based palliative care included symptom control, advance care planning, psychological and mental assessments and interventions, disease education, and self-management education. Most studies found that the experimental group had higher quality of life scores, lower healthcare resource usage, and reduced anxiety and depression compared to the control group.Conclusions:Home-based palliative care can improve symptom burden, enhance quality of life, alleviate anxiety and depression, and promote the implementation and discussion of advance care planning for patients with advanced chronic heart failure. It can also reduce healthcare costs and caregiver burden to some extent.

Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.