Objective To explore the potential molecular mechanism of Sangma Xingbei Tang （SMXBT） in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. Methods TCMSP and TCMID databases were searched for the active ingredients of SMXBT, the targets of the active ingredients were predicted by SwissTargetPrediction database, and the AECOPD-related targets were searched by GeneCards and OMIM databases; the drug-active ingredient-target network and protein interaction network were constructed, and the GO enrichment and KEGG pathway enrichment were analyzed by the DAVID database. The drug-active ingredient-target network and protein interaction network were constructed, and the GO enrichment and KEGG pathway enrichment were analyzed by DAVID database, and molecular docking was performed by AutoDock Tools software. Animal experiments were conducted for validation. Results 192 active ingredients were obtained and 1066 targets were predicted in SMXBT. Network analysis showed that the top 3 active ingredients in SMXBT were quercetin, kaempferol, and glycyrrhizin, and the top 3 therapeutic targets were TNF, ALB, and IL-1β, etc. The GO analysis and KEGG showed that the main pathways were the cancer pathway, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Molecular docking showed that the binding energies of glycyrrhizin and AKT1, IL-1β, GFR, SRC, and quercetin and kaempferol and IL-1β were all <−5 kcal·mol. Animal experiments showed that Sangma Xingbei Decoction could treat AECOPD by anti-inflammatory effects and reduce changes in lung tissue structure. Additionally, it could lower the serum inflammatory levels of TNF-α, IL-6, and IL-8. Conclusion SMXBT may act on the targets of AKT1, IL-1β, EGFR, SRC, etc., reduce the serum inflammation levels of TNF-α, IL-6, IL-8, and improve the lung tissue structure and inflammatory response to achieve the therapeutic effect on AECOPD through the modulation of the PI3K/Akt signaling pathway, the MAPK signaling pathway, the cancer pathway, and other pathways of action.

Endoscopic full-thickness resection (EFTR) is a minimally invasive technique that is increasingly used for gastrointestinal stromal tumors (GISTs) originating from the muscularis propria. Despite its advantages over conventional surgery, such as complete tumor resection and faster recovery, EFTR faces challenges related to its efficacy, safety, and feasibility, particularly in gastric GISTs. By summarizing the literature published over the past decade, this review provides a comprehensive overview of the clinical outcomes of EFTR and the evolution of defect closure devices.

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.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Objective To investigate the effect of levosimendan on the cyclic guanosine monophosphate-adenosin monophosphate synthase-interferon gene stimulating factor(cGAS-STING)signaling pathway during suspension-reperfusion in isolated rat myocardium.Methods The rats were divided into four groups(n=12)using random number table:continuous perfusion group(CO group),suspension-reperfusion group(SR group),suspension-reper-fusion+levosimendan group(SR-L group),and suspension-reperfusion+levosimendan+STING activator:DMXAA group(SR-LD group).Heart rate(HR),left ventricular end-diastolic pressure(LVEDP),left ventricular develop-mental pressure(LVDP),maximum rate of increase in left ventricular pressure(+dp/dtmax)and maximum rate of decrease in left ventricular pressure(-dp/dtmax),and Reperfusion Arrhythmia scores were recorded at the end of equilibrium perfusion(T0),30 min of reperfusion(T1),and 60 min of reperfusion(T2)respectively.Western blot was used to detect cGAS-STING signaling pathway and autophagy-related protein expression.The size of myocardial infarction was measured by using triphenyl tetrazolium chloride(TTC).Results Compared with CO group,SR group had decreased HR,LVDP,+dp/dtmax,and-dp/dtmax at T1 and T2,increase of LVEDP,Reperfusion Arrhythmia score,percentage of myocardial infarcted area,expression of myocardial tissue cGAS and STING pro-teins and increased LC3 Ⅱ/Ⅰratio,while p62 decreased(P<0.05);compared with SR group,SR-L group car-diac function indexes improved,myocardial tissue cGAS,STING protein expression was down-regulated,LC3 Ⅱ/Ⅰ ratio was decreased,and p62 was elevated(P<0.05);SR-LD group reversed the improvement of myocardial injury by levosimendan compared with SR-L.Conclusions Levosimendan may protect myocardial tissue by inhibi-ting the cGAS-STING signaling pathway,down-regulating cardiomyocyte autophagy and reducing myocardial infarc-tion size,so to improve cardial function.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Objective To investigate the population composition,seasonal dynamics,and infestation levels of cockroaches in Lanzhou,China,and to provide information for the scientific development of cockroach control strategies.Methods Monitoring was conducted at three locations using the sticky trap method.Habitats included farm product markets,catering establishments,hotels,hospitals,and residential areas.Results From 2016 to 2023,the average cockroach density was 0.77 insects per board,with an average infestation rate of 10.84%.Blattella germanica was the dominant species.Seasonal density of cockroaches showed an approximately unimodal distribution,peaking in September.The highest average density and infestation rates were observed in farm product markets.Conclusions Cockroach density and infestation levels in Lanzhou remained relatively low.A comprehensive prevention and control strategy focusing on environmental management in key areas should be implemented according to the seasonal fluctuations.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

OBJECTIVE To observe the changes of serum proteins in the mice with carbapenem-resistant hyperviru-lent Klebsiella pneumoniae(CR-hvKP)bloodstream infection by using liquid chromatogram-mass spectrometer(LC-MS),find out the differentially expressed proteins and carry out corresponding biological function analysis.METHODS The models of ICR mice with CR-hvKP and classical Klebsiella pneumoniae(cKP)bloodstream infec-tions were established,the serum specimens were collected from the mice at 12 hours of establishment of the in-fection models and were detected by using LC-MS.The result of LC-MS was identified by using Maxquant soft-ware.The corresponding bioinformatics analysis was performed for the differentially expressed proteins.RESULTS As compared with the normal control group,there were 24 upregulated proteins and 20 downregulated proteins in CR-hvKP group.As compared with cKP group,there were 107 upregulated proteins in the CR-hvKP group.The 134 differentially expressed proteins were retrieved one by one from Uniprot database,it was found that the pro-teins were involved in biological regulation,immune process,biological interaction,movement,metabolic process,response to stimulation,signal transduction,inflammatory response,oxidative stress and angiogenesis.The signal pathway analysis involved multiple metabolism-related pathways,including complement and coagula-tion cascades,cholesterol metabolism,bacterial infection,heme clearance,and assembly,remodeling and clear-ance of plasma lipoprotein.In terms of the proteins being attached great importance,the expression levels of kal-likrein B1(KLKB1)and serpin family A(Serpina)1b were downregulated as compared with the normal control group and were upregulated as compared with the cKP group;the expression levels of serum amyloid A protein(SAA)1,SAA2,Vanin-3(VNN3)and hemoglobinβpolypeptide chain b2(HBB-b2)were upregulated as com-pared with both the cKP group and the normal control group.CONCLUSIONS The CR-hvKP bloodstream infection involves the activation and action of multiple proteins.The rise of SAA1,SAA2,VNN3 and HBB-b2 or the de-cline of KLKB1 and Serpina1b may indicate the CR-hvKP bloodstream infection.