Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

ObjectiveTo investigate the effects of zinc finger E-box binding homeobox 1 （ZEB1） on the proliferation， migration， and invasion of lung adenocarcinoma H322 cells， as well as its underlying molecular mechanisms. MethodsThe gene expression characteristics of the transcription factor ZEB1 in lung adenocarcinoma were analyzed using data from the GEO and TCGA public databases. RT-qPCR and Western blot were employed to measure mRNA and protein expression levels of ZEB1 in lung adenocarcinoma cell lines （H322， A549， 95-D） and normal human bronchial epithelial cells （BEAS-2B）. Lentiviral transduction was utilized to establish stable ZEB1-overexpressing （Oe-ZEB1） and vector control （Oe-NC） H322 cell lines. Cell proliferation was assessed using CCK-8， colony formation， and EdU assays， while apoptosis was evaluated by Hoechst33258/PI double staining. Wound healing and Transwell assays were performed to examine cell migration and invasion capabilities. Cell cycle distribution was determined by flow cytometry， and Western blot was used to analyze protein expression changes in relevant signaling pathways. ResultsThe findings from GEO and TCGA indicated that ZEB1 expression in lung adenocarcinoma varied with tumor malignancy grade. RT-qPCR and Western blot analyses revealed significantly higher ZEB1 expression in lung adenocarcinoma cell lines compared to BEAS-2B cells （P0.05）. Results from the CCK-8， colony formation， EdU， wound healing， and Transwell assays demonstrated that， compared with the un-transfected control （Control） group， Oe-ZEB1 H322 cells exhibited enhanced proliferation， migration， and invasion capabilities （P0.05）. Hoechst33258/PI double staining and flow cytometry analyses showed that， relative to the Control group， apoptosis was reduced in Oe-ZEB1 H322 cells （P0.05）. Additionally， a decreased proportion of cells in the G₁ phase and an increased proportion in the S phase were observed in Oe-ZEB1 cells， indicating accelerated cell cycle progression. Western blot analysis further revealed that， compared with the Control group， Oe-ZEB1 H322 cells exhibited upregulated expression of N-cadherin， mutant p53 （mutp53）， and Cyclin D1 （P0.05）， while expression levels of E-cadherin， murine double minute 2 （MDM2）， and p21 were downregulated （P0.05）. ConclusionOverexpression of ZEB1 promotes the proliferation， migration， and invasion of lung adenocarcinoma H322 cells and may facilitate cell cycle progression by modulating the MDM2/mutp53/p21 signaling pathway， thereby promoting the transition of cells from the G₀/G₁ phase to the S phase.

ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

The advancement of microbiome technologies has facilitated a growing interest in the interactions between urinary microbiota and urinary stone formation. This article systematically reviews the technological evolution, and the reciprocal mechanism of microbiota involvement in lithogenesis and its clinical significance. It specifically highlights the changes within the urinary microbiota of calcium oxalate stone patients, notably a depletion of Lactobacillus populations and an enrichment of pathogenic taxa such as Enterobacteriaceae. Furthermore, it delineates the mechanisms whereby microbes participate in stone formation through metabolic regulation, physical adhesion, and inflammatory processes. The article also explores the influence exerted by distinct stone types on the structural composition and functional dynamics of the urinary microbiota. Integrated multi-omics analyses offer novel perspectives for unraveling the intricate microbiome-host interaction network. This approach is anticipated to facilitate significant advances in developing precision-focused prophylactic and therapeutic strategies for urinary stones from a microecological standpoint.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

Objective To investigate the effects of ulinastatin(UTI)combined with somatostatin(SOM)on intestinal damage in acute pancreatitis(AP)rats and the possible mechanisms of action.Methods The rats were randomly divided into sham-operated(sham)group,AP group,UTI group,UIT+SOM group and UIT+SOM+JAK2 activator(CA1)group,15 rats/group,respectively.Twelve hours after administration,the intestinal permeability,serum biochemical indicators,and inflammatory factor of rats were detected.HE staining was applied to observe the pathological changes in pancreatic and intestinal tissues.TUNEL method was applied to detect apoptosis in intestinal tissue.Western blot was applied to detect the expression of JAK2/STAT3 signaling pathway proteins.Results Compared with the sham group,the pancreatic tissue of rats in the AP group showed obvious inflammatory cell infiltration,edema and bleeding,while the intestinal mucosa showed inflammatory cell infiltration,irregular villi,shedding and necrosis of intestinal epithelial cells in the intestinal tissue.The intestinal permeability,serum amylase(AMY),lipase(LIPA)activities,diamine oxidase(DAO)activities,tumor necrosis factor α(TNF-α),interleukin-6(IL?6)level,pancreatic and intestinal histopathological scores,intestinal tissue cell apoptosis rate,and p?JAK2/JAK2,p?STAT3/STAT3 ratio all significantly increased(P<0.05).Compared with the AP group,the pancreatic and intestinal tissue injury of rats in the UTI group and UIT+SOM group was reduced,and inflammatory cell infil?tration was reduced.The intestinal permeability,serum AMY,LIPA activities,DAO activities,TNF?α,IL?6 level,pancreatic and intestinal histopathological scores,intestinal tissue cell apoptosis rate and p?JAK2/JAK2,p?STAT3/STAT3 ratio were all decreased(P<0.05).The pancreatic and intestinal tissue injury of rats in the UIT+SOM+CA1 group were more severe,and the trends of the above indicators were opposite to those found in UIT+SOM group(P<0.05).Conclusions The combination of UTI and SOM attenuated intestinal injury in AP rats,and potential mechanism may involve in the inhibition of the JAK2/STAT3 signaling pathway.

Objective To investigate plasma protein expression changes in heatstroke patients using proteomics technology and to identify reliable prognostic biomarkers.Methods A retrospective analysis was conducted on 20 heatstroke patients hospitalized at the 908th Hospital of the Chinese PLA Joint Logistics Support Force from July 2022 to February 2024.Patients were divided into survival(n=16)and death groups(n=4)based on 28-day outcomes.Fasting venous blood samples were collected from both groups for proteomic analysis.Liquid chromatography-mass spectrometry(LC-MS/MS)was used to identify and screen differentially expressed proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed.LASSO regression was applied to screen key prognostic biomarkers,and receiver operating characteristic(ROC)curve analysis was used to evaluate their predictive value.Results A total of 27 upregulated and 90 downregulated proteins were identified between the two groups.These proteins were primarily involved in biological processes such as immune responses,complement activation,and metabolic processes.LASSO regression analysis indicated that actin-related protein 2(ARP2),cysteine-rich scavenger receptor type 1 M130(CD163),and catalase(CAT)could serve as effective biomarkers for evaluating heatstroke prognosis.ROC curve analysis demonstrated that ARP2 had higher diagnostic efficacy(AUC=0.98,sensitivity=0.80,specificity=1.00)compared to CD163(AUC=0.94,sensitivity=0.76,specificity=1.00),CAT(AUC=0.96,sensitivity=0.67,specificity=1.00),and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(AUC=0.79,sensitivity=0.44,specificity=1.00).Conclusion Elevated plasma ARP2 level has good clinical value for predicting poor prognosis in heatstroke patients.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Degenerative cervical myelopathy(DCM)is a group of diseases caused by cervical spine degeneration that compresses the spinal cord.It is a major cause of spinal cord dysfunction in adults,and its incidence is increasing globally.In the late stage,DCM could lead to paralysis due to spinal cord injury,which makes rapid,effective,and accurate medical diagnosis clinically significant.Deep learning(DL)technology can assist physicians in the rapid and accurate diagnosis of DCM by analyzing and processing a large amount of imaging data to extract features of the affected regions.In recent years,DL algorithm models have been leveraged for DCM-related research,which has become a focal point of intelligent medical development.In this review,domestic and international literature is surveyed,and the research progress and application of DL technology in the auxiliary diagnosis and prognosis evaluation of DCM are systematically summarized,aiming to provide a reference for intelligent diagnosis in clinical practice.