ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Formaldehyde is a prevalent organic solvent in industrial and indoor environment,which can seriously harm human health,so it is of great significance to develop highly sensitive formaldehyde sensors with fast response,low detection limit and long life.In this study,the NiO-In2O3 composite structure was prepared using indium-based metal organic framework(In-MOF)as the precursor,and the formaldehyde gas sensor was constructed with In2O3 and NiO-In2O3 composite structure as the sensitive material.The results demonstrated that the In2O3 material had a microflower-like structure,while the NiO-In2O3 composite structure was composed of NiO nanoparticles attached to the surface of In2O3.The sensor exhibited excellent detection performance for formaldehyde in the environment of relative humidity of 33%and 75%,especially the response characteristic of the NiO-In2O3 composite structure sensor to formaldehyde was considerably better than that of the In2O3 sensor under the same test conditions,which was closely related to the catalytic effect of NiO and the heterogeneous structure formed between NiO and In2O3.The NiO-In2O3 composite structure sensor had a response value of 21.3 and 12.6 to 10 μL/L formaldehyde when the relative humidity was 33%and 75%at 200℃.The response/recovery time was 4/6 s and 7/10 s,and the limit of detection(LOD)was 1.2×10-7 μL/L and 4.1×10-5 μL/L respectively.Meanwhile,the sensor had excellent selectivity and long-term stability.This sensor showed a wide application prospect in the field of high-performance detection of low concentration of formaldehyde gas.

[Abstract] Objective To study the effects of pranlinide on cognitive behavior, β amyloid(Aβ) protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice. Methods Thirty two 5×FAD mice and 16 WT mice were selected. All were female. 5×FAD mice were randomly divided into blank group and treatment group; No treatment was given in WT group. Blank group was intraperitoneally injected with PBS; treatment group was received intraperitoneal injection of pranlinide once a day for 8 weeks. The changes of cognitive ability were measured by Morris water maze test. The expression of Aβ6E10 protein in mice hippocampal cells and retina was detected by immunohistochemistry. Tumor necrosis factor α(NF-α) was determined by enzyme-linked immunosorbent assay. The same method was also used for interleukin-1β(IL-1β) detection (The content of inflammatory factors). The arrangement and morphology of nerve cells in mouse hippocampal tissue were determined by hematoxylin-eosin (HE) staining. Results The latency time of treatment group was shorter than that of 5×FAD group,and the times of crossing the platform and the percentage of target quadrant stay in the treatment group were higher than those in the 5×FAD group, and the differences were statistically significant (P<0. 05). Compared with the retinal area and the brain area of Aβ6E10 in the 5×FAD group and in the treatment group, the content was halved (P<0. 05). There was positive correlation between Aβ6E10 in retina and brain (P<0. 05).There was no significant difference in TNF-α and IL-1β in brain and retina between treatment group and 5×FAD group (P>0. 05). Compared with the 5×FAD group, the nerve cells in the treatment group were arramged in order and clear relatively. The distribution of glial cells was concentrated; The surrounding clearance was small. Conclusion Pranlinide can improve the cognitive ability of mice. The arrangement of nerve cells is regular, the shape is regular and the boundary is clear; The distribution of glial cells is concentrated; surrounding of clearance decrease. Aβ6E10 is synchronized in brain and retina.

Rats ; Animals ; Astrocytes ; Exosomes/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Biological Transport

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

ObjectiveTo study the effects of Toddalia asiatica alcohol extract on autophagy and apoptosis of non-small cell lung cancer A549 cells， and to explore its possible mechanism. MethodA549 cells were cultured in vitro. Cell counting kit-8 （CCK-8） was used to detect the proliferation of A549 cells， and cell survival rate was calculated to screen the drug concentration. The apoptosis in each dose group and that after the use of 3-methyladenine （3-MA）， an autophagy inhibitor， were detected by flow cytometry combined with Annexin V-FITC/PI double staining. Western blot was used to detect the expression levels of apoptosis-related proteins such as B cell lymphocytoma-2（Bcl-2）， Bcl-2-associated X protein（Bax）， microtubule-associated protein 1 light chain 3 （LC3）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， activated poly （Adenosine diphosphate） ribonucleotide polymerase （cleaved PARP1）， PARP1， activated death activator （t-Bid）， Bid， and ubiquitin-binding protein p62 in each group and those after the use of 3-MA. ResultCompared with the conditions in the control group， the cell survival rate in 0.25 g·L^-1 group （P<0.05）， and 0.5， 1， 2， 4 g·L^-1 groups （P<0.01） was decreased after 24 h intervention. Additionally， the cell survival rate was reduced in a concentration-dependent manner at 48 h and it was less than 10% at 4 g·L^-1 （P<0.01）. Compared with the conditions in the control group， the total apoptosis rate in 0.5 g·L^-1 group was increased （P<0.05）， and the apoptosis rate in 1 and 2 g·L^-1 groups was also increased （P<0.01）. Compared with the 2 g·L^-1 group and 3-MA group， the 3-MA combined with T. asiatica alcohol extract had significantly decreased apoptosis rate （P<0.01）. Compared with the conditions in the control group， elevated expression of pro-apoptotic proteins cleaved PARP1， Bax and t-Bid in 1 and 2 g·L^-1 groups （P<0.05， P<0.01）， and reduced expression of Bid in the 2 g·L^-1 group （P<0.01） were found. Compared with the conditions in the control group， the expression of anti-apoptotic protein Bcl-2 （P<0.05， P<0.01） and the level of p62 （P<0.01） were down-regulated in 0.5， 1， 2 g·L^-1 groups， while the level of LC3 Ⅱ protein was up-regulated （P<0.01）， with certain concentration dependence. ConclusionT. asiatica alcohol extract could significantly inhibit the proliferation of A549 cells， which might be related to promoting autophagy and inducing apoptosis.

OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.
Histones ; Humans ; Multiple Myeloma/genetics* ; Neoplasm Recurrence, Local ; Oligopeptides/therapeutic use* ; Prognosis ; Receptors, CXCR4