ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

ObjectiveTo explore the changes in color， odor and chemical components during wine-processing of Chuanxiong Rhizoma（CR）， identify differential markers， and provide a basis for standardizing the process and establishing quality standards. MethodsFifteen batches of CR samples from 4 producing areas were collected. Colorimeter and electronic nose were used to detect the color changes and odor components of CR before and after wine-processing. Multivariate statistical methods including partial least squares-discriminant analysis（PLS-DA）， principal component analysis（PCA）， discriminant factor analysis（DFA） and Fisher discriminant analysis were applied to identify wine-processed CR at different processing stages and establish discriminant models， and differential components were screened out based on variable importance in the projection（VIP） value1. Then， high performance liquid chromatography（HPLC） was employed to detect the content changes of four components（ferulic acid， senkyunolide I， senkyunolide A and ligustilide） during the processing stages. ResultsThe differences of wine-processed CR at various stages were primarily reflected in color parameters L^*（brightness value）， a^*（red-green value） and b^*（yellow-blue value）. Based on chromaticity differences， the color reference ranges were established for moderately processed CR， including L^* of 46.75-48.24， a^* of 5.37-6.07 and b^* of 20.32-21.70. In odor analysis， DFA revealed significant differences among processing stages， and 11 odor markers were identified， with four differential markers（4-hydroxy-3-butylphthalide， isopropyl butyrate， L-limonene and 1-methoxyhexane） based on VIP values. HPLC results showed that there was no significant difference of the four components except for ligustilide in wine-processed CR at different stages. ConclusionThis study achieved rapid identification of wine-processed CR with different processing degrees by electronic sensory technology and differential component content detection， with discrimination accuracy rates of 92.4% and 93.272% for color and odor， respectively. This paper also established the reference ranges of main colorimetric parameters for wine-processed CR at different stages， and four differential components were screened out， providing a basis for standardizing the processing of wine-processed CR and establishing quality standards for this decoction pieces.

ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

ObjectiveTo explore the changes in color， odor and chemical components during wine-processing of Chuanxiong Rhizoma（CR）， identify differential markers， and provide a basis for standardizing the process and establishing quality standards. MethodsFifteen batches of CR samples from 4 producing areas were collected. Colorimeter and electronic nose were used to detect the color changes and odor components of CR before and after wine-processing. Multivariate statistical methods including partial least squares-discriminant analysis（PLS-DA）， principal component analysis（PCA）， discriminant factor analysis（DFA） and Fisher discriminant analysis were applied to identify wine-processed CR at different processing stages and establish discriminant models， and differential components were screened out based on variable importance in the projection（VIP） value1. Then， high performance liquid chromatography（HPLC） was employed to detect the content changes of four components（ferulic acid， senkyunolide I， senkyunolide A and ligustilide） during the processing stages. ResultsThe differences of wine-processed CR at various stages were primarily reflected in color parameters L^*（brightness value）， a^*（red-green value） and b^*（yellow-blue value）. Based on chromaticity differences， the color reference ranges were established for moderately processed CR， including L^* of 46.75-48.24， a^* of 5.37-6.07 and b^* of 20.32-21.70. In odor analysis， DFA revealed significant differences among processing stages， and 11 odor markers were identified， with four differential markers（4-hydroxy-3-butylphthalide， isopropyl butyrate， L-limonene and 1-methoxyhexane） based on VIP values. HPLC results showed that there was no significant difference of the four components except for ligustilide in wine-processed CR at different stages. ConclusionThis study achieved rapid identification of wine-processed CR with different processing degrees by electronic sensory technology and differential component content detection， with discrimination accuracy rates of 92.4% and 93.272% for color and odor， respectively. This paper also established the reference ranges of main colorimetric parameters for wine-processed CR at different stages， and four differential components were screened out， providing a basis for standardizing the processing of wine-processed CR and establishing quality standards for this decoction pieces.

Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective To explore the non-invasive diagnostic criteria of magnetocardiography (MCG) for coronary microvascular dysfunction (CMVD), and its value in dynamically assessing drug treatment for CMVD. Methods Patients who presented with chest tightness or chest pain at Zhongshan Hospital, Fudan University from September 2024 to March 2025 were consecutively enrolled, and all of whom had non-obstructive coronary arteries on angiography. Using the coronary angiography-derived index of microcirculatory resistance (caIMR) as the gold standard, patients were divided into a normal microcirculation group (caIMR≤40 U) and a CMVD group (caIMR＞40 U). MCG testing was performed using a domestic device (MD-U041001, Mind Medical). Patients in the CMVD group received adenosine treatment and underwent repeat MCG after medication. Differences in MCG parameters between the two groups were analyzed, and a diagnostic model was established. The value of the diagnostic model was analyzed using receiver operating characteristic (ROC) curves. Results A total of 311 patients were included, with 135 in the normal microcirculation group and 176 in the CMVD group. The CMVD group had a significantly higher proportion of males (61.9% vs 47.4%, P＝0.012), and lower high-density lipoprotein cholesterol (HDL-C) levels ([1.16±0.31] mmol/L vs [1.24±0.29] mmol/L, P＝0.029) than the normal group. Eleven MCG parameters showed significant differences between the two groups (P＜0.05), among which increased values of mfm_QR_epav, mfm_RS_epmse, space_zeroRTrot, as well as decreased value of mfm_QR_v1 were independent predictors of CMVD. The diagnostic model based on these 11 MCG parameters yielded an area under the curve (AUC) of 0.688 (95%CI 0.629-0.747). The integrated diagnostic model combining clinical risk factors (male, smoking history, HDL-C) with MCG parameters had an AUC of 0.701 (95%CI 0.643-0.759). After adenosine treatment, patients in the CMVD group showed significant decreases in mfm_QR_epav (P＝0.010), mfm_RS_sad (P＝0.013), and mfm_RS_epmse (P＝0.046). Conclusions The model based on MCG parameters demonstrates good diagnostic ability for CMVD; dynamic changes in MCG parameters following adenosine intervention may serve as potential objective indicators for evaluating microcirculatory treatment efficacy.

Allergic conjunctivitis is a common ocular inflammatory disease, with intense itching being the most typical and distressing symptom for patients. In recent years, with the in-depth study of the interaction between the nervous and immune systems, significant progress has been made in understanding the mechanism of itching in allergic conjunctivitis. This review elaborates on the neurobiological basis of itching in allergic conjunctivitis, with a focus on the complex dialogue between immune cells and sensory neurons, particularly the core role of the IL-33-ST2-CGRP signaling axis in mediating itching. Additionally, this article introduces new findings in genetic susceptibility research, including the identification of susceptibility genes for allergic conjunctivitis through transcriptome-wide association studies. The sensory nervous system not only transmits itch signals but also actively participates in the formation of antigen channels related to conjunctival goblet cells, thereby regulating the local uptake of allergens and the initiation of the immune response. Moreover, targeted novel therapeutic strategies offer hope for patients with refractory allergic conjunctivitis. Exploring the molecular and cellular mechanisms of itching in allergic conjunctivitis will provide a theoretical basis for the development of more effective treatment methods.