ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

This article adopts Professor CHEN Chaozu′s " sanjiao composed by membrane-striae" theory as its foundation to explore the relationship between irritable bowel syndrome and functional/structural abnormalities of the membrane-striae. Sanjiao encompasses both the tangible membrane and the intangible striae. These striae permeate the entire body，and their pathological changes comprehensively reflect qi，body fluids，and fasciae. Based on the physiological function of the membrane-striae in regulating qi and fluids，the pathogenesis of irritable bowel syndrome is characterized by a disharmony of membrane-striae and an imbalance of the qi-fluid interactions. In the early stage，external pathogens，emotional factors，or dietary stimuli often cause membrane-striae constriction and disordered qi-fluid circulation. In the middle stage，stagnant fluids gradually transform into phlegm retention，leading to membrane-striae obstruction. In the late stage，deficiency of vital qi becomes predominant，manifesting as laxity of membrane-striae with impaired control or weakened conduction. The treatment of irritable bowel syndrome should adopt " unblocking" as the guiding principle. In the early stage，therapy should focus on eliminating pathogenic factors and soothing membrane-striae to promptly restore qi-fluid circulation，thereby attaining unblocking through spasm relief. In the middle stage，treatment should focus on resolving tangible obstructions in membrane-striae，achieving unblocking via dredging. In the late stage，the emphasis should shift to reinforcing healthy qi，particularly by strengthening spleen-kidney yang qi，and achieving unblocking through supplementation. Concurrently，throughout the entire treatment process，the regulation of mental state and easing of emotional tension should be integrated to alleviate patient′s anxiety，achieving the goal of holistic treatment of both body and mind.

OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.

Objective To explore the efficacy of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in distinguishing the properties of abnormal lymph nodes and its role in assessing the prognosis of patients with related diseases, and to provide more precise evidence for clinical diagnosis and treatment regimen formulation. Methods The clinical data of 97 patients with malignant tumors diagnosed with abnormal lymph nodes at Wuxi People’s Hospital Affiliated to Nanjing Medical University between April 2024 and June 2025 were retrospectively analyzed. Patients were divided into a malignant lymph node group (n=47) and a benign lymph node group (n=50) based on pathological results. PET/CT metabolic parameters [maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were compared between the two groups of patients. Receiver operating characteristic curves were used to evaluate the diagnostic value of ¹⁸F-FDG PET/CT parameters for abnormal lymph nodes. Progression-free survival was compared among patients in the malignant lymph node group stratified by different levels of SUV_max, SUV_mean, MTV, and TLG. Results SUV_max, SUV_mean, MTV, and TLG were significantly higher in the malignant lymph node group than in the benign lymph node group (P < 0.05). The areas under the receiver operating characteristic curves for predicting malignant lymph nodes with SUV_max, SUV_mean, MTV, and TLG were 0.761, 0.855, 0.860, and 0.792, with sensitivities of 74.47%, 82.98%, 74.47%, and 70.21%, and specificities of 76.00%, 76.00%, 90.00%, and 82.00%, respectively (P < 0.05). Comparison of progression-free survival in patients with malignant lymph nodes with different ¹⁸F-FDG PET/CT parameter levels revealed that patients with lower levels of SUV_max, SUV_mean, MTV, and TLG had significantly longer progression-free survival than those with higher levels (Log-rank χ²=4.297, P=0.038; Log-rank χ²=6.569, P=0.010; Log-rank χ²=5.970, P=0.015; and Log-rank χ²=7.422, P=0.006, respectively). Conclusion ¹⁸F-FDG PET/CT metabolic parameters (SUV_max, SUV_mean, MTV, and TLG) demonstrate high efficacy in the differential diagnosis of benign and malignant abnormal lymph nodes and prognostic evaluation, providing significant guidance for clinical treatment decisions.

Objective To explore the efficacy of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in distinguishing the properties of abnormal lymph nodes and its role in assessing the prognosis of patients with related diseases, and to provide more precise evidence for clinical diagnosis and treatment regimen formulation. Methods The clinical data of 97 patients with malignant tumors diagnosed with abnormal lymph nodes at Wuxi People’s Hospital Affiliated to Nanjing Medical University between April 2024 and June 2025 were retrospectively analyzed. Patients were divided into a malignant lymph node group (n=47) and a benign lymph node group (n=50) based on pathological results. PET/CT metabolic parameters [maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were compared between the two groups of patients. Receiver operating characteristic curves were used to evaluate the diagnostic value of ¹⁸F-FDG PET/CT parameters for abnormal lymph nodes. Progression-free survival was compared among patients in the malignant lymph node group stratified by different levels of SUV_max, SUV_mean, MTV, and TLG. Results SUV_max, SUV_mean, MTV, and TLG were significantly higher in the malignant lymph node group than in the benign lymph node group (P < 0.05). The areas under the receiver operating characteristic curves for predicting malignant lymph nodes with SUV_max, SUV_mean, MTV, and TLG were 0.761, 0.855, 0.860, and 0.792, with sensitivities of 74.47%, 82.98%, 74.47%, and 70.21%, and specificities of 76.00%, 76.00%, 90.00%, and 82.00%, respectively (P < 0.05). Comparison of progression-free survival in patients with malignant lymph nodes with different ¹⁸F-FDG PET/CT parameter levels revealed that patients with lower levels of SUV_max, SUV_mean, MTV, and TLG had significantly longer progression-free survival than those with higher levels (Log-rank χ²=4.297, P=0.038; Log-rank χ²=6.569, P=0.010; Log-rank χ²=5.970, P=0.015; and Log-rank χ²=7.422, P=0.006, respectively). Conclusion ¹⁸F-FDG PET/CT metabolic parameters (SUV_max, SUV_mean, MTV, and TLG) demonstrate high efficacy in the differential diagnosis of benign and malignant abnormal lymph nodes and prognostic evaluation, providing significant guidance for clinical treatment decisions.

Objective To explore the efficacy of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in distinguishing the properties of abnormal lymph nodes and its role in assessing the prognosis of patients with related diseases, and to provide more precise evidence for clinical diagnosis and treatment regimen formulation. Methods The clinical data of 97 patients with malignant tumors diagnosed with abnormal lymph nodes at Wuxi People’s Hospital Affiliated to Nanjing Medical University between April 2024 and June 2025 were retrospectively analyzed. Patients were divided into a malignant lymph node group (n=47) and a benign lymph node group (n=50) based on pathological results. PET/CT metabolic parameters [maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were compared between the two groups of patients. Receiver operating characteristic curves were used to evaluate the diagnostic value of ¹⁸F-FDG PET/CT parameters for abnormal lymph nodes. Progression-free survival was compared among patients in the malignant lymph node group stratified by different levels of SUV_max, SUV_mean, MTV, and TLG. Results SUV_max, SUV_mean, MTV, and TLG were significantly higher in the malignant lymph node group than in the benign lymph node group (P < 0.05). The areas under the receiver operating characteristic curves for predicting malignant lymph nodes with SUV_max, SUV_mean, MTV, and TLG were 0.761, 0.855, 0.860, and 0.792, with sensitivities of 74.47%, 82.98%, 74.47%, and 70.21%, and specificities of 76.00%, 76.00%, 90.00%, and 82.00%, respectively (P < 0.05). Comparison of progression-free survival in patients with malignant lymph nodes with different ¹⁸F-FDG PET/CT parameter levels revealed that patients with lower levels of SUV_max, SUV_mean, MTV, and TLG had significantly longer progression-free survival than those with higher levels (Log-rank χ²=4.297, P=0.038; Log-rank χ²=6.569, P=0.010; Log-rank χ²=5.970, P=0.015; and Log-rank χ²=7.422, P=0.006, respectively). Conclusion ¹⁸F-FDG PET/CT metabolic parameters (SUV_max, SUV_mean, MTV, and TLG) demonstrate high efficacy in the differential diagnosis of benign and malignant abnormal lymph nodes and prognostic evaluation, providing significant guidance for clinical treatment decisions.

ObjectiveTo explore the mechanism by which exosomes derived from gastric cancer cells MGC-803 promote tumor progression through the upregulation of ABCG8 expression. MethodsUltra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） lipidomics， quantitative real-time PCR （qPCR） and Western blot were used to verify the role of ABCG8 in gastric cancer progression. Exosomes derived from gastric cancer cells were introduced， and a series of in vitro experiments were conducted to evaluate their effect on ABCG8 expression， as well as on cell proliferation， migration， and clonogenic ability in normal gastric mucosal epithelial GES-1 cells. ResultsUPLC-MS/MS lipidomics analysis revealed significant changes in triacylglycerol （TG） among the differential lipids. qPCR and Western blot analysis showed that the mRNA and protein expression levels of ABCG8 in the GC-Exo-treated group were higher than those in the GES-1 cell group （P<0.05）. Colony formation and Transwell migration assays revealed that， compared with the GES-1 cell group， the GC-Exo-treated group exhibited a greater number of colonies （P<0.05） and migrated cells （P<0.05） after 48 h of treatment. CCK-8 assay results showed that the proliferation rate in the GC-Exo-treated group （50 μg/mL） was higher than that in the GES-1 cell group （P<0.001）. Lipidomics analysis revealed that， compared with the GES-1 cell group， TG levels were upregulated in the GC-Exo-treated group， accompanied by decreased levels of phosphatidylcholine （PC） PC（38：2e）. ConclusionExosomes derived from gastric cancer cells MGC-803 may promote tumor progression by upregulating ABCG8 expression to mediate cholesterol efflux， thereby triggering pro-carcinogenic lipid metabolic reprogramming in normal gastric mucosal epithelial cells.