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.

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 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

ObjectiveTo compare the clinical efficacy of traditional Chinese medicine （TCM） manipulative reduction combined with small splint fixation versus surgical treatment for type A distal radius fracture （DRF） and to explore the factors influencing the choice of treatment. MethodsA multi-center retrospective study was conducted， collecting data from 1237 type A DRF patients treated in 11 hospitals in Jiangsu province from September， 2023 to April， 2025. Among them， 851 patients in the TCM group received manipulative reduction combined with small splint fixation， and 386 patients in the surgical group underwent open reduction and internal fixation. Visual analog scale （VAS） scores for pain and radiographic indicators including palmar tilt， ulnar deviation， and radial height were compared before treatment， 5-7 days after treatment， and 4-6 weeks after treatment. The wrist joint function scores including Dienst and Gartland-Werley scores at 12 weeks after treatment were recorded. Subgroup analysis was conducted for the excellent rate of Dienst and Gartland-Werley scores， stratified by age （＜50， 50-59， 60-69， ≥70 years old） and AO subtypes （A1， A2， A3）. A multivariate logistic regression model was used to identify independent factors influencing treatment choice. ResultsOn 5-7 days after treatment， the surgical group had lower VAS scores than the TCM group， while 4-6 weeks after treatment， the TCM group showed lower VAS scores than the surgical group （P＜0.01）. In terms of radiographic indicators， except for the palmar tilt before treatment being higher in the surgical group than in the TCM group （P＜0.01）， there were no significant differences in palmar tilt， ulnar deviation， and radial height at other timepoints （P＞0.05）. Twelve weeks after treatment， the surgical group had a higher average Gartland-Werley score and the excellent rate than the TCM group （P＜0.01）. Subgroup analysis showed that in patients with A2 type DRF aged 50-59 and 60-69 years old， the excellent rates of Dienst and Gartland-Werley scores in the TCM group were higher than those in the surgical group （P＜0.05）. Multivariate logistic regression analysis revealed that age， palmar tilt， ulnar deviation， and the degree of swelling on the affected side were independent factors influencing the choice of treatment （P＜0.05）. ConclusionBoth TCM manipulative reduction combined with small splint fixation and surgical treatment for type A DRF can achieve good therapeutic effects. TCM manipulative reduction combined with small splint fixation has certain advantages in medium- and long-term pain relief， especially in elderly patients， where wrist joint function recovery is more stable. Age， palmar tilt， ulnar deviation， and swelling degree are the main factors influencing the treatment choice.

ObjectiveTo analyze the expression level and clinical significance of Y‑box binding protein‑1（YB1） in tissues and cells of oral squamous cell carcinoma （OSCC）. MethodsBioinformatics analysis， immunohistochemistry， Western blot and qRT-PCR were used to detect the expression of YB1 in OSCC tissues， and the prognosis and survival analysis were performed. The effects of YB1 on the proliferation， migration and invasion of OSCC cells were evaluated by CCK-8， scratch assay and Transwell assay， and the expression changes of phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway and epithelial-mesenchymal transition （EMT） related markers after YB1 knockdown were detected by Western blot. ResultsBioinformation analysis showed that the expression level of YB1 in OSCC samples was higher than that in normal samples （P0.001）， and its expression was correlated with gender （P=0.022） and tumor differentiation degree （P0.001）. Kaplan-Meier plotter survival analysis showed that the survival rate of YB1 was low （Log-rank P=0.012）. Immunohistochemistry， Western blot and qRT-PCR experiments verified that the expression level of YB1 in OSCC tissues was higher than that of normal tissues. The results of cell experiments showed that knockdown of YB1 inhibited the malignant biological behaviors such as proliferation， migration and invasion of OSCC cells. Western blot results showed that the knockdown of YB1 could reduce the protein expression levels of p-PI3K and p-AKT， and inhibit EMT. ConclusionYB1 is highly expressed in tissues and cells in OSCC， and reveals the important role of the YB1/PI3K/AKT axis in the process of EMT of OSCC， which is expected to become a new tumor marker for early diagnosis and treatment and prognosis evaluation of OSCC.

Background: To investigate directional deviations between pilot holes and final pedicle screw trajectories in freehand placement and analyze risk factors for misplacement. While pedicle screws are widely used in thoracolumbosacral surgery, directional deviations between pilot holes and final screw trajectories remain understudied as potential risk factors for misplacement. Methods: Thirty-three patients undergoing posterior fixation were prospectively enrolled. Inertial measurement units (IMUs) tracked the spatial positions of pedicle finders and screwdrivers via custom software. Surgeons (n = 6) were stratified into senior, middle, and junior groups. Analyzed variables included the use of tapping, surgeon experience, spinal deformity status, screw tip morphology, and surgical parameters. Results: Among 198 implanted screws (6.00 ± 2.88/patient), all exhibited trajectory deviations (8.12° ± 3.47°). Tapping significantly reduced deviations (7.23° ± 3.23° vs. 8.87° ± 3.31°, p < 0.01). Senior surgeons achieved smaller deviations (7.34° ± 3.33°) than the middle group (8.60° ± 3.51°, p = 0.039) and junior group (8.68° ± 3.49°, p = 0.022). Multivariate analysis confirmed tapping (p = 0.001) and senior experience (p = 0.023) as protective factors. No significant associations emerged for spinal deformity (8.43° ± 3.73° vs. 7.97° ± 3.35°, p = 0.377), screw tip type (cylindrical, 8.43° ± 3.26° vs. tapered, 8.07 ± 3.51°; p = 0.637), obesity, or surgical position parameters. Conclusions Freehand pedicle screw placement consistently produces trajectory deviations from pilot holes, and surgeon experience and tapping are modifiable protective factors. The IMU-based tracking system enables quantitative surgical motion analysis, suggesting its utility for training optimization and technique standardization.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.