ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

ObjectiveTo compare the effects of different formulations of Yinqiao Powder （银翘散， YP） on inflammation and immune function in a rat model of acute pharyngitis induced by ammonia water. MethodsA rat model of acute pharyngitis was established by spraying 15% ammonia water into the pharynx of male SD rats using a laryngeal atomizer twice daily （three sprays each time） for three consecutive days. Successfully modeled rats were randomly divided into 5 groups， including a model group （normal saline， 10 ml/kg）， YP decoction group （10.73 g/kg）， YP granule group （10.73 g/kg）， cydiodine group （0.39 mg/kg） and blank control group （normal saline， 10 ml/kg）， with 12 rats in each group. All groups received intragastric administration once daily for 10 consecutive days. After the final gavage administration， frequency of back arching per minute， frequency of vibrissae grooming per minute， and grooming episodes per five minutes were recorded in rats. The cumulative body weight change was calculated as the difference in body weight between day 10 and day 1 of gavage administration. Behavioral observations were performed using the open field test， and the total distance traveled was recorded. After sample collection， the lung index and thymus index were calculated. Histopathological changes in the pharyngeal and tracheal tissues were observed using HE staining. Serum inflammatory markers including eosinophil cationic protein （ECP）， angiotensin-converting enzyme 2 （ACE2）， and C-reactive protein （CRP）， as well as immune parameters including immunoglobulin M （IgM）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， CD4， CD4/CD8 ratio， and CD8 were measured by ELISA. In addition， ELISA was used to determine the levels of inflammatory mediators in pharyngeal tissues， including phospholipase A2 （PLA2）， cyclooxygenase-1 （COX-1）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， vascular cell adhesion molecule-1 （VCAM-1）， C-X-C motif chemokine ligand 1 （CXCL1）， vascular endothelial growth factor （VEGF）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared to the blank control group， the model group exhibited significantly increased frequencies of back arching per minute， vibrissae grooming per minute， and grooming episodes per five minutes， and lung index， and decreased cumulative body weight change， thymus index， and total distance traveled， as well as elevated serum levels of ECP， ACE2， and CD8， reduced levels of IgM， IgA， IgG， CD4， and CD4/CD8 ratio， and increased levels of PLA， COX-1， COX-2， PGE2， VCAM-1， CXCL1， VEGF， and MMP-9 in pharyngeal tissues （P＜0.05）. Histopathological examination revealed keratinization of the superficial epithelial layer of the pharyngeal mucosa， accompanied by congestion and edema in the lamina propria and infiltration of inflammatory cells； in the tracheal mucosa， extensive inflammatory cell infiltration， ciliary disruption， and goblet cell damage were observed. Compared to the model group， except for CRP， IgG， and CD4， all above mentioned indicators were improved in the YP granule group， YP decoction group， and cydiodine group （P＜0.05）. Histopathological lesions in the pharyngeal and tracheal tissues were also alleviated. Compared to the YP decoction group， rats in the YP granule group exhibited decreased frequencies of back arching per minute， vibrissae grooming per minute， and grooming episodes per five minutes， as well as reduced serum ECP levels. Meanwhile， the cumulative body weight gain and serum levels of IgM， IgA， IgG， and CD4/CD8 increased， whereas CD8 levels decreased （P＜0.05）. ConclusionYP can effectively alleviate symptoms of acute pharyngitis in a rat model， improve inflammatory responses and immune-related indicators， demonstrating superior therapeutic effects in the dosage form of granule.

Retinal degenerative diseases are a group of blinding ocular disorders characterized by progressive and irreversible loss of retinal neural cells. They mainly include age-related macular degeneration and retinitis pigmentosa. At present, there are no curative clinical therapies capable of reversing the disease course. Patients have poor long-term visual prognosis, imposing a heavy public-health burden on families and society. Mesenchymal stem cell(MSC)-derived exosomes, as a novel cell-free therapeutic vector, have emerged as a research hotspot due to their low immunogenicity, no tumorigenic risk, and excellent tissue barrier penetration ability. This review systematically summarizes the core mechanisms of MSC-derived exosomes in regulating immune inflammation, inhibiting apoptosis, and promoting retinal neuroprotection and structural/functional recovery via miRNA and tsRNA, compares the efficacy differences and existing controversies among exosomes from different sources, and outlines the advances in intraocular delivery technologies and engineering modification strategies. Combined with preclinical and clinical data, the current bottlenecks and safety evidence for clinical translation were objectively described. Meanwhile, in view of the heterogeneity among existing studies, this review proposes future directions including standardized preparation and the establishment of efficacy evaluation systems, so as to provide theoretical references for the development of novel therapeutic strategies for retinal degenerative diseases.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective To analyze the acupoint selection law in acupuncture treatment for sinusitis using data mining techniques.Methods Relevant literature on acupuncture treatment for sinusitis was retrieved from CNKI,Wanfang Data,VIP and CBM from January 1,2000 to December 20,2024.Descriptive statistics were performed on the frequency of acupoint usage,meridian tropism,and regional distribution.SPSS Modeler 18.0,Cytoscape 3.10.3 and Origin Pro were employed to conduct association rule mining,co-occurrence network analysis,and systematic cluster analysis on the acupoints.Results A total of 69 articles were included,yielding 114 acupoint prescriptions involving 65 distinct acupoints.The most frequently used acupoints were Yingxiang,Yintang and Hegu,etc.;the most commonly used meridians were large intestine meridian,Governor Vessel,gallbladder meridian and bladder meridian.Acupoint selection was predominantly concentrated in the head/neck region,lower limbs and upper limbs.Among the specific acupoint categories,Jiaohui acupoint,Wushu acupoint and Yuan acupoint were used most frequently.The acupoint combinations with the strongest associations were Hegu-Yingxiang,Hegu-Yintang-Yingxiang and Fengchi-Yingxiang.The top 22 high-frequency acupoints could be grouped into 5 clusters.Conclusion Acupuncture treatment for sinusitis can exert the functions to disperse wind and unblock the orifices,drain heat and resolve turbidity,expel pathogens and alleviate pain,tonify deficiency and dissipate cold,as well as harmonize qi and blood.The characteristics of acupoint combination include a primary focus on local points supplemented by distal points,pattern differentiation-based selection,and a propensity for unblocking yang qi.The core acupuncture formula is Yingxiang-Yintang-Hegu-Fengchi.

OBJECTIVE To investigate the current status and characteristics of occupational exposure in a stomato-logical hospital and explore the influencing factors for occupational exposure among dentists so as to propose pre-ventive and control measures for occupational exposure in the stomatological hospital.METHODS A retrospective study was carried out to analyze 180 incidents of occupational exposures in Qingdao Stomatological Hospital Affili-ated to Qingdao University from 2020 to 2024,involving the departments,names,genders,age,average annual workload,average annual outpatient days,exposure links,instruments leading to exposures,exposure sources,occupational type and professional titles.The incidence of occupational exposure was compared among the subjects with different occupations,professional titles and department affiliations.Logistic regression analysis was per-formed for the influencing factors for the occupational exposures among the dentists.RESULTS The incidence of occupational exposures was 7.52％(180/2395)within the 5 years,and the sharp instrument injury(99.40％)was the predominant exposure approach.The department of oral and maxillofacial surgery,department of restorative dentisty and department of prosthodontics were the departments at high risk of occupational exposures.There was significant difference in the incidence of occupational exposures among the staff and the doctors with different pro-fessional titles(P＜0.05).The subjects for whom the exposure source was positive or failed to be tracked accoun-ted for 56.11％.The professional title(OR=0.328)was a protective factor for the occupational exposure among the doctors,and the high-risk department(OR=4.912)was a risk factor for the occupational exposure(P＜0.05).CONCLUSIONS The occupational exposures to the stomatology department staff are characterized by high prevalence,monotonous type,concentrated distribution of populations and uncontrollable occupational exposures.It is necessary to complete the preoperative screening of infectious diseases,strengthen the awareness of prevention,standardize the technical procedures and boost the innovation of auxiliary instruments so as to re-duce the incidence of occupational exposures.

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.