To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

Extracellular vesicles (EVs) are pivotal mediators of intercellular communication within the tumor immune microenvironment (TME). They are broadly categorized into exosomes, microvesicles, and apoptotic bodies based on their distinct biogenesis pathways. Exosomes originate from the endosomal system via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF‑β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)‑compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.

ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess， and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 （STAT3）/vascular endothelial growth factor （VEGF） signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine， 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method， with 30 cases in each group. The control group received conventional treatment， while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7^th， 14^th and 21^st day after operation， enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. Hematoxylin eosin （HE） staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 （p-STAT3） and vascular endothelial growth factor （VEGF） proteins， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain， secretion volume score， and healing rate of patients on the 3^rd， 7^th， 14^th， and 21^st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group （P<0.05）. For intra-group comparison， the pain score of the control group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The secretion volume score decreased on the 14^th and 21^st days after operation （P<0.05）. The pain score and secretion volume score of the treatment group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The levels of various inflammatory factors decreased in both groups （P<0.05）. Compared with those on the surgical day， the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7^th and 21^st days after operation （P<0.05）. There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period （P<0.01）. For inter-group comparison， on the 7^th and 14^th days after operation， the pain score in the treatment group was lower than that in the control group. On the 7^th， 14^th and 21^st days after operation， the secretion volume scores and healing rate of the treatment group were better than those of the control group （P<0.05）. The levels of various inflammatory factors in the treatment group were lower than those in the control group （P<0.05）， and the decline rate was faster （P<0.05）. On the 7^th day after operation， the levels of p-STAT3， VEGF protein， and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group （P<0.05）. HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly， and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery， reduce secretions， and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β， IL-6， and TNF-α， reducing the inflammatory response of the wound， upregulating the expression of p-STAT3 and VEGF proteins， and stimulating the STAT3/VEGF signaling pathway， thereby accelerating angiogenesis and promoting wound healing.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

Objective:To compare the application effects of upper arm autogenous arteriovenous fistula (AVF) and forearm arteriovenous graft (AVG) in maintenance hemodialysis (MHD) patients, and to analyze the factors influencing the long-term patency rate of arteriovenous fistulas in MHD patients.Methods:It was a retrospective cohort study. The data of MHD patients treated in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2021 to May 2023 was collected. Participants were stratified into two groups: forearm AVG and upper arm AVF. The parameters including urea clearance index (Kt/V), serum C-reactive protein (CRP), albumin levels, access-related costs, complication rates, and long-term primary patency were compared. The end event was defined as arteriovenous fistula failure, that was, the arteriovenous fistula could not be used for dialysis puncture, or the arteriovenous fistula lost function after adequate blood flow was achieved. Kaplan-Meier survival curves with log-rank tests were employed to compare access survival, while multivariable Cox regression was used to analyze the independent associated factors of patency.Results:A total of 71 MHD patients were enrolled in this study, including 35 males, with age of (64.9±11.7) years and fistula establishment time of 30.0(17.0, 58.0) months. There were 32 cases (45.1%) in the forearm AVG group and 39 cases (54.9%) in the upper arm AVF group. Compared with the forearm AVG group, the upper arm AVF group had higher serum albumin levels [38.9 (37.0, 42.1) g/L vs. 38.0 (34.6, 40.0) g/L, Z=-2.364, P=0.018], higher pain scores [3.0(2.0, 5.0) points vs. 2.0(1.0, 3.0) points, Z=-3.012, P=0.003], and higher long-term patency rates of arteriovenous fistulas (at 3, 6, 12, and 24 months, all P<0.01), while the complication rate[61.5% (24/39) vs. 93.7% (30/32), χ2=10.015, P=0.002], the cost of the access [0 (0, 9,117.0) yuan·year -1·person -1vs. 10 380.5 (7 186.0, 30 228.5) yuan·year -1·person -1, Z=-4.094, P<0.001] were lower, and the length of the available puncture vessel segment was shorter [3.5(3.0, 5.0) cm vs. 6.5(6.0, 8.0) cm, Z=-6.477, P<0.001].The Kaplan-Meier survival analysis results showed that the primary patency rate of the upper arm AVF group was significantly higher than that of the forearm AVG group (Log-rank test, χ2=23.690, P<0.001). The multivariate Cox regression analysis results indicated that the type of fistula being forearm AVG (with upper arm AVF as reference, HR=4.907, 95% CI 1.740-13.840) and increased complications number ( HR=1.234, 95% CI 1.040-1.464) were the independent factors promoting the arteriovenous fistula failure in MHD patients. Conclusions:The type of internal fistula and the complications are the factors affecting the long-term patency rate of internal fistula in MHD patients.Upper arm AVF offers cost-effectiveness and sustained patency advantages over forearm AVG but requires careful consideration of puncture challenges and patient discomfort. Individualized access selection should balance anatomical constraints with clinical priorities.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective This study explores the clinical correlation between different low-density lipoprotein cholesterol(LDL-C)levels and prognosis,providing evidence-based guidance for the development of personalized lipid-lowering goals.Methods Patients who underwent elective percutaneous coronary intervention(PCI)treatment at Beijing Anzhen Hospital from January 2020 to June 2023 and received lipid-lowering therapy with the addition of Evolocumab were selected.Based on the results of blood lipid rechecks 3 to 6 months after surgery,the patients were divided into five groups:low-density lipoprotein＜0.5 mmol/L,0.5 to＜1.0 mmol/L,1.0 to＜1.4 mmol/L,1.4 to＜1.8 mmol/L,and above 1.8 mmol/L.All patients were followed up for more than one year,and clinical conditions and major adverse cardiovascular events(MACE)were recorded.Results A total of 1 106 patients undergoing PCI were enrolled;after propensity score matching and exclusion of patients lost to follow up,550 remained(110 per group).During 12 months of follow-up,58 patients(10.5％)experienced a MACE,with incidence rising step-wise across LDL-C categories.In multivariable Cox models adjusted for age,sex,diabetes,hypertension,baseline LDL-C,follow-up LDL-C,estimated glomerular filtration rate(eGFR),and left ventricular ejection fraction,the hazard ratios[HR(95％CI)]for MACE,relative to the＜0.5 mmol/L group,were 1.810(0.507-6.454,P=0.361),3.036(0.945-9.749,P=0.062),5.228(1.737-15.735,P=0.003),7.708(2.633-22.565,P＜0.001)for LDL-C levels of 0.5 to＜1.0,1.0 to＜1.4,1.4 to＜1.8 and≥ 1.8 mmol/L,respectively.A restricted cubic spline model demonstrated a significant non-linear positive association between LDL-C and MACE(P-overall≤0.001;P-non-linear=0.008).Stratified analyses by age,sex,hypertension and diabetes showed consistent HR with no significant interactions(all P＞0.05).There were no statistically significant differences among the groups in the incidence of bleeding events,elevated creatinine levels,or abnormal liver function(all P＞0.05).Conclusions In patients using PCSK9 after PCI,there is a significant positive correlation between LDL-C levels and the risk of MACE,and no correlation was observed between different LDL-C levels and the risk of adverse events such as bleeding.

Objective To explore the value of peripheral blood monocyte subsets and their CD169 expression levels in the diagnosis of common respiratory viral infections and the immune mechanism of the infection in children.Methods A total of 125 children with re-spiratory viral infections(virus infection group),71 children with bacterial respiratory infections(bacteria infection group),and 35 healthy children(healthy control group)admitted to the Third Affiliated Hospital of Zhengzhou University from February 2022 to Octo-ber 2023 were included in this study.The counts of peripheral blood monocytes and lymphocytes were detected by hematologic analyzer.The proportions of lymphocyte subsets,monocyte subsets,and the expression levels of CD169 were detected by a flow cytometry.Mono-cyte subsets were classified into three types:classical monocytes(CM),intermediate monocytes(IM),and non-classical monocytes(NCM).ANOVA and Kruskal-Wallis H tests were used to screen for differentially expressed indicators among the three groups,and the receiver operator characteristic(ROC)curve was used to evaluate their diagnostic performance.Paired t-tests were used to analyze the differences in the indicators between the first day and the seventh day of hospitalization in the virus group.Spearman rank correlation a-nalysis was used to explore the relationship between CD 169 expression levels in monocyte subsets and the quantity of lymphocyte sub-sets.Results Statistically significant differences in the expression levels of CD169 in monocytes of CM,IM,and NCM types were ob-served in peripheral blood between the children's respiratory viral infection group and the healthy control group(all P＜0.01).In con-trast,no statistically significant differences in CD169 expression levels were found in monocytes of CM and IM type between the respira-tory viral infection group and the bacterial infection group(all P＞0.05).The differences in CD 169 expression levels among the groups were statistically significant in the NCM subset(P=0.008).The area under the ROC curve(AUC)of CD169 expression level in NCM type monocytes for diagnosing respiratory viral infections was 0.897(P＜0.01),with a cutoff point of ≥ 62.75％,sensitivity of 68.60％,and specificity of 91.80％.The quantity and proportion of CM,IM,and NCM type monocytes did not show statistically signif-icant differences between the respiratory viral infection group and the bacterial infection group(all P＞0.05).However,there were sig-nificant differences in the quantity and proportion of CM and IM type monocytes,as well as the proportion of NCM type monocytes,be-tween the virus infection group and the healthy control group(all P＜0.05).The proportions of CM,IM,and NCM type monocytes,the quantity of IM type monocytes,and the CD169 expression levels of monocyte subsets showed statistically significant differences between the first day and the seventh day after admission(all P＜0.05).There were no statistically significant differences in the quantity of CM and NCM type monocytes between the first day and the seventh day after admission(all P＞0.05).The expression levels of CD169 in peripheral blood CM,IM,and NCM type monocytes were negatively correlated with the number of CD8+T cells with correlation coeffi-cients of-0.65,-0.63,and-0.66,respectively(all P＜0.01).Conclusion The expression level of CD169 in NCM type monocytes could be used as an auxiliary diagnostic marker for the children with respiratory viral infection.The changes of monocyte subsets during respiratory viral infection course in children may involve that more CM type monocytes differentiate into IM type monocytes,and some IM type monocytes do not differentiate into NCM type monocytes in proportion.IM and NCM type monocytes may play important roles in the early stage of respiratory viral infections in children.CD169 serves as a marker of monocyte activation.