BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

OBJECTIVE To analyze the differences in chemical components of Gardenia jasminoides before and after processing with ginger， and to evaluate the quality differences among different producing areas. METHODS Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry was used to analyze the compositional differences of G. jasminoides before and after processing with ginger. The water content， total ash， and ethanol-soluble extract content of ginger- processed G. jasminoides were determined according to the 2020 edition of Chinese Pharmacopoeia. High performance liquid chromatography was adopted to determine the contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ in ginger- processed G. jasminoides. RESULTS A total of 49 chemical components were identified from raw G. jasminoides and ginger- processed G. jasminoides， including 14 flavonoids， 15 iridoids， 10 organic acids， 2 alkaloids and 8 other compounds. Among them， 42 components were detected in raw G. jasminoides， 28 in ginger-processed G. jasminoides， and 21 components were common to both. After processing with ginger， raw G. jasminoides lost 21 components （including iridoids， flavonoids， alkaloids， and others）， while 7 chemical components were added （including coumarins， organic acids， organic acid esters， and flavonoids）. For the 15 batches of ginger-processed G. jasminoides， the water content ranged from 5.64% to 7.11%， total ash from 2.92% to 4.87%， and ethanol-soluble extract from 40.61% to 58.02%. The average contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ were 0.108 7， 0.542 2， 0.565 0， and 0.012 5 mg/g， respectively. CONCLUSIONS After processing with ginger， G. jasminoides loses 21 components， while 7 new components are added. Differences are observed in the water content， total ash， ethanol-soluble extract， and the contents of genipin gentiobioside， geniposide， crocin Ⅰ， and crocin Ⅱ of ginger-processed G. jasminoides from different producing areas. Notably， samples from Fujian exhibit high contents of genipin gentiobioside and ethanol-soluble extract， while samples from Jiangxi have a high content of crocin Ⅰ.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

Occupational disease diagnostician (ODD) is the core technology professional who is responsible for occupational disease diagnosis and identification and the main inspection work for occupational medical examination. The implementation of regular assessment management for ODDs is a key component of standardized workforce management, which facilitates dynamic evaluation of professional competence, regulation of medical practice, and assurance of medical safety. Since January 2025, Guangdong Province has implemented regular assessment management for ODDs within its administrative region. The assessment adopts an integrated model consisting of three components including professional competency evaluation, performance appraisal, and professional ethics evaluation, with each assessment cycle lasting three years. ODDs who passed all three components are classified as qualified ODD, whereas those who failed to pass any one of the three components result in an unqualified assessment outcome. In the implementation of ODD regular assessment management, Guangdong Province has emphasized integrating assessment with quality evaluation, strengthening full-cycle supervision of ODDs′ professional conduct, optimizing assessment strategies for special groups of ODDs, and reinforcing the primary management responsibility of medical institutions. Meanwhile, ODDs′ professional competence, service quality, and professional integrity have been continuously promoted by adopting human-computer interactive assessments, information-based assessment management, and "elimination" mechanism.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

OBJECTIVE To explore the short-term efficacy,safety and related influencing factors of subcutaneous immunotherapy(SCIT)in children with allergic rhinitis(AR).METHODS Retrospective analyzed the clinical data of 147 children with AR who underwent SCIT at Shenzhen Hospital of Southern Medical University from August 2020 to May 2024.The clinical characteristics and laboratory parameters were collected,the visual analogue scale(VAS),total symptom score(TSS),total medication score(TMS)and combined symptom medication score(CSMS)were compared at the baseline and 3,6 and 12 months after treatment.The incidence of local adverse reactions(LRs)and systemic adverse reactions(SRs)during treatment was also documented.RESULTS A total of 147 children with AR aged 5-18 years were included in the study.A significant reduction was observed in VAS,TSS,TMS and CSMS at months 3,6 and 12 of follow up compared with baseline(all P<0.001),and the short-term onset time was months 3 after treatment.The level of VitD3 in the effective group was significantly higher than that in the ineffective group(P<0.001).Serum VitD3 level was negatively correlated with clinical symptom(R=-0.3,P=0.026).The total number of injections in 147 children was 3201.LRs occurred in 52 children(35.4％),the number of injections was 69(2.2％).SRs occurred in 21 children(14.3％),and the number of injections was 34(1.1％).No grade Ⅲ or Ⅳ SRs occurred.In the logistic regression analysis,body mass index(BMI)was a risk factor for LRs(OR:2.220,95％CI:1.009-4.887,P=0.048).CONCLUSION SCIT demonstrates significant early efficacy and a favorable safety profile safety in children with AR.Serum Vitamin D3 deficiency can affect the short-term efficacy of SCIT.Overweight and obese children are prone to develop local adverse reactions.

Objective To investigate the relationship between serum glucagon-like peptide-1(GLP-1),monocyte chemoattractant protein-1(MCP-1),insulin-like growth factor binding protein-3(IGFBP-3)and glycolipid metabolism,bone metabolism and microvascular complications(MC)in children with type 1 diabe-tes mellitus(T1DM).Methods A total of 211 children with T1DM(T1DM group)admitted to Handan Cen-tral Hospital,Xingtai Traditional Chinese Medicine Hospital,Baoding First Central Hospital and Handan Ma-ternal and Child Health Hospital from January 2021 to February 2023 were selected,patients were divided into MC group(63 cases)and non-MC group(148 cases)according to whether MC was complicated within 1 year,and 108 healthy children who underwent physical examination during the same period were selected as control group.The levels of serum GLP-1,MCP-1,IGFBP-3 and glucose and lipid metabolism indexes[fasting plasma glucose(FPG),fasting insulin(FINS),glycosylated hemoglobin(HbA1c),homeostasis model assessment of insulin resistance(HOMA-IR),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)]and bone metabolism indexes[bone specific alkaline phosphatase(BALP),osteocalcin(OST),type I collagen cross-linked C-terminal peptide(CTX)]were detec-ted.The correlation between serum GLP-1,MCP-1,IGFBP-3 and glucose and lipid metabolism,bone metabo-lism in children with T1DM were analyzed by Pearson and Spearman correlation coefficient.Taking MC in children with T1DM as the dependent variable,the influencing factors were determined by multivariate uncon-ditional Logistic regression model,and the predictive value of serum GLP-1,MCP-1 and IGFBP-3 for MC were analyzed by receiver operating characteristic curve.Results The levels of serum GLP-1,FINS,HDL-C,BALP,OST and CTX in the T1DM group were lower than those in the control group,while the levels of MCP-1,IGFBP-3,FPG,HbA1c,HOMA-IR,TG and LDL-C in the T1DM group were higher than those in the control group,the differences were statistically significant(P<0.05).Serum GLP-1 in children with T1DM was negatively correlated with FPG,HbA1c,HOMA-IR,TG and LDL-C,and positively correlated with FINS,HDL-C,BALP,OST and CTX(P<0.05).MCP-1 and IGFBP-3 were positively correlated with FPG,HbA1c,HOMA-IR,TG and LDL-C,and negatively correlated with FINS,HDL-C,BALP,OST and CTX(P<0.05).Follow-up for 1 year,the incidence of MC in 211 children with T1DM was 29.86%(63/211).Elevated HbA1c,HOMA-IR,LDL-C,MCP-1 and IGFBP-3 were independent risk factors for MC in children with T1DM,and elevated GLP-1 was an independent protective factor(P<0.05).The area under the curve of ser-um GLP-1,MCP-1 and IGFBP-3 combined to predict MC in children with T1DM was 0.919,which was grea-ter than 0.781,0.788 and 0.794 predicted by serum GLP-1,MCP-1 and IGFBP-3 alone(P<0.05).Conclu-sion The decrease of serum GLP-1 level and the increase of MCP-1 and IGFBP-3 levels are related to glyco-lipid metabolism,bone metabolism disorder and MC in children with T1DM,the combined application of ser-um GLP-1,MCP-1 and IGFBP-3 has a good predictive value for MC in children with T1DM.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.