1.Application of Engineered Exosomes in Tumor-targeted Therapy
Jia-Lu SONG ; Yi-Xin JIN ; Xing-Yu MU ; Yu-Huan JIANG ; Jing WANG
Progress in Biochemistry and Biophysics 2025;52(5):1140-1151
Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.
2.Hemolysis rates of three red blood cell components at the end of storage: a 5-year retrospective study
Zhenping LU ; Fufa LIU ; Meiyan KANG ; Xianbin WU ; Yanting WANG ; Xing LONG ; Xinlu QIU ; Jin LI
Chinese Journal of Blood Transfusion 2025;38(6):828-832
Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.
3.Quality evaluation of diagnosis and treatment guidelines and expert consensus for children with immune thrombocytopenic purpura
Yaping XING ; Ying DING ; Shanshan HAN ; Wenchao XING ; Lu JIA ; Min TONG ; Xiaodan REN
China Pharmacy 2025;36(13):1671-1676
OBJECTIVE To evaluate the quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura (ITP) published domestically and internationally, in order to provide reference for clinical practice and future guideline/expert consensus development and improvement. METHODS A systematic search was conducted across multiple databases, including PubMed, Cochrane Library, Embase, CNKI, Wanfang data, VIP, CBM; additionally, supplementary searches were carried out on websites such as Medlive, the Chinese Medical Association’s official website, and National Institute for Health and Clinical Excellence in the UK. The retrieval time ranged from the inception to September 2, 2024. Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ (AGREE Ⅱ) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT). RESULTS A total of 11 guidelines/consensuses were included. The average scores for the six domains of AGREE Ⅱ tool respectively were “range and purpose” ([ 66.67±17.98)% ], “participants” [58.33% (13.89%,73.61%)], “rigor” ([ 41.81±23.85)% ], “clarity”([ 69.57±19.35)%], “applicability” ([ 35.98±17.83)%], and “independence” [27.08% (0,75.00%)]; out of 11 articles, 9 had a recommendation level of B, 2 had a recommendation level of C, and there were no A-level articles. The average reporting rates of the 7 areas in the RIGHT tool were “basic information” ([ 72.35±12.95)% ], “background” ([ 54.55±15.40)%],“ evidence” ([ 36.36±24.81)%],“ recommended opinions” ([ 53.25±19.20)%],“ review and quality assurance” [0 (0, 25.00%)], “funding and conflict of interest statement and management” [12.50%(0,25.00%)], and other aspects [8.33%(0, 50.00%)]. In addition, there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses (P>0.05). CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high, with a recommended level of B or C. It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them. The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved, and there is no integrated guideline/consensus for traditional Chinese and Western medicine. It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.
4.Recommendations for Standardized Reporting of Systematic Reviews and Meta-Analysis of Animal Experiments
Qingyong ZHENG ; Donghua YANG ; Zhichao MA ; Ziyu ZHOU ; Yang LU ; Jingyu WANG ; Lina XING ; Yingying KANG ; Li DU ; Chunxiang ZHAO ; Baoshan DI ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2025;45(4):496-507
Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population, intervention, comparison and outcome (PICO) question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research: Reporting of in Vivo Experiments (ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.
5.Meta-analysis of Distribution Frequency of Traditional Chinese Medicine Syndrome in Primary Osteoporosis
Hailong WU ; Tianying CHANG ; Yan LU ; Zongjian LUO ; Xiangyang LENG ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):111-117
ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine(TCM) syndromes of primary osteoporosis(POP) in China by using evidence-based medicine methods, and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure(CNKI), VIP Chinese Science and Technology Journal Database(VIP), WanFang Data Knowledge Service Platform(WanFang) and China Biology Medicine(CBM) were searched to obtain representative literature, and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1, 2023. Two researchers independently screened literature according to the criteria, extracted data, and cross-checked them. Meta analysis was conducted using R4.1.3, and subgroup analysis was performed. ResultA total of 56 Chinese papers were included, involving 14 415 patients. After standardized classification of syndromes, 11 articles were excluded, and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%[95% confidence interval(CI) 0.24-0.31], 32%(95% CI 0.29-0.36), 36%(95% CI 0.30-0.42). Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south(P<0.05). In addition, the incidence of TCM syndrome fractures in different types of POP was 15%(95% CI 0.09-0.24) for liver-kidney Yin deficiency syndrome, 20%(95% CI 0.12-0.30) for spleen-kidney Yang deficiency syndrome, and 31%(95% CI 0.25-0.39) for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency, accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures, and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent, and in the future, it is necessary to focus on their determination standards to obtain consensus research results, at the same time, conduct large-scale syndrome research to obtain representative research results, providing a basis for clinical practice and research.
6.Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury
Guojing XING ; Longlong LUO ; Lifei WANG ; Shunna WANG ; Xiaofeng ZHENG ; Lixia LU ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(3):633-638
The incidence rate of drug-induced liver injury (DILI) is increasing year by year with unknown mechanisms, and the treatment methods for DILI mainly include drugs, liver support systems, and liver transplantation, all of which have certain limitations. Therefore, the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation, promoting hepatocyte proliferation and regeneration, inhibiting the apoptosis of hepatocytes, improving oxidative stress, and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI, so as to provide a reference for further research.
7. Investigating the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination in ameliorating psoriatic lesions
Xing-Kang WU ; Lu WANG ; Yang LI ; Yu-Shuang MA ; Xue-Mei QIN ; Xing-Kang WU ; Lu WANG ; Yang LI ; Yu-Shuang MA ; Xue-Mei QIN ; Xing-Kang WU
Chinese Pharmacological Bulletin 2024;40(1):171-180
Aim In this study, a mouse model of psoriasis-like lesions induced by 62. 5 mg imiquimod was used to explore the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for the topical treatment of psoriasis. Methods Firstly, the topical administration of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for treating psoriasis in progressive and recurrent stages was evaluated by psoriatic mouse model and HE staining. Secondly, immunohistochemistry was used to study the regulatory effects of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination on the pivotal pathological mechanism of psoriasis-the positive feedback loop between the abnormal proliferation of keratinocytes and skin immune microenvironment. Finally, metabolomics technology was used to explore whether Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination topically treat psoriasis by regulating inflammation-related metabolism and lipid metabolism pathways. Results The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae alleviated psoriasis-like lesions in mice. It effectively relieved the recurrence after the cure of psoriatic lesions in mice, and the efficacy is comparable to that of benweimod. The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae inhibited the proliferation of mouse epidermal keratinocytes and reduced the number of T cells in the skin. The potential molecular mechanism was that the combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae regulated arachidonic acid metabolism, sphin- golipid metabolism, tryptophan metabolism and phenylalanine metabolism. Conclusions The combination of Sophora Flavescens Radix and Rhizoma Smilacis Glabrae can relieve psoriasis-like lesions in mice by inhibiting the proliferation of epidermal keratinocytes and reducing the number of T cells in the skin and regulating metabolism to intervene psoriasis recurrence. This study provides a potential topical drug of psoriasis for relieving psoriasis recurrence.
8.Analysis of HUANG Feng's Medication Rules for Low Back Pain Based on Data Mining
Wen-Xing ZENG ; Min-Hua HU ; Yuan-Lan FENG ; Jing-Tao ZHANG ; Lu-Yao MA ; Hong-Song YAN ; Feng HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1030-1035
Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.
9.Efficacy and safety of nicorandil and ticagrelor de-escalation after percutaneous coronary intervention for elderly patients with acute coronary syndrome
Xiang SHAO ; Ning BIAN ; Hong-Yan WANG ; Hai-Tao TIAN ; Can HUA ; Chao-Lian WU ; Bei-Xing ZHU ; Rui CHEN ; Jun-Xia LI ; Tian-Chang LI ; Lu MA
Medical Journal of Chinese People's Liberation Army 2024;49(1):75-81
Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.
10.Construction of nursing quality evaluation index system for pediatric orthopedics
Nan WANG ; Wei JIN ; Yanzhen HU ; Jie HUANG ; Dan ZHAO ; Juan XING ; Changhong LI ; Yanan HU ; Yi LIU ; Xuemei LU ; Zheng YANG
Chinese Journal of Practical Nursing 2024;40(9):655-664
Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.

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