1.Regulatory Mechanism of Extracellular Vesicles in The Tumor Immune Microenvironment and Its Application in Diagnosis and Treatment
Zi-Qi WANG ; Jing WANG ; Yuan-Yu HUANG ; Mei LU
Progress in Biochemistry and Biophysics 2026;53(4):968-981
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.
2.Important factors affecting depression:modulatory effects of Cx43 on neuroinflammation
Xuan ZENG ; Zi-han YAN ; Zhi-feng TIAN ; Hong-bin WANG ; Qi-di AI ; Mei-yu LIN ; Xuan LIU ; Nai-hong CHEN ; Song-wei YANG ; Yan-tao YANG
Chinese Pharmacological Bulletin 2025;41(11):2027-2031
Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.
3.Antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae strains isolated from Hebei Children's Hospital from 2018 to 2020
Wenjing YU ; Mei LI ; Yinghui GUO ; Qianru XU ; Yuanlong LI ; Qi WANG
Chinese Journal of Infection and Chemotherapy 2025;25(2):181-186
Objective To investigate the antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from children for better prevention,treatment,and control of CRKP infections in children.Methods A total of 182 clinical CRKP strains were collected between January 2018 and December 2020 in Hebei Children's Hospital.All CRKP strains were identified by matrix-assisted laser desorption ionization-time of flight(MALDI-TOF)mass spectrometry.The common carbapenemase genes(blaKPC,blaNDM,blaIMP,blaVIM,blaOXA-48)of CRKP isolates were studied by PCR.Multilocus sequence typing(MLST)was performed for homology analysis.Results The 182 children infected with CRKP were mainly infants(>28 days to<1 years),accounting for 49.45%(90/182),followed by newborns(≤28 days),accounting for 36.26%(66/182).The main source of the 182 CRKP isolates was sputum(50.55%,92/182),blood(15.93%,29/182),and urine(13.19%,24/182).The strains were mainly isolated from patients in neonatology(30.22%,55/182),general surgery(21.43%,39/182),cardiac surgery(13.19%,24/182),and intensive care unit(11.54%,21/182).Antimicrobial susceptibility testing showed that all of the 182 CRKP strains were resistant to cefepime,ceftazidime,piperacillin-tazobactam,and cefoperazone-sulbactam(100%).Overall,97.8%,71.4%,81.9%,75.8%,69.2%,and 2.7%of the strains were resistant to aztreonam,amikacin,ciprofloxacin,levofloxacin,doxycycline,and tigecycline,respectively.The prevalence of carbapenemase gene blaKPC-2 was the highest(73.63%,134/182),followed by blaNDM-5(15.38%,28/182),and blaNDM-1(11.54%,21/182).A total of 15 different sequence types(ST)were identified by MLST,of which ST11 was the most common type(72.53%,132/182),followed by ST17(11.54%,21/182).Conclusions CRKP isolates in Hebei Children's Hospital showed high level resistance to antimicrobial agents.Antimicrobial therapy should be prescribed cautiously according to the results of antimicrobial susceptibility testing to avoid the emergence of resistant strains.KPC-2-producing ST1 1 type CRKP strains may be prevalent in this hospital.Effective control measures should be taken to avoid further spread of such CRKP strains.
4.Important factors affecting depression:modulatory effects of Cx43 on neuroinflammation
Xuan ZENG ; Zi-han YAN ; Zhi-feng TIAN ; Hong-bin WANG ; Qi-di AI ; Mei-yu LIN ; Xuan LIU ; Nai-hong CHEN ; Song-wei YANG ; Yan-tao YANG
Chinese Pharmacological Bulletin 2025;41(11):2027-2031
Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.
5.CNV Encompassing SNP Detection by Cross-reactivity Probe
Xiao-Mei HU ; Chen ZHOU ; Pin-Zheng ZHANG ; Yang CHEN ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):895-902
Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.
6.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
7.Comparative effectiveness of small optical zone orthokeratology lenses and repeated low-level red-light therapy for controlling myopia in adolescents
Shi-mei LIU ; Li CHEN ; Da LUO ; Qi-hui LUO ; Yu CHENG ; Ren-xiang TANG ; Wei YANG ; Bo LIU
Journal of Regional Anatomy and Operative Surgery 2025;34(11):972-976
Objective To compare the effect of small optical zone orthokeratology lenses(OK lenses)and repeated low-level red-light(RLRL)therapy in controlling myopia progression for adolescents,and the therapeutic effectiveness of RLRL is evaluated.Methods A retrospective analysis was conducted on the clinical data of 80 adolescent myopic patients in the First Affiliated Hospital of Army Medical University.The patients were divided into the RLRL group and the OK lenses group according to different intervention methods,with 40 cases in each group.Patients in the RLRL group received RLRL therapy combined with single-vision spectacles,and patients in the OK lenses group were treated with OK lenses.The changes of spherical equivalent(SE),axial length and subfoveal choroidal thickness(SFCT)1,3,6,and 12 months after treatment compared with the baseline,and color vision of patients were assessed.Based on the mean baseline axial length of the RLRL group,the patients in this group were subdivided into the short axial group and the long axial group,and the changes of the axial length and SFCT were further analyzed.Results The diopter 1,3,6,and 12 months after treatment in the RLRL group were not significantly different from the baseline(P>0.05).Axial lengths of patients in the RLRL group progressively shortened after treatment and returned close to the baseline 12 months after treatment.In contrast,axial lengths of patients in the OK lens continued to grow within 12 months after treatment;the axial lengths at each time point after treatment of patients in the two groups were significantly different from the baseline(P<0.05).The changes of axial length of patients in the RLRL group at each time point after treatment were significantly smaller than those in the OK lenses group(P<0.05).The SFCT changes of patients in the RLRL group at each time point after treatment were all greater than those in the OK lenses group(P<0.05).The SFCT at each time point after treatment in the RLRL group were significantly different from the baseline(P<0.05),whereas the SFCT at each time point after treatment in the OK lenses group were not significantly different from the baseline(P>0.05).The changes of axial length at each time point after treatment of patients in the long axial group were all greater than those in the short axial group(P<0.05);the SFCT changes 6 months after treatment of patients in the long axial group was greater than that in the short axial group(P<0.05);the SFCT at each time point after treatment of patients in the two groups were signifi-cantly different from the baseline(P<0.05).Color vision tests revealed no abnormities after treatment in the RLRL group and the OK lenses group.Conclusion RLRL therapy is effective in controlling myopia progression and demonstrates superior axial length control compared to orthokeratology lenses.
8.Dual Gain Effect of Hyperbaric Oxygen Combined with Vestibular Rehabilitation Training on Patients with Tinnitus and Dizziness
Ya-qi WANG ; Yan-mei YANG ; Cui-ling YANG ; Yuan YU ; Shu-man LIU
Progress in Modern Biomedicine 2025;25(17):2857-2864
Objective:To analyze the dual gain effect of hyperbaric oxygen combined with vestibular rehabilitation training on patients with tinnitus and dizziness.Methods:This study was a retrospective analysis,and 90 patients with tinnitus and dizziness who visited the outpatient department of our hospital from January 2022 to January 2025 were selected to carry out the study,and were divided into observation group and control group according to the treatment methods,with 45 cases in each group.The matched group patients were treated with conventional medication,while the observation group received hyperbaric oxygen combined with vestibular rehabilitation training on the basis of the matched group.The clinical efficacy of the two groups was compared,including the concentration of oxygenated hemoglobin in the cerebral cortex,vestibular function,severity of tinnitus,and severity of dizziness before and after treatment.Results:The total effective rate of the observation group was higher than the matched group(P<0.05);Post-treatment,there was no significant change in the concentration of oxygenated hemoglobin in the parietal and occipital cortex between the two groups(P>0.05).However,the concentration of oxygenated hemoglobin in the temporal lobe,dorsolateral prefrontal cortex,and frontal polar cortex increased,and the observation group was higher than the matched group(P<0.05);Post-treatment,the values of hemiparesis,total area of center of gravity movement(CA),and total length of center of gravity movement(PL)in both groups decreased,and the observation group was lower than the matched group(P<0.05);Post-treatment,the severity score of tinnitus in both groups decreased,and the observation group was lower than that in the matched group(P<0.05);Post-treatment,the degree score of vertigo in both groups decreased,and the observation group was lower than that in the matched group(P<0.05).Conclusion:Hyperbaric oxygen combined with vestibular rehabilitation training has a significant dual gain effect on patients with tinnitus and dizziness,which can improve clinical efficacy,promote cortical neural activity,improve vestibular function,and thereby alleviate the severity of tinnitus and dizziness.
9.Rapid identification of morphological abnormalities of microcytic hypochromic erythrocytes and implications for medical selection of flying cadets
Jing LIU ; Li DING ; Yinghong AN ; Mei XUE ; Yuan YU ; Yan HUANG ; Qi QI ; Xuefeng WANG ; Dongrui YU ; Kai LIN
Chinese Journal of Aerospace Medicine 2025;36(2):107-112
Objective:To quickly identify the causes of morphological abnormalities of microcytic hypochromic erythrocytes that are detected during health checkups for recruitment of flying cadets, and to explore its role in medical selection.Methods:Students with hemoglobin (Hb)≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes detected during the 2023 medical selection of flying cadets by Guangzhou Selection Center were selected. Their medical history was collected, and iron metabolism, Hb electrophoresis and hemoglobin H (HbH) inclusion bodies were examined to screen for thalassemia and iron deficiency. The diagnosis of thalassemia was confirmed by thalassemia gene testing. Those with iron deficiency received iron supplementation therapy and the recovery of Hb was observed.Results:Ninety-one students were diagnosed with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, accounting for 4.35% of the total. Among these cases, 85 with abnormal Hb electrophoresis and/or positive HbH inclusion body detection were confirmed as thalassemia minor via thalassemia genetic testing, and 3 cases with normal iron metabolism, Hb electrophoresis, and negative HbH inclusion body detection. A total of 88 cases of thalassemia minor were diagnosed, accounting for 96.70% of the total. Among them, 2 cases were complicated with iron deficiency while 3 were diagnosed with iron deficiency erythropoiesis. Out of the 91 students with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, 9 were recruited, including 7 cases with thalassemia minor (Hb≥130 g/L), 1 case with thalassemia minor combined with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation), and 1 case with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation). Among the 9 recruits, 8 were followed up for over one year and the results of their military physical fitness tests all reached or exceeded the standards, but the remaining one dropped out and lost contact.Conclusions:Among physical examinees during medical selection of flying cadets in South China, thalassemia is the leading cause of morphological abnormalities of microcytic hypochromic erythrocytes. Results of iron metabolism, Hb electrophoresis, and HbH inclusion body detection can help identify thalassemia and iron deficiency quickly. Cases of morphological abnormalities of microcytic hypochromic erythrocytes caused by iron deficiency can be considered eligible for selection after Hb levels return to normal following iron supplementation therapy. Students who are diagnosed with thalassemia with Hb<130 g/L can be determined as ineligible. Such rapid identification can facilitate the medical selection of the above 2 types of students.
10.Antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae strains isolated from Hebei Children's Hospital from 2018 to 2020
Wenjing YU ; Mei LI ; Yinghui GUO ; Qianru XU ; Yuanlong LI ; Qi WANG
Chinese Journal of Infection and Chemotherapy 2025;25(2):181-186
Objective To investigate the antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from children for better prevention,treatment,and control of CRKP infections in children.Methods A total of 182 clinical CRKP strains were collected between January 2018 and December 2020 in Hebei Children's Hospital.All CRKP strains were identified by matrix-assisted laser desorption ionization-time of flight(MALDI-TOF)mass spectrometry.The common carbapenemase genes(blaKPC,blaNDM,blaIMP,blaVIM,blaOXA-48)of CRKP isolates were studied by PCR.Multilocus sequence typing(MLST)was performed for homology analysis.Results The 182 children infected with CRKP were mainly infants(>28 days to<1 years),accounting for 49.45%(90/182),followed by newborns(≤28 days),accounting for 36.26%(66/182).The main source of the 182 CRKP isolates was sputum(50.55%,92/182),blood(15.93%,29/182),and urine(13.19%,24/182).The strains were mainly isolated from patients in neonatology(30.22%,55/182),general surgery(21.43%,39/182),cardiac surgery(13.19%,24/182),and intensive care unit(11.54%,21/182).Antimicrobial susceptibility testing showed that all of the 182 CRKP strains were resistant to cefepime,ceftazidime,piperacillin-tazobactam,and cefoperazone-sulbactam(100%).Overall,97.8%,71.4%,81.9%,75.8%,69.2%,and 2.7%of the strains were resistant to aztreonam,amikacin,ciprofloxacin,levofloxacin,doxycycline,and tigecycline,respectively.The prevalence of carbapenemase gene blaKPC-2 was the highest(73.63%,134/182),followed by blaNDM-5(15.38%,28/182),and blaNDM-1(11.54%,21/182).A total of 15 different sequence types(ST)were identified by MLST,of which ST11 was the most common type(72.53%,132/182),followed by ST17(11.54%,21/182).Conclusions CRKP isolates in Hebei Children's Hospital showed high level resistance to antimicrobial agents.Antimicrobial therapy should be prescribed cautiously according to the results of antimicrobial susceptibility testing to avoid the emergence of resistant strains.KPC-2-producing ST1 1 type CRKP strains may be prevalent in this hospital.Effective control measures should be taken to avoid further spread of such CRKP strains.

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