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.

By elaborating on the theoretical framework of the pulse acupuncture based on systematic syndrome differentiation， this paper briefly analyzes the correspondence between pulse and acupuncture， and further explores its core principle of "establishing acupuncture based on pulse， and applying acupuncture when the pulse is balanced". This therapeutic system employs a three-step acupoint selection method， relying on the systematic integration and analysis of pulse elements at different levels to determine the nature of disease， syndrome type， and location. Treatment principles are guided by the concepts of form and spirit transformation， aiming to treat both simultaneously. Pulse diagnosis also serves as a standard for evaluating therapeutic efficacy and predicting prognosis， providing a theoretical basis for clinical acupuncture. Using stroke as a case example， this paper illustrates the practical clinical application of this approach， offering valuable insight for acupuncture.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

Objective To understand the awareness rate and willingness of parents of school-age infants and young children in Huangpu District, Shanghai to receive the 13 valent pneumococcal conjugate vaccine (PCV13) and its influencing factors, and to provide basic data for formulating community health education policies. Methods A stratified random sampling method was used to conduct a full coverage questionnaire survey on the PVC13 awareness rate and vaccination willingness of 1030 parents of infants and young children in 10 communities. Results A total of 1000 questionnaire surveys were completed, with an accurate response rate of 97.08%. The awareness rate of PCV13 was 85.50%, and the awareness rate of complications was less than 80%. The PCV13 vaccination rate was 55.60%. 38.74% of the reasons for not being vaccinated were concerned about vaccine side effects, and 32.21% were concerned about vaccine quality. The higher the education level of parents and the per capita annual income of the family, the higher the awareness rate of pneumococcal vaccine knowledge and the willingness to receive vaccination. Parents with registered residence in other places had low willingness to vaccinate PCV13. Conclusion The public has a higher awareness of PCV13 and a higher willingness to receive vaccination. It is necessary to strengthen the scientific popularization of complications of pneumococcal pneumonia and vaccine safety, strengthen vaccine safety supervision and disclosure of regulatory results, and strengthen PCV13 science popularization for parents of infants and young children with registered residence outside the city.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Objective To elucidate the potential mechanisms by which mesothelin(MSLN)contributes to chemotherapy resistance in high-grade serous ovarian cancer(HGSOC).Methods A Meta-analysis utilizing public ovarian cancer databases was performed to evaluate the correlation between MSLN expression levels and overall survival(OS)in ovarian cancer patients.Pathway enrichment analysis was employed to identify key signaling pathways regulated by MSLN and their roles in chemotherapy resistance.Additionally,the TCGA-HGSOC database was analyzed to examine genomic features associated with MSLN-mediated chemotherapy resistance.To validate the biological function of MSLN in chemotherapy resistance,an intraperitoneal metastasis model was established using MSLN-knockdown ID8 ovarian cancer cells in mice.Results Elevated MSLN expression was significantly associated with poor patient prognosis(HR:1.42,95%CI:1.16-1.74).Differential gene expression and pathway enrichment analyses revealed that high MSLN expression upregulates resistance-associated genes and pathways involved in drug metabolism and DNA-binding signaling.Genomic association analysis showed a negative correlation between high MSLN expression and chromosomal instability features,specifically CX3,CX11,and CX13 scores.In vivo studies demonstrated that MSLN knockdown enhanced the tumor-suppressive effects of cisplatin.Conclusion High MSLN expression represents a potential biomarker for poor prognosis and chemotherapy resistance in HGSOC patients,suggesting MSLN as a promising target for therapeutic intervention.

Objective Exploring the mechanism of electroacupuncture's anti anxiety effect through methods such as hippocampal metabolomics and 16S rRNA sequencing.Methods Rats were randomly divided into normal group,model group,electroacupuncture group,and diazepam group.A rat model of anxiety disorder was prepared using chronic restraint stress method.During the modeling period of the electroacupuncture group,simultaneous"Zusanli"acupoint electroacupuncture intervention was performed for 30 minutes each time,once a day,for 21 days.The diazepam group received daily gavage of diazepam for a total of 21 days.After the completion of modeling,open field experiments and elevated cross maze experiments were conducted to observe the behavior of rats.Subsequently,pathological staining was performed to observe the pathological changes in the hippocampus and colon of rats.Metabolomics detection of changes in metabolites in the hippocampus of rats.16S rRNA and short chain fatty acid analysis were used to detect changes in gut microbiota and short chain fatty acids in rats.Western blot detection of Occludin in the colon and TLR4,NF-κB P65 and NLRP3 in the hippocampus of rats.Immunofluorescence detection of IBA-1,NLRP3,and IL-1β in the hippocampus Protein expression.Result The results of the open field experiment showed that compared with the normal group,the total activity distance(P<0.001),central area activity distance(P<0.01),and average velocity(P<0.01)of the model group decreased.Compared with the model group,the total activity distance(P<0.05,P<0.001),central area activity distance(P<0.05,P<0.01),and average velocity(P<0.05,P<0.01)of the electroacupuncture group and diazepam group all increased.The results of the elevated cross maze experiment showed that compared with the normal group,the model group had a decrease in OE%(P<0.001)and OT%(P<0.001).Compared with the model group,both the electroacupuncture group and the diazepam group could increase OE%(P<0.05,P<0.001)and OT%(P<0.01,P<0.001).The HE staining results of the hippocampus showed that the CA1 area of the hippocampus in the normal group rats showed clear and hierarchical structures in various regions of the hippocampus.In the hippocampus of the model group,a small amount of neural cell nuclei in the CA1 area were observed to be wrinkled and deeply stained,with unclear cell boundaries and irregular arrangement,and the cytoplasm was vacuolate.The intervention of electroacupuncture and diazepam can alleviate the above pathological phenomena to varying degrees,respectively;The results of hippocampal metabolomics showed that electroacupuncture can improve hippocampal metabolic disorders caused by modeling,mainly involving taurine and low taurine metabolism,cysteine and methionine metabolism,and regulation of glycine,serine,and threonine metabolic pathways;The results of 16S rRNA sequencing and short chain fatty acid detection showed that electroacupuncture can improve the disturbance of intestinal microbiota caused by modeling,and can regulate serum LPS and levels of butyric acid,caproic acid,and valeric acid.HE staining and Western blot results showed that the model group had pathological damage to the intestine,and compared with the normal group,the expression of Occludin in the colon of the model group decreased(P<0.05).However,the intervention of electroacupuncture and diazepam could improve the pathological damage of the colon and upregulate the expression of Occludin(P<0.05,P<0.05).The immunofluorescence results showed that compared with the normal group,the expression levels of IBA-1,NLRP3,and IL-1β in the hippocampus of the model group increased(P<0.05,P<0.01,P<0.01),while compared with the model group,the electroacupuncture group and diazepam group could reduce the expression levels of IBA-1(P<0.05,P<0.05),NLRP3(P<0.05,P<0.05),and IL-1β(P<0.05,P<0.05).Western blot results showed that compared with the normal group,the expression levels of TLR4,NF-κB P65,and NLRP3 proteins in the hippocampus of the model group increased(P<0.05,P<0.001,P<0.05).Compared with the model group,the electroacupuncture group and diazepam group were able to downregulate the expression levels of NF-κB P65(P<0.01,P<0.001)and NLRP3(P<0.05,P<0.05)proteins.Conclusion The anxiolytic of electroacupuncture involves the regulation of the"microbiota-gut-brain"axis.