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.

Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

Aim To preliminarily evaluate the effects of hypobaric hypoxia on organism damage in rats with post-traumatic stress disorder(PTSD),with a view to laying a foundation for drug research in plateau PTSD.Methods The rats were randomly divided into four groups,namely,the control(Control)group,the sin-gle-prolonged stress(SPS)group,the hypobaric hy-poxia(HH)group and the single-prolonged stress combined with hypobaric hypoxia(SPS+HH)group.The PTSD model was firstly constructed using the SPS method for rats in the SPS and SPS+HH groups.On the second day,rats in the HH group and SPS+HH group were placed in a low-pressure hypoxia chamber at a simulated altitude of 6000 m for 14 days.General condition,behavior,blood tests,and histomorphology were examined in order to evaluate the damage caused by low pressure hypoxia in PTSD rats.Results The body mass of rats in the SPS+HH group was signifi-cantly reduced;the feces were partly hard and lumpy,and some of them were seen to have high viscosity.Anxiety-like and depression-like behaviors were ob-served in all groups except in the control group,in which hypobaric hypoxia aggravated the behavioral ab-normalities in SPS rats.Rats in both the SPS and SPS+HH groups had coagulation dysfunction and abnor-mally increased blood viscosity,which was significantly abnormal in the SPS+HH group;erythrocytes,hemo-globin,and erythrocyte specific volume in whole blood of rats in the SPS+HH group were significantly in-creased compared with those of rats in the SPS group;and serum TP,LDH and GLU levels were abnormal in rats in the SPS+HH group.Dilated and congested blood vessels were seen in hippocampal tissue,conges-ted central veins were seen in hepatic tissue,and dilat-ed and congested liver sinusoids with mild granuloma-tous degeneration of hepatocytes were seen in rats of the SPS+HH group.Conclusion Hypobaric hypoxia exacerbates depression-like and anxiety-like behaviors in PTSD rats,as well as hematological indices and his-tomorphometric abnormalities in PTSD rats.

Aim To evaluate the effect of Pien Tze Huang(PTH)on influenza virus susceptibility in re-straint stress-induced H1N1 influenza susceptibility model in mice with emotional disorders and internal heat,guided by the theory of emotional pathogenesis.Methods Mice were infected with H1N1 influenza vi-rus following 18 h of restraint stress.The signs and weight changes of mice were recorded,and the morbid-ity of mice were analyzed.On the fourth day post viral infection,the lung tissue was collected.The pathologi-cal changes and inflammatory factors in lungs were de-tected by HE staining.The expression of NP was as-sessed by immunohistochemistry and Western blot.The level of lipid peroxidation end products was detected u-sing a commercial kit and western blot.Redox phos-pholipidomics was analyzed in lung tissue by HPLC-MS/MS.Results PTH significantly reduced the mor-tality of influenza-susceptible mice induced by emotion-al stress,inhibited the expression of NP and the re-lease of inflammatory factors,improved inflammation in lung tissue,and alleviated the accumulation of lipid peroxidation end products.Phospholipid oxidation a-nalysis revealed the elevated levels of oxidized phos-pholipid choline and phosphatidylethanolamine in lung tissue of influenza-susceptible mice,which were signif-icantly reduced by PTH administration.Conclusions PTH exhibits promising efficacy in ameliorating influ-enza virus susceptibility induced by internal heat,and its mechanism of action may be related to the regulation of phospholipid peroxidation.

Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P＜0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P＜0.05),and improve inflammation and de-myelination of spinal cords(P＜0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P＜0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

Objective To analyze and compare the clinical effects of femoral neck dynamic cross screw system(FNS)and cannulated screws(CS)in the treatment of vertically unstable femoral neck fractures.Methods The clinical data and short-term follow-up results of 40 patients with vertically unstable femoral neck fractures admitted from July 2020 to August 2021 were retrospectively analyzed.According to different internal fixation methods,40 patients were divided into two groups,20 cases in FNS group included 11 males and 9 females with a median of 58.5(50.3,62.5)years old,and 20 in CS group included 9 males and 11 females with a median of 52.0(40.5,58.0)years old.The operation time,knife edge length,blood loss and treatment cost of two gruops were observed and compared.The postoperative fracture healing and internal fixation were evaluated with X-ray imaging data,and the femoral neck shortening of the affected side was measured.The incidence of thigh irritation,the time of partial weight bearing and full weight bearing,early necrosis of femoral head,reoperation revision and Harris scores were compared between two groups.Results FNS group was followed up for 18.0(15.0,19.0)months,CS group for 17.0(15.0,18.8)months.There was no significant difference in operation time,incision length and blood loss between two groups(P＞0.05).The cost of diagnosis and treatment in FNS group was higher than that in CS group(P＜0.001).In FNS group,there was no irritation sign of the affected side thigh,while in CS group,there were 6 cases with discomfort or irritation sign of the lateral thigh(P＜0.05).The average time of partial weight bearing activity in CS group was later than that in FNS group(P＜0.05);However,there was no significant difference in the activity time of complete weight bearing between two groups(P=0.011＞0.05).At the last follow-up,the shortened length of the affected femoral neck in CS group was greater than that in FNS group(P＜0.05).There was no early necrosis of femoral head and reoperation in both groups.There was no significant difference in Harris score be-tween two groups 12 months after operation(P＞0.05).Conclusion FNS treatment of vertically unstable femoral neck fractures can significantly reduce the incidence of lateral thigh irritation sign,and effectively reduce the postoperative shortening rate of vertically unstable femoral neck fractures,which can provide a relatively stable anti rotation force and anti cutting force,so that patients can go to the ground relatively early,which is conducive to the recovery of the affected hip joint function after surgery.It is a new option for the surgical treatment of vertically unstable femoral neck fractures.However,due to the high cost of treat-ment,In clinical practice,appropriate surgical treatment is selected according to the actual situation.

Objective To screen the differentially expressed genes of lung metastasis of osteosarcoma by bioinformatics,and explore their functions and regulatory networks.Methods The data set of GSE14359 was screened from GEO database(http://www.ncbi.nlm.nih.gov/gds)and the differentially expressed gene(DEG)was identified using GEO2R online tool.Download osteosarcoma disease related miRNAs from the online HMMD database(http://www.cuilab.cn/hmdd)and then FunRich software was used to predict the target gene,intersects with DEG to obtains the target gene.The miRNA-mRNA rela-tionship pairs were formed according to the targeted joints,then the data was imported into Cytoscape for visualization,DAVID was used to performe GO and KEGG analysis on target genes,STRING was used to construct PPI network,Cytoscape visualiza-tion,CytoHubba plug-in screening central genes and online website for expression and survival analysis.Results Total 704 DEGs were identified,consisting of 477 up-regulated genes and 227 down regulated genes.FunRich predicted 7 888 mRNAs and 343 target genes were obtained through intersection of the two.KEGG analysis showed that it was mainly involved in focal adhesion,ECM receptor interaction,TNF signal pathway,PI3K-Akt signal pathway,IL-17 signal pathway and MAPK signal pathway.Ten central genes(CCNB1,CHEK1,AURKA,DTL,RRM2,MELK,CEP55,FEN1,KPNA2,TYMS)were identified as potential key genes.Among them,CCNB1,DTL,MELK were highly correlated with poor prognosis.Conclusion The key genes and functional pathways identified in this study may be helpful to understand the molecular mechanism of the occurrence and progression of lung metastases from osteosarcoma,and provide potential therapeutic targets.

Objective To explore the neuroprotective effect and related mechanism of Zhenbao pill on rats with spinal cord injury.Methods A total of 60 SD rats were randomly divided into the control group,the model group and the Zhenbao pill group.Rats in the control group only exposed the spinal cord,and rats in the model group and the Zhenbao pill group established spinal cord injury models.After the model was successfully established,rats in the Zhenbao Pill group was given 0.6 g/kg Zhenbao pill orally once every 24 hours for 28 days,and rats in the control group and the model group were given the same dose of normal saline by gavage.Basso,Beattie,Bresnahan(BBB)score was used to evaluate the changes in motor behavior of rats in each group before and 4 weeks after intervention treatment.At the end of the experiment,the spinal cord tissue samples were collected,and the histopathological changes and apoptosis of nerve cells were observed and evaluated by HE staining and TUNEL staining.The expression of inflammatory factors TNF-α,IL-6 and IL-10 was detected by qRT-PCR.The expression of nuclear factor κB(NF-κB)/p65 pathway related proteins was detected by Western blot.Results After 4 weeks of intervention treatment,the BBB score of rats in the model group was lower than that in the control group,and the BBB score of rats in the Zhenbao pill group was higher than that in the model group,and the differences were statistically significant(P<0.05).The structure and morphology of spinal cord tissue of rats in the control group were normal;the spinal cord tissue structure of rats in the model group was disordered,with obvious bleeding,necrosis and edema,and a large number of inflammatory cells infiltrated;the degree of lesion of spinal cord tissue of rats in the Zhenbao pill group was significantly reduced than that in the model group.The number of apoptosis of spinal cord tissue in the Zhenbao pill group was decreased compared with that in the model group,and the difference was statistically significant(P<0.05).Compared with the control group,the expressions of TNF-α and IL-6 in spinal cord tissue in the model group were increased,while the expression of IL-10 was decreased,with statistically significant differences(P<0.05).Compared with the model group,the expressions of TNF-α and IL-6 in spinal cord tissue in the Zhenbao pill group were significantly decreased,while the expression of IL-10 was increased,with statistically significant differences(P<0.05).The protein expressions of NF-κB/p65 and p-NF-κB/p65 in spinal cord tissue of rats in the model group was up-regulated compared with those in the control group,and the differences were statistically significant(P<0.05);the protein expressions of NF-κB/p65 and p-NF-κB/p65 in spinal cord tissue of rats in the Zhenbao pill group were down-regulated compared with those in the model group,and the differences were statistically significant(P<0.05).Conclusion Zhenbao pill can effectively improve the behavioral symptoms of rats with spinal cord injury,alleviate its pathological changes,which has neuroprotective effects.Its mechanism may be related to blocking the NF-κB/p65 pathway and inhibiting the expression of inflammatory factors.

Transcatheter aortic valve replacement(TAVR)has emerged as a promising therapeutic alternative for addressing aortic valve-related pathologies.However,the occurrence of rapid arrhythmias linked to TAVR procedures is progressively drawing scrutiny.Presently,pharmacologic interventions constitute the mainstay of managing atrial arrhythmias related to TAVR,while the potential of ablation as a viable treatment modality remains undefined.Notably,in cases where the arrhythmia's genesis is presumed to be intricately linked to the prosthetic valve,the practicality and safety of ablation procedures remain unverified.Our institution has successfully ventured into radiofrequency ablation for a distinctive patient presenting with this intricate condition,thereby tentatively affirming the efficacy and safety of catheter ablation administered on the surface of prosthetic valves.