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.

Objective To compare the application effect of intermittent androgen deprivation(IAD)and continued androgen deprivation(CAD)on advanced prostate cancer and influence on prognosis.Methods The patients with advanced prostate cancer were divided into treatment group(86 cases)and control group(62 cases)according to the cohort method.The treatment group was given IAD regimen(subcutaneous injection of 3.6 mg goserelin once every 28 days)combined with oral administration of flutamide(250 mg every 3 times a day)or combined with oral administration of bicalutamide(50 mg once a day),and the control group was treated with CAD regimen(bilateral orchiectomy combined with continuous flutamide or bicalutamide orally,with the same dosage as the treatment group).The observation follow-up time of both groups was ≥9 months.Efficacy,serum total testosterone(TT),prostate specific antigen(PSA)and vascular endothelial growth factor(VEGF)were compared between the two groups after treatment,and the side effects of treatment,quality of life[Functional Assessment of Cancer Therapy-Prostate(FACT-P)]and disease progression were evaluated.Results At 9 months after treatment,the objective response rates(ORR)in treatment group and control group were 30.99％(22 cases/71 cases)and 29.09％(16 cases/55 cases),and the disease control rates(DCR)were 71.83％(51 cases/71 cases)and 69.09％(38 cases/55 cases)respectively(P＞0.05).Serum TT levels in treatment group and control group were(25.53±9.44)and(22.51±8.28)ng·dL-1,PSA levels were(4.48±1.02)and(4.32±0.95)ng·mL-1,and VEGF levels were(121.03±35.26)and(118.65±33.42)pg·mL-1 respectively(all P＞0.05).The incidence rates of hot flash in treatment group and control group were 21.13％and 56.36％,the incidence rates of breast swelling pain were 16.90％and 34.55％,and the incidence rates of osteoporosis were 8.45％and 25.45％respectively(all P＜0.05).The scores of physical condition of FACT-P in treatment group and control group were(24.15±4.22)and(20.28±3.71)points,the scores of life condition were(20.28±2.94)and(17.81±2.84)points,scores of prostate cancer specific(PCS)module were(33.21±6.32)and(28.42±5.43)points,respectively,the difference were all statistically significant(all P＜0.05).The cumulative progression-free survival rates in treatment group and control group were 61.97％and 58.18％(P＞0.05).Conclusion IAD is as effective as CAD in the treatment of advanced prostate cancer and has a similar effect on the prognosis of patients,but the former one has fewer side effects of treatment and helps to improve the quality of life of patients.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

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.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.

Objective To explore the efficacy of camrelizumab injection combined with transcatheter arterial chemoembolization(TACE)in the treatment of patients with primary liver cancer.Methods Patients with primary liver cancer were retrospectively studied and divided into control group and treatment group according to different treatment regimens.The control group was treated with TACE,while the treatment group was intravenously injected with 200 mg of camrelizumab injection once every 3 weeks on the 3rd day-7th day after first TACE on the basis of treatment in control group.All patients were treated for 12 weeks.The efficacy[objective response rate(ORR),disease control rate(DCR)],liver function[total bilirubin(TBil),glutamic oxalacetic transaminase(GOT),glutamic pyruvic transaminase(GPT)],serum tumor-related markers[alpha fetoprotein(AFP),hepatocyte growth factor(HGF),intercellular adhesion moleclar-1(ICAM-1)],T lymphocyte subsets(CD4+/CD8+ratio)and the safety was evaluated.Results There were 38 cases in treatment group and 42 cases in control group.After treatment,the ORR in treatment group and control group were 65.79％(25 cases/38 cases)and 42.86％(18 cases/42 cases),the DCR were 89.47％(34 cases/38 cases)and 71.43％(30 cases/42 cases),the differences were statistically significant(all P＜0.05).After treatment,serum TBil levels in treatment group and control group were(18.34±5.52)and(21.03±6.32)μmol·L-1;GOT levels were(54.79±17.07)and(60.57±18.29)U·L-1;GPT levels were(47.23±6.15)and(54.48±7.68)U·L-1;serum AFP levels were(96.94±28.17)and(152.49±41.22)ng·mL-1;HGF levels were(75.08±8.26)and(90.17±9.03)ng·mL-1;ICAM-1 levels were(432.38±131.43)and(526.15±184.36)ng·mL-1,respectively;CD4+/CD8+ratios were 1.31±0.23 and 1.16±0.21,respectively(all P＜0.05).Compared with the control group,the above indexes in treatment group were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group were mainly reactive cutaneous capillary hyperplasia,gastrointestinal reaction and hand-foot syndrome,while the adverse drug reactions in the control group were mainly hand-foot syndrome and gastrointestinal reaction.The incidence of reactive cutaneous capillary hyperplasia in test group and control group was 52.63％and 0,the difference was statistically significant(P＜0.05).Conclusion Camrelizumab injection combined with TACE has significant efficacy in the treatment of patients with primary liver cancer.It can effectively reduce the levels of serum AFP,HGF and ICAM-1,and improve the immune function.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.