Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

OBJECTIVES: To evaluate the protective effect of Lycium barbarum polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. METHODS: Human granulosa-like tumor cell line (KGN) were treated with 2.5 µg/mL cisplatin for 24 h, followed by treatment with 100, 500, and 1000 mg/L LBP, and the changes in cell viability, apoptosis, level of anti-Müllerian hormone (AMH), and cell ultrastructure were detected with CCK-8 assay, flow cytometry, ELISA and transmission electron microscopy. The cellular expressions of Bax, caspase-3, Bcl-2, and the PI3K/AKT pathway proteins were analyzed using Western blotting, and the expression of miR-23a was detected with RT-qPCR. KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP. RESULTS: Cisplatin treatment significantly inhibited cell viability, induced apoptosis, decreased AMH level, caused ultrastructural abnormalities, increased Bax and caspase-3 expression, and lowered Bcl-2 expression in KGN cells. Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells. LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells, and in particular, LBP treatment at the medium dose for 24 h significantly improved KGN cell viability, reduced apoptosis, enhanced their endocrine function, and ameliorated ultrastructural abnormalities. Mechanistically, medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells, subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2. Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP. CONCLUSIONS LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway, suggesting a potential therapeutic strategy for ovarian function preservation.
Humans ; Cisplatin/adverse effects* ; MicroRNAs/genetics* ; Female ; Granulosa Cells/cytology* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Down-Regulation ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Survival/drug effects*

Objective: To explore the intervention effect of group counseling integrating teadrinking on depression, social avoidance and distress, coping styles and selfesteem among college students, so as to provide references for promoting the psychological health of students. Methods: From March to June 2021, a convenience sampling method was used to recruit 46 college students from a university in Nanjing for intervention project. There were 23 students in intervention group and control group, respectively. The intervention was conducted for 2.5 hours per week across a 6 week period. The intervention group received two sessions of group counseling that incorporated teadrinking experience, and the sessions involved tea knowledge explanation, observation and learning, embodied experience, emotional expression, interpersonal assistance and emotional support, cultural customs and life integration. After the intervention was completed, the control group received onetime group counseling that integrated teadrinking. The Wilcoxon difference test and Mann-Whitney U test were performed to compare the scores of each scale within and between the groups, and the χ2 test was used to compare the detection rates. Results: There were no statistically significant differences in the scores of positive coping, negative coping, selfesteem, social avoidance and distress between the intervention group and the control group (Z=-1.20, -0.33, -0.35, 1.31,P>0.05). There were statistically significant differences in positive coping styles, selfesteem, social avoidance and distress between the intervention group and the control group after the intervention(27.70±5.60，22.05±4.30；30.52±3.63，28.27±4.06；7.43±7.38，13.64±6.79) (Z=-3.31, -2.10, 3.22, P<0.05). The intervention group showed statistically significant differences in social avoidance and distress scores before and after the intervention(11.96±7.47,7.43±7.38) (Z=-2.88), and the depression detection rate decreased(60.9%，30.4%) (χ2=4.29) (P<0.05). There were no statistically significant differences in positive coping, negative coping, selfesteem, social avoidance and distress scores, and depression detection rate between the control group before and after the intervention (Z/χ2=-0.28, -0.42, -1.24, -1.25；1.39, P>0.05). The followup results 1year later showed that there was a statistically significant difference in social avoidance and distress(6.57±6.21,14.16±9.22), and in the detection rates of depression(21.7%,52.2%) between the intervention group and the control group (Z/χ2=2.70,4.57,P<0.05). Conclusions Group counseling integrating teadrinking could improve interpersonal relationships, emotional states, selfesteem levels and coping strategies among college students. Group psychological counseling that incorporates teadrinking can be adopted to improve the mental health status of college students.

Objective:To evaluate the cardiac morphological and functional parameters of patients with persistent atrial fibrillation (per-AF) and paroxysmal atrial fibrillation (PAF) using two-dimensional speckle tracking echocardiography (2D-STE) and real-time three-dimensional echocardiography (RT-3DE), and to explore their predictive value for the occurrence and progression of atrial fibrillation.Methods:A retrospective study was conducted on 30 per-AF patients (per-AF group), 30 PAF patients (PAF group) and 25 non-AF subjects (control group) who underwent echocardiography at Wuhan University People′s Hospital from May 2022 to May 2023. The left/right atrial longitudinal strain of reservoir, conduct and contraction (LASr/RASr, LAScd/RAScd, LASct/RASct), and calculated left atrial stiffness (LASI) were assessed by 2D-STE. Three-dimensional left and right atrial maximum volume index (LAVImax/RAVImax), minimum volume index (LAVImin/RAVImin) and emptying fraction (LAEF/RAEF) were obtained by RT-3DE. Then, patients with atrial fibrillation were divided into the normal LAVI group and enlarged LAVI group, and the differences of atrial strain among each group were compared. ROC curve was used to evaluate the overall diagnostic efficiency and cutoff values of ultrasonic parameters in patients with normal volume of atrial fibrillation. Finally, a multivariate Logistic regression model was established to identify the ultrasonic parameters associated with the occurrence and progression of different types of atrial fibrillation.Results:①Structurally, LAD, RAD and RAVImin in control, PAF and per-AF groups increased gradually, while LAEF and RAEF decreased gradually (all P<0.05). ②In terms of strain, LASr in control, PAF and per-AF groups decreased gradually (all P<0.05); Compared with the control group, LAScd, RASr and RAScd in PAF and per-AF groups were significantly decreased, and LASct and RASct in PAF group were significantly decreased (all P<0.05). ③Compared with the normal LAVI group, the LASr, LAScd and LASct in the enlarged LAVI group were significantly decreased, while LASI was significantly increased (all P<0.05); Compared with control group, the left and right atrial strain parameters in LAVI normal group were decreased, and LASI was increased (all P<0.05). The atrial strain parameter ROC was constructed in all subjects with normal left atrial volume, and RASr was the most sensitive indicator.④Multi-factor Logistic regression analysis showed that LAVImin and RASr were the influence factors of PAF ( OR=1.521, 0.907; 95% CI=1.173-1.972, 0.825-0.998; P=0.002, 0.044), LASr was the influence factor of pre-AF ( OR=0.858, 95% CI=0.802-0.917, P<0.001). Conclusions:2D-STE and RT-3DE can be used to evaluate the structural and functional changes of both atria, especially LAVImin, LASr and RASr, which have certain predictive value for the occurrence and progression of atrial fibrillation.

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

Objective:To observe the in vivo microscopic histological changes during the treatment of melasma using reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT), and to explore its application value in evaluating therapeutic efficacy. Methods:Clinical data were collected from 30 melasma patients treated at the Department of Dermatology, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, from January to October 2023. Retrospective analyses were performed on clinical photographs taken before treatment and at weeks 4, 8, 12, and 16 after the start of treatment, and the efficacy was evaluated by using the melasma area and severity index (MASI) scores. Meanwhile, changes in RCM imaging indicators, such as pigment distribution patterns, melanocyte morphology and spatial distribution patterns, and inflammatory infiltration in the superficial dermis in melasma lesions, were retrospectively analyzed. For clear elucidation of concepts and subsequent quantitative analysis, characteristic microscopic histological changes in melasma lesions before treatment were classified into several patterns based on RCM findings and previous literature reports. Additionally, optical coherence signals collected by OCT were used to asses characteristic vessel parameters in the lesions before and after treatment. Finally, correlations between various microscopic histological changes and clinical efficacy were analyzed using Spearman's correlation analysis.Results:With the increase in treatment duration, the proportions of pigment distribution patterns Ⅱ and Ⅲ observed by RCM gradually decreased, while the proportion of the nearly normal pattern Ⅰ markedly increased; the proportions of the 4 heterogeneous morphological patterns of melanocytes all decreased, while the pattern Ⅱ melanocytes were still focally distributed in the lesions at the last time of observation; meanwhile, the proportions of melanocyte spatial distribution patterns Ⅱ and Ⅲ decreased, which gradually restored to the normal pattern Ⅰ; the infiltration of melanophages and inflammatory cells in the superficial dermis diminished, and the proportion of the pattern Ⅲ inflammatory infiltration markedly decreased at week 4, but it lasted for a long time. The decrease rate of MASI scores was significantly correlated with the decrease rate of the proportions of pigment distribution patterns Ⅱ and Ⅲ ( r = 0.82, 0.97, respectively, both P < 0.05), melanocyte morphological patterns Ⅰ, Ⅲ, and Ⅳ ( r = 0.84, 0.83, 0.83, respectively, all P < 0.05), and inflammatory infiltration patterns Ⅰ and Ⅲ ( r = 0.85, 0.81, respectively, both P < 0.05), as well as the increase rate of the proportion of melanocyte spatial distribution pattern Ⅰ ( r = 0.89, P < 0.05), indicating that these indicators can be sensitive evaluation indicators for clinical efficacy. Moreover, OCT revealed a decrease in the average diameter and density of vessels in the lesions after treatment, and the decrease rates were correlated with the decrease rate of MASI scores ( r = 0.76, 0.78, respectively, both P < 0.05) ; there was no significant difference between the pre- and post-treatment average depth of vascular plexuses. Conclusion:During the treatment of melasma, RCM combined with OCT could serve as a non-invasive approach with objective and robust evidence for evaluating the therapeutic efficacy.

Objective:To quantitatively evaluate and compare the morphology and dynamics parameters of mitral valve devices in patients with atrial functional mitral regurgitation (AFMR) and ventricular functional mitral regurgitation (VFMR) by real-time three-dimensional ultrasound, in order to provide theoretical basis for diagnosis and clinical treatments of the two types of regurgitation patients.Methods:A retrospective study was conducted on 20 AFMR patients (AFMR group) and 20 VFMR patients (VFMR group) who underwent transesophageal echocardiography at Wuhan University People′s Hospital from May to November 2022. Additionally, 20 patients who underwent transesophageal echocardiography at our hospital during the same period due to patent foramen ovale or non cardiac surgery monitoring were selected as the control group. All subjects were measured mitral annulus anteroposterior diameter (AP diameter), anterolateral posteromedial diameter (ALPM diameter), anteroposterior diameter/anterolateral posteromedial diameter (AP/ALPM), commissural width (CW), annular area (AA), annular circumference (AC), annular height (AH), coaptation depth (CD), tenting volume (TV), non-planar angle (NPA) and posterior leaflet angle at isovolumic relaxation time, early diastole, mid diastole, late diastole, isovolumic contraction time, early systole, mid systole, and late systole. The total change rate and systolic change rate of the above parameters were calculated, the differences in structure and dynamic changes of the mitral valve device among three groups were compared, and the correlations between the change rate of mitral annular parameters and left ventricular long axis strain (GLS) were analyzed.Results:①The GLS of three groups were as follows: control group>AFMR group>VFMR group, and the differences between the groups were statistically significant (all P<0.05). ②Static structure: The AP diameter, ALPM diameter, AA, AC, and total leaflet area (TLA) of the AFMR group and VFMR group were significantly larger than those of the control group (all P<0.05), but there was no statistically significant difference between the AFMR group and VFMR group (all P>0.05). Compared with the other two groups, the TV, CD, and posterior leaflet angle of the VFMR group were significantly increased, exhibiting the mitral valve tethering; the control group had the largest AH/CW and the deepest saddle shape; the AFMR group had the smallest TLA/AA and the least mitral valve remodeling; there was no statistically significant difference in the junction area among the three groups (all P>0.05). ③Dynamic changes: AP diameter, ALPM diameter, AA and AC in the control group showed regular changes throughout the cardiac cycle, gradually decreased from isovolumic relaxation time to late diastole, and gradually increased from isovolumic contraction time to late systole; The changes in the above parameters in the AFMR and VFMR groups appeared more disordered. In addition, compared with the control group, the total change rate and systolic change rate of AP diameter in the AFMR group were significantly reduced, but the total change rate of ALPM diameter was significantly increased (all P<0.05). ④The total change rate of AA, ALPM diameter and AP diameter were moderately correlated with GLS ( r=0.353, P=0.006; r=-0.304, P=0.018; r=0.300, P=0.020), while the systolic change rate of posterior leaflet angle was weakly correlated with GLS ( r=0.267, P=0.039). Conclusions:There are differences in the morphology and dynamics parameters of mitral valve device in patients with AFMR and VFMR.Different clinical strategies can be used for the two kinds of functional mitral regurgitation.

Proanthocyanidin (PA), as a kind of natural plant polyphenol, have a variety of biological functions, such as promoting remineralization, inducing collagen cross-linking, inhibiting protease activity and inhibiting bacteria. Therefore, PA could be broadly used in the clinical application of treatment and repair of deep caries in the future; for example, PA could promote dentin remineralization, improve resin-dentin bonding durability and improve the dentin acid erosion effect. This application potential of PA arises from several features, firstly, PA can not only promote dentin remineralization on its own or with other remineralizers but also exhibits antibacterial effects, which can inhibit acid production while reducing the formation of cariogenic pathogens and their biofilms. Based on the above features, PA can reduce the incidence of caries disease; thus, PA improves deep caries and long-term effects after treatment. In addition, PA added to adhesives or etch agents can improve the etching and bonding effect of dentin by inducing collagen cross-linking and inhibiting protease activity, thus achieving the ultimate goal of improving the bonding performance of deep caries. This paper summarizes recent progress of research on PA for the treatment and repair of deep caries, including the promotion of dentin remineralization and antibacterial activity as well as the improvement in dentin bonding and acid etching effect, to provide a more comprehensive reference for treating and restoring deep caries in clinical practice.

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.