Extracellular vesicles (EVs) are membrane-bound vesicles secreted by cells, including exosomes, microvesicles, and apoptotic bodies, which play critical roles in intercellular communication, material transport, and signal transduction. In recent years, increasing evidence has highlighted the essential function of EVs in early embryo development. By carrying bioactive molecules such as proteins, nucleic acids (e.g., mRNA and miRNA), and lipids, EVs regulate embryonic gene expression, cell proliferation, differentiation, and the microenvironment. Studies have shown that EVs derived from various segments of the female reproductive tract can enhance embryonic developmental potential, improve embryo quality, and facilitate implantation. Additionally, EVs secreted by embryos themselves participate in intercellular communication and play pivotal roles during embryogenesis. This review summarizes recent advances in understanding the functions of EVs in early embryo development, discusses their roles in mediating cell-cell communication and regulating gene expression, and explores their potential applica-tions in reproductive medicine and clinical practice, offering new perspectives for optimizing assisted reproductive technologies.

Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

To explore the differences in biological gas production in the waterlogged zone of a coal seam fire-affected area, in this study the in-situ gas production experiment was conducted with the mine water from aquitard layers in coal seam fire zones in Xinjiang. The results showed that the biogas production first increased and then decreased with the increase in distance, and the highest gas production reached 216.55 mL. The changes in key metabolic pathways during the anaerobic fermentation of coal were analyzed, which showed that as the distance from the aquitard layer in the coal seam fire zone increased, the methanogenesis pathways gradually shifted from acetic acid decarboxylation and carbon dioxide reduction to acetic acid decarboxylation and methylamine methanogenesis. The significant variability in the in-situ mine water reservoir conditions contributed to the differences. In addition, the reservoir pressure and temperature increased as the distance from the fire zone became longer, and the salinity of the farthest mine water in the reverse fault was the highest due to the lack of groundwater supply. Pearson correlation analysis revealed significant correlations of microbial communities with key functional genes and the types and concentrations of ions. The ions significantly influencing microbial enzymatic metabolic activities included Al³⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Mg²⁺, PO₄^3-, and Mo⁶⁺. The differences in metabolic pathways were attributed to the integrated effects of a co-occurring environment with multiple ions. The gas production simulation experiments and metagenomic analyses provide data support for the practical application of in-situ biogas experiments, laying a foundation for engineering applications.
Biofuels ; Coal ; Methane/biosynthesis* ; Fires ; Groundwater ; Coal Mining ; Fermentation ; China ; Anaerobiosis

Objective To explore the effects of sacral neuromodulation (SNM) on urodynamic parameters during the storage phase in patients with neurogenic bladder (NB), so as to provide reference for evaluating the efficacy of SNM. Methods A total 49 NB patients undergoing SNM at our hospital during Oct.2012 and May 2025 were enrolled. Baseline data and video-urodynamic parameters were collected. Changes in maximum cystometric capacity, maximum detrusor pressure during storage phase, and bladder compliance before and after treatment were assessed. Improvements in detrusor overactivity (DO) and vesicoureteral reflux (VUR) were also analyzed. Results Among the 49 patients,27 were male and 22 were female, with a mean age of (37.41±15.15) years, a median disease duration of 5.0 (2.0,15.5) years, and a median follow-up of 11 (1,32) months. Up to 37 patients (75.5%) received permanent sacral nerve pulse generator implantation (permanent implant group), while the remaining 12 were classified as the non-permanent implant group. Before and after the test period, all patients showed a significant increase in maximum cystometric capacity [ (218.0 (93.0,358.5) mL vs.300.0 (238.5, 400.0) mL, P<0.001], a decrease in maximum detrusor pressure during the filling phase [32.0 (13.5,71.0) cmH_2 O vs. 20.0 (9.0,50.0) cmH_2 O, P<0.001], and an improvement in bladder compliance [11.8 (8.3,25.6) mL/cmH_2 O vs.26.7 (8.6,44.1) mL/cmH_2O, P<0.001]. In the permanent implant group, comparisons before and after the test period showed an increase in maximum bladder capacity [ (239.16±147.23) mL vs. (312.24±121.83) mL, P<0.001], a decrease in maximum detrusor pressure during filling[32.0 (15.0,58.0) cmH_2 O vs.15.0 (9.0,41.0) cmH_2 O, P<0.05], and improved bladder compliance [10.8 (8.3,23.6) mL/cmH_2 O vs.28.6 (8.6,41.4) mL/cmH_2 O, P<0.001]. No statistically significant differences in these parameters before and after the test period were observed in the non-permanent implant group (P>0.05). A total of 17 patients in the permanent implant group underwent follow-up video urodynamics. Compared to pre-test values, significant improvements were observed in maximum detrusor pressure during filling, and bladder compliance both at the end of the test period and at the last follow-up (P<0.05). However, no statistically significant differences were found in maximum cystometric capacity, maximum detrusor pressure during filling, and bladder compliance between the end of the test period and the last follow-up (P>0.05). Among the 49 patients,21 had DO and 20 had VUR. Both DO and VUR showed improvement after the test period and at the last follow-up. Conclusion SNM can effectively improve storage function in NB patients, ameliorate detrusor overactivity and bladder compliance, and relieve or eliminate VUR in some patients. Long-term follow-up confirms that SNM provides stable therapeutic effects, demonstrating significant clinical value.

Objective To analyze the impact factors on the occurrence of in-hospital adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI)in elderly patients with coronary heart disease(CHD),and to construct a prediction model in the form of a column-line diagram and to evaluate the effectiveness of the model.Methods The clinical data of 304 elderly coronary heart disease patients who underwent PCI from February 2021 to March 2024 in our hospital were collected.Patients were divided into MACE group(n=81)and non-MACE group(n=223)based on the occurrence of in-hospital MACE.The optimal cutoff values of each fac-tor were obtained by receiver operating characteristic(ROC)curve analysis.Logistic multiple regression modeling was used to investigate the risk factors of in-hospital MACE after PCI in elderly patients with CHD and a predictive model with columnar graphs was constructed.The correction curve was used for the internal validation of the column chart model and the decision curve was used for evaluating the pre-diction efficacy of the column chart model.Results The proportion of angina pectoris,Gensini score,the proportion of the implanted stent number＞2,and the levels of PAG,Scr,hs-CRP,Lp-PLA2 and Lp(a)were higher in the MACE group than in the non MACE group,and the difference was statistically significant(P＜0.05).The results of ROC curve analysis showed that the optimal cut-off val-ues for Gensini integral,PAG,Scr,hs-CRP,Lp-PLA2 and Lp(a)were 21 points,38.64％,96.92μmol/L,8.56mg/L,247.67μg/L and 475.14mg/L,respectively.The results of Logistic multiple regression modeling showed that the number of implanted stents,Gensi-ni score,PAG,Scr,hs-CRP,Lp-PLA2 and Lp(a)were risk factors for the occurrence of in-hospital MACE after PCI in elderly pa-tients with CHD.Internal validation shows that the C-index of the column-line graph model constructed in this study was 0.991(0.982-0.999).The observed values aligned well with the predicted values.The column-line diagram model with a threshold＞0.08 provided net clinical benefits above the number of implanted stent,Gensini score,PAG,Scr,hs-CRP,Lp-PLA2 and Lp(a).Conclu-sion In this study,the column-line graph prediction model constructed based on the number of implantated stent,Gensini score,PAG,Scr,hs-CRP,Lp-PLA2 and Lp(a)had good predictive value for the occurrence of in-hospital MACE after PCI in elderly patients with CHD,which may provide a basis for targeted clinical interventions to reduce the occurrence of in-hospital MACE.

Objective:To investigate the molecular mechanism of miR-886-5p targeting BCL-2-associated X protein (BAX) to inhibit the proliferation, migration, and invasion of liver cancer cells.Methods:mRNA expression data of HCC patients were obtained from the Starbase database, including 370 liver cancer samples and 50 normal liver tissue samples adjacent to the cancer. Analyze the expression of miR-886-5p in the previously obtained data and investigate the relationship between miR-886-5p and BAX in liver cancer samples. After transfection of the corresponding plasmids into Huh7 and HepG2 cells, the following groups were established. Analyze the interaction between miR-886-5p and BAX in vitro, detect the protein expression by Western blotting, and verify the targeting relationship between the two by dual luciferase reporter gene assay.Results:Starbase database analysis found that the standardized expression level of miR-886-5p in 370 liver cancer samples was lower than that in normal liver tissue samples (0.12±0.07 vs. 0.73±0.27, t=-15.71, P<0.001), and the expression level of miR-886-5p was positively correlated with the expression level of BAX ( r=0.152, P=0.003). qRT-PCR analysis showed that the expression level of miR-886-5p in HL-7702 cells was higher than that in Huh7 (4.57±0.06 vs. 1.61±0.40, t=32.48) and HepG2 (4.57±0.06 vs. 1.03±0.13, t=143.9), and the expression level of BAX in HL-7702 cells was higher than that in Huh7 (4.01±0.12 vs. 1.28±0.09, t=82.20) and HepG2 (4.01±0.12 vs. 1.30±0.11, t=80.76), the differences were statistically significant (all P<0.001). The proliferation, migration, and invasion abilities of Huh7 and HepG2 cells decreased after transfection with miR-886-5p mimics, while the expression levels of BAX at the mRNA and protein levels increased. However, after inhibiting the expression of miR-886-5p, the above indicators of cells were the opposite, and the dif-ferences were statistically significant (all P<0.05). The viability, EdU positivity rate, cell migration rate, and number of transmembrane cells in the miR-886-5p+ BAX group were lower than those in the BAX group, and the relative expression levels of miR-886-5p, BAX mRNA, and BAX protein were higher than those in the BAX group. However, the above indicators in the Sponge+ BAX group showed opposite trends, and all differences were statistically significant (all P<0.05). There was a targeted binding site between miR-886-5p and BAX. Conclusion:Both miR-886-5p and BAX are downregulated in liver cancer, and miR-886-5p inhibits the proliferation, migration, and invasion of liver cancer cells by targeting BAX.

OBJECTIVE To investigate the effect and underlying mechanism of hydroxytyrosol(HT)on mouse chondrocyte injury induced by oxidative stress.METHODS Mouse chondrocytes were incubated with varying concentrations of HT 0-400 μmol L-1 for 24 h,and the viability of the mouse chondrocytes was assessed using CCK-8 kit.An oxidative stress model of chondrocytes was estab-lished by the addition of H2O2 200 μmol L-1.The experimental groups included the cell control group,H2O2 group,and H2O2+HT 10,50 and 250 μmol·L-1 groups.After 24 h,the mRNA expression levels of interleukin-6(IL-6),cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),inducible nitric oxide synthase(iNOS),matrix metalloproteinase-3(MMP-3),MMP-13,a disintegrin and metalloproteinase with throm-bospondin motifs-4(ADAMTS-4),ADAMTS-5,SRY-box transcription factor-9(SOX-9)and aggrecan(ACAN)in mouse chondrocytes were detected by real-time quantitative PCR,the intracellular reactive oxygen species(ROS)level in chondrocytes was measured with 2,7-dichlorodihydrofluorescein diace-tate(DCFH-DA)staining,while the mitochondrial membrane potential was evaluated using JC-1 staining.After 48 h,the protein expression levels of iNOS,COX-2,MMP-13,and type Ⅱ collagen(Col-2)in mouse chondrocytes were detected using Western blotting.RESULTS HT at concentrations≤350 μmol·L-1 had no significant effect on the survival of mouse chondrocytes.Compared with the cell control group,after 24 h,the mRNA expression levels of IL-6,COX-2,PGE2,iNOS,MMP-3,MMP-13,ADAMTS-4 and ADAMTS-5 in the chondrocytes of mice in the H2O2 group were increased,while the mRNA expression levels of SOX-9 and ACAN were decreased.Additionally,there was an elevation in the ROS level and a significant loss of mitochondrial membrane potential in the chondrocytes of mice.Compared with the H2O2 group,after treatment with HT 10,50 and 250 μmol·L-1,there were significant decreases in mRNA expression levels of IL-6,COX-2,PGE2,iNOS,MM P-3,MMP-13,ADAMTS-4 and ADAMTS-5,the mRNA expressions of SOX-9 and ACAN were increased,the ROS level was lowered.After treatment with HT 50 and 250 μmol L-1,the loss of mitochondrial membrane potential was ameliorated.Compared to the cell control group,the protein expressions of iNOS,COX-2 and MMP-13 were upregulated in the H2O2 group,while the protein expression of Col-2 was downregulated after 48 h.Compared to the H2O2 group,treatment with HT at concentrations of 10,50 and 250 μmol·L-1 resulted in decreased protein expressions of iNOS,COX-2 and MMP-13 in mouse chondrocytes,but the protein expression of Col-2 increased following treatment with HT 50 and 250 μmol L-1.CONCLUSION HT can ameliorate H2O2-induced chondrocyte injury by reducing intracellular ROS levels and alleviating the loss of mitochondrial membrane potential,suppressing the release of inflammatory cytokines,inhibiting catabolic processes,and promoting anabolic activities.

Objective:To investigate the safety and efficacy of trans-breast endoscopic approach for lateral neck dissection (LND) in the treatment of thyroid cancer.Methods:A retrospective analysis was conducted on 80 patients who underwent trans-breast endoscopic LND at the Second Affiliated Hospital of Zhejiang University School of Medicine from Dec. 2023 to Aug. 2024. Demographic characteristics, operative duration, postoperative complications, and pathological results were analyzed, with data presented using descriptive statistics.Results:The cohort included 7 males and 73 females, with a mean age of (30.0 ± 6.7) years. The mean diameter of thyroid cancer lesion was (1.3 ± 0.7) cm. The average operative duration was (4.6 ± 1.5) hours, with a 0.0% (0/80) rate of conversion to open surgery. Intraoperative recurrent laryngeal nerve (RLN) "loss of signal" occurred in 6.3% (5/80) of cases. The mean hospital stay was (2.3 ± 1.0) days. Postoperative complications included transient hoarseness in 3.8% (3/80) and transient hypoparathyroidism in 10.0% (8/80), with no cases of permanent hoarseness or hypoparathyroidism. The mean total number of dissected lymph nodes was 47.8 ± 18.6, with 8.3 ± 6.2 metastatic lymph nodes. The incidence of postoperative lymphatic leakage was 3.8% (3/80), and no cases of incision infection were observed. The mean visual analog scale (VAS) score for pain was 4.2 ± 0.4. The mean follow-up duration was 10.3 months, at 3-month follow-up, the cosmetic satisfaction score was 4.5 ± 0.4.Conclusions:The trans-breast endoscopic approach for LND is safe and effective, with high patient cosmetic satisfaction. With appropriate patient selection, it can be considered a viable surgical option for lateral neck dissection in the treatment of thyroid cancer.

Objective:To investigate the safety and efficacy of trans-breast endoscopic approach for lateral neck dissection (LND) in the treatment of thyroid cancer.Methods:A retrospective analysis was conducted on 80 patients who underwent trans-breast endoscopic LND at the Second Affiliated Hospital of Zhejiang University School of Medicine from Dec. 2023 to Aug. 2024. Demographic characteristics, operative duration, postoperative complications, and pathological results were analyzed, with data presented using descriptive statistics.Results:The cohort included 7 males and 73 females, with a mean age of (30.0 ± 6.7) years. The mean diameter of thyroid cancer lesion was (1.3 ± 0.7) cm. The average operative duration was (4.6 ± 1.5) hours, with a 0.0% (0/80) rate of conversion to open surgery. Intraoperative recurrent laryngeal nerve (RLN) "loss of signal" occurred in 6.3% (5/80) of cases. The mean hospital stay was (2.3 ± 1.0) days. Postoperative complications included transient hoarseness in 3.8% (3/80) and transient hypoparathyroidism in 10.0% (8/80), with no cases of permanent hoarseness or hypoparathyroidism. The mean total number of dissected lymph nodes was 47.8 ± 18.6, with 8.3 ± 6.2 metastatic lymph nodes. The incidence of postoperative lymphatic leakage was 3.8% (3/80), and no cases of incision infection were observed. The mean visual analog scale (VAS) score for pain was 4.2 ± 0.4. The mean follow-up duration was 10.3 months, at 3-month follow-up, the cosmetic satisfaction score was 4.5 ± 0.4.Conclusions:The trans-breast endoscopic approach for LND is safe and effective, with high patient cosmetic satisfaction. With appropriate patient selection, it can be considered a viable surgical option for lateral neck dissection in the treatment of thyroid cancer.