Bacterial extracellular vesicles (BEVs) are nanoscale, lipid bilayer-enclosed vesicles that are actively or passively released by bacteria. They carry diverse bioactive cargos, including proteins, nucleic acids, and lipids, and mediate information exchange between microbial communities and hosts. Increasing evidence indicates that BEVs play important roles in the initiation and progression of dental caries and periodontitis. In dental caries, BEVs derived from cariogenic bacteria such as Streptococcus mutans can promote biofilm formation and maturation, enhance the acidic microenvironment, and exacerbate demineralization of dental hard tissues. In periodontitis, BEVs released by key periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, may disrupt the mucosal barrier, trigger inflammatory responses, and activate bone resorption-related pathways, thereby promoting periodontal tissue destruction. Owing to their detectability, BEVs in oral samples such as saliva, dental plaque, and gingival crevicular fluid show promise as diagnostic biomarkers and also provide new therapeutic opportunities for targeted interventions. In addition, emerging studies suggest that oral BEVs may contribute to distal inflammatory amplification through an “oral-systemic axis”; therefore, while focusing on the local pathogenic mechanisms of BEVs in dental caries and periodontitis, this review also briefly outlines their potential systemic implications as an extension. Overall, BEVs may offer novel mechanistic insights and translational directions to support precise prevention and management of dental caries and periodontitis.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

Objective To investigate the effect of hyperglycemia activated CCAAT enhancer binding protein β(C/EBPβ)promoting the expression of thyroid hormone nuclear receptor α1(THα1)on diabetic cardiomyopathy(DCM).Methods Twenty healthy male Wistar rats were randomly divided into diabetes mellitus(DM,n=10)group and DCM(n=10)group.Cardiomyocyte were divided into four groups:DM-cell,glucose intervention(Glu),knockdown C/EBPβ group(cardiomyocyte were transfected with plasmids targeting knockdown C/EBPβ)and si-NC group(cardiomyocyte were transfected with nagetive control sequence of plasmids).HE and Masson staining was performed to detect myocardial injury and collagen deposition.Echocardiography was used to evaluate left ventricular function.The mRNA and protein expression of C/EBP β and THα1 was detected using RT-qPCR,Western blot and immunofluorescence staining in myocardial cells.Apoptosis was analyzed using flow cytometric.Contraction frequency was counted by microscopy.Results Compared to DM group,count of fibroblasts,collagen volume fraction,end-systolic dimension of left ventricular,and the mRNA and protein expression of C/EBPβ and THα1 as well as fluorescence intensity increased(P<0.05);left ventricular ejection fraction and left ventricular fractional shortening(LVFS)decreased in DCM group(P<0.05).The mRNA and protein expression of C/EBPβ and THα1 were higher in the Glu group than in DM-cell group(P<0.05).The percentage of apoptosis,the mRNA and protein expression of THα1 of myocardial cells were lower in the si-C/EBPβ group than in the si-NC group(P<0.05),and LVFS was higher in the si-NC group(P<0.05).Conclusions High glucose regulates C/EBPβ expression,which in turn drives THα1 expression in myocardial tissue,leading to adverse effects on myocardial tissue.Conversely,silencing C/EBPβ downregulates THα1 expression,and exerts a protective effect on cardiomyocytes.

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.

Objective To explore the feasibility of using cell-free DNA(cfDNA)in blastocyst fluid for preimplantation embryo aneuploidy.Methods A total of 17 patients undergoing assisted reproductive technology at Taizhou Hospital of Zhejiang from 2023 to 2024.A total of 38 discarded blastocysts were collected.Whole-genome amplification and next-generation sequencing were performed on both blastocyst fluid cfDNA and trophoblast cells.Using the trophoblast cells as reference,the amplification success rates of blastocyst fluid cfDNA were compared.The consistency,specificity,and sensitivity of the detection results were evaluated.Results The success rate of cfDNA amplification in the blastocyst fluid was 78.95％,and that of the trophoblast cells was 90.61％,with a consistency of 57.1％.The sensitivity of cfDNA amplification in the blastocyst fluid was 100％,the specificity was 66.7％,the positive likelihood ratio was 3,and the negative likelihood ratio was 0.Conclusion Blastocyst fluid cfDNA screening can be used as a screening method to exclude chromosomal embryos aneuploidy and can be used for preimplantation embryo selection.

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To explore the trend of influenza positive rate in Beijing by using classic autoregressive integrated moving average (ARIMA) model, autoregressive integrated moving average model with exogenous variables (ARIMAX) and vector autoregression model (VAR) to compare the performance of three models in influenza prediction and select the most suitable one for Beijing.Methods:The weekly positive rate of influenza virus nucleic acid test and meteorological data in Beijing from week 1 of 2013 to week 40 of 2024 were collected. The data were divided into four groups with expanding training sets and corresponding testing sets. The training set of the first group was from week 1 of 2013 to week 40 of 2016, and the testing set was from week 41 of 2016 to week 40 of 2017. Subsequent groups extended the training set by one year each time. Data from 2020 to 2023 were excluded due to COVID-19 pandemic. The fourth group used data from the week 1 of 2013 to week 40 of 2023 for training and from the week 41 of 2023 to week 40 of 2024 for testing.Results:The incidence of influenza had seasonality in Beijing with higher incidence in winter and spring. The positive rate of influenza virus was positively correlated with the weekly average atmospheric pressure ( r=0.482, P<0.001) and weekly average wind speed ( r=0.003, P=0.034), and negatively correlated with the weekly average temperature ( r=-0.541, P<0.001). The ARIMAX model incorporating meteorological factors had the best prediction performance, with test set's root mean square error ( RMSE) of 0.115 3 and mean absolute error ( MAE) of 0.076 7 (the RMSE and MAE values for ARIMA and VAR models were 0.117 1 and 0.163 8, and 0.078 6 and 0.122 3, respectively). The prediction results of the optimal model showed that the positive rate of influenza virus would continue to rise in Beijing after October 2024 and reach peak in the second week of 2025, but the peak positive rate would be lower than that of previous influenza season. Conclusions:Compared with the ARIMA model and the VAR model,the ARIMAX model which used meteorological parameters is more suitable for prediction of long-term influenza trend in Beijing. The influenza trend peak was predicted to occur in the second week of 2025, but lower than that in previous influenza season.

Objective:To evaluate the perceived level of home exercise behavior in elderly patients with ovarian cancer and analyze its influencing factors, so as to promote home exercise behavior of patients and improve the quality of life.Methods:A total of 227 elderly patients with ovarian cancer from January 1, 2021 to October 1, 2023 in the First Affiliated Hospital, School of Medicine, Zhejiang University were selected by convenience sampling method. A cross-sectional survey was conducted by General Information Questionnaire, Exercise Benefits/Barriers Scale (EBBS), Social Support Rating Scale (SSRS), General Self-efficacy Scale (GSES) and Brief Fatigue Inventory (BFI). The influencing factors on the perceived level of home exercise behavior in elderly patients with ovarian cancer were analyzed.Results:There were 227 elderly female patients with ovarian cancer, including 151 patients aged<70 years old and 76 patients aged ≥70 years old. The scores of EBBS, SSRS, GSES, BFI were (123.37±11.02), (37.68±7.44), (29.35±6.54), (5.82±2.01) points. The perception of exercise behavior was positively correlated with general self-efficacy and social support ( r=0.752, 0.901, both P<0.01), was negatively correlated with cancer-related fatigue ( r=-0.198, P<0.01). The results showed that general self-efficacy, social support, age≥70 years old, no spouse, not being informed of the benefits of exercise,fatigue due to moderate and severe cancer, duration of disease ≥12 months were the influencing factors ( t values were -4.56 - 4.46, all P<0.05). Conclusions:Elderly patients with ovarian cancer need to improve their perception level of home exercise behavior. In the formulation of home exercise behavior for elderly patients with ovarian cancer, education and cognition on the perceived benefits of home exercise behavior should be strengthened, and patients′ physical and mental status should be evaluated before exercise to actively reduce cancer-related fatigue. At the same time, the combination of family support can improve the perceived level of exercise behavior of elderly patients with ovarian cancer at home, so as to promote home exercise behavior of patients.

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.