ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Objective: To explore the related factors of college students social network addiction based on problem behavior theory, so as to provide a basis for improving social networking addiction in this population. Methods: From May to June 2023, a method combining convenient sampling and cluster random sampling was used to select 1 768 college students from five universities in Shanghai for a questionnaire survey on social networking addiction, self esteem, loneliness, depressive symptoms, social support, interpersonal needs, sense of distress and frustration; at the same time, the physical exercise, smoking and drinking of college students were investigated. Multivariate Logistic regression analysis was applied to explore the association between the three systems of the problem behavior theory (personality, behavior, and social environment) and social networking addiction among college students. Results: The score on the Social Network Addiction Tendency Scale was (21.08±6.29) among college students, and the detection rate of social networking addiction was 66.29%. After adjusting for gender, family economic status, parental divorce status, and whether being an only child, multivariate Logistic regression analysis showed that in the personality system, higher loneliness ( OR =1.66) and higher depressive symptoms ( OR =2.18) were associated with increased risk of social networking addiction among college students; in the behavior system, alcohol consumption ( OR =1.42) was associated with higher risk of soical networking addiction compared to non drinkers; and in the social environment system, low social support ( OR =1.43) was associated with increased risk of social networking addiction (all P <0.05). Conclusions The rate of social networking addiction among college students is relatively high, and the systems of personality, behavior, and social environment are all related to social network addiction. Providing social support, cultivating healthy lifestyle habits, and increasing interpersonal interactions may help reduce excessive dependence on social networking among college students.

Objective To explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n＝75) and the non-sepsis group (n＝45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P＜0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P＜0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR＝1.12, 95% CI 1.07–1.17, P＜0.001). Survival analysis demonstrated that patients with E/e′ ＞10.9 had lower 28-day survival rates (P＝0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P＜0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.

ObjectiveTo explore the 28-day mortality risk of Klebsiella pneumoniae (KP) bloodstream infections (BSI) and its related influencing factors, thereby providing a scientific basis for the effective control of KP-BSI and improvement of patient prognosis. MethodsFrom January 2018 to December 2024, a retrospective review was conducted on hospitalized patients aged >18 years old treated for KP-BSI at a tertiary hospital in Hangzhou. Logistic and Cox regression analyses were performed to identify the epidemiological characteristics and the risk factors for the 28-day mortality associated with KP-BSI. ResultsA total of 123 patients with KP-BSI were included in this study, comprising 64 cases infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) and 59 cases infected with carbapenem-susceptible Klebsiella pneumoniae (CSKP). Compared with CSKP-BSI, patients with CRKP-BSI more frequently presented with chronic pulmonary disease (χ²=4.29, P=0.038), concomitant infections at other sites (χ²=10.90, P=0.001), and a higher frequency of invasive procedures prior to infection (central venous catheterization, mechanical ventilation, and indwelling urinary catheter), as well as glucocorticoid use, hemodialysis, and blood transfusion (all P<0.05). The 28-day mortality was significantly higher in BSI cases caused by CRKP compared to that caused by CSKP (37.50% vs 5.08%, P<0.001). Cox regression analyses revealed that carbapenem resistance (HR=6.67, 95%CI: 1.48‒30.08, P=0.014) and blood transfusion (HR=3.58, 95%CI: 1.15‒11.19, P=0.028) were risk factors for the 28-day mortality in KP-BSI, while removal of central venous catheters after infection (HR=0.24, 95%CI: 0.08‒0.67, P=0.006) was associated with a reduced risk for the 28-day mortality. ConclusionCarbapenem resistance is associated with mortality outcomes in patients with KP-BSI. Strengthening infection control measures targeting the identified risk factors for CRKP-BSI may improve patient prognosis.

Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

ObjectiveTo define hyaluronidase treatment parameters that efficiently remove the extracellular matrix from zygotes without impairing embryo development， thereby providing a basis for standardized assisted reproductive procedures. MethodsMouse zygotes were treated with hyaluronidase at 40， 80， or 120 IU/mL for 60， 90， or 120 s. Following treatment， embryos were cultured in Krebs-ringer bicarbonate-based solution for organismal media （KSOM） medium， and blastocyst formation was monitored using a Time-lapse imaging system. ResultsA concentration of 40 IU/mL was insufficient for effective matrix removal， whereas 120 IU/mL markedly reduced blastocyst formation. In contrast， 80 IU/mL achieved efficient matrix clearance with minimal impact on development. Blastocyst rates were comparable between the 60 s and 90 s groups， with a slight advantage for the 60 s under the experimental conditions. ConclusionHyaluronidase treatment at 80 IU/mL for 60 s represents optimal processing conditions for mouse zygotes. These findings provide experimental basis and standardized reference for embryo handling in assisted reproductive technologies.

ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer （CAC） by constructing an azoxymethane （AOM）/dextran sulfate sodium （DSS）-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal， model， and polydatin groups （0.045 g·kg^-1）. The CAC mouse model was established using AOM/DSS， and samples were collected at 4， 7， and 10 weeks. Body weight change rate， disease activity index （DAI）， and tumor formation were assessed. Hematoxylin-eosin （HE） staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry （IHC） was performed to detect zonula occludens-1 （ZO-1） expression in colonic tissues， and Western blot was used to detect the expression of E-cadherin， N-cadherin， and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A （IL-17A）， Wnt3a， β-catenin， T cell factor 1 （Tcf1）， E-cadherin， N-cadherin， and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8⁺T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium， and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A （IL-17RA）， Wnt3a， β-catenin， Tcf1， E-cadherin， N-cadherin， and Vimentin in DLD-1 cells. ResultsCompared with the normal group， the model group at all three time points showed significantly decreased body weight change rate （P<0.01）， significantly shortened colon length （P<0.01）， and markedly increased DAI scores （P<0.01）. HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group， accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced （P<0.01）. The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway （Wnt3a， β-catenin， Tcf1） was significantly elevated （P<0.05）. The mRNA and protein expression of epithelial-mesenchymal transition （EMT） markers N-cadherin and Vimentin was significantly upregulated （P<0.05）， while E-cadherin expression was significantly downregulated （P<0.05）. The proportion of tumor-infiltrating CD8⁺T cells expressing immunosuppressive molecules （TIM-3， LAG-3， PD-1） was significantly increased （P<0.05）. Compared with the model group， the polydatin group showed significant improvement in body weight and DAI score （P<0.01）， as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased （P<0.01）， while IL-17A， Wnt3a， β-catenin， Tcf1， N-cadherin， and Vimentin expression levels were significantly decreased （P<0.05）， and E-cadherin expression was significantly increased （P<0.01）. Tumor-infiltrating CD8⁺ T cells expressing immunosuppressive molecules were significantly reduced （P<0.05）. In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells （P<0.01） and reversed the upregulation of IL-17RA， Wnt3a， β-catenin， N-cadherin， and Vimentin mRNA， as well as the downregulation of E-cadherin mRNA （P<0.05）. ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression， improves the immune microenvironment， blocks activation of the Wnt/β-catenin signaling pathway， suppresses EMT markers （N-cadherin and Vimentin）， and restores tight junction protein expression in intestinal epithelial cells， thereby delaying the progression from colitis to colorectal cancer in mice.

Lonicerae Japonicae Flos refers to the dried flower buds or flowers about to open of Lonicera japonica （Caprifoliaceae）. Its dried flower buds or early blooming flowers are listed in the Pharmacopoeia of the People's Republic of China （2020 edition） as official medicinal materials. As a Chinese medicine with "heat-clearing and detoxifying" properties and a classic medicinal-edible resource， it is mainly produced in northern authentic producing regions such as Shandong， Henan， and Hebei in China. Lonicerae Japonicae Flos contains abundant bioactive substances that are considered safe and effective， with functions including relieving sore throat， antibacterial and anti-inflammatory effects， and immune regulation. In recent years， with the modernization of traditional Chinese medicine （TCM） and the rapid development of the "big health" industry， Lonicerae Japonicae Flos has become a research hotspot in the fields of natural medicines and functional foods due to its multi-target pharmacological activities and broad application potential. To date， chemical constituents identified from Lonicerae Japonicae Flos include organic acids， flavonoids， iridoids， triterpenes， triterpenoid saponins， and volatile oils. Modern pharmacological studies have shown that Lonicerae Japonicae Flos possesses anti-inflammatory， antibacterial， antioxidant， antiviral， antidiabetic， cardiovascular and neuroprotective， and immunomodulatory activities. In terms of modern applications， Lonicerae Japonicae Flos has developed into a full industrial chain covering pharmaceuticals， health products， daily chemical products， and food additives， demonstrating high medicinal and health value. Strengthening the development of Lonicerae Japonicae Flos-based health products is of great significance. Based on relevant domestic and international literature， this paper systematically reviews the innovative applications of Lonicerae Japonicae Flos in traditional medicine， modern clinical formulations， health foods， and daily chemical products from the perspectives of chemical composition， pharmacological effects， and modern applications， aiming to further deepen basic research on Lonicerae Japonicae Flos. Meanwhile， this paper analyzes and proposes suggestions for promoting applied research on Lonicerae Japonicae Flos， in order to provide a scientific basis for its sound development and to offer references for the rational development and comprehensive utilization of medicinal and edible resources.

BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.