BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

Head and neck squamous cell carcinoma(HNSCC)is the sixth most common malignant tumor in the world.Due to its high incidence,poor prognosis,relapse-prone characteristics,and the existence of treatment resist-ance,HNSCC has a serious impact on patients'daily lives.As a bridge between innate immunity and adaptive immu-nity,dendritic cell(DC)plays a crucial role in tumor progression.In recent years,numerous studies have found that DC has complex and diverse functions in the tumor microenvironment(TME),and has a significant impact on the oc-currence and development of HNSCC.In this article,we provide a review of the mechanism of DC in HNSCC TME.

Objective:To observe the clinical efficacy of against-lateral correction Tuina(Chinese therapeutic massage)in treating atlanto-axial joint disorder(AAJD)and imaging changes.Methods:A total of 142 patients with AAJD were recruited.They were randomly allocated to a trial group and a control group using the random number table method,with 71 participants in each group.The trial group was treated with against-lateral correction Tuina 3 times weekly.The control group was offered conventional physical traction therapy once daily.The interventions lasted 2 weeks in both groups.The two groups of participants were observed before and after treatment for their changes in the global pain scale(GPS)score,visual analog scale(VAS)score for dizziness assessment,cervical range of motion(ROM)in rotation,and the extent of atlanto-dental displacement.Results:The GPS and VAS scores dropped after treatment in both groups(P<0.05)and were lower in the trial group than in the control group after treatment and at the follow-up(P<0.05).Participants in the trial group achieved a significant increase in the cervical ROM in rotation after treatment and at the follow-up compared to the pre-treatment value(P<0.05)and surpassed the control group(P<0.05);the control group only showed an increase in the left-side rotation(P<0.05).After the intervention,neither the intra-group nor the between-group comparison revealed significant differences in the extent of atlanto-dental displacement(P>0.05),though the trial group presented an improving tendency.Conclusion:Compared to physical traction,the against-lateral correction Tuina method works more significantly in improving pain,dizziness,and ROM in AAJD patients.

Objective To explore the injury types,associated injuries,and correlations of the lateral meniscus posterior root(LMPR),and to improve the comprehensive understanding of LMPR and its associated injuries.Methods The patients with LMPR who underwent knee MRI examination were retrospectively selected.A total of 223 patients with LMPR injury were classified into 4 types.The integ-rity of the meniscofemoral ligament and the grading of the cartilage injuries in the lateral tibiofemoral compartment were recorded.The relationship between the types of LMPR injury and the lateral meniscus tear locations,as well as lateral meniscus extrusion were analyzed.The relationship between the integrity of the meniscofemoral ligament and lateral meniscus extrusion was analyzed.The correlation between the time to clinical presentation after injury and the grading of the cartilage injuries was analyzed in patients with anterior cruciate ligament(ACL)ruptures.Results The incidence of LMPR injury was 1.02％,with males affected 2.19 times more frequently than females.Among patients with ACL ruptures,the incidence was 13.17％.Both type Ⅰ and type Ⅱ LMPR inju-ries predominantly involved only the posterior root,while type Ⅲ injuries mainly affected the posterior root extending to the posterior horn and body.The incidence of the lateral meniscus extrusion was higher in type Ⅲ LMPR injury than in type Ⅱ.When the menis-cofemoral ligament was not intact,the incidence of the lateral meniscus extrusion increased.In patients with ACL ruptures,a longer time to clinical presentation after injury was associated with more severe cartilage injuries grading in the lateral tibiofemoral compart-ment.Conclusion Males are more susceptible to LMPR injuries than females.The classification of LMPR injuries is correlated with the location of the lateral meniscus tears and the incidence of the lateral meniscus extrusion.The integrity of the meniscofemoral lig-ament is related to the incidence of the lateral meniscus extrusion.The time to clinical presentation after injury is related to the sever-ity of cartilage injury in ACL rupture patients.

Objective To investigate the neuroprotective effect of rhein(RHE)on ischemic mice and its potential mechanism of reducing inflammatory response and neuronal apoptosis by inhibiting Notch/nuclear factor(NF)-κB signaling pathway.Methods The classical middle cerebral artery occlusion(MCAO)method was used to construct ischemic stroke mouse models.The mice were randomly divided into 5 groups including the sham operation group(sham),the model group(MCAO),the MCAO+edaravone group(Eda),the MCAO+RHE-treated group(RHE),and the MCAO+RHE+Notch activitor Jagged 1 group(RHE+J).Each group has 18 mice.The Bederson scoring system,balance beam walking test and accelerated rotating rod test were used to assess the neurological function and locomotor ability of mice in each group.2,3,5-triphenyltetrazolium chloride(TTC)staining,hematoxylin eosin staining,and TUNEL method were used to assess cerebral infarction,hippocampal morphological damage,and neuronal apoptosis.ELISA was used to analysis the levels of interleukin(IL)-6 and tumor necrosis factor α(TNF-α)in hippocampal tissue.Western blotting was used to analysis caspase-3,Notch 1,Hes1,and NF-κB p65 protein expression.Results Compared with the sham group,Bederson score,balance beam score,cerebral infarct volume,IL-6 and TNF-α levels,the proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression were significantly increased in the MCAO group,whereas the latency to fall decreased significantly(P＜0.05).Compared with the MCAO group,Bederson score,balance beam score,cerebral infarct volume,IL-6 and TNF-α levels,proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression were significantly lower in both Eda and RHE groups,whereas the latency to fall increased significantly(P＜0.05).Compared with the RHE group,Bederson score,balance beam score,cerebral infarction volume,IL-6 and TNF-α levels,the proportion of TUNEL-positively stained cells,caspase-3,Notch1,Hes1,and p-NF-κB p65 protein expression increased significantly in the RHE+J group,whereas the latency to fall decreased significantly(P＜0.05).Conclusion Rhein can significantly improve nerve function in ischemic mice by inhibiting Notch/NF-κB signaling pathway activation,suggesting that rhein has potential clinical application value.

Objective:To analyze the research hotspots and trends in the stigmatization of adolescents living with HIV/AIDS.Methods:Relevant literature was retrieved from the Web of Science Core Collection database, with the search covering from database inception to May 1, 2024. CiteSpace software was used to conduct bibliometric analysis, including the distribution of countries, institutions, authors, keywords, and cited references. Knowledge maps were generated to visualize the findings.Results:A total of 414 articles were included in the analysis. The number of publications has shown an overall upward trend. The United States had the highest number of publications (244 articles), the most productive institution was University of Cape Town (31 articles), and the most productive author was Linda-Gail Bekker (9 articles). Research hotspots mainly focused on stigmatization, behavioral patterns, mental health, treatment adherence, social support, and intervention models.Conclusions:Research on the stigmatization of adolescents living with HIV/AIDS is currently at a critical stage. Future studies should continue to explore the multidimensional impact of stigma and focus on the development of region-specific and individualized intervention models, while actively constructing a comprehensive support system within the field of public health.

Background and purpose:Diffuse large B-cell lymphoma(DLBCL)is subclassified into germinal center B-cell-like(GCB)and non-GCB subtypes,which differ in prognosis and treatment response.However,current distinction still relies on invasive pathological assays.This study developed radiomics and deep-learning models based on multiparametric magnetic resonance imaging(MRI)to non-invasively differentiate the two subtypes preoperatively,thereby reducing dependence on histopathological examination.Methods:This study retrospectively included patients with pathologically confirmed DLBCL diagnosed at Huashan Hospital,Fudan University,and other institutions between March 2013 and December 2024.Using multiparametric MRI data,we developed DLBCL-subtype classification models that combined 4 radiomics-based machine-learning algorithms:support vector machine(SVM),logistic regression(LR),Gaussian process(GP)and Naive Bayes(NB),with 3 deep-learning architectures[densely-connected convolutional networks 121(DenseNet121),residual network 101(ResNet101)and EfficientNet-b5].Additionally,two radiologists with different experience levels independently classified DLBCL on MRI in a blinded fashion.Model and radiologist performance were quantified using the area under the receiver operating characteristic curve(AUC),accuracy(ACC),and F1-score to evaluate their ability to distinguish GCB from non-GCB subtypes.This study was approved by the Ethics Committee of Huashan Hospital of Fudan University(No.KY2024-663),and all patients signed informed consents.Results:A total of 173 patients were enrolled(55 with GCB subtype and 118 with non-GCB subtype).Radiomics and deep learning methods effectively distinguished DLBCL subtypes.Among these,the GP radiomics model(based on T1-CE+T2-FLAIR+ADC sequences)and DenseNet121 deep learning model(based on T1-CE+T2-FLAIR+ADC sequences)demonstrated optimal performance.Both achieved excellent results on the internal validation set(GP:AUC=0.900,ACC=0.896,F1=0.840;DenseNet121:AUC=0.846,ACC=0.854,F1=0.774)and maintained robustness on the external validation set.Furthermore,the classification efficacy of the optimal AI model surpassed that of experienced radiologists(highest physician AUC=0.678).Conclusion:Radiomics and deep-learning models based on multiparametric MRI features can effectively differentiate GCB from non-GCB subtypes of DLBCL.Among them,GP and DenseNet121 exhibit outstanding performance,especially when integrating multi-sequence feature sets for classifying DLBCL subtypes on complex imaging data.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.