Aim To explore the protective effect of the isochroman compound Asperisochroman B(AB)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury of neurons based on the PI3K/AKT/Foxo1 path-way and to reveal the related mechanism.Methods Primary neurons were cultured and the OGD/R model was constructed.The primary neurons were divided in-to the blank control group,OGD/R group,and AB low,medium,and high concentration(3,10,30 μmol·L-1)groups.The effects of AB on primary neurons were determined by CCK-8 assay,lactate dehydrogen-ase(LDH)release assay,and Hoechst 33342 stai-ning.The expression levels of PI3K,AKT,and Foxo1-related proteins were detected by Western blot.After intervention with the PI3K inhibitor(LY294002)and re-modeling and intervention with high concentra-tion of AB(30 μmol·L-1),the expression of PI3K/Foxo1 pathway-related proteins was detected by West-ern blot.Results Compared with the OGD/R group,AB could significantly increase the cell survival rate of primary neurons and reduce the release of LDH.The results of Hoechst 33342 and immunofluorescence stai-ning showed that AB reduced apoptosis after OGD/R injury.Western blot results showed that compared with the OGD/R group,after AB intervention,the expres-sion levels of Bcl-2 and NeuN proteins in neurons sig-nificantly increased(P＜0.01),and the expression level of Bax protein significantly decreased(P＜0.01).At the same time,it upregulated the expres-sion levels of p-AKT and PI3K proteins,promoted Foxo1 phosphorylation,and downregulated the expres-sion of Foxo1.Compared with the high-dose AB group,LY294002 could inhibit the changes of the a-bove indicators and reverse the protective effect of AB on OGD/R-injured primary neurons.Conclusions AB can alleviate oxygen-glucose deprivation/reoxygen-ation-induced neuronal injury,and its mechanism may be related to the activation of the PI3K/AKT/Foxo1 signaling pathway.

Objective To develop a nomogram diagnostic model to differentiate peripheral small cell lung cancer(PSCLC)from peripheral lung adenocarcinoma(PADC)using clinical and multi spiral computed tomography features.Methods A retrospective analysis was conducted on the CT characteristics and clinical presentations of 50 PSCLC and 100 PADC.Univariate and multivariate logistic regression analyses were employed to identify significant features.A nomogram was constructed to quantify the influencing factors.The efficacy and clinical applicability of the model were assessed using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Smoking,neuron-specific enolase(NSE),smooth margin,spindle/branching shape,and lymphadenopathy were independent risk factors for PSCLC(P＜0.05),whereas rough margin and lobulation sign were independent risk factors for PADC(P＜0.05).The nomogram model demonstrated high diagnostic efficacy,and the calibration curve exhibited a good degree of calibration(Brier=0.079).The DCA indicated that the nomogram model possesses substantial clinical utility.Conclusion The nomogram model developed based on six indicators,including smoking,NSE≥17 ng/mL,margin characteristics,spindle/branching shape,lobulation sign,and lymphadenopathy can well distinguish PSCLC from PADC.

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

Objective To develop a nomogram diagnostic model to differentiate peripheral small cell lung cancer(PSCLC)from peripheral lung adenocarcinoma(PADC)using clinical and multi spiral computed tomography features.Methods A retrospective analysis was conducted on the CT characteristics and clinical presentations of 50 PSCLC and 100 PADC.Univariate and multivariate logistic regression analyses were employed to identify significant features.A nomogram was constructed to quantify the influencing factors.The efficacy and clinical applicability of the model were assessed using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Smoking,neuron-specific enolase(NSE),smooth margin,spindle/branching shape,and lymphadenopathy were independent risk factors for PSCLC(P＜0.05),whereas rough margin and lobulation sign were independent risk factors for PADC(P＜0.05).The nomogram model demonstrated high diagnostic efficacy,and the calibration curve exhibited a good degree of calibration(Brier=0.079).The DCA indicated that the nomogram model possesses substantial clinical utility.Conclusion The nomogram model developed based on six indicators,including smoking,NSE≥17 ng/mL,margin characteristics,spindle/branching shape,lobulation sign,and lymphadenopathy can well distinguish PSCLC from PADC.

Aim To explore the protective effect of the isochroman compound Asperisochroman B(AB)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury of neurons based on the PI3K/AKT/Foxo1 path-way and to reveal the related mechanism.Methods Primary neurons were cultured and the OGD/R model was constructed.The primary neurons were divided in-to the blank control group,OGD/R group,and AB low,medium,and high concentration(3,10,30 μmol·L-1)groups.The effects of AB on primary neurons were determined by CCK-8 assay,lactate dehydrogen-ase(LDH)release assay,and Hoechst 33342 stai-ning.The expression levels of PI3K,AKT,and Foxo1-related proteins were detected by Western blot.After intervention with the PI3K inhibitor(LY294002)and re-modeling and intervention with high concentra-tion of AB(30 μmol·L-1),the expression of PI3K/Foxo1 pathway-related proteins was detected by West-ern blot.Results Compared with the OGD/R group,AB could significantly increase the cell survival rate of primary neurons and reduce the release of LDH.The results of Hoechst 33342 and immunofluorescence stai-ning showed that AB reduced apoptosis after OGD/R injury.Western blot results showed that compared with the OGD/R group,after AB intervention,the expres-sion levels of Bcl-2 and NeuN proteins in neurons sig-nificantly increased(P＜0.01),and the expression level of Bax protein significantly decreased(P＜0.01).At the same time,it upregulated the expres-sion levels of p-AKT and PI3K proteins,promoted Foxo1 phosphorylation,and downregulated the expres-sion of Foxo1.Compared with the high-dose AB group,LY294002 could inhibit the changes of the a-bove indicators and reverse the protective effect of AB on OGD/R-injured primary neurons.Conclusions AB can alleviate oxygen-glucose deprivation/reoxygen-ation-induced neuronal injury,and its mechanism may be related to the activation of the PI3K/AKT/Foxo1 signaling pathway.

Aim To explore the relevant mechanisms of isoliquiritigenin(ISL)in inhibiting the proliferation and migration of vascular smooth muscle cells(VSMCs)by regulating the GRB2/ERK signaling pathway.Methods Human primary vascular smooth muscle cells(hVSMCs)were cultured,and stimulated with different concentrations of ISL and fixed concen-trations of growth factors PDGF-BB and EGF,respec-tively.Subsequently,the effect of overexpressing GRB2 on the efficacy of ISL was observed.CCK-8 assay was used to detect cell proliferation;BrdU assay was used to detect DNA synthesis;Western blot was used to de-tect the expression levels of OPN,ICAM-1,VCAM-1,GRB2,ERK1/2,and p-ERK1/2;wound healing assay was used to detect cell migration;transwell assay was used to detect cell invasion.Results Compared with the blank control group and the ISL 20 mg·L-1 group,the PDGF-BB group and the EGF group showed increased cell viability and DNA synthesis,decreased cell migration distance,and increased number of inva-sive cells.Additionally,the expression levels of GRB2 and p-ERK1/2 increased.Compared with the PDGF-BB 40 μg·L-1group or the EGF 10 mg·L-1 group,the ISL drug intervention group showed decreased cell viability and DNA synthesis,increased migration dis-tance of cells,decreased number of invasive cells,and decreased expression levels of GRB2 and p-ERK1/2.Compared with the ISL 20 mg·L-1+PDGF-BB and ISL 20 mg·L-1+EGF groups,the groups with ISL+PDGF-BB+pcDNA-GRB2 group and ISL+EGF+pcDNA-GRB2 group showed increased expression lev-els of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Compared with the ISL+PDGF-BB+pcDNA-GRB2 group and the ISL+EGF+pcDNA-GRB2 group,the pcDNA-GRB2+PDGF-BB group or the pcDNA-GRB2+EGF group showed increased expres-sion levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Conclusions Isoliquiritigenin inhibits the proliferation and migration of vascular smooth mus-cle cells by regulating the GRB2/ERK signaling path-way.

Objective:To explore the diagnostic value of shear wave elastography(SWE)for clinically significant prostate cancer(csPCa).Methods:We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer(PCa)in Baoji Central Hospital from June 2017 to July 2023.All the patients underwent the following examinations in the order of serum prostate-spe-cific antigen(PSA)testing,transrectal ultrasonography(TRUS),measurement of the stiffness of the entire prostate gland by SWE,and TRUS-guided prostate puncture biopsy.The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base,middle,and apex of the prostate,including the maximum Young's modulus(Emax),mean Young's modulus(Emean),and minimum Young's modulus(Emin).We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results,focusing on their diagnostic performance for csPCa.Results:Of the 359 cases,189 were diag-nosed by pathological puncture biopsy as BPH,26 as non-csPCa,and 144 as csPCa.The PSA level,Emax,Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups(all P＜0.01),but showed no statistically significant difference between the BPH and non-csPCa groups(all P＞0.05).The area under the receiver operating characteristic curve(AUC),optimal cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accura-cy of Emax in the diagnosis of csPCa were 0.852,143.92 kPa,72.22％,84.65％,75.91％,81.98％and 79.67％;those of Emean were 0.868,82.42 kPa,67.36％,91.16％,83.62％,80.66％and 81.62％;and those of Emin were 0.682,32.73 kPa,47.22％,89.30％,73.91％,71.54％and 72.14％,respectively.In the non-csPCa group,Emax,Emean and Emin were found be-low the optimal cut-off value in 73.08％(19/26),92.31％(24/26)and 88.46％(23/26),respectively.Conclusion:The stiff-ness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa,reduces unnecessary detection of non-csPCa,and provides some reference for its active surveillance.

The pathogenesis of central precocious puberty(CPP)is due to the early initiation of the function of the hypothalamic-pituitary-gonadal axis,which is driven by the gonadotrophin-releasing hor-mone(GnRH)from the hypothalamus.The increase of GnRH secretion will promote the secretion of gon-adotropin by the pituitary gland,which leads to the development of reproductive organs and the secretion of sex hormones.The timing of puberty onset is influenced by the interaction between nutritional,envi-ronmental,and socioeconomic factors.In the study of pathogenic genes,loss-of-function mutations of MKRN3,LIN28 and DLK1 genes can lead to early onset of puberty,among which loss-of-function muta-tions of MKRN3 are one of the most common single-gene causes of familial CPP.Since 2013,when the MKRN3 mutation was first identified in five CPP families,the role of MKRN3 in adolescence has gradu-ally been discovered.MKRN3 is a member of the E3 ubiquitin ligase family and is expressed in the cen-tral nervous system of many eukaryotes.MKRN3 may act as an E3 ubiquitin ligase to inhibit GnRH activ-ity.Recently,more and more studies have explored the molecular mechanism of MKRN3 in CPP,revea-ling a variety of genes and proteins that interact with MKRN3.For example,MKRN3 can inhibit KISS1 and TAC3 activities,thereby affecting the expression of kisspeptin and neurokinin B to regulate GnRH se-cretion.MKRN3 also inhibited GNRH1 mRNA translation through PABPC1 ubiquitination.In addition,there are other targets such as MBD3,IGF2BP1 and NPTX1,all of which are involved in GnRH regula-tion downstream of MKRN3.Upstream of MKRN3,miR-30 can bind to three sites in the 3'-untranslated region of the MKRN3 gene to block MKRN3 transcription.Here we review the role of MKRN3 in the path-ogenesis of CPP and the research progress of its molecular mechanism,which will help to better under-stand the pathogenesis of CPP,provide new ideas and treatment methods for CPP-related fields in the fu-ture,and lay a theoretical foundation for further exploration of the molecular mechanism of MKRN3.

Objective To investigate the efficacy of an interpretable integrated learning model combining clinical indicators,CT image features and radiomics features for the differential diagnosis of lung squamous cell carcinoma and adenocarcinoma,so as to provide references for clincal treatment decisions.Methods A retrospective analysis was conducted on clinical and imaging data from 220 patients(231 lesions)with primary non-small cell lung cancer at Jiangjin Central Hospital of Chongqing(Center 1)and 83 patients(84 lesions)at Chongqing General Hospital(Center 2).In Center 1,the squamous cell carcinoma group consisted of 60 patients(60 lesions),while the adenocarcinoma group included 160 patients(171 lesions).In Center 2,the squamous cell carcinoma group comprised 18 patients(18 lesions),and the adenocarcinoma group involved 65 patients(66 lesions).The patients were categorized into squamous cell carcinoma and adenocarcinoma groups based on pathological findings.Center 1 was randomly partitioned into a training set and a validation set at a 7∶3 ratio,while Center 2 served as the independent test set.Firstly,a deep learning model,VB-Net,was used to automatically segment the tumor region on the lung window image;secondly,the SMOTE(synthetic minority oversampling technique)method was used to balance the categories in the training set and standardize the extracted features with Z-scores;thirdly,the least absolute shrinkage and selection operator(LASSO)were used to select the optimal radiomics features and calculate the radiomics score(Radscore),and univariate and multivariate logistic regression was used to screen clinical indicators and independent clinical factors for differentiating lung squamous cell carcinoma and adenocarcinoma in CT image features;finally,three ensemble learning algorithms(AdaBoost,Bagging decision tree and XGBoost)were used to combine independent clinical factors and Radscore to construct the model.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of the models.SHAP technique was used to analyze the feature contribution and model decision-making process.Results Among the evaluated ensemble models,AdaBoost and Bagging decision trees demonstrated overfitting tendencies.In contrast,the XGBoost model showed the best performance,achieving AUC values of 0.939,0.887 and 0.853 in the training,validation and independent test sets,respectively.SHAP indicated that Radscore was the most important feature affecting the performance of the model.The decision diagram enabled the visualization of the diagnostic process of the model.Conclusion The interpretable integrated learning model based on clinical indicators,CT image and radiomics features is expected to non-invasively diagnose lung squamous cell carcinoma and adenocarcinoma before treatment and assist clinicians make treatment decisions as early as possible.[Chinese Medical Equipment Journal,2025,46(7):12-20]

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.