ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

ObjectiveTo explore whether the intestinal absorption solution containing Banxia Xiexintang （BXT） can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1 （SDF1）-CXC chemokine receptor 4 （CXCR4） axis in tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs）. MethodsThe intestinal absorption solution containing BXT was prepared， and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8 （CCK-8） assay. A co-culture system was established comprising TA-BMSCs conditioned medium （TA-BMSCs-CM） and gastric cancer MFC cells. The experiment was conducted with a blank control group， a TA-BMSCs-CM group， an SDF1 inhibitor （LY2510924） group， and intervention groups with varying concentrations （55%， 70%， 85%） of the intestinal absorption solution containing BXT. Cell proliferation was assessed by the CCK-8 assay. Horizontal and vertical cell migration were evaluated via scratch and Transwell assays， respectively. Cell invasion was examined by a Transwell assay with Matrigel. Cell apoptosis was detected by flow cytometry. The levels of factors such as SDF1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）， as well as the protein levels of macrophage migration inhibitory factor （MIF）， CXCR4， VEGFA， and MMP-9， were quantified by ELISA and Western blot， respectively. ResultsThe CCK-8 assay results indicated that compared with the 24 h intervention， the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells （P<0.01）. The half-maximal inhibitory concentration （IC₅₀） of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%， and subsequent intervention concentrations were selected as 55%， 70%， and 85%. Compared with the TA-BMSCs-CM group， the intestinal absorption solution containing BXT （particularly at concentrations of 70% 85%） suppressed the proliferation， migration， and invasion of MFC cells， promoted the cell apoptosis （P<0.05， P<0.01）， decreased the levels of SDF1， MMP-9， and VEGFA， and downregulated the protein levels of MIF， CXCR4， VEGFA， and MMP-9 （P<0.05， P<0.01）. The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor （P<0.01）. ConclusionThe intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs. The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.

ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 （PD-L1） expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells （BMSCs） through the protein kinase B （Akt）/c-myelocytomatosis oncogene （c-Myc） signaling axis， and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal， model， Banxia Xiexintang （10% serum containing Banxia Xiexintang）， PD-L1 monoclonal antibody （10% blank serum containing PD-L1 antibody）， and combination （10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody） groups. The suspension of BMSCs was added to the upper chamber of each group， with the normal group receiving serum culture medium without exosomes in the lower chamber， and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group received 10% serum containing Banxia Xiexintang， 10% blank serum containing PD-L1 monoclonal antibody， and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody， respectively， in the upper chamber. After 96 h， BMSCs from the upper chamber were collected， and the protein levels of p-Akt， Akt， c-Myc， and PD-L1， as well as the mRNA levels of Akt， c-Myc， and PD-L1， were determined by Western blot and Real-time PCR， respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group， the model group showed increases in protein levels of p-Akt， c-Myc， and PD-L1， as well as mRNA levels of c-Myc and PD-L1 （P<0.05， P<0.01）， and no significant change in the protein and mRNA levels of Akt. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in protein levels of p-Akt， c-Myc， and PD-L1 （P<0.01）. In addition， they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.05）. Compared with the normal group， the model group showed increases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）， with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.01）. ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover， it has a synergistic effect when being used together with PD-L1， possibly related to the regulation of the Akt/c-Myc signaling axis.

ObjectiveTo explore whether the intestinal absorption solution containing Banxia Xiexintang （BXT） can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1 （SDF1）-CXC chemokine receptor 4 （CXCR4） axis in tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs）. MethodsThe intestinal absorption solution containing BXT was prepared， and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8 （CCK-8） assay. A co-culture system was established comprising TA-BMSCs conditioned medium （TA-BMSCs-CM） and gastric cancer MFC cells. The experiment was conducted with a blank control group， a TA-BMSCs-CM group， an SDF1 inhibitor （LY2510924） group， and intervention groups with varying concentrations （55%， 70%， 85%） of the intestinal absorption solution containing BXT. Cell proliferation was assessed by the CCK-8 assay. Horizontal and vertical cell migration were evaluated via scratch and Transwell assays， respectively. Cell invasion was examined by a Transwell assay with Matrigel. Cell apoptosis was detected by flow cytometry. The levels of factors such as SDF1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）， as well as the protein levels of macrophage migration inhibitory factor （MIF）， CXCR4， VEGFA， and MMP-9， were quantified by ELISA and Western blot， respectively. ResultsThe CCK-8 assay results indicated that compared with the 24 h intervention， the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells （P<0.01）. The half-maximal inhibitory concentration （IC₅₀） of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%， and subsequent intervention concentrations were selected as 55%， 70%， and 85%. Compared with the TA-BMSCs-CM group， the intestinal absorption solution containing BXT （particularly at concentrations of 70% 85%） suppressed the proliferation， migration， and invasion of MFC cells， promoted the cell apoptosis （P<0.05， P<0.01）， decreased the levels of SDF1， MMP-9， and VEGFA， and downregulated the protein levels of MIF， CXCR4， VEGFA， and MMP-9 （P<0.05， P<0.01）. The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor （P<0.01）. ConclusionThe intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs. The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.

ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 （PD-L1） expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells （BMSCs） through the protein kinase B （Akt）/c-myelocytomatosis oncogene （c-Myc） signaling axis， and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal， model， Banxia Xiexintang （10% serum containing Banxia Xiexintang）， PD-L1 monoclonal antibody （10% blank serum containing PD-L1 antibody）， and combination （10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody） groups. The suspension of BMSCs was added to the upper chamber of each group， with the normal group receiving serum culture medium without exosomes in the lower chamber， and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group received 10% serum containing Banxia Xiexintang， 10% blank serum containing PD-L1 monoclonal antibody， and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody， respectively， in the upper chamber. After 96 h， BMSCs from the upper chamber were collected， and the protein levels of p-Akt， Akt， c-Myc， and PD-L1， as well as the mRNA levels of Akt， c-Myc， and PD-L1， were determined by Western blot and Real-time PCR， respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group， the model group showed increases in protein levels of p-Akt， c-Myc， and PD-L1， as well as mRNA levels of c-Myc and PD-L1 （P<0.05， P<0.01）， and no significant change in the protein and mRNA levels of Akt. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in protein levels of p-Akt， c-Myc， and PD-L1 （P<0.01）. In addition， they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.05）. Compared with the normal group， the model group showed increases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）， with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.01）. ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover， it has a synergistic effect when being used together with PD-L1， possibly related to the regulation of the Akt/c-Myc signaling axis.

Objective To observe the value of 18F-D3FSP PET/CT machine learning(ML)models for evaluating subjective cognitive decline(SCD).Methods Thirty-two SCD patients(SCD group)and 16 healthy volunteers(control group)who received 18F-D3FSP PET/CT were selected from Sino Longitudinal Study on Cognitive Decline(SILCODE)and divided into training set(n=34)and test set(n=14)at a ratio of 7∶3.Support vector machine(SVM),random forest(RF)and logistic regression(LR)models were constructed based on Hamilton anxiety scale(HAMA)and standard uptake value ratio(SUVR)of brain regions being significantly different between groups to evaluate SCD.Then PET/CT data were amplified by format conversion and divided into training set(including 8 775 CT images and 1 833 PET images)and test set(including 2 025 CT images and 423 PET images)at the ratio of 8∶2.VGG16 models were constructed based on CT and PET images to evaluate SCD,respectively.Results The area under the receiver operating characteristic curve(AUC)of SVM,RF and LR model for evaluating SCD in training set was all 1.000,while was 0.863,0.872 and 1.000 in test set,respectively.LR model was overfitting,and RF model had better performance.The accuracy of VGG16 model for evaluating SCD based on CT and PET images tended to be stable after the 175th and 150th iterations,with the highest accuracy of 67.11％ and 65.35％ in training set,which tended to be stable after the 165th and 145th iterations,with the highest accuracy of 62.43％ and 59.16％ in test set,respectively.Conclusion 18F-D3FSP PET/CT ML models could be used to evaluate SCD.

Hereditary breast cancer(HBC)is one of the important subtypes of breast cancer(BC),primarily characterized by mutations in the BRCA1/2 genes.Accurate identification of BRCA1/2 mutation carriers remains a significant clinical challenge.Traditional genetic testing methods for BRCA1/2 mutations are often expensive and complex.In recent years,advancements in radiomics and artificial intelligence(AI)have opened new avenues for non-invasive prediction of BRCA1/2 mutations.This review summarized the current research progresses in utilizing radiomics and AI for screening and predicting of BRCA1/2-related HBC.

Objective:To establish the HPLC fingerprints and multi-component content determination method of Yinchen Wuling Powder; To evaluate the quality of Yinchen Wuling Powder combined with chemical pattern recognition technology.Methods:A wavelength-switching HPLC method was used to establish the fingerprint profiles of different batches of Yinchen Wuling Powder and determine the contents of seven components of neochlorogenic acid, chlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, cinnamic acid, cinnamaldehyde. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to evaluate the quality. Quality difference biomarkers were screened.Results:The fingerprint profiles of 24 batches of Yinchen Wuling Powder were identified with 20 common peaks, and 7 components were recognized. The similarity between the 24 batches of samples and the control profile was 0.966-0.994, and the attribution analysis showed that peaks 1, 2, 3 were common to Artemisia Scoparia and Alismatis Rhizoma. Chromatographic peaks 4 (neochlorogenic acid), 5, 6, 7 (chlorogenic acid), 8, 9, 10, 11, 12, 13, 14 (isochlorogenic acid B), 15 (isochlorogenic acid A), 16 (isochlorogenic acid C), and 19 were from Artemisia Scoparia, and peaks 17, 18 and 20 were from Cinnamomi Ramulus. Principal component analysis classified the 24 batches of samples into 4 categories, and partial least squares discriminant analysis was used to determine 11 quality difference biomarkers, including isochlorogenic acid B and neochlorogenic acid.Conclusions:The established method of determining fingerprint and multi-component content is accurate and with good repeatability. The results can provide a certain basis for the quality evaluation of Yinchen Wuling Powder.

Objective To observe the clinical efficacy of modified Zhi Gancao Decoction combined with acupuncture in the treatment of ventricular arrhythmia with qi and yin deficiency type.Methods Sixty patients with ventricular arrhythmia of qi and yin deficiency type admitted to the wards and outpatient clinics of Hospital of Traditional Chinese Medicine of Qiqihar between January 2023 and January 2024 were selected,and the patients were randomly divided into the observation group and the control group according to the random number table method,with 30 patients in each group.The control group was treated with Mexiletine Hydrochloride Tablets,and the observation group was treated with modified Zhi Gancao Decoction combined with acupuncture on the basis of the treatment of the control group,the course of treatment covered two consecutive weeks.After two weeks of treatment,the efficacy of traditional Chinese medicine(TCM)syndrome and Lown grading were evaluated between the two groups,the changes of the number of ventricular premature beats,the total beat ratio,and TCM syndrome scores before and after treatment in the two groups were observed.The changes of QT interval and Tp-ec interval before and after treatment were compared between the two groups.Results(1)After treatment,the number of premature ventricular beats and the total beat ratio of the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)The total effective rate of TCM syndrome in the observation group was 90.00%(27/30),and 60.00%(18/30)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(4)The total effective rate of Lown grading efficacy was 93.33%(28/30)in the observation group and 76.67%(23/30)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(5)After treatment,the QT interval and Tp-ec interval of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).Conclusion Modified Zhi Gancao Decoction combined with acupuncture in the treatment of ventricular arrhythmia with qi and yin deficiency type can significantly improve the clinical symptoms of the patients.

Objective:To investigate effect and mechanism of hydroxysafflor yellow A(HSYA)activating neuronal autophagy on cerebral ischemia-reperfusion injury through a combination of in vitro and in vivo experiments.Methods:SD rat MCAO/R model was established by improved suture method.Rats were randomly divided into sham surgery(Sham)group,MCAO/R group and MCAO/R+HSYA group,following indicators were detected to determine extent of cerebral ischemia-reperfusion nerve damage:Z-Longa neu-rological function score was detected,TTC staining to measure cerebral infarction area,and TUNEL staining to measure cell apopto-sis;Western blot was used to detect protein expressions of autophagy related markers LC3,Beclin1,P62 and SIRT1 in rat brain tis-sue;immunofluorescence staining was used to observe expression of LC3 co-localization with neurons.OGD/R injury model of SH-SY5Y cells was established and randomly divided into Normal group,OGD/R group,OGD/R+HSYA group,OGD/R+SIRT1 inhibitor(EX-527)group and OGD/R+EX-527+HSYA group.Western blot was used to detect protein expressions of LC3,Beclin1,P62 and SIRT1.Results:Compared with Sham group,model group rats showed impaired neurological function,significantly increased neu-robehavioral scores,widespread cerebral infarction,significantly increased neuronal cell apoptosis,significantly increased autophagy related protein Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,significantly decreased P62 expression,significantly increased LC3/NeuN co-stained cells,and decreased SIRT1 expression;compared with model group,HSYA intervention group showed a significant decrease in neurological functional scores,a significant reduction in cerebral infarction area,a significant decrease in neuronal cell apoptosis,a further increase in Beclin1 expression and LC3-Ⅱ/LC3-Ⅰ,a further decrease in P62 expression,number of LC3/NeuN and P62/NeuN co-stained cells also increased,and SIRT1 expression significantly increased.Expression trends of Beclin1,LC3-Ⅱ/LC3-Ⅰ,P62 and SIRT1 of cells between normal group,model group and HSYA intervention group were same as animal experiment;compared with model group,expressions of SIRT1,Beclin1 and LC3-Ⅱ/LC3-Ⅰ in OGD/R+EX-527 group were significantly reduced,while expression of P62 was significantly increased;compared with OGD/R+EX-527 group,there was no significant change in SIRT1 expression in OGD/R+EX-527+HSYA group,LC3-Ⅱ/LC3-Ⅰ and Beclin1 expression were significantly increased,and P62 expres-sion was significantly decreased.Conclusion:HSYA can significantly improve neurological deficits in rats after cerebral ischemia-reperfusion,reduce cerebral infarction area,and decrease neuronal cell apoptosis rate,whose neuroprotective effect may be related to its activation of SIRT1,which significantly enhances neuronal autophagy.