Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

OBJECTIVE To construct a prediction model of mild cognitive impairment(MCI)in elderly patients with hyperten-sion based on the bi-dimensional features of Chinese and western medicine with the help of machine learning(ML).METHODS The clinical data of 502 patients over 60 years old with essential hypertension treated in hospital from January 2020 to March 2023 were collected and analyzed,randomly divided into training set and verification set according to a ratio of 7∶3,and divided into cognitive impairment group(n=104)and cognitive normal group(n=398).LASSO regression analysis was used to reduce the dimension of clin-ical indicator data and screen out the core predictors.Six ML algorithms,logistic regression,XGBoost,AdaBoost,SVM,GNB,and MLP were used to construct the models,and ROC curves were plotted to compare the AUC,accuracy,sensitivity,specificity,and F1 scores of the 6 models.SHAP models were adopted to reveal the characteristic importance of predictors.RESULTS Waist-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose were the core predictors of early MCI in elderly hypertensive patients.The AUC,accuracy,sensitivity,specificity,and F1 scores of the XGBoost model were 0.938,0.885,0.846,0.896,and 0.755 respectively,which were superior to those of other algorithmic models.CONCLUSION The XGBoost model constructed on the basis of waist-to-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose has the best prediction performance,which can provide a reference basis for early identifi-cation of MCI risk and diagnostic and therapeutic decision-making in the clinical elderly hypertensive population.

Objective Exploring the mechanism of electroacupuncture's anti anxiety effect through methods such as hippocampal metabolomics and 16S rRNA sequencing.Methods Rats were randomly divided into normal group,model group,electroacupuncture group,and diazepam group.A rat model of anxiety disorder was prepared using chronic restraint stress method.During the modeling period of the electroacupuncture group,simultaneous"Zusanli"acupoint electroacupuncture intervention was performed for 30 minutes each time,once a day,for 21 days.The diazepam group received daily gavage of diazepam for a total of 21 days.After the completion of modeling,open field experiments and elevated cross maze experiments were conducted to observe the behavior of rats.Subsequently,pathological staining was performed to observe the pathological changes in the hippocampus and colon of rats.Metabolomics detection of changes in metabolites in the hippocampus of rats.16S rRNA and short chain fatty acid analysis were used to detect changes in gut microbiota and short chain fatty acids in rats.Western blot detection of Occludin in the colon and TLR4,NF-κB P65 and NLRP3 in the hippocampus of rats.Immunofluorescence detection of IBA-1,NLRP3,and IL-1β in the hippocampus Protein expression.Result The results of the open field experiment showed that compared with the normal group,the total activity distance(P<0.001),central area activity distance(P<0.01),and average velocity(P<0.01)of the model group decreased.Compared with the model group,the total activity distance(P<0.05,P<0.001),central area activity distance(P<0.05,P<0.01),and average velocity(P<0.05,P<0.01)of the electroacupuncture group and diazepam group all increased.The results of the elevated cross maze experiment showed that compared with the normal group,the model group had a decrease in OE%(P<0.001)and OT%(P<0.001).Compared with the model group,both the electroacupuncture group and the diazepam group could increase OE%(P<0.05,P<0.001)and OT%(P<0.01,P<0.001).The HE staining results of the hippocampus showed that the CA1 area of the hippocampus in the normal group rats showed clear and hierarchical structures in various regions of the hippocampus.In the hippocampus of the model group,a small amount of neural cell nuclei in the CA1 area were observed to be wrinkled and deeply stained,with unclear cell boundaries and irregular arrangement,and the cytoplasm was vacuolate.The intervention of electroacupuncture and diazepam can alleviate the above pathological phenomena to varying degrees,respectively;The results of hippocampal metabolomics showed that electroacupuncture can improve hippocampal metabolic disorders caused by modeling,mainly involving taurine and low taurine metabolism,cysteine and methionine metabolism,and regulation of glycine,serine,and threonine metabolic pathways;The results of 16S rRNA sequencing and short chain fatty acid detection showed that electroacupuncture can improve the disturbance of intestinal microbiota caused by modeling,and can regulate serum LPS and levels of butyric acid,caproic acid,and valeric acid.HE staining and Western blot results showed that the model group had pathological damage to the intestine,and compared with the normal group,the expression of Occludin in the colon of the model group decreased(P<0.05).However,the intervention of electroacupuncture and diazepam could improve the pathological damage of the colon and upregulate the expression of Occludin(P<0.05,P<0.05).The immunofluorescence results showed that compared with the normal group,the expression levels of IBA-1,NLRP3,and IL-1β in the hippocampus of the model group increased(P<0.05,P<0.01,P<0.01),while compared with the model group,the electroacupuncture group and diazepam group could reduce the expression levels of IBA-1(P<0.05,P<0.05),NLRP3(P<0.05,P<0.05),and IL-1β(P<0.05,P<0.05).Western blot results showed that compared with the normal group,the expression levels of TLR4,NF-κB P65,and NLRP3 proteins in the hippocampus of the model group increased(P<0.05,P<0.001,P<0.05).Compared with the model group,the electroacupuncture group and diazepam group were able to downregulate the expression levels of NF-κB P65(P<0.01,P<0.001)and NLRP3(P<0.05,P<0.05)proteins.Conclusion The anxiolytic of electroacupuncture involves the regulation of the"microbiota-gut-brain"axis.

This article reviews relevant literature on the prevention and treatment of cancer with hesperidin published in the past 10 years by searching electronic databases such as China National Knowledge Infrastructure（CNKI）， Wanfang， and PubMed， and summarizes the research progress on the anticancer mechanism of hesperidin. Hesperidin has a wide range of pharmacological effects， including anti-inflammatory， antioxidant， antibacterial， antiviral， anticancer， immune-regulatory， anti-radiation， neuroprotective and cardiovascular protective properties and so on. Its anticancer mechanisms mainly include inhibiting cancer cell proliferation， promoting apoptosis， reducing angiogenesis， inhibiting invasion and migration of cancer cells， regulating immunity and autophagy， and exerting antioxidant and anti-inflammatory effects. As a broad-spectrum anticancer drug， hesperidin manifests chemo-preventive and therapeutic effects across various cancers， contingent upon its multifaceted anticancer mechanisms. Furthermore， this article summarizes the synergistic effects of hesperidin in combination with cisplatin， doxorubicin， cyclophosphamide and paclitaxel. It elucidates that hesperidin can enhance the cytotoxicity of these anticancer drugs against cancer cells while mitigating drug resistance and adverse side effects. Nonetheless， the clinical use is somewhat constrained due to its poor water solubility and limited bioavailability. Therefore， this article also outlines the current strategies for enhancing hesperidin's bioavailability， including structural modification， combination with other chemical substances， and utilization of nano drug carriers.The discovery of derivatives of hesperidin not only preserves the anticancer efficacy of hesperidin, but also effectively overcomes the shortcomings of poor water solubility and low bioavailability of hesperidin, effectively predicting the good application prospects of hesperidin and its derivatives.

OBJECTIVE To construct a prediction model of mild cognitive impairment(MCI)in elderly patients with hyperten-sion based on the bi-dimensional features of Chinese and western medicine with the help of machine learning(ML).METHODS The clinical data of 502 patients over 60 years old with essential hypertension treated in hospital from January 2020 to March 2023 were collected and analyzed,randomly divided into training set and verification set according to a ratio of 7∶3,and divided into cognitive impairment group(n=104)and cognitive normal group(n=398).LASSO regression analysis was used to reduce the dimension of clin-ical indicator data and screen out the core predictors.Six ML algorithms,logistic regression,XGBoost,AdaBoost,SVM,GNB,and MLP were used to construct the models,and ROC curves were plotted to compare the AUC,accuracy,sensitivity,specificity,and F1 scores of the 6 models.SHAP models were adopted to reveal the characteristic importance of predictors.RESULTS Waist-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose were the core predictors of early MCI in elderly hypertensive patients.The AUC,accuracy,sensitivity,specificity,and F1 scores of the XGBoost model were 0.938,0.885,0.846,0.896,and 0.755 respectively,which were superior to those of other algorithmic models.CONCLUSION The XGBoost model constructed on the basis of waist-to-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose has the best prediction performance,which can provide a reference basis for early identifi-cation of MCI risk and diagnostic and therapeutic decision-making in the clinical elderly hypertensive population.