ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure （ACLF） based on sarcopenia and other clinical indicators， and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital， Capital Medical University， from January 2019 to January 2022 were enrolled， and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group， CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra （L3）， and L3 skeletal muscle index （L3-SMI） was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors， and a nomogram was developed for presentation. The area under the ROC curve （AUC） was used to assess the predictive performance of the model， the calibration curve was used to assess the degree of calibration， and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=1.962， 95% confidence interval ［CI］： 1.185‍ ‍—‍ ‍3.250， P=0.009）， total bilirubin （HR=1.003， 95%CI： 1.002‍ ‍—‍ ‍1.005， P<0.001）， international normalized ratio （HR=1.997， 95%CI： 1.674‍ ‍—‍ ‍2.382， P<0.001）， and lactic acid （HR=1.382， 95%CI： 1.170‍ ‍—‍ ‍1.632， P<0.001） were included in the sarcopenia-ACLF model. In the training cohort， the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF （0.80 vs 0.73， Z=1.97， P=0.049）. In the test cohort， the sarcopenia-ACLF model had a significantly larger AUC than MELD score （0.79 vs 0.69， Z=2.70， P=0.007） and MELD-Na score （0.79 vs 0.68， Z=2.92， P=0.004）. The calibration curve showed that the model had good calibration ability， with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities， the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients， which provides support for clinical decision-making and helps to optimize treatment strategies.

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

Objective: To determine the latent class of dietary patterns and their association with depressive symptoms among first grade students from multi ethnic middle schools in Yunnan Province, so as to provide a reference basis for promoting mental health among border middle school students. Methods: A cluster random sampling involving 8 500 first grade middle school students from 11 counties in Yunnan Province was conducted by a questionnaire survey between October to December 2022. The Children s Depression Inventory (CDI) was used to assess the depressive symptoms and the Food Frequency Questionnaire was used to collect eating behavior data. The latent profile analysis model was used to fit the latent class of dietary patterns among students. The association between the dietary pattern latent class and depressive symptoms was analyzed by Logistic regression. Results: The depressive symptom detection rate among firstgrade middle school students was 28.3%. Prevalence of depressive symptom in girls (30.9%) was higher than boys (25.5%) with a statistically significant difference ( χ 2=29.83, P <0.01). The dietary patterns among first grade middle school students were classified into four latent classes, as follows:class 1 (low consumption of all dietary components), class 2 (high consumption of fruit, milk and dairy products), class 3 (high consumption of vegetables and meat, and low consumption of processed foods) and class 4 (low consumption of milk, dairy products and eggs, and high consumption of processed foods). After adjusting for confounding variables, the class 3 dietary pattern was negatively correlated with depressive symptoms ( OR=0.62, 95%CI =0.52-0.74) and the class 4 dietary pattern was positively correlated with depressive symptoms ( OR= 1.28 , 95%CI =1.05-1.57) ( P <0.05), compared with the class 1 dietary pattern. Conclusions Multi ethnic first grade middle school students in Yunnan Province follow various dietary patterns. Unhealthy dietary patterns increase the risk of depressive symptoms. The dietary patterns of multi ethnic middle school students in Yunnan Province should be adjusted to promote the establishment of healthy dietary patterns and reduce the risk of depression symptoms in middle school students.

Objective To investigate the repair mechanism of baicalin on gastric mucosa of chronic atrophic gastritis mice based on the network pharmacology and animal experiments.Methods(1)Applied network pharmacology to predict and analyze the potential key targets of baicalin in the treatment of chronic atrophic gastritis.(2)Animal experiment:40 C57BL/6N mice were randomly divided into normal group,model group,Vitacoenzyme group and baicalin group,10 mice in each group.Except for the normal group,the other three groups of mice were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)by gavage combined with hunger and satiety disorder method to construct a chronic atrophic gastritis model.At the end of drug administration,the histopathological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining,the changes of gastrin(GAS)and prostaglandin E2(PGE2)levels in serum were detected by enzyme-linked immunosorbent assay(ELISA),and the mRNA and protein expression levels of Janus tyrosine kinase 1(JAK1),signal transducer and activator of transcription 3(STAT3)in the gastric mucosa were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)and protein immunoblotting(Western Blot)methods,respectively.Results The results of network pharmacology showed that baicalin could spontaneously bind to the core targets JAK1 and STAT3.The results of animal experiments showed that compared with the normal group,the gastric mucosa of mice in the model group suffered from atrophy,disordered gland arrangement,the presence of a large number of lymphocytes,a significant increase in apoptotic index of the gastric mucosa(P＜0.05),a significant decrease in the levels of GAS and PGE2 in serum(P＜0.05),and a significant increase in the levels of mRNA and protein expressions of JAK1 and STAT3 in the gastric mucosa(P＜0.05);compared with the model group,the pathological changes of gastric mucosa in the Vitacoenzyme group and baicalin group were alleviated,the glands were arranged relatively neatly,the structure was more intact,the apoptosis index of gastric mucosal cells was significantly decreased(P＜0.05),the levels of GAS and PGE2 in serum were significantly increased(P＜0.05),and the mRNA and protein expression levels of JAK1 and STAT3 in gastric mucosa were significantly decreased(P＜0.05).There was no significant difference in the above-mentioned indexes between the baicalin group and the Vitacoenzyme group(P＞0.05).Conclusion Baicalin can effectively repair gastric mucosal lesions in mice with chronic atrophic gastritis,and its mechanism may be related to the down-regulation of mRNA and protein expressions of JAK1 and STAT3.

BACKGROUND:Hypoxia is strongly associated with the development and progression of osteoarthritic chondrocyte injury,but the specific targets and regulatory mechanisms are unclear. OBJECTIVE:A machine learning approach was used to identify KDEL(Lys-Asp-Glu-Leu)receptor 3(KDELR3)as a characteristic gene for osteoarthritis hypoxia and immune infiltration analysis,to provide new ideas and methods for the treatment of osteoarthritis. METHODS:The osteoarthritis-related datasets were downloaded from the GEO database and the GSEA website to obtain hypoxia-related genes.The osteoarthritis datasets were batch-corrected and immune infiltration analyzed using R language,and osteoarthritis hypoxia genes were extracted for differential analysis.Differentially expressed genes were analyzed for GO function and KEGG signaling pathway.Weighted correlation network analysis(WGCNA)and machine learning were also used to screen osteoarthritis hypoxia signature genes,and in vitro cellular experiments were performed to validate expression and correlate immune infiltration analysis using the datasets and qPCR. RESULTS AND CONCLUSION:(1)8492 osteoarthritis genes were obtained by batch correction and principal component analysis,mainly strongly associated with immune cells such as Macrophages M2 and Mast cells resting;200 hypoxia genes were also obtained,resulting in 41 osteoarthritis hypoxia differentially expressed genes.(2)GO analysis involved mainly biological processes such as response to nutrient levels and glucocorticoids;cellular components such as lysosomal lumen and Golgi lumen;and molecular functions such as 14-3-3 protein binding and DNA-binding transcriptional activator activity.(3)KEGG analysis of osteoarthritis hypoxia differentially expressed genes was associated with signaling pathways such as PI3K-Akt,FoxO,and microRNAs in cancer.(4)The characteristic gene KDELR3 was obtained after using WGCNA analysis and machine learning screening.(5)The gene expression of KDELR3 was found to be higher in the test group than in the control group in the synovium(P=0.014)but lower in the meniscus(P=0.024)after validation by gene microarray.(6)In vitro chondrocyte assay showed that the expression of KDELR3 was higher in cartilage than in the control group(P=0.005),while KDELR3 was closely associated with Macrophages M0(P=0.014)and T cells follicular helper(P=0.014).Using a machine learning approach,we confirmed that KDELR3 can be used as a hypoxic signature gene for osteoarthritis and may intervene in osteoarthritis pathogenesis by improving hypoxia,expecting to provide a new direction for better treatment of osteoarthritis.

BACKGROUND:Ferroptosis is strongly associated with the occurrence and progression of osteoarthritis,but the specific characteristic genes and regulatory mechanisms are not known. OBJECTIVE:To identify osteoarthritis ferroptosis signature genes and immune infiltration analysis using the WGCNA and various machine learning methods. METHODS:The osteoarthritis dataset was downloaded from the GEO database and ferroptosis-related genes were obtained from the FerrDb website.R language was used to batch correct the osteoarthritis dataset,extract osteoarthritis ferroptosis genes and perform differential analysis,analyze differentially expressed genes for GO function and KEGG signaling pathway.WGCNA analysis and machine learning(random forest,LASSO regression,and SVM-RFE analysis)were also used to screen osteoarthritis ferroptosis signature genes.The in vitro cell experiments were performed to divide chondrocytes into normal and osteoarthritis model groups.The dataset and qPCR were used to verify expression and correlate immune infiltration analysis. RESULTS AND CONCLUSION:(1)12 548 osteoarthritis genes were obtained by batch correction and PCA analysis,while 484 ferroptosis genes were obtained,resulting in 24 differentially expressed genes of osteoarthritis ferroptosis.(2)GO analysis mainly involved biological processes such as response to oxidative stress and response to organophosphorus,cellular components such as apical and apical plasma membranes,and molecular functions such as heme binding and tetrapyrrole binding.(3)KEGG analysis exhibited that differentially expressed genes of osteoarthritis ferroptosis were related to signaling pathways such as the interleukin 17 signaling pathway and tumor necrosis factor signaling pathway.(4)After using WGCNA analysis and machine learning screening,we obtained the characteristic gene KLF2.After validation by gene microarray,we found that the gene expression of KLF2 was higher in the test group than in the control group in the meniscus(P=0.000 14).(5)In vitro chondrocyte assay showed that type Ⅱ collagen and KLF2 expression was lower in the osteoarthritis group than in the control group in chondrocytes(P<0.05),while in osteoarthritis ferroptosis,mast cells activated was closely correlated with dendritic cells(r=0.99);KLF2 was closely correlated with natural killer cells(r=-1,P=0.017)and T cells follicular helper(r=-1,P=0.017).(6)The findings indicate that using WGCNA analysis and machine learning methods confirmed that KLF2 can be a characteristic gene for osteoarthritis ferroptosis and may improve osteoarthritis ferroptosis by interfering with KLF2.

Objective:To study influence of Connect-Introduce-Communicate-Ask-Respond-Exit(CICARE)communication mode on patients with acute heart failure(AHF).Methods:A total of 156 AHF patients treated in our hospital were randomly and equally divided into routine nursing group and CICARE group(received CICARE communication mode based on routine nursing group).Both groups were intervened for one month.General clinical data,hospitalization indexes,scores of Hamilton rating scale for depression(HAMD),Hamilton rating scale for anxiety(HAMA),general self-efficacy scale(GSES)and quality of life scale(QOL-35)before and after inter-vention and incidence of complications were compared between two groups.Results:Compared with routine nursing group,there were significant reductions in first aid time[(42.06±9.77)s vs.(20.27±3.77)s],visit time[(95.67±23.18)min vs.(50.07±11.21)min],admission time[(3.22±0.36)min vs.(2.60±0.67)min]and hospital stay[(22.33±4.82)d vs.(14.13±2.42)d];and scores of HAMD[(14.02±1.42)scores vs.(6.04± 1.57)scores]and HAMA[(13.24±2.07)scores vs.(7.16±2.17)scores]after intervention,and significant rise in scores of GSES[(14.25±3.14)scores vs.(32.03±6.06)scores]and QOL-35[(70.67±5.75)scores vs.(86.93±5.51)scores]in CICARE group after intervention(P=0.001 all).Incidence rate of complications in CICARE group was significantly lower than that of CICARE group(5.13％vs.20.51％,P=0.004).Conclusion:CICARE communication mode can significantly alleviate adverse emotions and improve self-efficacy in patients with acute heart failure.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

AIM To optimize the processing technology of red Notoginseng Radix et Rhizoma and evaluate its blood tonifying activity.METHODS On the basis of a single factor experiment,with steaming temperature,steaming time,drying temperature,and drying time as influencing factors,the total contents of notoginsenoside R1,ginsenoside Rg1,Rb1,Rk3,Rh4,and 20(R)-ginsenoside Rg3 as evaluation indicators,Box-Behnken response surface method ology was used to optimize the processing technology.Upon the anemic mouse models jointly induced by 1-acetyl-2-phenylhydrazine(APH)and cyclophosphamide(CTX),the investigation of the blood tonifying activity of red Notoginseng Radix et Rhizoma was carried out in contrast to that of the steamed Notoginseng Radix et Rhizoma.RESULTS The optimal conditions,contributing saponin content of 8.326%and RSD of 0.087%,were determined as follows:steaming temperature of 130℃,steaming time of 4 hours,drying temperature of 60℃,and drying time of 48 h.The pharmacological activity revealed that the different processing techniques were responsible for the different blood enriching activity of notoginseng,with red Notoginseng Radix et Rhizoma displaying a better efficacy than that of steamed Notoginseng Radix et Rhizoma.CONCLUSION This stable and feasible method can be used to control the production of red Notoginseng Radix et Rhizoma.