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.

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.

Hepatic ischemia-reperfusion injury （HIRI） is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy， and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies， in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.

Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers. Despite continuous advances in medical strategies, the overall survival of lung cancer patients is still low, probably due to disease progression or drug resistance. Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides, and its dysregulation is implicated in cancer development. Preclinical evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment outcomes. In this review, we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.

AIM:This study aims to examine the ependymin-related protein 1(EPDR1)expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes(db/db)mice.The impact of EPDR1 on lipid accumulation in al-pha mouse liver 12(AML12)hepatocytes was also investigated.METHODS:Western blot was used to detect EPDR1 protein expression in the heart,liver,spleen,lung,kidney,gastrocnemius,brown adipose and brain tissues of C57BL/6 mice.Western blot and immunohistochemical(IHC)staining were also used to compare EPDR1 protein expression in the liver,gastrocnemius muscle,heart and kidney tissues of db/db and C57BL/6 mice.To develop an AML12 cell lipid deposi-tion model,palmitic acid(PA)+oleic acid(OA)was used,and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein(rEPDR1).ELISA was conducted to determine intracellu-lar triglyceride(TG)content,and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells.RESULTS:Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tis-sues of wild-type mice,with the liver exhibiting the highest protein expression level.However,EPDR1 expression was down-regulated in the liver,gastrocnemius muscle,heart and kidney tissues in diabetic db/db mice compared with wild-type mice.Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to re-duced lipid accumulation.Furthermore,the TG content significantly decreased compared with the model group(P<0.05).CONCLUSION:EPDR1 is expressed in various tissues of wild-type mice,but showed diminished expression in the liver tissues of diabetic mice.Nevertheless,enhancing the expression of EPDR1 can aid in reducing lipid accumula-tion in hepatocytes.These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue.

Objective:To construct a risk identification model based on dynamic Bayesian network(DBN),and to explore its application value in the operation management of orthopedic equipment in hospital.Methods:Risk factors in orthopedic equipment management were identified based on DBN model,and risk evaluation index set was established to provide early warning and prevention for possible risk factors.12 pieces of orthopedic medical equipment in clinical use in The Second Affiliated Hospital of Air Force Medical University from January 2020 to February 2022 were selected,the traditional orthopedic equipment quality operation management method(referred to as traditional mode)and the DBN-based risk identification mode(referred to as DBN mode)were adopted for equipment management respectively.The equipment operation effects,risk incidence rates and treatment efficiency of the two modes were compared.Results:The start-up operation efficiency and equipment quality qualification rate of the equipment in DBN mode were(93.54±4.05)%and(97.51±6.68)%,respectively,which were higher than those in the traditional mode;the troubleshooting time and the equipment component damage rate were(7.14±1.64)hours and(0.48±0.11)%,respectively,which were lower than those in the traditional mode,the difference was statistically significant(t=8.862,8.228,32.994,73.047,P<0.05).The function failure rate,parts damage rate,unqualified cleaning and disinfection rate and improper management rate of equipment in 479 equipment usage data,897 operations,300 equipment disinfection records and 500 equipment daily inspection records in the DBN mode were 0.21%(1/479),0.33%(3/897),1.33%(4/30)and 2.0%(10/500),respectively,which were lower than those in the traditional mode,the difference was statistically significant(x2=21.527,12.964,3.485,6.914,P<0.05).The effective rate of 500 cases of orthopedic medical equipment treatment of DBN mode was 97.8%(489/500),which was significantly higher than that of traditional mode,the difference was statistically significant(x2=12.617,P<0.05).Conclusion:The application of risk identification model based on DBN to the management of orthopedic medical equipment in hospital can strengthen the quality of orthopedic equipment management,improve the efficiency of equipment operation and treatment,and prevent and avoid equipment risks.

OBJECTIVE To study the effect of different proportion compatibility of Astragali Radix and Chuanxiong Rhizoma on the extraction kinetics of flavonoids. METHODS The content determination method of flavonoids(with rutin as the control substance) was established, and the concentrations of flavonoids in the extracts of Astragali Radix membranicum and Chuanxiong Rhizoma in different proportions(1∶1, 1∶2, 1∶3, 1∶4, 1∶5, 2∶1, 3∶1, 4∶1, 5∶1) were determined dynamically within 2 h, respectively. The extraction kinetics model was established according to Feck's first diffusion law. The extraction rate constant was calculated and the difference of dissolution kinetics was compared. RESULTS The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma had significant effects on the extraction rate and concentration of flavonoids. The extraction kinetics models of flavonoids were consistent with the characteristics of the first-order kinetic equation. The extraction rate was the fastest when Astragali Radix ∶ Chuanxiong Rhizoma was 3∶1, the extraction rate was the slowest when Chuanxiong Rhizoma∶ Astragali Radix was 2∶1. The equilibrium concentration of flavonoids was the highest when Chuanxiong Rhizoma∶ Astragali Radix was 3∶1, when the ratio of Astragali Radix∶Chuanxiong Rhizoma was 5∶1, it was the lowest. CONCLUSION The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma has a significant effect on the extraction rate and concentration of flavonoids.

OBJECTIVE To investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism. METHODS Fifty mice were randomly divided into blank group， model group， diazepam group， raw S. chinensis group and wine-processed S. chinensis group， with 10 mice in each group. Except for blank group， the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia； at the end of each day’s modeling， the corresponding doses of diazepam，raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded， and the total activity distance and upright times of the mice were detected； the EEG and EMG signals of mice were recorded， and the time ratio of sleep wake time （wake）， non-rapid eye movement （NREM） and rapid eye movement （REM） was analyzed； the contents of neurotransmitters [γ-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， dopamine （DA）， norepinephrine （NE）， cortisol （CORT）] in brain suprachiasmatic nucleus （SCN） were detected； and the expressions of tumor necrosis factor α （TNF-α） and interleukin 1β （IL-1β） were detected； the mRNA expressions of clock gene Bmal1， circadian clock gene Clock and cycle gene Per2 were all detected. RESULTS Compared with the blank group， the mental state of the model group mice was relatively depressed， the amount of food and water increased， the body mass decreased， the hair was rough and shiny， and the circadian rhythm was irregular； the total activity distance and upright times decreased significantly； the time ratio of wake increased significantly， while the time ratios of REM and NREM decreased significantly； the content of 5- HT in brain SCN decreased significantly， while the content of NE， DA and CORT increased significantly； the fluorescence intensity of IL-1β and TNF-α was significantly increased； the relative expression level of Bmal1 and Clock mRNA was significantly increased， while the relative expression level of Per2 mRNA was significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， the general state of mice in diazepam group， raw S. chinensis group and wine-processed S. chinensis group was improved obviously， and most of the above index levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Raw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice， the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male ; Female ; Humans ; Adult ; Rhinitis, Allergic, Seasonal/drug therapy* ; Nasal Sprays ; Quality of Life ; Administration, Intranasal ; Rhinorrhea ; Double-Blind Method ; Treatment Outcome ; Rhinitis, Allergic/drug therapy*