Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Four furan α-butenolactones were isolated from 50% acetone extract of tuber of Alisma orientale by silica gel column, chromatography gel column and high performance liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as (5R)-5-hydroxy-3,4-dimethylfuran-2(5H)-one (1), 5-hydroxy-3,5-dimethylfuran-2(5H)-one (2), 5-hydroxy-4-(1-methylethyl)-2(5H)-furanone (3) and alismanoid A (4). Compound 1 was new compound and compounds 2–4 were first isolated from Alisma orientale. Compound 1-4 had potential antifibrotic activities.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P＜0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P＜0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

Objective To investigate the formation and mechanism of dipeptidylpeptidase-4 inhibitor anagliptin inhibiting lung metastasis of colorectal cancer.Methods Twenty-four male BALB/c mice were randomly divided into normal group,model group,anagliptin group.The control group did not undergo any treatment.The model group was injected with 0.1 ml CT-26 cells of 109 cells/L.once through the tail vein of the mouse to construct a lung metastasis model,while the anagliptin group was injected intraperitoneally 20 mg/(kg d)0 day after constructing a lung metastasis model.The mice were sacrificed after 14 days.HE staining was used to detect the morphological alteration.Determination of CT-26 cell viability through MTT assay and CT-26 cell apoptosis was detected by flow cytometry and live/dead cell staining.Reactive oxygen species(ROS)production was measured by ROS kit.Western blotting was conducted to measure the expression level of Bcl-2,Bax,cleaved-caspase-3,superoxide dismutase(SOD-1)and SOD-2.Results HE staining showed that the administration of anagliptin could significantly inhibit the abnormal changes in the model group.Anagliptin inhibited the viability of CT-26 cells above 2 mmol/L.Anagliptin promoted the apoptosis of CT-26 cells.Incubation of anagliptin in CT-26 cells significant promoted the production of ROS.Incubation of anagliptin stimulated the expressions of Bax and cleaved-Caspase-3,while down-regulated the expression of Bcl-2 in CT-26 cells.Administration of anagliptin decreased the expression of SOD-1,but not SOD-2.Conclusion Anagliptin promotes apoptosis of colorectal cancer cells and inhibits the formation of lung metastatic tumors through the SOD-1/ROS pathway.

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ² test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
Humans ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; China ; Nucleic Acids

AIM: To analyze the changes of serum homocysteine(Hcy), vitamin B12(VitB12)and folic acid in the serum of patients with diabetic retinopathy(DR), and to explore their significance in the occurrence and development of DR.METHODS: A case-control study was designed. A total of 95 patients with DR(DR group), 94 patients with diabetes mellitus(DM group)treated in endgcrinology department and 87 patients with age-related cataract(normal control group)from the ophthalmology department of Shenzhen People's Hospital between July 2021 and January 2022 were selected. Fasting venous blood was collected and serum was separated. The concentration of Hcy in serum was detected by enzyme linked immunosorbent assay(ELISA), and chemiluminescence immunoassay was used to detect the concentration of VitB12 and folic acid. Pearson linear correlation analysis was used to evaluate the correlation between Hcy and clinical parameters. Multivariate linear regression analysis was used to evaluate the main factors which affect Hcy level. Receiver operating characteristic(ROC)curve was designed to analyze the diagnostic value of serum Hcy, VitB12 and folic acid in DR.RESULTS: The concentration of serum Hcy in DR group was 16.52±3.54 μmol/L, which was significantly higher than that in DM group(10.86±3.47 μmol/L)and control group(6.84±1.39 μmol/L; all P<0.05); The concentration of VitB12 in the serum of the control group was 501.79±108.95 pmol/L, which was higher than that in DM group(478.57±57.85 pmol/L)and DR group(455.88±181.49 pmol/L), but the difference was not statistically significant(P=0.054); The concentration of folic acid in serum of control group was 10.31±2.43 nmol/L, which was higher than that of DM group(9.94±1.90 nmol/L)and DR group(7.27±2.79 nmol/L), and the difference between DR group and DM group was statistically significant(P<0.05); In DR group, Hcy expression was weakly positively correlated with triglyceride and low density lipoprotein(r=0.208, P=0.043; r=0.240, P=0.019). Multivariate linear regression showed that low density lipoprotein was an important factor which affect the expression of Hcy in DR patients. ROC curve shows that Hcy has important value in the diagnosis of DR.CONCLUSIONS: Hcy, VitB12 and folic acid are differentially expressed in DR group, DM group and normal control group. Hcy may be involved in the pathogenesis of DR, and it has important value in the diagnosis of DR. In addition, low density lipoprotein is also an important factor which affects the expression of Hcy.