Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Objective:To analyze the relationship between red cell distribution width (RDW) and disease severity in patients with non-ST-elevation myocardial infarction.Methods:Seventy patients with non-ST-elevation myocardial infarction who received treatment in Chaozhou People's Hospital from June 2019 to June 2020 were included in the observation group. An additional 70 patients with ST-elevation myocardial infarction who concurrently received treatment in the same hospital were included in the control group. All patients underwent electrocardiography and blood biochemical index examination. RDW was compared between the observation and control groups. The relationship between RDW and the severity of non-ST-elevation myocardial infarction was analyzed.Results:RDW in the observation group was significantly higher than that in the control group [(14.60 ± 1.00) % vs. (13.06 ± 1.70) %, t = 5.884, P = 0.012). The detection rate of coronary artery thrombosis in the observation group was significantly higher than that in the control group [70.00% (49/70) vs. 50.00% (35/70), χ2 = 7.563, P = 0.002]. In the observation group, the area under the receiver operating characteristic (ROC) curve plotted taking RDW as the variable was 0.649 (95% CI 0.546-0.753, P = 0.006). When the critical value of RDW was 14%, the sensitivity and specificity of RDW in the prediction of non-ST-elevation myocardial infarction were 73% and 59% respectively. RDW was positively correlated with cardiac troponin I level ( r = 0.19, P = 0.006). Conclusion:In patients with non-ST-elevation myocardial infarction, the increase in RDW is related to myocardial injury and the increase in cardiac troponin I level. RDW can be used as an effective index to predict the severity of non-ST-elevation myocardial infarction.

ObjectiveTo explore the characteristics and correlation of intelligence development and socioemotional development in 1~3 years old children with expressive language disorder,and provide a basis for early intervention.Methods125 cases with expressive language disorder(language disorder group) and 126 normal children (normal group) are evaluated in two parts (intelligence and social mood) with 0~6 years old neuropsychological development diagnosis scale and Chinese version of urban infant-toddler social and emotional assessment.Results (1)The scores in language disorder group were lower than normal group in the area of free movements (81.60±10.40 vs 89.62±7.94),adaptability (81.48±10.95 vs 91.25±8.89),language (67.46±7.20 vs 89.13±8.24),social behavior (76.61±9.73 vs 90.12±8.13) and total developmental quotient (80.17±6.39 vs 91.15±6.05) (P<0.05).(2) There were significant differences between language disorder group and normal group in the area of externalizing behavior(56.28±10.15 vs 53.57±7.91),deregulation (56.45±10.61 vs 51.11±9.32) and capabilities(46.79±9.08 vs 51.25±7.47) (P<0.05).The boys' scores in internalizing behavior were lower than the girls' (49.19±10.76 vs 54.71±9.90) (P<0.05).(3) The scores of gross motor had positive correlation with externalizing behavior (r=0.220,P<0.05).The scores of language had negative correlation with externalizing behavior and deregulation(r=-0.650,P<0.05;r=-0.470,P<0.05).The scores of social behavior had negative correlation with externalizing behavior (r=-0.208,P<0.05).There was also a negative correlation between total development and deregulation (r=-0.184,P<0.05).(4) Multiple stepwise linear regression results showed that the externalizing behavior domain and mothers' education could predict 44.1% of variances in the language area.ConclusionThe children with expressive language disorder not only show backward in level of language development,but also in the development of other areas,and also bad social behavior and emotional problems.Individualized parenting interventions should be adopted to promote these children's intelligent development in an all-round way.

Objective To research the effect of radiosurgery in combination of temozolomide therapy in vitro on invasion and endocrine function of rat pituitary adenoma cells.Methods Rat pituitary adenoma cell lines GH3 and MMQ were divided into control group,10 Gy irradiation group,20 Gy irradiation group,temozolomide treatment group,and radiosurgery in combination of temozolomide group;cells without exposure were used as control group,cells treated with gamma knife radiation respectively with marginal doses of 10 and 20 Gy (all to the 99％ isodose line) were used as 10 Gy irradiation group and 20 Gy irradiation group,cells treated with 250 μmol/L and 615 μmol/L temozolomide for 24 h after 20 Gy radiation were used as radiosurgery in combination of temozolomide group,and cells treated with 250 μmol/L and 615 μmol/L temozolomide for 24 h were used as temozolomide treatment group.Real time-PCR and Western blotting were employed to measure the mRNA and protein expressions of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF);and secretion of prolactin (PRL) and growth hormone (GH) was detected by ELISA.Results As compared with the control group,the 10 Gy irradiation group and 20 Gy irradiation group had significantly lower mRNA and protein expressions of MMP-9 and VEGF,and secretion of PRL and GH (P＜0.05);and these levels in the 20 Gy irradiation group were significantly lower than those in the 10 Gy irradiation group (P＜0.05);As compared with the 10 Gy irradiation group,20 Gy irradiation group,and temozolomide treatment group,the radiosurgery in combination of temozolomide group had significantly lower mRNA and protein expressions of MMP-9 and VEGF,and secretion of PRL and GH (P＜0.05) Conclusion Gamma knife radiosurgery combined temozolomide could significantly inhibit the invasive ability and endocrine function of rat pituitary adenoma cell lines GH3 and MMQ,which has better effect than radiotherapy or temozolomide treatment alone.

Objective To evaluate the effect of ultra short-term low-dose gamma knife radiation on invasive properties of glioma cells at the genetic level.Methods Malignant glioma cell lines U87 and U251 were treated with gamma knife radiation,respectively,with a marginal doses of 0,4,6,8 and 10 Gy (all to the 80％ isodose line).Real time-PCR was used to measure the mRNA expressions of AKT-1,AKT-2,β-catenin and TCF-4 at 30 min after radiation.Results The expressions of AKT-1,AKT-2,β-catenin,TCF-4 in glioma cell lines after low-dose gamma knife radiation with a marginal dose of 6-8 Gy were significantly increased as compared with those after 0 Gy (P＜0.05); reduced expressions ofAKT-1,AKT-2,β-catenin and TCF-4 after a marginal dose of 10 Gy were found as compared with those after 0 Gy (P＜0.05); the β-catenin and AKT-1 mRNA expressions in U87 cells and TCF-4,AKT-1 and AKT-2 mRNA expressions in U251 cells enjoyed the most obvious increase at a marginal dose of 6 Gy; the TCF-4 and AKT-2 mRNA expressions in U87 cells and β-catenin mRNA expression in U251 cells enjoyed the most obvious increase at a marginal dose of 8 Gy.Conclusion Low-dose gamma knife radiation (6-8 Gy) could increase the β-catenin,TCF-4,AKT-1 and AKT-2 expressions,while high dose (10 Gy) could inhibit these effects in a short time period of 30 min.

OBJECTIVETo study chemical constituents of aerial parts of Gueldenstaedtia stenophylla.

METHODChemical constituents were extracted with 95% alcohol and separated by repeated silica gel column, MCI, Sephadex LH-20 and RP C18 column chromatographic separation from aerial parts of G. stenophylla. Their structures were identified on the basis of the physiochemical properties and spectral data.

RESULTTwenty-two compounds were separated and identified as apigenin (1), chrysoeriol (2), farnisin (3), diosmetin (4), 4', 7-dihydroxyflavone (5), luteolin (6), 3', 4', 7-trihydroxyflavone (7), quercetin (8), m-hydroxy benzoic acid (9), trans-ferulic acid (10), isovanillic acid (11), E-beta-hydroxy-cinnamic acid (12), salicylic acid (13), trans-p-coumaric acid (14), protocatechuic acid (15), (S) -2-hydroxyphenylpropionic acid (16), esculetin (17), 7-methoxy coumarin (18), phaseic acid (19), blumenol A (20), (6S, 9R)-roseoside (21), kaempferol-7-O-alpha-L-rhamnopyranoside (22).

CONCLUSIONExcept compounds 1, 5, 8 and 15, the rest compounds were separated from genus Gueldenstaedtia for the first time.

OBJECTIVETo study chemical constituents in the seeds of Datura Stramonium (Solanaceae family).

METHODCompounds were isolated and purified by silica gel, MCI and Sephadex LH-20 column chromatography, and their structures were determined based on physicochemical constants and spectroscopic analysis including NMR and MS.

RESULTTwelve compounds were isolated and identified from Datura stramonium, they were N-trans-feruloyl tryptamine (1), hyoscyamilactol (2), scopoletin (3), umckalin (4), daturaolone (5), daturadiol (6), N-trans-ferulicacyl- tyramine (7), cleomiscosin A (8), fraxetin (9), scopolamine (10), 1-Acetyl-7-hydrox-beta-carbol-ine (11), 7-hydroxy-beta-carbolinel-propionic acid (12).

CONCLUSIONCompound 2, 7, 9 and 12 were obtained from Datura genus for the first time, whereas compound 1, 4, 8 and 11 were obtained from the Solanaceae family for the first time.

OBJECTIVETo study the chemical constituents in the tubers of Dioscorea bulbifera.

METHODCompounds were isolated and purified with silica gel, ODS and Sephadex LH-20 column chromatography, their structures were determined by using spectroscopic methods including MS and NMR.

RESULTFourteen compounds were isolated and identified as stigmasterol (1), mono-arachidin (2), 1,7-bis-(4-hydroxyphenyl)-1E,4E,6E-heptatrien-3-one (3), behenic acid (4), demethyl batatasin IV (5), 2,3'-di-hydroxy-4',5'-dimethoxybibenzyl (6), diosbulbin B (7), diosbulbin D (8), docosyl ferulate (9), 7-bis-(4-hydroxyphenyl) -4E, 6E-heptadien-3-one (10), 5,3,4-trihydroxy-3,7-dimethoxyflavone (11), tristin(12), protocatechuic acid (13), adenosine (14).

CONCLUSIONCompounds 24, 6, 9, 10, 12, 14 were isolated from the genus Dioscorea for the first time.

AIM:To study the chemical constituents in aerial parts of Arachis hypogea L. METHODS:Compounds were isolated and purified with silica gel and Sephadex LH-20 column chromatography,and their structures were determined by using spectroscopic analysis including MS and NMR. RESULTS:Four compounds were isolated and identified as ?-sitosterol(Ⅰ)、isomedicarpin(Ⅱ)、soyasapogenol B(Ⅲ)、daucosterol(Ⅳ). CONCLUSION:Compound Ⅱ was isolated from this plant for the first time.