Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

Objective:A multi-center and large sample volume study was conducted on the verification and improvement of the early established criteria for intelligent routine urinalysis validation (including the microscopic review rules and manual validation rules, referred to as intelligent criteria for short), in order to improve the clinical application of this intelligent criteria.Methods:A total of 31 456 urine specimens were collected from the inpatients and outpatients in six hospitals in China, from March to September 2019. Firstly, 3105 specimens were analyzed for preliminary verification and improvement of the intelligent criteria based on the results of the microscopic examination and manual validation. Secondly, 28 351 specimens were used to verify the clinical application of the improved intelligent criteria. All samples were manually validated as reference.Results:The approval inconsistency rate of the manual validation rules in the original intelligent criteria was 8.59% (202/2 352), and the interception inconsistency rate was 8.84% (208/2 352). The false negative rate and the microscopic review rate of the microscopic review rules were similar to the previous results. Based on an in-depth analysis of big data and the discussions by senior technicians from eight hospitals, one microscopic review rules and four manual validation rules were added, meanwhile two manual validation rule was deleted. The manual validation standards were unified. Finally, the intelligent criteria was improved. Based on the improved intelligent criteria, for microscopic review rules, the false positive rate, false negative rate (misdiagnosis rate), and microscopic review rate did not change significantly, which were 14.72% (457/3 105), 4.06% (126/3 105), and 24.73% (768/3 105), respectively. The approval inconsistency rate and the interception inconsistency rate of manual validation rules were both reduced to 0; the total manual validation rate of the intelligent criteria was 50.89% (1 580/3 105), and the auto-validation rate was 49.11% (1 525/3 105). The large sample volume verification results were consistent with the preliminary verification results of the improved intelligent criteria.Conclusion:This multi-center and large sample volume study had shown that the improved intelligent criteria had better clinical performance.

Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60　and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.

Objective To investigate PSP on bone microstructures,Ca,P,OPG and RANKL of osteoporotic rat model.Methods Thirty female rats randomly divided into five groups:Sham,OVX,H-,M-,L-PSP.Sham and OVX were irrigated stomachsaline;PSP solution was gavaged to other groups.After 8-week,bone microstructures of tibial metaphyseal,Ca,P,OPG and RANKL were measured.Results Body weight,Ca,P,RANKL,Tb.Sp of OVX were significantly increased compared to Sham,OPG,BV/TV,Tb.Th,Tb.N decreased.Body weight of H-,M-PSP,Ca and Tb.Sp of PSP,P and RANKL in H-PSP were decreased compared to OVX,OPG in H-,M-PSP,BV/TV,Tb.Th,Tb.N of PSP group increased.The differences were statistically significant (P ＜ 0.05).Conclusion PSP prevents osteoporosis by improving the microstructure of trabecular bone,reducing bone turnover,increasing OPG and reducing RANKL expression.

This study aimed to elucidate the effects of different soil water contents on the yield and quality of R.glutinosa.Different soil water contents were adjusted in different periods of growth of R.glutinosa.The yield,content of water extract,catalpol,verbascoside and polysaccharide were determined and analysed by the grey pattern recognition after harvests.The impacts of soil water content from the most important to the least important were medium moisture content (M2),high moisture content (M3),low moisture content (M1) and blank (M4).In the cultivation of R.glutinosa,the soil water content should be remained in the range of 40％-50％ at seedling stage,while 50％-60％ at the stage of root formation and tuber enlargement,and 20％-30％ during harvesting,which can significantly improve the yield and quality of R.glutinosa.

This article was aimed to study the correlation between iron content inCornus officinalis leaves and its yield as well as quality. The method of microwave digestion atomic absorption spectrophotometer was used to determine the content of iron element inCornus officinalis leaves. HPLC was used to determine the content of loganin and ursolic acid in fruits. Correlation analysis was made among the content of iron element, yield of fruits, loganin and ursolic acid in fruits. The results showed that iron element in leaves of different yield level cornus officinalis was different. It also had some correlation with yield and quality of fruits. It was concluded that the research can improve relations of source-sink inCornus ofifcinalis, adjust source-sink balance, guide farmers to master the period of spraying iron fertilizer, and increase production and quality ofCornus ofifcinalis.

Objective To investigate the risk factors and clinical features of mild cognitive impairment (MCI) in patients with ischemic cerebral small vessel disease (SVD) for early diagnosis and prevention.Methods Montreal Cognitive Assessment Scale (MoCA) was used to screen MCI.The related risk factors and other clinical data were collected,and other neuropsychological tests were conducted.SVD was divided into leukoaraiosis (LA),lacunar infarction (LI),and LA + LI.Results A total of 143 patients with SVD were enrolled (68 in an MCI group,75 in a non-MCI group).Univariate analysis showed that there was no significant difference in the constituent ratio of age and gender between the MCI group and the non-MCI group,but the years of education in the MCI group was shorter than that in the non-MCI group,while the composition ratios of hypertension (69.11％ vs.45.33 ％;x2 =8.215,P =0.004),diabetes (57.35％ vs.40.00％;x2 =4.301,P =0.038),hyperlipidemia (48.53％ vs.24.00％ ; x2 =9.352,P =0.002),carotid atherosclerosis (41.18％ vs.21.33％ ;x2 =6.592,P =0.010),and smoking (32.35％ vs.14.67％ ;x2 =6.285,P =0.012),as well as the levels of uric acid (351.81 ± 83.21 mmol/L vs.323.03 ± 80.43 mmol/L; t =2.102,P =0.037) and total cholesterol (5.26 ± 1.26 mmol/L vs.4.56 ± 1.23 mmol/L; t =3.326,P =0.001) were significantly higher than those in the non-MCI group.Multivariate logistic regression analysis showed that hypertension (odds ratio OR]2.227,95％ confidence interval [CI],1.001-4.954; P =0.026),diabetes (OR 2.056,95％ CI 1.862-4.937; P =0.046),hyperlipidemia (OR 2.528,95％ CI 1.361-5.770; P =0.028),carotid atherosclerosis (OR 2.658,95％ CI 1.110-6.367; P =0.029),smoking (OR 2.566,95％ CI 1.017-6.474; P =0.046),and years of education (OR 0.825,95％ CI 0.745-0.914; P =0.000) were the independent risk factors for the occurrence of MCI in patients with SVD.The subscores in the MCI group,including MoCA total score (18.44 ± 5.60 vs.27.09 ± 1.37; t =-12.422; P =0.000),as well as visuoconstructional skills (2.65 ± 1.39 vs.4.49 ± 0.74; t =-9.762; P =0.000),attention (4.48 ± 1.70vs.5.89 ± 0.31; t =6.706,P=0.000),language (1.69 ± 0.80vs.2.41 ± 0.95 ; t =4.893,P=0.018),abstraction (0.85 ± 0.69 vs.1.71 ± 0.53; t=-7.081,P=0.000),delayed recall (1.29 ±1.01 vs.4.04 ± 0.99; t =13.824,P =0.000) were significantly lower than those in the non-MCI group,and there were no significant differences in naming and orientation scores.In the MCI group,the subscores such as theMoCA total score in the LA+LI group (17.04 ± 6.15 vs.21.04 ± 3.98; P＜0.05),as well as visuoconstructional skills (1.68 ± 1.16 vs.3.24 ± 1.13; P ＜ 0.05),attention (3.92 ± 2.03 vs.5.19 ±0.87; P ＜0.05),delayed recall (1.35 ± 1.01 vs.1.86 ± 1.58; P ＜0.05) were significantly lower than those in the LI group; the subscores such as the MoCA total score in the LA group (18.18 ± 5.31 vs.21.04 ± 3.98; ＜ =0.05),as well as visuoconstructional skills (2.56 ± 1.78 vs.3.24 ± 1.13; P＜0.05),language (0.64 ± 0.23 vs.1.24 ± 0.83; P ＜0.05),delayed recall (0.69 ± 0.58vs.1.86 ± 1.58;P＜0.01)were significantly lower than those in the LI group; the visuoconstructional skills in the LA + LI group was significantly lower than that in the LA group (1.68 ± 1.16 vs.2.56 ± 1.78; P＜0.05) and the LI group (1.68 ± 1.16 vs.3.24 ± 1.13; P＜ 0.05).Conclusions Hypertension,diabetes,hyperlipidemia,carotid atherosclerosis,smoking,and the low level of education were the independent risk factors for MCI in patients with SVD.After SVD,the cognitive impairment in MCI presented as multiple cognitive domains impairments,including visuoconstructional skills and delayed recall.Cognitive impairment differed among the different types of SVD.

Objective To investigate the relationship between hypertension,other vascular risk factors and mild cognitive impairment and its subtype.Methods A total of 297 outpatients and inpatients were collected from the Departments of Neurology in 4 municipal hospitals in Qingdao from April 2011 to September 2011.The unified questionnaires of cognitive impairment status in the departments of neurology in Qingdao city were developed.The risk factors for mild cognitive impairment and its subtype were investigated.Results Univariate analysis showed that low levels of education (odds ratio [ OR] 0.239,95％ confidence interval [ CI] 0.129 -0.442; P =0.000),hypertension (OR 1.928,95％ CI 1.107 - 3.358; P =0.019) and hyperlipidemia (OR 1.812,95％ CI 1.041 -3.155; P =0.034) were all the risk factors for mild cognitive impairment; Multivariate logistic regression analysis showed that low levels of education (OR 0.807,95％ CI 0.742 - 0.878; P =0.000) and hypertension (OR 1.788,95％ CI 1.004 -3.146; P =0.048 ) were the independent risk factors for mild cognitive impairment; and hypertension (OR 2.091,95％ CI 1.030 -4.242; P=0.041) was an independent risk factor for non-amnestic mild cognitive impairment,and was mainly impaired visuospatial and executive abilities (P =0.026).Conclusions Hypertension is an independent risk factor for mild cognitive impairment and its subtype-non-amnestic mild cognitive impairment,and it mainly impairs executive ability.

Objective To explore the association of risk factors with amnestic versus nonamnestic of mild cognitive impairment.Methods All the subjects with mild cognitive impairment (MCI) aged 65-75 years were recruited from Neurology Department of 3 third-class hospitals of Qingdao,admitted from January 2011 to September 2011.They were systematically evaluated with mini-mental state examination( MMSE )and Montreal cognitive assessment (MoCA),then health conditions were collected.According to Petersen's standards,patients were divided into 89 cases with amnestic mild cognitive impairment(aMCI) and 51 cases with non-amnestic mild cognitive impairment (non-aMCI)groups to compare different risk factors between them.Results There were statistical differences in high total cholesterol (P=0.011),diabetes mellitus (P=0.009),MoCA score (P=0.040) between aMCI and non-aMCIgroups.MoCAscore (OR=1.081,95％CI:1.001-1.204,P=0.040) in the aMCI group was lower than that in non aMCI group.Diabetes mellitus ratio (OR=0.258,95％CI:0.096-0.695,P=0.009) was higher in non-aMCI group than in aMCI group.The level of total-cholesterol(OR=13.345,95％CI:1.127-158.085,P=0.011) in aMCI group was higher than that in non-aMCI group.The high total cholesterol was a independent risk factor for aMCI.Conclusions Different risk factors appear to exert different effects for aMCI and nonaMCI.

Objective To investigate the differences of the vascular risk factors for anterior circulation and posterior circulation ischemic stroke.Methods The unified diagnosis and treatment questionnaires of ischemic stroke in Qingdao city were developed.The data of 943 consecutive patients with acute ischemic stroke treated in the Departments of Neurology in 11 hospitals with imaging facilities such as computerized tornography (CT) or magnetic resonance imaging (MRI) in Qingdao city and its surrounding counties from June 2008 to February 2009 were retrospectively collected.The risk factors for anterior circulation and posterior circulation ischemic stroke were analyzed.Results Univariate analysis showed that there were significant differences in the age,sex,history of coronary heart disease,hyperlipidemia,atrial fibrillation and basdine National Institutes of Health Stroke Scale (NIHSS) score between anterior circulation and posterior circulation ischermic stroke (all P ＜0.05).Multivariate logistic regression analysis showed that the age (odds ratio [ OR ] 1.025,95％ confidence interval [ CI ] 1.009-1.042) and the baseline NIHSS score (OR 1.052,95％ CI 1.019-1.086) tended to the interior circulation ischernic stroke,whereas coronary heart disease (OR 0.512,95％ CI 0.341-0.768) and hyperlipidemia (OR 0.585,95％ CI 0.386-0.884) tended to posterior circulation ischemic stroke,and hyperlipidemia was an independent risk factors for posterior circulation ischemic stroke.Conclusions Vascular risk factors exerted different effects on anterior circulation and posterior circulation ischemic stroke.