Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

The value of virtual monoenergetic images and electron density map derived from dual-layer spectral detector CT in differentiating benign from malignant pulmonary ground glass nodules / 中华放射学杂志

Objective:To investigate the clinical value of virtual monoenergetic images (VMI) and electron density map (EDM) derived from the dual-layer spectral detector CT (DLCT) in the differential diagnosis of benign and malignant pulmonary ground glass nodules (GGN).Methods:From July 2019 to August 2020, a total of 65 patients with lung GGN (27 benign GGNs and 38 malignant GGNs) confirmed by pathology were retrospectively enrolled in Gulou Clinical Medical College of Nanjing Medical University. All the patients underwent DLCT plain scanning within two weeks before the surgery. The conventional 120 kVp polyenergetic image (PI), EDM and 40-80 keV VMI were reconstructed. The differences of CT and electron density (ED) values between benign and malignant lesions on different images were compared by Mann-Whitney U test. Independent t-test was used to compare the lesion size and χ 2 test was used to analyze the CT features (including lesion location, shape, edge, internal structure, adjacent structure, nodule type) between benign and malignant lesions. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of different energy spectrum quantitative parameters in the differential diagnosis of benign and malignant GGN. The statistically significant CT signs and energy spectrum quantitative parameters were analyzed by logistic regression analysis to find out the independent risk factors of malignant GGN, and then ROC curve analysis was performed for each independent risk factor alone or in combination. Results:There were significant differences in lesion shape, spiculation, lobulation, location and size between benign and malignant groups ( P<0.05). The CT value of pulmonary GGN in PI, 40-80 keV VMI and the ED value in EDM were statistically different between benign and malignant lesions ( P<0.05). The area under ROC curve (AUC) were 0.680, 0.682, 0.683, 0.686, 0.694, 0.676 and 0.722, respectively, among which the ED value had the highest AUC. Binary logistic regression analysis was carried out with GGN shape, spiculation, lobulation, location, size, ED value and CT value in PI, 40-80 keV VMI as independent variables, and malignant GGN as dependent variables. The results showed that ED value (OR=1.045, 95%CI 1.001-1.090, P=0.044), lesion size (OR=1.582, 95%CI 1.159-2.158, P=0.004), spiculation sign (OR=11.352, 95%CI 2.379-54.172, P=0.002) were independent risk factors for malignant GGN. ROC curve analysis showed the AUC of ED value, lesion size, spiculation sign and combination of the three for differential diagnosis of benign and malignant GGN were 0.722, 0.772, 0.698 and 0.885. The AUC for the combined parameters was the largest, with sensitivity of 92.1% and specificity of 74.1%. Conclusion:The diagnostic efficacy of EDM is higher than that of other VMI in the differential diagnosis of pulmonary GGN by DLCT images; The efficacy is further improved when EDM is combined with lesion size and spiculation sign for comprehensive diagnosis.

Investigation and analysis on resources and radiation protection status of interventional radiology in Beijing / 中华放射医学与防护杂志

Objective:To ascertain the distribution of interventional radiodiagnosis and treatment resources and the current situation of radiological protection in Beijing, standardize the interventional radiodiagnosis and treatment, and promote the implementation of radiation protection regulatory measures.Methods:Various medical institutions at differetn levels that perform interventional radiodiagnosis and treatment in Beijing were identified as the survey objects. With special questionnaires designed, the investigation groups at two levels of municipality and district was established to investigate the basic situation of interventional radiology and occupational health monitoring by the end of 2020. The indexes and parameters were analyzed and evaluated under the relevant national regulations and standards.Results:By the end of 2020, there were 93 medical institutions performing interventional radiology in Beijing, together with 236 digital subtraction angiography machines (DSA) with higher than 800 mA. A total of 135 593 cases of interventional radiological surgical operation were performed. There were 40 hospitals annually performing more than 1 000 cases and 41 hospitals perfoming 10-1 000 cases. There were 3 539 interventional radiological workers, with 99.0% holding radiological worker certificates. The passing rates of occupational health examination, personal dose monitoring and radiation protection training were 96.9%, 99.5% and 95.8%, respectively. A total of 3 532 sets of protective articles were provided for the workers, of which 98.9% were equipped with split or integrated lead clothing, but 6.5% were not equipped with lead protective glasses and 54.9% were not equipped with lead protective gloves.Conclusions:The radiation protection management for the interventional radiodiagnosis and treatment is generally good. However, the regulatory mechanism should be further improved based on the current distribution of interventional radiodiagnosis and treatment resources, with focus on strengthening the occupational health examination, the radiation protection training, and the configuration and use of protective equipment.

Analysis of radiation health management in health examination institutions in Beijing / 中国辐射卫生

Objective To understand the situation of radiological diagnosis and treatment of health examination institutions in our city, and standardize the behavior of radiological diagnosis and treatment of health examination institutions. Methods According to the requirements of the circular issued by Beijing Institute of health and family planning on carrying out special supervision and inspection of radiation diagnosis and treatment in health examinaion institutions in 2019, on-site investigation and on-site interviews were conducted. Results The investigation on the health examination institution shows that the radiation hygiene management work of Beijing health examination institution is generally good, and the holding rate of radiological diagnosis and treatment permit is 100%. The radiological diagnosis and treatment of health examination institutions is mainly based on X ray photograph. A total of 215 institutions were configured with 822 radiological diagnosis and treatment equipment, including 138 CT machines and 20 physical examination vehicles, respectively. X ray radiography equipment in health examination institutions accounted for 93% of total application frequency, and CT accounted for 7%. The annual radiodiagnosis frequency of the 215 health examination institutions was about 5 million. The penal institutions accounted for a relatively low proportion, only 2.8%. Among them, 6 were warned, 2 fined, 6 issued penalties and 3 required to rectify. Conclusion The radiation hygiene management work of Beijing health examination institutions is generally good. There are still some problems in the rational application of CT machines and the configuration of protective equipment.

Association between HLA-DQ gene polymorphisms and different outcomes of hepatitis B virus infection / 中华流行病学杂志

Objective To understand the association between two single-nucleotide polymorphism (HLA-DQ rs28567185 and rs9275572) and different outcomes of hepatitis B virus (HBV) infection.Methods A total of 825 HBV infection related cases were enrolled,and peripheral blood samples were collected from them for DNA extraction.The single-nucleotide polymorphism in HLA-DQ region were genotyped by using matrix-assisted laser desorption/ionization time of flight mass spectrometry.Logistic regression analysis was conducted to evaluate the association between HLA-DQ gene polymorphism and different outcomes of hepatitis B virus infection.Results Our study indicated that cases with HLA-DQ rs2856718G (524 cases) and rs9275572A (369 cases) had reduced susceptibility to HBV infection (OR=0.702,95％CI:0.558-0.856,P=0.001;OR=0.548,95％C1:0.365-0.847,P=0.005) and higher HBV natural clearance (OR=0.589,95％ CI:0.478-0.892,P=8.81 × 10-3;OR=0.673,95％CI:0.457-0.860,P=0.014).Moreover,rs9275572A was also associated with the lower risk of the development of hepatocellular carcinoma (OR=0.759,95％CI:0.538-0.914,P=0.041).Conclusion Our study suggested that HLA-DQ loci might be associated with the different outcomes of HBV infection in Chinese in Han ethnic group in northern China,rs2856718G and rs9275572A might be protective factors for HBV infection,HBV natural clearance and HBV-related disease progress.

Research progression of PPARgamma to bone remodeling / 生物医学工程学杂志

Peroxisome proliferator activated receptor gamma interacts with bone morphogenetic protein, Wnt, TAZ, and insulin-like growth factor-I, which are required for the process of osteoblast differentiation, regulating the mesenchymal stem cells (MSCs) into adipocytes and osteoblasts differentiation, thus impact on the osteoblast-mediated bone formation in bone remodeling, and, through RANKL and other factors directly or indirectly, regulate osteoclast-mediated bone resorption. This article reviews new researches for the influence of peroxisome proliferator activated receptor gamma on osteoblast and osteoclast function in bone remodeling.

Determination of mangiferin in rat plasma and aqueous humor by HPLC / 中国中药杂志

A HPLC method was developed for the determination of mangiferin in rat plasma and aqueous humor. 4-Nitrophenol was used as internal standard. Analysis was performed on a Cosmosil ODS C18 analytical column (4.6 mm x 250 mm, 5 microm) with mobile phase consisting of methanol-water (40: 60) with 2% glacial acetic acid at a flow rate of 1.0 mL x min(-1). The calibration curve of mangiferin in rat plasma and aqueous humor showed excellent linear behaviors over the investigated concentration of 0. 50-250.00 mg x L(-1) in plasma and 0.10-10.00 mg x L(-1) in aqueous humor, respectively, and the correlation coefficients were all above 0.995 4. The intra-day and inter-day precisions for all samples were measured to be below 12%. The limit of quantitation was 0.10 mg x L(-1) and low enough for the determination of mangiferin in all samples. The validated method has been successfully applied to preliminary pharmacokinetics study of mangiferin in rat plasma and aqueous humor.

Effect of the Wnt/LRP5/β-catenin signaling pathway on the pathogenesis of postmenopausal osteoporosis / 中华妇产科杂志

Objective To investigate the role of the Wnt/LRPS/3-catenin signaling pathway in the pathogenesis of postmenopausal osteoporosis.Methods Fifty female Wistar rats aged 6-month-old,were randomly divided into control group ( NS,n =24 ) and ovariectomized group ( NOVX,n =26),NOVX underwent bilateral ovariectomy.At 0,4 and 8 weeks,all of rats were measured blood estrogen ( E2 ) and bone mineral density (BMD),4 and 8 weeks,low density lipoprotein receptor-related protein 5 (LRP5),3-catenin and Runx2 mRNA in bone were measured respectively by reverse transcription (RT)-PCR.Results In 4 and 8 weeks,compared with NS which had (117±29) and (114+15) pmol/L in E2 level,(0.098 ± 0.016 ) and (0.095 ± 0.028 ) g/cm2 in BMD,NOVX had significantly decreased to ( 92±15 ) and(95±22) pmol/L in E2 level ( P＜0.05 ),( 0.076 ± 0.016) and ( 0.052 ± 0.013 ) g/cm2 in BMD values ( P ＜ 0.01 ).And bone tissue LRP5,β-catenin and Runx2 mRNA expression was 1.02 ± 0.06,1.04 ±0.05,1.07 ±0.21 in NS,NOVX was significantly reduced to 0.97 ± 0.04,0.58 ± 0.05,0.86 ±0.03 (P＜0.05).Conclusion Wnt/LRP5/β-catenin signaling pathway may be important in the pathogenesis of postmenopausal osteoporosis.

Effects of acute injection of BRL 37344 on hemodynamics and β-adrenoreceptors expression in myocardium of rats with heart failure / 中国药理学与毒理学杂志

AIM To observe whether acute stimulation of BRL 37344, a β3-adrenergic receptor (β3-AR) agonist, has the same effects of exacerbating hemodynamics and increasing in β3-AR expression on rats with failing heart as chronic administration. METHODSRats received two doses of isoprenaline (Iso, 340 mg·kg-1, sc, with a 24-h interval) to prepare heart failure model. After 8 weeks, rats were given iv BRL 37344 0.4 nmol·kg-1·min-1 for 10 min. Hemodynamics were measured at 0, 10, 30 min, 1, 2, 3 h, 1, 2 and 7 d after BRL 37344. Levels of β-AR mRNA in myocardium were measured at 0, 1, 2 and 7 d after BRL 37344 by reverse transcription-polymerase chain reaction. RESULTSCompared with Iso group, heart rate, left ventricular end systolic pressure and +dp/dtmax were significantly higher, and left ventricular end diastolic pressure was significantly lower during 1-3 h after BRL 37344 injection in Iso+BRL group. Then, they were restored to the same level as that prior to BRL 37344 injection. Compared with normal control, the levels of β1-, β2- and β3-AR mRNA displayed no significant change in BRL group;the level of β1-AR mRNA was lower and the level of β3-AR mRNA was higher in Iso group. In Iso+BRL group, much more lower β1-AR mRNA level and much higher β3-AR mRNA level were shown on d 2 and d 7 than Iso group. CONCLUSION Acute administration of β3-AR agonist has a shorter improved hemodynamics. But it caused the same result as chronic administration in reduction of β1-AR mRNA and increment of β3-AR mRNA in failure hearts, which may aggravate the cardiac functions.

Protective effect of resveratrol on rats with acute myocardial ischemia / 中国组织工程研究

BACKGROUND: Resveratrol is a naturally occurring phytoalexin present in grapes, peanut and some herbs. It has been demonstrated to produce a variety of biological actions, such as anticancer, antiinflammation. Accumulating line of evidence supported the view that resveratrol may exert protective effect on cardiovascular system. However, its protective mechanism is not completely understood.OBJECTIVE: To investigate the anti-ischemic effect and mechanism of resveratrol (Res) on acute myocardial infarction in rats.DESIGN: Randomly grouping paralleled control study.SETTING: Pharmacological Laboratory of Harbin Medical University, Biopharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory.MATERIALS: The experiment was carried out in Department of Pharmacology of Harbin Medical University from March 2005 to July 2005.Totally 80 male Wistar rats weighting 250-300 g were selected in this study. Among them, 60 rats after operation successful modeling were randomly grouped into 5 groups: sham operation group, blank control group,resveratrol 5 mg/kg, 15 mg/kg and 45 mg/kg groups with 12 in each group.METHODS: Acute myocardial infarction (AMI) model was induced by ligation of the anterior branch of the left coronary artery in rat, Sham operation group: The same suture was put through but not ligated. Resveratrol group: Rats were injected with 5, 15 and 45 resveratrol mg/kg provided by Hunan Huaguang Biological Products Company Limited (batch number: 20050221, purity ≥99%) and ligated after 10 minutes. Model group: The same volume saline was injected for 10 minutes and then rats were ligated. Observe and record ST segment of standard limb lead Ⅱ electrocardiogram (ECG)after 1, 5, 10, 15, 30 minutes after ligating the left anterior decendingcoronary artery. After 6-hour ischemia, the infarct size areas was identified with the myocardium by 2, 3, 5-triphenyltetrazolium chloride (TTC) stain; the activities of serum .creatine kinase (CK)and lactate dehydrogenase (LDH) were determined by spectrophotometric method; the apoptosis in cardiomyocyte was detected by d-UTP end labeling method mediated with tagged deoxynucleotide transferase in situ (TUNEL); apoptosis-related proteins of Bcl-2, Bax and Fas expression were measured with estreptomicina avidin peroxidase chain. Measurement data were compared with t test.MAIN OUTCOME MEATURES: ST increase; the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH); the infarct size areas and the apoptosis rate in cardiomyocyte; the. expression of apoptosis-related proteins of Bcl-2, Bax and Fas.RESULTS: All of the 60 rats entered the final analysis. ① ST segment raise in high dosage group was lower than that in model group 1, 5 and 10 minutes after ligation (P ＜ 0.05), and it was also lower than that in model 15 and 30 minutes after ligation (P ＜ 0.05). This effect was dose-dependent. ② Infarct size in each dosage group was smaller than that in model group (P ＜ 0.05). This effect was dose-dependent. ③ The activities of CK and LDH in different dosages of resveratrol groups were significantly lower than those in model group (P ＜ 0.05). This effect was dose-dependent. ④ Apoptosis index in model group was higher than different dosages of resveratrol groups (P ＜ 0.05); The expression levels of Bax and Fas proteins in model group were higher than those in high and middle dosages of resveratrol groups (P ＜ 0.05); The expression level of Bcl-2 protein was lower than that in high and middle dosges of resveratrol groups (P ＜ 0.05).These effects were dose-dependent.CONCLUSION: Resveratrol can protect acute myocardial ischemic injury induced by coronary artery of ligated rats, and the effect is dose-dependent.Effect of resveratrol on myocardial ischemia is related to adjusting expressions of Fas, Bcl-2 and Bax and inhibiting myocardial apoptosis.

Modulation of HERG/I_(Kr) in pathological condition and effect of traditional chinese medicine on HERG/I_(Kr) / 中国药理学通报

HERG/IKr plays an important role in repolarization of cardiac action potential. In pathological condition such as cardiac ischemia, congestive heart failure and myocardial hypertrophy, the density and kinetic properties of HERG/IKr will change. This review is about modulation of HERG/IKr in pathological condition and effect of traditional chinese medicine on HERG/IKr.

Correlation of CT findings with histopathology in patients with T1 non-small cell lung cancer / 医学研究生学报

Initial studies suggested a low prevalence of nodal metastases in T1 lung cancer.However,several recent studies have reported a relatively high prevalence of mediastinal lymph node metastases.The extrathoracic metastases in T1 lung cancer differs widely(0%-24%).In this article,we discuss the thinsection CT and FDG-PET findings in T1 non-small cell lung cancer and also discuss the correlation of CT findings with prognosis and survival,the correlation between tumor size and survival,and extrathoracic metastasis of T1 lung cancer.

Fe(CN)3-6 Chemiluminescence System for the Determination of Rutin / 分析化学

A novel chemiluminescence (CL) system combined with flow injection analysis for the determination of rutin is presented . It is based on the CL reaction of rutin and hexacyanoferrate*# in sodium hydroxide medium. The proposed method has a linear range of 1×10-4g/mL ～ 1×10-6 g/mL with a RSD of 3.7%(5×10-6g/mL,n=11) and a sample throughput of 60 h-1. The method was successfully applied to the determination of rutin in a pharmaceutical preparation.

Cervical Spondylopathy Treated with Elevating--rota-tion Reduction: Report of 368? cases / 中医杂志

Based on the limitation of the segmental activityand signs of local tenderness,location diagnosis andtreatment for cervical pain and referred pain was per-formed with elevating—rotation reduction.Clinically, attention should be given to the combination of X—rayfilm and signs and symptom.The total effective ratefor 3687 eases thus treated was rather high.

Effect of carvedilol on HERG K~+ channels electric physiological function and protein expression / 中国药理学通报

Aim To investigate the direct effects and mechanism of carvedilol on HERG channel stably expressing in human embryonic kidney-293(HEK293) cells.Methods Whole-cell patch-clamp technique was used to record HERG current and kinetic curves in single cells.Western blot methods were used to investigate the expression of HERG channel in different concentration of carvedilol.Result Carvedilol decreased HERG current in a concentration-dependent manner with an IC50 539.6 nmol?L-1,Hillslope-0.64.The time constants of onset of inactivation and deactivation were accelerated.Other kinetcs(activation,inactivation,recovery from inactivation)had no significant changes.Based on western result,carvedilol had no effect on the generation and trafficking of HERG protein.Conclusion Carvedilol inhibits the transfected HERG channels by influencing the open state which is the probable anti-arrhythmic mechanism.There is no relationship between carvedilol and HERG channel expression.