How to identify active constituents of traditional Chinese medicines (TCMs) and study their interactions are key problems in the development of TCMs. The inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in this study. Main active constituents of RC were confirmed by comparing their contributions to the bacteriostatic effect, and the interactions among active constituents were further researched. According to the result, in 0.8 mg-mL-1 extract of RC, the contributions of six active alkaloids including berberine, coptisine, epiberberine, palmatine and the combination of jatrorrhizine and columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore, berberine and coptisine were the main active constituents of RC that inhibited the growth of S. dysenteria. The study of interactions among the six alkaloids indicated that, 1 there were some contstituents antagonizing the inhibitory effect of RC, 2 there was a synergy effect between berberine and coptisine, 3 there were additive effects between other four alkaloids and the main active constituents. These results may provide some useful references for the establishment of the quality standard for RC and the development of multi-component TCMs.
Alkaloids ; analysis ; pharmacology ; Berberine ; analogs & derivatives ; analysis ; pharmacology ; Berberine Alkaloids ; analysis ; pharmacology ; Coptis ; chemistry ; Drug Interactions ; Drug Synergism ; Plants, Medicinal ; chemistry ; Quality Control ; Rhizome ; chemistry ; Shigella dysenteriae ; drug effects ; growth & development

Background Retinal development continues during the early postnatal period in mammals.Correct arrangement of layers and precise location of various cells in the retina are vital for forming normal visual function during critical period plasticity.Spectral-domain optical coherence tomography(SD-OCT)provides highquality in vivo retinal imaging and the possibility to measure retinal thickness longitudinally. Objective The present study was to investigate the changes of retinal thickness during critical period plasticity in rats. Methods In vivo consecutive scanning of retinal image was performed in 10 SPF Sprague-Dawley rats at postnatal day 14(P14),P18,P21,P24 and P42 with SD-OCT,and retinal histopathological examination was used to detect retinal morphologic changes at the same postnatal ages in 20 matched rats.The whole retinal thickness,the thickness from inner limiting membrane(ILM)to inner plexiform layer(IPL),the thickness of inner nuclear layer(INL)and the thickness from outer nuclear layer(ONL)to retinal pigment epithelium(RPE)were measured using Cirrus HD-OCT system and HMIAS-2000 Imaging System in retinal sections.The measurement parameters by Cirrus HD-OCT and those by hematoxylin-eosin staining were compared.The use of animals followed the Statement of National Institute of Health (USA). Results In vivo high-resolution images of rat retinas with SD-OCT compared well with histology,which enabled quantitative comparison of the SD-OCT and histological data during critical period plasticity in rats.From P14 to P42,the retinal thickness gradually decreased with the increase of rat ages(F=15.425,P=0.000),and so were the thickness from ILM to IPL,the thickness of INL and the thickness from ONL to RPE(F=3.973,P=0.007;F=17.529,P=0.000;F=7.038,P=0.000).The retinal thickness,thickness of INL.thickness from ONL to RPE measured by Cirrus HD-OCT were significantly correlated with those measured by retinal sections among P14,P18,P21,P24 and P42 rats(r=0.794,P=0.000;r=0.784,P=0.000;r=0.681,P=0.000). Conclusion SD-OCT is a demonstratably valuable technology to study the structure of retinas in rats.The retinal thickness is shown to reduce in thickness throughout the development of the retina during critical period plasticity due to the decrease in thickness of INL and the distance from the ONL to RPE,as illustrated by OCT scanning.

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
Animals ; Biomarkers ; Cardiotoxicity ; Drugs, Chinese Herbal ; toxicity ; Glutathione ; blood ; Least-Squares Analysis ; Male ; Metabolomics ; methods ; Principal Component Analysis ; Rats ; Rats, Wistar

The aim of present study is to investigate the cardioprotective effect of a new compound acetyl ferulaic isosorbide (AFI), composed of ferulaic acid (FA) and isosorbide mononitrate (ISMN) by esterification in myocardial ischemia/reperfusion (MI/R). Male Sprague-Dawley rats, subjected to 30 minutes of myocardial ischemia and 3 hours of reperfusion, randomly received one of the following treatments separately: SHAM, I/R (MI/R + solvent), SF (MI/R+SF, 40 mg x kg(-1), ig), ISMN (MI/R + ISMN, 30 mg x kg(-1), ig), SF + ISMN (MI/R + SF + ISMN, 40 mg x kg(-1) + 30 mg x kg(-1), ig) and AFI (MI/R + AFI, 10 mg x kg(-1), ig). Left ventricle developed pressures (LVDP) and the maximal first derivative of developed pressure ( +/-dP / dtmax) were monitored throughout the experiments. Myocardial infarction size, serum creatine kinase (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) production were determined at the end of reperfusion. Compared with SF, ISMN or SF + ISMN treatment groups, AFI treatment decreased infarction size (n=8, P < 0.01), improved cardiac function as evidenced by increased LVDP and +/- dP/dtmax (n=8, P < 0.05), increased serum SOD activity, reduced serum CK and LDH activities, H2O2 and MDA production (n=8, P < 0.05). The new compound AFI showed a stronger cardioprotective effect against MI/R injury than SF, ISMN or their combined administration did.
Animals ; Cardiotonic Agents ; chemical synthesis ; chemistry ; pharmacology ; Creatine Kinase ; blood ; Electrocardiography ; Hydrogen Peroxide ; blood ; Isosorbide Dinitrate ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Reperfusion Injury ; blood ; pathology ; physiopathology ; prevention & control ; Myocardium ; pathology ; Nitric Oxide ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

OBJECTIVETo measure levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α in children with newly diagnosed type 1 diabetes and to analyze their correlation with clinical indices such as infection and onset time.

METHODSA total of 33 children with newly diagnosed type 1 diabetes were assigned to the case group, and 27 healthy children to the control group. The case group was further divided into increased white blood cell (WBC) and normal WBC subgroups according to peripheral WBC level. The serum levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α were measured by enzyme-linked immunosorbent assay. Blood pH, blood sugar, blood lactate, fructosamine, peripheral leukocytes and neutrophils and some other clinical indices were also measured.

RESULTSThe level of IL-12 in the case group was higher than in the control group (P<0.001). In the case group, the level of IL-18 was negatively correlated with onset time (r=0.413, P=0.015), the neutrophil count was positively correlated with IL-1β level (r=0.413, P=0.023) and the WBC count was positively correlated with IL-18 level (r=0.352, P=0.038). IL-1β, IL-12 and IL-18 levels in the increased WBC subgroup were higher than in the normal WBC subgroup (P<0.05 for all comparisons).

CONCLUSIONSCytokine secretion disorders of Th1 cells exist in children with type 1 diabetes. Infections may induce cytokine secretion and might contribute to the early onset of diabetes.

Adolescent ; Child ; Child, Preschool ; Cytokines ; blood ; Diabetes Mellitus, Type 1 ; immunology ; Female ; Humans ; Infant ; Male ; Th1 Cells ; immunology

Abstract: To explore the clinical characteristics, diagnosis and treatment of imported severe malaria and COVID-19 co-infection cases, and to provide scientific basis for epidemic prevention and control measures. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment process and prognosis of 4 cases of severe malaria and COVID-19 co-infection with confirmed diagnosis were analyzed retrospectively. Four cases of severe malaria were African returnees of the same batch, male, aged 40-54 years old, with the same journey track. They all had African work and life history and acute onset. The main clinical manifestations were fever (4/4), chills (3/4), chills (3/4), nausea and vomiting (3/4), diarrhea (4/4), fatigue and anorexia (4/4). Two cases had headache and dizziness, confusion, muscle aches, two cases had cough, one cases had sputum, sore throat and runny urine. All 4 cases were confirmed by positive nucleic acid detection of the new coronavirus (2019-nCOV) in throat swabs. Plasmodium falciparum was found by microscopic examination of peripheral blood smears of all patients, and all of them were consistent with high altitude helminthiasis. All cases were accompanied by abnormal liver function and severe hypoproteinemia, two cases were hyperbilirubinemia, three cases were dyslipidemia, three cases were involved in abnormal tertiary hemogram with different degrees of elevation of procalcitonin, two cases were lactic acid poisoning, and one case was hypoglycemia. One case showed viral pneumonia on chest CT. All cases were treated individually according to the different conditions and were discharged after improvement, and were rechecked for 2019-nCOV nucleic acid and microscopic examination of blood smear negative for Plasmodium.During the global COVID-19 epidemic, the emergence of coinfection cases of con-infection of imported malaria parasites and severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) makes the clinical diagnosis and treatment more complicated. It is important to establish the awareness of simultaneous prevention and diagnosis of COVID-19 and malaria for local prevention and control and early warning of severe cases, and timely and effective formulation of treatment plan to improve the comprehensive treatment efficiency.

A method for the determination of trace elements such as lead, arsenic and mercury in cream cosmetics by total reflection X-ray fluorescence spectrometry (TXRF) with suspension sampling was developed. The mixed solvents of water,tetrahydrofuran,methanol and were used to disperse paste, cream, and additives of triton X-100 to promote the test liquid uniform. The test suspension fluid were taken into the sample carrier,drying and then introduced into TXRF. Poly(1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VAc)) was added to curing sediments,inhibiting proliferation. Triton X-100 and P(VP-co-VAc) were found to have the function of reducing mercury loss in the drying process. The loss of elements in the drying process and the effect of triton X-100 and P(VP-co-VAc) were investigated. The effect of cream matrix, element interference, spectral line and the inner standard were discussed. The calibration curves for quantitative analysis were established using matrix standards, so the error of software decomposition peak and the error caused by thick sample were avoided within a certain range. In this work,the linear correlation coefficients of Pb,As and Hg calibration curve were greater than 0.998 The detection limit of Pb,As and Hg in the solution were 0.005,0.004 and 0.006 μg/mL,respectively. Relative standard diviations(RSDs, n=11) of Pb, As and Hg were 7.8%-14.9%,6.6%-13.3% and 7.6%-14.6% respectively. The results of Pb, As, and Hg in cream cosmetics determinated by this method agreed with those obtained from inductively coupled plasma atomic emission spectrometry and the value of standard reference material. The TXRF method was proved to be accurate,simple and valuable in determination of trace heavy metal ions in cosmetic samples.

OBJECTIVETo explore the effect of pro-angiogenic factors and their receptors on angiogenesis in hepatocellular carcinoma.

METHODSExpression of VEGF/KDR and Angiopoietins/Tie2 was detected by RT-PCR and Western blot in 15 cases with hepatocellular carcinoma, 15 tumor adjacent tissues (<1 cm, >5 cm), 8 cirrhotic liver, and 4 normal liver. Immunohistochemistry (IHC) was used to detect CD34 expression, and the relationship between neovascular density and angiogenesis was analyzed.

RESULTSThe expression levels of VEGF and Ang2 were significantly higher in hepacellular carcinoma group than those in the other groups (P < 0.01), and so did the expression of CD34. The expressions of KDR and Ang1/Tie2 showed no significant difference in all groups, but they indeed increased to various levels in tumor and tumor adjacent tissues as compared with those in cirrhosis and normal liver.

CONCLUSIONVEGF/KDR and Angiopoietins/Tie2 may be the crucial signal pathways in the development of hepatocellular carcinoma.

Adult ; Aged ; Angiopoietin-2 ; biosynthesis ; genetics ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Humans ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Middle Aged ; Neovascularization, Pathologic ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, TIE-2 ; biosynthesis ; genetics ; Signal Transduction ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis ; genetics

BACKGROUNDThere is no research, either at home or abroad, focusing on assessing the cardiopulmonary functional reserve and exercise tolerance in patients with pulmonary embolism (PE), but the benefits of early exercise are well recognized. The goals of this study were to assess cardiopulmonary functional reserve in treated PE patients using the inert gas rebreathing method of the cardiopulmonary exercise test (CPET), and to compare it with traditional methods.

METHODSCPET on the bicycle ergometer were performed in 40 patients with age, gender, body mass index, systolic blood pressure, and pulmonary function matched. The first group was the PE group composed of 16 PE patients (5 male, 11 female) who were given the standard antithrombotic therapy for two weeks. The second group was composed of 24 normal individuals (10 male, 14 female). Both groups were evaluated by cardiac ultrasound examination, 6-minute walking test (6MWT), and CPET.

RESULTS(1) Right ventricular systolic pressure (RVSP) in the PE group increased significantly compared to the control group, (34.81 ± 8.15) mmHg to (19.75 ± 3.47) mmHg (P < 0.01). But neither right atrial end-systolic diameter (RASD) nor right ventricular end-diastolic diameter (RVDD) in the PE patients had changed when compared with the controls. The 6-minute walk distance was significantly reduced in the PE patients compared with normal subjects, (447.81 ± 79.20) m vs. (513.75 ± 31.45) m (P < 0.01). Both anaerobic threshold oxygen consumption (VO(2)AT) and peak oxygen consumption (VO(2)peak) were significantly lower in patients with PE, while CO(2) equivalent ventilation (VE/VCO(2) slope) was higher; VO(2)AT (9.44 ± 3.82) ml×kg(-1)×min(-1) vs. (14.62 ± 2.93) ml×kg(-1)×min(-1) (P < 0.01) and VO2peak (12.26 ± 4.06) ml×kg(-1)×min(-1) vs. (23.46 ± 6.15) ml×kg(-1)×min(-1) (P < 0.01) and VE/VCO(2) slope 35.47 ± 6.66 vs. 26.94 ± 3.16 (P < 0.01). There was no significant difference in resting cardiac output (CO) between the PE and normal groups, whereas peak cardiac output (peak CO) and the difference between exercise and resting cardiac output (ΔCO) were both significantly reduced in the PE group; peak CO (5.97 ± 2.25) L/min to (8.50 ± 3.13) L/min (P < 0.01), ΔCO (1.29 ± 1.59) L/min to (3.97 ± 2.02) L/min (P < 0.01). (2) The 6-minute walk distance did not correlated with CPET except for the VO2 peak in patients with PE, r = 0.675 (P < 0.01).

CONCLUSIONSThe cardiopulmonary functional reserve was reduced in patients with PE. CPET is an accurate, quantitative evaluation of cardiopulmonary functional reserve for PE patients.

Aged ; Exercise Test ; methods ; Exercise Tolerance ; physiology ; Female ; Humans ; Male ; Middle Aged ; Oxygen Consumption ; physiology ; Pulmonary Embolism ; physiopathology ; therapy

OBJECTIVETissue factor (TF) is an important factor in extrinsic coagulation. Tissue factor pathway inhibitor (TFPI) is a negative regulator of coagulation mediated by TF. Studies on TF and TFPI focus mainly on adult objects, seldom have been done on newborns, especially on sick newborns. The aim of this study was to observe the changes of TF and TFPI in plasma of newborns with infection jaundice and to research the effect of jaundice and infection on the balance of TF and TFPI in newborns.

METHODSThe content of TF and TFPI in plasma of 21 jaundiced newborns with infection and 8 jaundiced newborns without infection as control was determined quantitatively with the enzyme-linked immunosorbent assay (ELISA).

RESULTSThe content of TFPI and TF in plasma of jaundiced newborn with infection was significantly higher than that of controls [TFPI (21.0 +/- 4.3) vs. (16.2 +/- 1.9) microg/L, P < 0.01; TF (177 +/- 79) vs. (51 +/- 24) ng/L, P < 0.01]. The ratio of TFPI/TF was significantly lower in newborn with infection jaundice than the controls (137 +/- 61 vs. 319 +/- 67, P < 0.01). The 21 jaundiced newborns with infection were divided into the severe hyperbilirubinemia group (serum bilirubin > or = 205.2 micromol/L, n = 10) and the mild hyperbilirubinemia group (serum bilirubin < 205.2 micromol/L, n = 11). There was no significant difference of TFPI level between the severe hyperbilirubinemia group and mild hyperbilirubinemia group (P > 0.05). The TF content in the severe hyperbilirubinemia group was higher than that in the mild hyperbilirubinemia group (216 +/- 79 vs.141 +/- 63, P < 0.01), while the ration of TFPI/TF was lower in the severe hyperbilirubinemia group than in the mild hyperbilirubinemia group (100 +/- 30 vs. 171 +/- 74, P < 0.01).

CONCLUSIONInfection might induce imbalance between the coagulation inhibition and activation in newborns. Hyperbilirubinemia can aggravate the imbalance induced by the infection through increasing plasma TF level.

Bacterial Infections ; blood ; complications ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; blood ; etiology ; Lipoproteins ; blood ; Male ; Thromboplastin ; analysis