Flavonoids is one of the biggest families of the plant-derived secondary metabolites with structural diversity. Until now, over 10 000 kinds of flavonoids with distinct structures have been purified and identified from plants, and some of them possess a range of important pharmacological effects, such as anticancer, anti-inflammatory and so on. So far, a number of genes and enzymes responsible for the biosynthesis of flavonoids have been reported, especially, a great of progress has been achieved in the synthetic biology of flavonoids in the recent years. Herein, based upon a brief introduction on the biosynthesis of flavonoids, this review summarizes the research advances in synthetic biology of flavonoids in the past two decades (2001-2021), highlighting the cell factories construction of the representative flavonoids. And, a brief discussion and prospects of the relevant metabolic bottlenecks and optimizing strategies are proposed.

Objective To analyze the clinical features of pandrug-resistant Acinetobacter baumannii (PDR-Ab) in a hospital and compare the efficacy of different antibiotic treatments on patients with pneumonia caused by PDR-Ab.Methods Data were ret- rospectively collected from all isolated PDR-Ab strains in our hospital from February 2004 to March 2005.The clinical features and outcomes were reviewed.Results A total of 77 strains of PDR-Ab were collected, 45 of which were pathogens causing clini- cal infections (35 strains from lower respiratory tract, 6 from bloodstream, 3 from drainage fluid, and 1 from wounds).Lower respiratory tract was the most common source of PDR-Ab.More than 90% of the isolated PDR-Ab strains produced OXA-23 type?-lactamase.Cefoperazone-sulbactam plus minocyeline showed good efficacy for patients with PDR-Ab pneumonia.The total clinical cure rate was 68.4%.Bacterial eradication rate was 42.1%.The factors influencing bacterial clearance were pro- longed mechanical ventilation prior to positive culture (17.5 d vs 5.5 d).mixed infection (100% vs 12.5%) and lower GCS score (9.1?0.7 vs 13.2?2.1).Concomitant septic shock (OR=13.8) and APACHEⅡscore (OR=2.1) were independent factors of clinical outcome.Conclusions Nosocomial infections caused by PDR-Ab are not untreatable.Our analysis suggests that cefoperazone-sulbactam plus minocycline may be an effective treatment for lower respiratory tract infections caused by PDR-Ab in our hospital.

This study was aimed to clone human intercellular adhesion molecule-1 (ICAM-1) gene, to transfect the constructed eukaryotic expression vector ICAM-1-GFP into CHO cells, as well as to detect ICAM-1-GFP expression in CHO cells binding with Molt-4 cells. ICAM-1 cDNA gene was amplified by RT-PCR and inserted in PMD(18)-T vector. Then ICAM-1 cDNA from pMD18-ICAM-1 vector was subcloned into eukaryotic expression vector pEGFP-C1 to construct recombinant ICAM-1-pEGFP-C1 vector. Restriction analysis and DNA sequencing were used to confirm the recombinant vector. After stable transfection of CHO-K1 cells with the recombinant vector, the expression and subcellular localization of ICAM-1-GFP were detected by RT-PCR, flow cytometry and fluorescence microscopy. The function of ICAM-1-GFP fusion protein was assessed by the binding of ICAM-1-GFP/CHO cells to Molt-4 cells. The results showed that 1622 bp full-length ICAM-1 cDNA obtained and was successfully ligated with pMD(18)-T-vector, subcloned to construct recombinant ICAM-1-pEGFP-C1 vector. Restriction analysis and DNA sequencing indicated that recombinant ICAM-1-GFP was successfully constructed and ICAM-1-GFP was expressed stably in CHO cells. ICAM-1-GFP expression was only observed in the cytoplasm of ICAM-1-GFP/CHO cells by fluorescence microscopy. The ICAM-1-GFP/CHO cells were bound to PMA-treated Molt-4 cells. The expression of MEM-148 was very weak in PMA-treated Molt-4 cells. It is concluded that the ICAM-1-GFP eukaryotic expression vector has been constructed successfully and expresses stably in CHO cells. PMA can increase the binding of Molt-4 cells to ICAM-1-GFP/CHO cells by inducing specialized form of ICAM-1 clustering.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; DNA, Complementary ; genetics ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; Recombinant Proteins ; genetics ; Transfection

A kind of intermittent pneumatic compression (IPC) apparatus is developed to prevent deep vein thrombosis (DVT),which is based on the theory of occurrence and prevention of the DVT and AT89C52 micro-controller. This paper introduces its principle, composition of electromechanical system and the software design. The apparatus has showed its characteristics of easy operation, high intelligence and high reliability.
Equipment Design ; Physical Therapy Modalities ; instrumentation ; Software ; Thrombolytic Therapy ; instrumentation ; Venous Thrombosis ; prevention & control

As a basic amino acid, histidine has a pK_a close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

Liver is regarded as one of the most important organs for drug clearance in the body, which mediates both the metabolism and biliary excretion of drugs. Transporters are a class of functional membrane proteins and control the movement of substances into or out of cells. Transporters, which are extensively expressed in the liver, play important roles in the drug hepatic disposition by regulating the uptake of drugs from blood into hepatocytes or the efflux of drugs and their metabolites into bile. In this review, the localization, functions and substrate selectivity of the major transporters in the liver will be summarized, and the impacts of these transporters on drug hepatic disposition, the potential drug-drug interactions as well as their genetic polymorphisms will also be reviewed.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Bile ; metabolism ; Biological Transport ; Drug Interactions ; Humans ; Liver ; metabolism ; Membrane Transport Proteins ; genetics ; metabolism ; Metabolic Clearance Rate ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Organic Anion Transporters ; genetics ; metabolism ; Organic Anion Transporters, Sodium-Dependent ; metabolism ; Organic Anion Transporters, Sodium-Independent ; genetics ; metabolism ; Organic Cation Transport Proteins ; genetics ; metabolism ; Pharmacokinetics ; Polymorphism, Genetic ; Symporters ; metabolism

Objective To investigate the mRNA and protein expression levels of interferon(IFN)-?in the peripheral blood of patients with systemic lupus erythematosus(SLE),to analyze the relationship between IFN-?and disease activity,and to evaluate the role of IFN-?in the pathogenesis of lupus.Methods SYBR green dyeⅠbased real-time quantatives PCR method was used to compare the mRNA expression levels of IFN-?in the peripheral blood leucocyte of SLE patients and healthy controls.Surum levels of IFN-?were measured with ELISA method.Results IFNA1 mRNA expression level in SLE patients(2.8?3.5)was signifi- cantly lower than that of normal controls(12.7?10.7,P=0.000).There was no significant difference between patients treated with glucocorticoid and those without in the expression level of IFNA1(P=0.549).Serum levels of IFN-?in SLE patients was significantly higher than that of normal controls(P=0.003).The SLEDAI score and anti-dsDNA antibody correlated positively,and complement components C3,C4 and leukocytes correlated negatively with serum concentration of IFN-?.IFN-?level correlated with the presence of fever and rash. Conclusion The close relationship between IFN-?serum level and disease activity in SLE patients suggests that IFN-?might be of importance in the disease process.

OBJECTIVETo observe the effects of warming yang method, nourishing yin method, activating blood method, and the combined treatment method on the ventricular remodeling (VR) and the heart function of heart failure (HF) rats of Shen-yang deficiency syndrome (SYDS).

METHODSThe Sprague-Dawley (SD) HF rat model of SYDS was established by continuously intravenous dripping adriamycin after economizing bilateral thyroid tissues. Rats were then randomly divided into the model group (administered with normal saline at the daily dose of 6 mL/kg by gastrogavage), the warming yang group (administered with Wenyang Jianxinling Extractum at the daily dose of 6 mL/kg by gastrogavage), the activating blood group (administered with Ligusticum Wallichii and Salvia Miltiorrhiza Extractum at the daily dose of 6 mL/kg by gastrogavage), the nourishing yin group (administered with Radix Ophiopogonis and Rhizoma Anemarrhenae Extractum at the daily dose of 6 mL/kg by gastrogavage), and the combined treatment group (administered with Yin-Yang Supplementing Extractum at the daily dose of 6 mL/kg by gastrogavage), 10 in each group. Another 10 SD rats were taken as the normal control group. They ate food and drank water freely. All rats were intervened for four successive weeks. The left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure of development ( +dp/dtmax), and maximal rate of left ventricular pressure of decline (-dp/dtmax) were observed. The systolic blood pressure (SBP) and the diastolic blood pressure (DBP) were determined. The mean arterial pressure (MAP) was calculated. The heart rate (HR) was recorded. Then all rats were killed and their hearts were taken out to weigh the heart mass (HM), the left ventricular mass (LVM), the right ventricular mass (RVM). The heart mass index (HMI) and the left ventricular mass index (LVMI) were calculated. The mRNA expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP1) in the myocardium were detected using RT-PCR. The serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), MMP-9, and TIMP-1 were assayed by double antibody sandwich ELISA.

RESULTSCompared with the normal control group, HR, LVEDP, HM, LVM, HMI, RVM, LVMI, NT-proBNP, MMP-9, and MMP-9 mRNA significantly increased, but SBP, DBP, MAP, LVSP, +/- dp/dtmax, TIMP-1, and TIMP-1 mRNA significantly decreased in the model group with statistical difference (P<0.05). Compared with the model group, SBP and DBP, +/-dp/dtmax increased,while LVEDP, NT-proBNP, and MMP-9 decreased in the warming yang group. HR, LVEDP, HM, LVM, HMI, RVM, LVMI, MMP-9 mRNA, NT-proBNP, and MMP-9 significantly decreased, while TIMP-1 mRNA increased in the activating blood group. HR, LVEDP, +/- dp/dtmax, LVMI, NT-proBNP, and MMP-9 decreased, while TIMP-1 increased in the combined treatment group, showing statistical difference (P<0.05). Compared with the warming yang group, SBP and +dp/dtmax decreased in the nourishing yin group; HR and MMP-9 mRNA decreased in the activating blood group, HR decreased in the combined treatment group, all showing statistical difference (P<0.05). There was no statistical difference in the rest indices (P>0.05).

CONCLUSIONActivating blood method and combined treatment method could regulate the expressions of MMP-9 and TIMP1 mRNA of HF rats of SYDS, effectively ameliorate the VR, and improve the HF.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Failure ; drug therapy ; metabolism ; physiopathology ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Ventricular Remodeling ; Yang Deficiency ; drug therapy ; metabolism ; physiopathology

OBJECTIVETo identify the anatomical variability of the left spermatic vein (LSV) and determine its effect on the induction of experimental left varicocele (ELV) in adolescent rats.

METHODSWe equally randomized 30 adolescent male SD rats to groups A (LSV collaterals fully ligated and the left renal vein constricted), B (only the left renal vein constricted), and C (sham operation), observed the courses of the LSVs and measured their diameters. At 30 days after operation, we analyzed the changes in the left kidneys and the diameters of the LSVs.

RESULTSIrregular collaterals were observed in 90% of the LSVs and no abnormal changes were found in the left kidneys after surgery. The postoperative LSV diameter was remarkably increased in group A as compared with the baseline ([1.47 +/- 0.15 ] vs [0.16 +/- 0.08] mm, P < 0.01), but showed no significant difference in group B ([0.31 +/- 0.49] vs [0.15 +/- 0.07] mm, P > 0.05) and C ([0.17 +/- 0.07] vs [0.16 +/- 0.06] mm, P > 0.05), and it was significantly longer in A than in B (P < 0.01). The success rate of ELV induction was 100% in group A and 10% in group B, but no varicocele was observed in group C.

CONCLUSIONCorrect identification of the anatomical course of the LSV and ligation of its irregular collaterals are essential for the establishment of a stable and consistent ELV model.

Animals ; Disease Models, Animal ; Kidney ; pathology ; Ligation ; Male ; Rats ; Rats, Sprague-Dawley ; Spermatic Cord ; blood supply ; Varicocele ; Veins ; abnormalities

Objective: To study the protective effects of Panax quinquefolium 20s-protopanaxdiolsaponins extracted from leaves of P.quinquefolium（PQDS）on acute myocardial infarction（AMI）in dogs. Method：The parameters of myocardial infart size , the serum CK and LDH activity, myocardial metabolism,free radicals and coronary circulation etc were determined by using the model of ligation of LAD in the anaesthetized open-chest dogs. Result：In dogs treated with PQDS（in a dosage of 10 and 20 mg*kg-1 iv infusion），the myocardial infarct size, the activity of serum CK ,LDH and the contents of serum FFA and LPO were decreased，whereas the activity of serum SOD and GSH-Px increased markedly.At the same time, myocardial blood flow was increased and coronary vascular resistance decreasedsignificantly. Conclusion：PQDS has protective effect on myocardial ischemia by modifying metabolic dysfunction of FFA, inhibiting oxygen free radicalmediated peroxidation of membrane lipids ， enhancing endogenous antioxidase activity and increasing myocardial blood supply.