Objective To evaluate correlations between left atrial(LA) and left ventricular(LV) function in patients with hypertension by acoustic quantification(AQ) technique. Methods Forty-eight hypertensive patients and twenty control subjects were studied. Patients with hypertension were divided into two groups by left ventricular mass index(LVMI),normal LVMI group(32 cases) and left ventricular hypertrophy(LVH) group(16 cases). Left atrial ejection fraction(LAEF),atrial emptying volume(AE),conduit volume(CV) and reservoir volume(RV) were measured with AQ technique. Results RV and AE significantly increased in normal LVMI subgroup and LVH subgroup;CV and LAEF respectively decreased or increased in LVH subgroup. LA booster pump function positively correlated to onset atrial emptying volume and RV,negatively correlate to CV and LV diastolic function. LA conduit function positively correlated to LV diastolic function,negatively correlated to LAEF and AE,RV as well as onset atrial emptying volume. LA reservoir function positively correlated to onset atrial emptying volume and LAEF,negatively correlated to CV. There was no significant correlation between LA reservoir function and LV diastolic function. Conclusions LV diastolic dysfunction induces decreased LA conduit function and increased reservoir function,which may facilitate early diastolic filling of the left ventricle. The changes of LA conduit function and reservoir function may increase of LA preload. Enhancement of LA preload and LA systole makes increased LA booster pump function,which facilitate late diastolic filling of left ventricle.

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Haplorhini ; Humans ; Indoles ; pharmacokinetics ; Models, Biological ; Pyrroles ; pharmacokinetics ; Rats ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; pharmacokinetics ; Tissue Distribution

Adult ; Cardiovascular Diseases ; physiopathology ; Cardiovascular Physiological Phenomena ; Case-Control Studies ; Female ; Heart ; physiopathology ; Humans ; Pregnancy ; Sports ; Stress, Psychological ; physiopathology

Objective To evaluate the efficacy and tolerance of preoperative concurrent chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer.Methods From June 2007 to June 2013,51 untreated patients with histopathologically proven rectal cancer (T3/T4 or N (+))were included in this study.Three-dimensional radiotherapy was delivered to the whole pelvic cavity at 45.0-50.4 Gy/25-28 fractions.Two cycles of chemotherapy with FOLFOX4 or XELOX were given concurrently at weeks 1 and 4 of radiotherapy.Surgery was performed at 4-8 weeks after chemoradiotherapy.Adjuvant chemotherapy with FOLFOX4 or XELOX was given within one month after surgery.The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for univariate analysis;the Cox regression model was used for multivariate prognostic analysis.Results Fortynine patients completed the preoperative chemoradiotherapy and surgery.The median follow-up was 2.9 years.The overall sphincter preservation rate was 65％;the overall downstaging rate was 59％.Ten (20.4％) of all patients achieved a pathologic complete response (pCR).Grade ≥3 toxicities occurred in 25％ of all patients,and the overall postoperative complication rate was 31％.The 3-and 5-year sample sizes were 24,12,respectively.The 3-and 5-year overall survival rates were 81％ and 69％,respectively;the 3-and 5-year disease-free survival (DFS) rates were 76％ and 60％,respectively;the 3-and 5-year local recurrence-free survival (LRFS) rates were 78％ and 70％,respectively;the distant metastasis-free survival rates were 82％ and 74％,respectively.The multivariate analysis showed that tumor downstaging was an independent prognostic factor for 5-year DFS and LRFS.Conclusions For locally advanced middle-low rectal cancer,preoperative radiotherapy with concurrent FOLFOX4/XELOX chemotherapy can increase pathologic downstaging rate,pCR rate,and sphincter preservation rate.Patients with tumor downstaging may have a better survival advantage.

Objective To explore the effect of urine neutrophil gelatinase-associated lipocalin(uNGAL) and urine interleukin-18(uIL-18) on the ill condition and prognosis in critically ill patients with acute kidney injury (AKI) at inception of continuous veno-venous hemofiltration (CVVH).Methods Children came from Department of Nephrology,PICU and health examination center in Guangzhou Women and Children's Medical Center were divided into 4 groups:critically ill patients with AKI receiving CVVH group(group A),critically ill patients with non-AKI receiving CVVH group(group B),critically ill patients with AKI didn't recevie CVVH group(group C),and healthy control group(group D).Serum creatinine(SCr),uNGAL and uIL-18 in all patients were analyzed.Results The uNGAL in group A and group C [(161.56 ± 71.44) μg/L,(153.69 ±51.33) μg/L] increased obviously when compared with group B and group D [(33.50 ± l 0.76) μg/L,(16.37 ± 6.20) μg/L] (all P ＜ 0.05).The uIL-18 in group A and group C[(4.16 ±1.13) μg/L,(3.81 ± 1.05) μg/L] was higher than that in group B and group D [(0.25 ± 0.04) μg/L,(0.19 ± 0.15) μg/L] (all P ＜ 0.05).There was no significance of uNGAL and uIL-18 between group B and group D(all P ＞ 0.05).The peak level of uNGAL[(241.76 ± 53.60) μg/L vs (196.32 ± 39.28) μg/L] and uIL-18[(5.15 ±0.78) μg/L vs (4.30 ±0.89) μg/L] in critically ill patients with AKI was higher in renal recoveries than in renal non-recoveries(P ＜0.05).The levels of uNGAL and uIL-18 critically ill patients at initiation of CVVH were higher in non-survivors when compared with survivors [(213.50 ± 104.78) μg/L vs (79.91 ± 55.81) μg/L,P ＜ 0.05],[(4.48 ± 2.32) μg/L vs (1.94 ± 1.88) μg/L,P ＜ 0.05].The levels of uNGAL and uIL-18 of critically ill patients with AKI at initiation of CVVH were higher in non-survivors than in survivors [(256.99 ± 49.33) μg/Lvs (127.11 ±38.99) μg/L,P＜0.05],[(5.48±0.67) μg/Lvs (3.65 ±0.98) μg/L,P＜0.05].The levels of uNGAL and uIL-18 at the first diagnosis time of AKI were higher in non-survivors than in survivors (P ＜ 0.05).Conclusions uNGAL and urine IL-18 at commencement of CVVH predicts short-term prognosis in critically ill patients with AKI.uNGAL and urine IL-18 can be as a prognostic value in the prediction of the need for renal replacement therapy initiation or mortality in critically ill patients with AKI.

OBJECTIVETo investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) on hyphae development of Candida albicans.

METHODInverted microscope, fluorescence microscope, SEM were applied to inspect the Morphological change of C. albicans treated by EAHD at different concentrations. Solid agar plate was utilized to evaluate the colony morphology. Quantitative Real-ime PCR(qRT-PCR) was adopted to observe the expression of hyphae-specific genes such as HWP1, ALS3, UME6, CSH1, SUN41, CaPDE2.

RESULTEAHD with concentration of 312 and 1 250 mg . L-1 could inhibit formation of hyphae and colony morphology. The expression of HWP1, ALS3, UME6, CSH1 were downregulated 4. 13, 3. 64, 2. 46, 2. 75 folds ,while the expression of SUN41 were upregulated 7. 26 folds, CaPDE2 keep unchanged.

CONCLUSIONEAHD could inhibit formation of hyphae and colony morphologies of C. albicans through downregulating HWP1, ALS3, UME6 and CSH1.

Acetates ; Biofilms ; drug effects ; growth & development ; Candida albicans ; cytology ; drug effects ; genetics ; growth & development ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Fungal Proteins ; genetics ; Gene Expression Regulation, Fungal ; drug effects ; Hyphae ; Medicine, Chinese Traditional ; Microscopy, Fluorescence ; Reverse Transcriptase Polymerase Chain Reaction

In recent years, with the constant increase in the population with hypoimmunity, bacterial and fungal infections have been increasing. Due to the drug resistance, clinically optional anti-bacterial and antifungal medicines become increasingly limited. Scutellaria baicalensis, a species of perennial herbaceous plant of scutellaria genus of lamiaceae family, and its effective components have multiple pharmacological effects such as anti-inflammation, anti-oxidation, anti-tumor, anti-microbial. Especially, its remarkable antibacterial and antifungal activities are of great significance to treat the increasing number of cases with drug-fast bacterial and antifungal infections. In this paper, the authors summarized the advance in studies on antibacterial and antifungal effects and mechanisms in recent years on the basis of the domestic and foreign studies on S. baicalensis and its effective ingredients.
Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Bacterial Infections ; drug therapy ; microbiology ; Humans ; Mycoses ; drug therapy ; microbiology ; Plant Extracts ; chemistry ; pharmacology ; Scutellaria ; chemistry ; Scutellaria baicalensis ; chemistry

A permeabilization method of Micrococcus cells has been established. The obtained penneabilized cells could be used for several batches and in the mean time the intracellular enzymes still keep high activity. This method will undoubtedly increase the productivity of the cells and cut down the cost; therefore, it will be a promising way in the treha-lose industrialization. The experiment shows: after being treated with 5% (v/v) methylbenzene for 40min, the cells in suspension were converted into permeabilized cells, then the latter acted on 10% liquefied starch to produce trehaloae, the conversion ratio could reach 70%. The penneabilized cells could be used at least for 6 batchs (12h per batch) and the intracellular enzyme activity kept steady.

The aim of this paper is to report the synthesis of the mPEG-PCL-g-PEI copolymers as small interfering RNA (siRNA) delivery vector, and exploration of the siRNA delivery potential of mPEG-PCL-g-PEI in vitro. The diblock copolymers mPEG-PCL-OH was prepared through the ring-opening polymerization. Then, the hydroxyl terminal (-OH) of mPEG-PCL-OH was chemically converted into the carboxy (-COOH) and N-hydroxysuccinimide (NHS) in turn to prepare mPEG-PCL-NHS. The branched PEI was reacted with mPEG-PCL-NHS to synthesize the ternary copolymers mPEG-PCL-g-PEI. The structure of mPEG-PCL-g-PEI copolymers was characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The mPEG-PCL-g-PEI/siRNA nanoparticles were prepared by complex coacervation, and the nanoparticles size and zeta potential were determined, separately. The cytotoxicities of mPEG-PCL-g-PEI/siRNA nanoparticles and PEI/siRNA nanoparticles were compared through cells MTT assays in vitro. The inhibition efficiencies of firefly luciferase gene expression by mPEG-PCL-g-PEI/ siRNA nanoparticle at various N/P ratios were investigated through cell transfection in vitro. The experimental results suggested that the ternary (mPEG5k-PCL(1.2k))1.4-g-PEI(10k) copolymers were successfully synthesized. (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k) could condense siRNA into nanoparticles (50-200 nm) with positive zeta potential. MTT assay results showed that the cytotoxicity of (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k)/siRNA nanoparticles was significantly lower than that of PEI(10k)/siRNA nanoparticles (P < 0.05). The expression of firefly luciferase gene could be significantly down-regulated at a range of N/P ratio from 50 to 150 (P < 0.01), and maximally inhibited at the N/P ratio of 125. The mPEG-PCL-g-PEI polymers could delivery siRNA into cells to inhibit the expression of target gene with very low cytotoxicity, which suggested that mPEG-PCL-g-PEI could serve as a new type of siRNA delivery vector.
Cell Line, Tumor ; Cell Survival ; Drug Carriers ; Genes, Reporter ; Genetic Vectors ; Humans ; Luciferases ; metabolism ; Molecular Weight ; Nanoparticles ; Particle Size ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Polyethyleneimine ; chemistry ; Polymers ; chemistry ; RNA, Small Interfering ; administration & dosage ; genetics ; metabolism ; Transfection

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.