OBJECTIVETo explore the inhibition of Hedyotis diffusa Willd Injection (HDI) on the proliferation of RPMI 8226 cells and its mechanisms.

METHODSThe inhibition of HDI on the proliferation of RPMI 8226 cells was detected by MTT and the drug concentrations for further researches were screened out. The apoptosis rate was detected using Annexin V-PI of flow cytometry. The cell cycle distribution was detected by PI. The expressions of adhesion molecule FITC-CD44 and PE-CD49d were detected. The IL-6 and VEGF concentrations of cell supernatants were tested by ELISA. The mRNA expressions of Bax, Bcl-2, Caspase-3, Survivin, IL-6, and VEGF were detected by RT-PCR.

RESULTSHDI could inhibit the proliferation of RPMI 8226 cells. Meanwhile, it induced their early apoptosis, arresting them at G1 phase in a concentration-dependent manner. The VEGF concentrations were down-regulated after acted by 0, 20, 40, and 60 microL/mL HDI in a dose-dependent manner (P< 0.01). The IL-6 content increased (P<0.01). The expressions of CD44 and CD49d were up-regulated in a concentration-dependent manner. After acted by 40 microL/mL HDI, the Survivin mRNA level was significantly downregulated (P<0.01), the mRNA levels of Bcl-2, IL-6, and VEGF were significantly up-regulated (P<0.01), but the up-regulation of Bax and Caspase-3 mRNA levels were not so obvious (P>0.05).

CONCLUSIONSHDI could inhibit the proliferation of RPMI 8226 cells. Its mechanisms might be correlated with early apoptosis induction, G1 phase arresting, VEGF secretion lowering, and Survivin mRNA transcription level down-regulating.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hedyotis ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Interleukin-6 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the relationship between alcohol consumption and risk factors for cardiovascular disease.

METHODSTwo hundreds and twenty six subjects were enrolled in the study and grouped to non-drinkers, mild drinkers, moderate drinkers and heavy drinkers. Serum GGT, hs-CRP, %CDT, HCY, lipoprotein were measured in all groups.

RESULTThere were significantly higher GGT levels with heavy drinkers than those with other groups (P <0.05), and GGT levels were increased with increasing alcohol intake; and there were significantly higher %CDT levels with heavy drinkers compared with those with no-drinkers; there was significant higher hs-CRP levels with heavy drinkers compared with those with mild and moderate drinkers (P<0.05); but in moderate drinkers there was significantly lower hs-CRP levels than non drinkers (P<0.05). Compared with non-drinkers, there were significantly lower LDL-C and TG levels with mild and moderate drinkers. There were no significant differences in CHOL, HDL-C, HCY, WBC, MCV levels among all groups. Heavy drinkers had higher smoking rate and higher prevalence of hypertension (P <0.05).

CONCLUSIONHeavy alcohol consumption results in increasing GGT,%CDT and hs-CRP and may increase cardiovascular disease risk along with other risk factors.Mild to moderate alcohol consumption is associated with lower hs-CRP concentration,which may protect the cardiovascular system through anti-inflammatory mechanism.

Adolescent ; Adult ; Aged ; Alcohol Drinking ; adverse effects ; blood ; Alcoholism ; blood ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; epidemiology ; China ; epidemiology ; Humans ; Male ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Transferrin ; analogs & derivatives ; metabolism ; Young Adult ; gamma-Glutamyltransferase ; blood

Incorrect treatment for femur head necrosis can cause collapse of femoral head and tresult in severe harm for the patients (especially for the patient with middle-aged and young). The structure and mechanics characteristics of tantalum rod is similar to bone tissue, it higher strength and can adapt the internal environment of organism, so it has a large potency in treating femur head necrosis. Treatment of early femur head necrosis with tantalum rod implanting had alreadly widey applied at home and abroad, the method has the advantages of simple operation, little risk, less complication and beseems the patient with stage I - II of ARCO. But reasons that the difficult diagnosis of early femur head necrosis, localized effect of tantalum rod, different experience of medical worker,caused the contentions about effect of tantalum rod implanting. With development of science, tantalum rod implanting combined with correlative biotechnology should raise the effect in treating femur head necrosis.
Femur Head Necrosis ; surgery ; Humans ; Prostheses and Implants ; Tantalum ; Treatment Failure

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

To solve the problem of real-time detection and removal of EEG signal noise in anesthesia depth monitoring, we proposed an adaptive EEG signal noise detection and removal method. This method uses discrete wavelet transform to extract the low-frequency energy and high-frequency energy of a segment of EEG signals, and sets two sets of thresholds for the low-frequency band and high-frequency band of the EEG signal. These two sets of thresholds can be updated adaptively according to the energy situation of the most recent EEG signal. Finally, we judge the level of signal interference according to the range of low-frequency energy and high-frequency energy, and perform corresponding denoising processing. The results show that the method can more accurately detect and remove the noise interference in the EEG signal, and improve the stability of the calculated characteristic parameters.
Algorithms ; Electroencephalography ; Signal Processing, Computer-Assisted ; Signal-To-Noise Ratio ; Wavelet Analysis

OBJECTIVE: To observe the rehabilitation effect of non-invasive positive pressure ventilation( NPPV) in treating pneumoconiosis patients with pulmonary dyspnea. METHODS: A retrospective analysis was used to analyze the treatment compliance,treatment time,treatment effect and adverse reactions of 295 pneumoconiosis patients who had undergone inpatient NPPV treatment. RESULTS: The median of NPPV treatment time of 295 pneumoconiosis patients was 14( 1-281)days. The treatment compliance rate was 79. 66 %( 235 /295). The dyspnea improvement rate was 73. 22 %( 216 /295).The Chi-square test results showed that the dyspnea improvement rate increased with the prolonged treatment time( P <0. 01). Among these,the dyspnea improvement rates of groups with treatment time of 10 days,20 days and ≥ 30 days were higher than group with treatment time < 10 days,the dyspnea improvement rate of the group with treatment time ≥30days was higher than 10 days group( P < 0. 01). The incidence of adverse reactions was 7. 12 %. CONCLUSION: NPPV treatment could improve dyspnea symptoms of pneumoconiosis patients with less adverse reaction.

This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Sodium Hydroxide ; Acrylic Resins ; Escherichia coli ; Nanoparticles

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
Adrenomedullin ; metabolism ; Animals ; Blood Pressure ; drug effects ; physiology ; Hypertension ; etiology ; Lipopolysaccharides ; pharmacology ; Male ; Neuropeptides ; metabolism ; Obesity ; complications ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; drug effects ; metabolism ; Sympathetic Nervous System ; drug effects ; metabolism ; Toll-Like Receptor 4 ; metabolism

The aim of the present study was to investigate the differences of the pathological changes and cognitive function after bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation. HE and Luxol fast blue staining were used to observe the pathological changes of gray matter (hippocampus), white matter (optical tract), optic nerve, and retina. The results showed that the survival rate of the W-BCCAO group was 62.5%, and PLR loss rate was 100%; whereas the survival rate of the S-BCCAO group was 100%, and PLR loss rate was 58.3%. In the W-BCCAO group, percentages of time spent and distance traveled in the light box were more than those in the W-sham group, but there was no statistical significance between the S-BCCAO and S-sham groups. In the S-BCCAO group, the percentages of time spent and distance traveled in the III arm (labyrinth arm) of the Y-maze were less than those in the S-sham group, but no statistical significance was found between the W-BCCAO group and W-sham group. In the S-BCCAO group, the discrimination ratio of the odor recognition task was less than that in the S-sham group, but no statistical significance could be seen between the W-BCCAO and W-sham groups. Ischemic injury was observed in the CA1 area of the hippocampus in the S-BCCAO group, but no readily visible damage was observed in the W-BCCAO group. Ischemic injury of the visual beam and optic nerve was observed in both the S-BCCAO and W-BCCAO groups. Compared with the corresponding sham groups, the S-BCCAO and W-BCCAO groups showed serious retinal damage with significant thinner retina. The ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer (OPL) were thinner in the S-BCCAO group, but no statistical significances were shown in the other layers. All the layers, except the outer nuclear layer (ONL), were significantly thinner in the W-BCCAO group. The results indicate that there are differences of the pathological changes in the hippocampus and visual conduction pathway after BCCAO between SD and Wistar rats, and the degree of learning and memory injury was also different, which suggests that the vascular dementia model of different rat strains should be selected according to research purpose.
Animals ; Brain ; pathology ; Carotid Artery Diseases ; pathology ; Carotid Artery, Common ; pathology ; Cognition ; Disease Models, Animal ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar