The preparation method, serum stability, efficiency of cellular uptake and apoptosis induction of the cell penetrating peptide TAT and cleavable PEG co-modified liposomes loaded with paclitaxel (C-TAT-Lipo) were investigated. The best preparation procedure was performed by orthogonal test based on single factor screening method. First, the paclitaxel (PTX)-loaded liposomes were prepared by filming-rehydration method, evaluated with entrapment efficiency and polydispersity index. The morphology of C-TAT-Lipo was characterized by transmission electron microscopy. Turbidity variations were monitored in the presence of fetal bovine serum (FBS) to evaluate the serum stability of the liposomes developed here. Next, the efficiency of cellular uptake of different Rho-PE-labeled liposomes on B16F1 cells in vitro was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry. The quantitative analysis of apoptosis induced by different PTX-loaded liposomes was performed by Annexin V-FITC/PI double staining. The optimal formulation was as follows: Chol : lipid: 1 : 8 (molar ratio); drug : lipid: 1 : 40 (mass ratio); lipid concentration: 3 mmol x L(-1); temperature of hydration: 25 degrees C. The mean size and polydispersity index of C-TAT-Lipo were about (97.97 +/- 3.68) nm and 0.196 +/- 0.037, the zeta potential was (-0.89 +/- 0.45) mV, the entrapment efficiency of paclitaxel was (90.16 +/- 1.53)%. The particle sizes did not exhibit significant variations in 50% FBS over 24 h at 37 degrees C. The efficiency of cellular uptake of the C-TAT-Lipo increased 1.40 fold following the cleavage of PEG. Apoptosis analysis showed 59.3% increase of the apoptosis and necrosis profile of C-TAT-Lipo after the detachment of PEG shells, which was markedly higher than that of N-TAT-LP with or without glutathione and SL, respectively. The results indicate that the C-TAT-Lipo is successfully prepared by filming-rehydration method and shows significant antitumor activities.
Animals ; Annexin A5 ; Apoptosis ; Cell Line, Tumor ; Cell-Penetrating Peptides ; pharmacology ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Liposomes ; chemistry ; Melanoma, Experimental ; Mice ; Microscopy, Confocal ; Paclitaxel ; pharmacology ; Particle Size ; Polyethylene Glycols ; chemistry

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; Boraginaceae ; chemistry ; Flavonoids ; pharmacology ; Heart ; Interleukin-6 ; Myocardial Infarction ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Protective Agents ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; Tumor Necrosis Factor-alpha ; bcl-2-Associated X Protein

creatinine concentration. Conclusion Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectivelywith mild adverse events.

BACKGROUNDAn elevated serum lipid is one of the major risk factors for coronary heart disease (CHD). Physicians' awareness contributes to successful adoption of practice guidelines. Community medical centers are the primary defense against chronic disease. This study aimed to investigate community physicians' awareness of cholesterol guidelines and their utilization.

METHODSSix hundred and one community physicians were randomly selected from four different regions, and completed a confidential and semi-structured questionnaire. Four hundred and ninety-one completed the questionnaire, and 486 valid questionnaires were available.

RESULTSThe physicians' fundamental knowledge of lipids was astonishingly poor, while the awareness of cholesterol guidelines was low. Only 24% and 14% of the physicians reported the right optimal low-density lipoprotein cholesterol (LDL-C) level for CHD and diabetes patients respectively. More than half of the physicians (55.8%) mistakenly considered elevated transaminases to be the lethal side effect of statins. More than half of the physicians (51.9%) would give up statin treatment in the case of transaminase elevation.

CONCLUSIONEducational interventions to improve cholesterol knowledge and to publicize standard treatment are needed among Chinese community physicians.

Adult ; China ; Cholesterol ; Cholesterol, LDL ; Clinical Competence ; Coronary Disease ; metabolism ; Data Collection ; Female ; Humans ; Logistic Models ; Male ; Physicians ; Risk Factors ; Surveys and Questionnaires

Eucommia ulmoides is a valuable traditional Chinese medicine, whose cortexes have long been used as medi cines. Due to the scarcity of its resources, people began using its leaves instead of cortexes in medicines. Eucommiae Folium and its leaves have many pharmacological effects and thereby being clinically applied as genuine traditional Chinese medicines. Modern pharmological studies have showed that Eucommiae Folium leaves have such effects as blood pressure reduction, blood lipid regulation, cardiovascular protection, anti-obesity, anti-inflammation, anti-virus, enhancement of immunologic function, resistance against senility and anti-fatigue. In clinic, Eucommiae Folium is mainly used to treat hypertention and obstetrical and gynecological disease. The essay summarizes the latest advance in domestic and foreign studie on pharmacological effeets and clinical applications of Eucommiae Folium leaves, and thus providing reference for studies on new drugs of Eucommiae Folium leave.
Animals ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; pharmacology ; therapeutic use ; Eucommiaceae ; chemistry ; Humans

Objective To investigate the prevalence of dyslipidemia and borderline dyslipidemia and other coronary heart disease(CHD)risk factors in residents from Beijing communities.Methods Resident samples were selected brv random cluster multistage method.Serum hpid level and CHD factors were obtained through questionnaire,physical examination and biocbemical analysis during June 2007 to August 2007 from 10 054 residents.Results Age-and sex-adjusted standardized prevalence of hypercholesterolemia,high low-density lipoprotein cholesterolemia,low high-density lipoprotein cholesterolemia,and triglyceridemia were 9.3%,2.56%,18.79%and 16.84%,respectively.Incidence of borderline hypercholesterolemia was 23.96%.Incidence of dyslipidemia and borderline dyslipidemia was 31.23%and 23.30%respectively,71.17%residents have at least 1 CHD major risk factor and 20.23%residents were in borderline CHD risks.Prevalence of hypertension,diabetes,smoking and obese was interval)in residents having 1 borderline CHD risk factor(RF),2 RF,and 3 RF versus none RF was 1.668,(95%CI:1.319-2.110),2.537(95%CI:1.989-3.235),and 3.203(95%CI:2.007-5.114).Condusions The prevalence of dyslipidemia of residents from Beijing communities is higher the average level of China(25.1%).Over 1 out of 5 residents were in increased risk for borderline dyslipidemia or CHD risks.Intensive control of dvslipidemia and CHD risk factors aro warranted in Beijing residents.

Objective To investigate the demand for scientific information among cervical cancer patients and to evaluate the quality of the relevant information available for these patients.Methods The demand for medical science information among patients with cervical cancer was investigated via questionnaire.The Discernn scoring system was used to score the cervical cancer science articles retrieved by Baidu and Sogou.A model was established to analyse the reading difficulty of these articles.Results Nearly half(53.6%)of the respondents searched for online science information at least weekly.The main target readings were the etiology and risk factors of diseases,symptoms,treatment options,adverse reactions of treatments,and prognosis.Most respondents(96.4%)thought that the network science information was reliable.Of the 104 search results included in the sample bank,13(12.5%)met the inclusion criteria,91(87.5%)were not selected,including 32 duplicates(30.8%),6 non-text webpages(5.8%),18 short texts(less than 300 Chinese characters)(17.3%),7 advertisements(6.7%),3 news articles(2.9%),22 forum posts(21.2%),and 3 academic articles(2.9%).According to the Discern scoring system,the reliability(=0.728, <0.001),the quality of treatment-related information(=0.431, <0.001),and the overall scores(=0.559,<0.001)of the enrolled 13 publications were consistent,as evaluated by two professional physicians.The mean overall score was 3.A lower score(less than 3)in the reliability assessment was due to the source of the content,generation methods,sponsors,citations,and the undefined parts.During the evaluation of treatment information,the average score was below 3 for each item.Analysis of the reading difficulty showed that,among these 13 articles,4 were at postgraduate thesis level(level 5),4 at undergraduate thesis level(level 4),0 at high school textbook level(level 3),and 8 was higher than middle school level(≥level 3).Eight articles(61.5%)were suitable for readers with an education background of higher middle school and only 5 articles(38.5%)were suitable for readers with an education background of middle school or lower(≤ level 2).Conclusions The vast majority of patients with cervical cancer search for clinical information through the Internet and trust their reliability.Chinese search engines have lower detection rates for high-quality medical science articles.The currently available high-quality medical science articles are small in number and difficult to read.More physicians are urged to write easy-to-read high-quality articles for these patients.
Female ; Health Services Needs and Demand ; Humans ; Information Seeking Behavior ; Internet ; Reproducibility of Results ; Search Engine ; Surveys and Questionnaires ; Uterine Cervical Neoplasms

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-

OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
Antifungal Agents ; pharmacology ; Burkholderia cenocepacia ; chemistry ; Candida albicans ; drug effects ; physiology ; Candidiasis ; drug therapy ; Drug Resistance, Fungal ; Fatty Acids, Monounsaturated ; adverse effects ; Fluconazole ; pharmacology ; Humans ; Microbial Sensitivity Tests ; Triazoles ; metabolism

Objective: This study aims to investigate the sleep quality of pregnant women in Xuhui District, Shanghai, and the related factors of sleep disturbances during pregnancy. Methods: From February 2019 to February 2021, we used online integrated sleep questionnaire (including PSQI, BQ, ESS, AIS) in Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, The International Peace Maternity and Child Health Hospitals of China Welfare Institution, and Shanghai Eighth People's Hospital, to investigate the sleep quality across pregnancy. We also collected maternal physical examination results, childbearing history, sociodemographic, and other clinical data. The prevalences and related factors of various sleep disturbances in pregnant women were analyzed, including insufficient/excessive nighttime sleep, low sleep efficiency, difficulty falling asleep, poor sleep quality, insomnia, daytime sleepiness, and high risk of sleep-disordered breathing (SDB). Results: This study includes 1 898 cases in the first trimester (T1), 3 099 cases in the second trimester (T2), and 1 539 cases in the third trimester (T3). Poor sleep quality (38.6%), daytime sleepiness (mild 41.9%, moderate 17.7%, severe 2.1%), and suspicious insomnia (32.3%) are most prevalent among women in T1 (P<0.01). In comparison, short sleep time (2.7%), long sleep time (8.6%), difficulty falling asleep (12.2%), poor sleep efficiency (35.4%), very poor sleep quality (6.7%), clinical insomnia (21.8%), and high-risk SDB (6.4%) are most prevalent among women in T3 (P<0.05). During pregnancy, late gestation (OR=1.016, 95%CI: 1.006-1.025) and multiple induced/drug abortions (OR=1.329, 95%CI: 1.043-1.692) are risk factors for poor sleep quality (PSQI>5), while multiple full-term deliveries (OR=0.800, 95%CI: 0.675-0.949) is its protective factor. Advanced maternal age (OR=0.976, 95%CI: 0.956-0.997), multiple full-term deliveries (OR=0.808, 95%CI: 0.680-0.959), late gestation (OR=0.983, 95%CI: 0.974-0.992) and hypertension (OR=0.572, 95%CI: 0.401-0.814) are protective factors for daytime sleepiness (ESS>6). The high-risk pregnancy category (OR=9.312, 95%CI: 1.156-74.978) is a risk factor for insomnia (AIS≥4), while multiple full-term deliveries (OR=0.815, 95%CI: 0.691-0.961) is its protective factor. High BMI (OR=1.334, 95%CI: 1.270-1.402) and hypertension (OR=4.427, 95%CI: 2.539-7.719) are risk factors for high-risk SDB in pregnant women. Conclusions: The prevalences of various sleep disturbances are high throughout pregnancy. Noticeably, symptoms of maternal SDB develop along with pregnancy. Different types of sleep disturbances are associated with different factors. Women of high-risk pregnancy category, in late gestation, with high BMI, hypertension, a history of induced/drug abortion, or without a history of full-term delivery can be at high risk of sleep disturbances during pregnancy.
Child ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Pregnancy ; Pregnancy Complications/epidemiology* ; Pregnant Women ; Sleep ; Sleep Quality