As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

BACKGROUND: Research on the relationship between residential altitude and hypertension incidence has been inconclusive. Evidence at low altitudes (i.e., <1,500 m) is scarce, let alone in older adults, a population segment with the highest hypertension prevalence. Thus, the objective of this study is to determine whether hypertension risk may be affected by altitude in older adults living at low altitudes. METHODS: This prospective cohort study collected data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We selected 6,548 older adults (≥65 years) without hypertension at baseline (2008) and assessed events by the follow-up surveys done in 2011, 2014, and 2018 waves. The mean altitude of 613 residential units (county or district) in which the participants resided was extracted from the Digital Elevation Model (DEM) of the National Aeronautics and Space Administration (NASA) and was accurate to within 30 m. The Cox regression model with penalized splines examined the linear or nonlinear link between altitude and hypertension. A random-effects Cox regression model was used to explore the linear association between altitude and hypertension. RESULTS: The overall rate of incident hypertension was 8.6 per 100-person years. The median altitude was 130.0 m (interquartile range [IQR] = 315.5 m). We observed that the exposure-response association between altitude and hypertension incidence was not linear. The shape of the exposure-response curve showed that three change points existed. Hypertension risk increased from the lowest to the first change point (247.1 m) and slightly fluctuated until the last change point (633.9 m). The risk decreased above the last change point. According to the categories stratified by the change points, altitude was only significantly associated with hypertension risk (hazard ratio [HR] = 1.003; 95% confidence interval [CI] = 1.002-1.005) under the first change point (247.1 m) after adjusting for related covariates. CONCLUSION Our study found that the association between altitude and hypertension risk might not be linear. We hope the further study can be conducted to confirm the generality of our findings.
Aged ; Altitude ; Humans ; Hypertension/etiology* ; Incidence ; Prevalence ; Prospective Studies

Objective: To investigate the ameliorative effects of Mushroom on adipose tissue inflammation and glucolipid metabolism in mice fed a high-fat diet, and to provide a theoretical basis for the mechanisms of Mushroom regulating glucolipid metabolism and inflammatory responses. Methods: C57 BL/6 J mice were fed with normal diet(LF) group, high-fat diet(HF)group and high-fat diet + Mushroom(HF+Mushroom) group for 15 weeks.Then, body weight subcutaneous and epididymal white adipose tissue weight were measured. The morphological changes of adipose tissues were compared by HE staining, and the expression of genes related to inflamation, glycolysis and fatty acid oxidation pathways were detected by RT-PCR and Western blot. Results: Compared with the LF group, the HF group had increased body weight, increased subcutaneous and epididymal white fat weight and adipocyte size, and upregulated expression of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), CD68, inducible nitric oxide synthase(iNOS), pyruvate kinase(PK), phosphofructokinase(PFK), hypoxia inducible factor-1α(HIF-1α) and peroxisome proliferator activated receptor alpha(PPARα) in adipose tissues, while the expression of carnitine palmitoyl transferase-1 A(CPT-1 A), cytochrome P450 4 a10(CYP4 a10) and medium-chain acyl-coenzyme a dehydrogenase(MCAD) were downregulated(P<0.05). Compared with the HF group, Mushroom supplementation reduced body weight, adipose tissue weight and adipocyte size, and downregulated the expression of pro-inflammatory factors and glycolytic pathway-related factors in adipose tissues, while the expression of fatty acid oxidation pathway-related factors were upregulated(P<0.05). Conclusion Mushroom can ameliorate inflammation and disorders of glycolipid metabolism in adipose tissues of obese mice.

Objective:To investigate the status quo of knowledge, belief and practice level of nurses on venous access device in three Class Ⅲ Grade A hospitals in Shandong Province and to analyze the influencing factors.Methods:Using the convenient sampling method, a total of 396 nurses from three ClassⅢ Grade A hospitals in Shandong Province were selected as the research objects from June to August 2020. The survey was conducted using the general information questionnaire, Nurses' Knowledge, Belief and Practice Scale on Venous Access Device, Nursing Work Environment Scale and Chinese Registered Nurses Ability Evaluation Scale. Univariate and multivariate analysis were used to analyze the influencing factors of knowledge, belief and practice of nurses on venous access devices. In this study, a total of 396 questionnaires were sent out and 385 were effectively received, with a valid recovery rate of 97.2%.Results:The total scores of Nurses' Knowledge, Belief and Practice Scale on Venous Access Device, Nursing Work Environment Scale and Chinese Registered Nurses Ability Evaluation Scale for 385 nurses in three Class Ⅲ Grade A hospitals were respectively (124.37±16.89) , (98.72±11.32) and (132.04±19.84) . The results of hierarchical regression analysis showed that after controlling for general data, the working environment and the core competence of nurses were important factors that affected the knowledge, belief and practice of nurses on venous access devices, which could explain 40.8% of the total variation of nurses' knowledge, belief and practice on venous access devices.Conclusions:In this study, the knowledge, belief and practice level of nurses on venous access devices in three ClassⅢ Grade A hospitals in Shandong Province is at a medium level, which is affected by a variety of factors. Nursing managers should pay attention to the improvement of nurses' core competence and working environment, so as to enhance their knowledge, belief and practice level of venous access devices and reduce the incidence of complications of venous access devices.

Objective The objective of this study was to investigate the expression of P28 and P43 in papillary thyroid carcinoma(PTC)and its relationship with clinicopathological features after TRa1 gene transcription.Methods Real-time fluorescence quantitative PCR(RT-PCR)and gel electrophoresis were used to determine the target fragments and to isolate the bands of different fragments.The optical density of each band was scanned by UV transmittance analyzer to detect 31 cases of PTC tissue and expression levels of P28 and P43 in para-cancerous tissues.Results The average gray value of P28 in thyroid carcinoma group was 0.77±0.34,which was significantly higher than that in para-cancer group(0.31±0.18).The average gray value of P43(0.85+0.21)in thyroid carcinoma group was significantly higher than that in para-cancer group(0.34±0.15)(P<0.05).The expression levels of P28 were not correlated with gender,age,tumor size,lymph node metastasis and clinical pathologic stage(P>0.05),The expression levels of P43 were not correlated with gender,age,tumor size and lymph node metastasis.(P>0.05)but they were related to clinical pathologic stage(P<0.05).There was no correlation between expression levels of P28 and P43(r=0.266,P=0.071).Conclusion The increased expression of P28 and P43 may have a high degree of malignancy and a certain clinical value in predicting the adverse prognosis of PTC.Both factors are helpful for the prevention and treatment of PTC.

Aim TostudytheeffectsofCuO,ZnOand TiO2 nanoparticles on the viability and metastatic po-tential of EC-9706 and EC-109 esophageal squamous carcinomacelllineinvitro.Methods Characteristics of CuO,ZnO and TiO2 nanoparticles were detected u-sing transmission electron microscope (TEM)and dy-namic light scattering (DLS ).EC-9706 and EC-109 cells were treated with different concentrations of CuO, ZnO and TiO2 (5 ~80 mg · L-1 ).The cell prolifera-tion was analyzed by MTT assay.The cell cycle and apoptotic rates were determined by flow cytometry (FCM).The cell invasion was assayed in Transwell chambers.The expression of Bcl-2 and caspase-3 pro-tein in cells was detected by Western blot method.Re-sults CuO,ZnOandTiO2nanoparticleswerespheri-cal with primary particle size 12,20. 6,12 nm.The particles were agglomerated in water and cell culture medium with negative charge.CuO and ZnO nanoparti-cles induced decreases in EC-9706 and EC-109 cell vi-ability dose-dependently.After exposed to increasing concentrations of CuO and ZnO nanoparticles,the cell cycle analysis revealed a decreasing proportion of cells in G2/Mand S phase,and up-regulation of the cells in G0/G1 phase.Apoptotic cells also increased along with decreased cell invasion upon CuO and ZnO treatment. Nanoparticles treatment after 48 h, the activated caspase-3 expression quantity increased significantly and the Bcl-2 expression quantity decreased obviously (P<0. 05 )compared with control group.TiO2 nanop-articles had no obvious effect on the EC-9706 and EC-109 cell proliferation,cell cycle,apoptosis and inva-sion.Conclusion ComparedwithTiO2,CuOand ZnO nanoparticles can inhibit EC-9706 and EC-109 cell viability and metastatic potential,the mechanism of action involves cell cycle arrest in G0/G1 phase and apoptosis.These findings can help the development of nanoparticles as anti-cancer therapeutics for esophageal cancer.

Objective To establish a rat model of nonalcoholic fatty liver disease (NAFLD) using high-fat diet,and to dynamically observe the influence of the changes in gut microbiota on the development and progression of NAFLD in rats during and after modeling.Methods Sprague-Dawley rats were given high-fat diet to establish the model of NAFLD,and these rats were randomly divided into high-fat group,antibiotic pretreatment group,antibiotic treatment group,restricted diet group,and control group.The rats were sacrificed in different feeding periods,and 16sRNA fluorescent quantitative PCR was used to analyze the changes in ileocecal microbiota in rats.The liver pathological scores were determined,and enzymatic colorimetry was used to measure blood lipid level in serum and liver homogenate.The sample mean t-test was used for comparison between groups.Results Compared with the high-fat group,the restricted diet group showed the most significant improvements in quality of life and biochemical parameters.In the restricted diet group,the number of probiotics (Bifidobacterium and Lactobacillus) at the end of the ileum gradually increased and tended to increase over the time of intervention,and the most significant difference between this group and the high-fat group occurred at the 10th week (Bifidobacterium:0.91±0.23 vs 0.28±0.12,P ＜ 0.05;Lactobacillus:0.78±0.04 vs 0.21±0.03,P ＜ 0.05),while the number of enterococci decreased.There were no significant differences in enteric bacilli between groups (all P ＞ 0.05).At the 10th week,the liver pathological scores in the control group,antibiotic treatment group,and restricted diet group were 1.13±1.74,4.86±0.86,and 2.94±1.91,respectively,significantly lower than 7.09±2.03 in the high fat group (all P ＜ 0.05).Conclusion Diet structure change and antibiotic intervention can adjust gut microecology,alleviate the lesions of NAFLD,and thus provide new strategies for the prevention and treatment of NAFLD from the perspective of microecology.

Objective To evaluate the efficacy of artificial liver support system ( ALSS) combined with conventional medical treatment for liver failure .Methods Literature retrieval of Wanfang Data , CQVIP, CNKI, Medline, Cochrane Library and PubMed from 2004 to 2014 was conducted to identify all studies on ALSS in treatment of liver failure .The quality of the literature was assessed according to Cochrane systematic guide manual , and meta-analysis was performed using RevMan 5.3.Random-effects or fixed-effects model was performed based on the heterogeneity , and publication bias was evaluated with Begg ’ s funnel pot .Results A total of 20 randomized controlled clinical trials involving 2 356 patients were included for systematic review , among which 1 247 patients were treated with ALSS combined with medical therapy, and 1 109 patients were treated with medical therapy only .Meta-analysis showed that the mortality of patients with liver failure treated with combined therapy was 25.3%(316/1247), which was lower than that with medical treatment alone (524/1 109, 47.2%) ( OR=0.36, 95%CI:0.30-0.43, Z=11.19, P<0.01).The mortality of patients with acute (subacute) and subacute-on-chronic liver failure treated with combined therapy (54/203, 26.6%) was lower than that with medical treatment group (76/188, 40.4%) (OR=0.53, 95%CI:0.34-0.81, Z=2.91, P<0.01).The mortality of patients with chronic liver failure treated with combined therapy was 25.6% (89/347), which was also lower than that with medical treatment group (171/340, 50.3%) (OR=0.32, 95%CI:0.23-0.45, Z=6.73, P<0.01). Mortality in patients received medical treatment plus molecular adsorption recirculation system , plasma exchange or multiple ALSS were 23.6% (26/110), 21.9% (126/575) and 29.7% (80/269), which were significantly lower than those in patients received only medical treatment [38.9%(42/108), 52.2%(257/492) and 45.4%(103/227)] (OR=0.48, 0.24 and 0.45, 95%CI:0.26-0.88, 0.18-0.31 and 0.31-0.67, Z=2.38, 10.14 and 4.02, all P<0.05 or <0.01).Conclusion ALSS combined with medical therapy can reduce the mortality of patients with various types of liver failures .

Ramie and kenaf were traditional fiber crops in China, but their stalk after decorticating has not been used effectively. The stalk contains a lot of cellulose, and can therefore be used for the production of bioethanol. We studied the effects of different chemical pretreatment on enzymatic digestibility of ramie stalk and kenaf stalk. Ramie and kenaf stalks pretreated with alkali were chosen to produce ethanol using quasi-simultaneous saccharification and fermentation (Q-SSF) process. The results show that for the stalks pretreated with 4% NaOH and 0.02% anthraquinone-2-sulfonic acid sodium salt (AQSS) as catalyzer at 170 degrees C for 1 h, the ethanol concentration could reach 51 g/L after fermentation for 168 h at 18% of solid substrate concentration. By fed-batch to 20% of solid substrate concentration, the ethanol concentration could reach 63 g/L, 77% and 79% of the cellulose conversion could get for ramie stalk and kenaf stalk, respectively. For kenaf stalk pretreated with 5.2% NaHSO3 and 0.2% H2SO4 at 170 degrees C for 1 h, the ethanol concentration and cellulose conversion could reach to 65 g/L and 72%, respectively.
Alkalies ; Biofuels ; Biotransformation ; Boehmeria ; Cellulose ; China ; Ethanol ; chemistry ; Fermentation ; Hibiscus ; Hydrolysis ; Plant Stems ; chemistry

Atherosclerosis is the common basic pathophysiology progresses of acute cardiovascular and cerebrovascular diseases. Atherosclerotic plaque rupture and consequently thrombosis are the major cause of mobility and mortality in atherosclerosis, and treatment aimed at stabilizing vulnerable plaques is of great clinical importance. However, an ideal drug for stabilizing vulnerable plaques is still lacking. Although Statins are considered as the most potent drugs for stabilizing plaques, their side effects are serious. Traditional Chinese medicine have multi-targets and less side effect, it might be the potential candidate for atherosclerosis treatment. This article reviewed the latest progresses on the stabilizing vulnerable plaques treatments.