The efficacy and safety of 5-fluorouracil/cisplatin/vincristine as a multi-agent chemotherapy regimen in gestational trophoblastic neoplasia.

Objective: To determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN). Methods: We performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU. The clinical characteristics, adverse events, and response rates were compared between the groups. Results: The patients in the FPV and FAV groups received a total of 228 and 190 courses of chemotherapy, respectively. Complete response (CR) was found in 88.89% (48/54) and 90.48% (38/42) of patients in the FPV group and FAV group, respectively (p = 0.801). Both chemotherapy regimens yielded CR in all low-risk patients (100% vs. 100%), whereas 86.67% and 88.24% of high-risk patients achieved CR (FPV vs. FAV, p = 0.836), respectively. The most common adverse events (AEs) were myelosuppression and gastrointestinal reactions including neutropenia (83.97%), anemia (60.05%), and nausea (46.41%). In comparison to those in the FAV group, patients in the FPV group reported higher rates of grade 1/2 nausea (53.51% vs. 37.89%, p = 0.001), hepatotoxicity (28.95% vs. 17.89%, p = 0.008), oral mucositis (23.25% vs. 10.53%, p = 0.001), and grade 3/4 neutropenia (47.37% vs. 27.37%, p < 0.001), while grade 1/2 diarrhea (7.46% vs. 13.68%, p = 0.037) and grade 3/4 oral mucositis (0 vs. 6.32%, p < 0.001) were much more common in the FAV group. The rate of overall survival at 5 years was 96.8% in the FPV group and 97.3% in the FAV group (p = 0.760), whereas the 5-year disease-free survival rates were 95.9% and 93.9% (p = 0.754), respectively. Conclusion: The FPV and FAV regimens with pulsed intravenous 5-FU yielded comparable CR rates and tolerability in patients with GTN with FIGO scores of >5. Further randomized controlled trials are warranted to validate their efficacy.

Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery.

Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs'/pesticides' bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1H)-one derivatives and evaluated their antibacterial behaviors. Compound B6 exhibited the highest bioactivity, with half-maximal effective concentration (EC50) values ranging fro9m 10.03 to 30.16 µg mL-1 against three plant pathogenic bacteria. The antibacterial mechanism showed that it could considerably reduce various virulence factors (such as extracellular enzymes, biofilm, and T3SS effectors) and inhibit the expression of virulence factor-related genes. In addition, the control efficiency of compound B6 against rice bacterial leaf blight at 200 µg mL-1 was 46.15-49.15%, and their control efficiency was improved by approximately 12% after the addition of pesticide additives. Thus, a new class of bactericidal candidates targeting bacterial virulence factors was developed for controlling plant bacterial diseases.

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes.

Mammalian centromeres are generally composed of dispersed repeats and the satellites such as α-satellites in human and major/minor satellites in mouse. Transcription of centromeres by RNA polymerase II is evolutionary conserved and critical for kinetochore assembly. In addition, it has been found that the transcribed satellite RNAs can bind DNA repair proteins such as MRE11 and PRKDC, and excessively expressed satellite RNAs could induce genome instability and facilitate tumorigenesis. During the maturation of female oocyte, centromeres are critical for accurate segregation of homologous chromosomes and sister chromatids. However, the dynamics of oocyte centromere transcription and whether it associated with DNA repair proteins are unknown. In this study, we found the transcription of centromeres is active in growing oocytes but it is silenced when oocytes are fully grown. DNA repair proteins like Mlh1, Mre11 and Prkdc are found associated with the minor satellites and this association can be interfered by RNA polymerase II inhibitor α-amanitin. When the growing oocyte is in vitro matured, Mlh1/Mre11/Prkdc foci would release from centromeres to the ooplasm. If the oocytes are treated with Mre11 inhibitor Mirin, the meiosis resumption of growing oocytes with Mre11 foci can be suppressed. These data revealed the dynamic of centromeric transcription in oocytes and its potential association with DNA repair proteins, which provide clues about how oocytes maintain centromere stability and assemble kinetochores.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo. The bioassays showed that some of the target compounds displayed excellent in vitro antibacterial activity toward three virulent phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa), affording the lowest EC50 values of 7.40 (7c), 5.44 (9a) and 12.85 (9a) µg/mL, respectively. Meanwhile, compound 7c possessed good in vivo protective and curative activities to manage rice bacterial leaf blight at 200 µg/mL, with control efficacies of 47.34% and 41.18%, respectively. Furthermore, compound 9a showed commendable in vivo protective and curative activities to manage kiwifruit bacterial canker at 200 µg/mL, with control efficacies of 46.05% and 32.89%, respectively, which were much better than those of the commercial bactericide TC (31.58% and 17.11%, respectively). In addition, the antibacterial mechanism suggested that these new types of title compounds could negatively impact the cell membranes of phytopathogenic bacteria cells and cause the leakage of the intracellular component, thereby leading to the killing of bacteria. All these findings confirm that novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles containing an imidazole fragment are promising lead compounds for discovering new bactericidal agents.

Development of thermostable sucrose phosphorylase by semi-rational design for efficient biosynthesis of alpha-D-glucosylglycerol.

Sucrose phosphorylase (SPase) can specifically catalyze transglycosylation reactions and can be used to enzymatically synthesize α-D-glycosides. However, the low thermostability of SPase has been a bottleneck for its industrial application. In this study, a SPase gene from Leuconostoc mesenteroides ATCC 12,291 (LmSPase) was synthesized with optimized codons and overexpressed successfully in Escherichia coli. A semi-rational design strategy that combined the FireProt (a web server designing thermostable proteins), structure-function analysis, and molecular dynamic simulations was used to improve the thermostability of LmSPase. Finally, one single-point mutation T219L and a combination mutation I31F/T219L/T263L/S360A (Mut4) with improved thermostability were obtained. The half-lives at 50 °C of T219L and Mut4 both increased approximately two-fold compared to that of wild-type LmSPase (WT). Furthermore, the two variants T219L and Mut4 were used to produce α-D-glucosylglycerol (αGG) from sucrose and glycerol by incubating with 40 U/mL crude extracts at 37 °C for 60 h and achieved the product concentration of 193.2 ± 12.9 g/L and 195.8 ± 13.1 g/L, respectively, which were approximately 1.3-fold higher than that of WT (150.4 ± 10.0 g/L). This study provides an effective strategy for improving the thermostability of an industrial enzyme. KEY POINTS: • Predicted potential hotspot residues directing the thermostability of LmSPase by semi-rational design • Screened two positive variants with higher thermostability and higher activity • Synthesized α-D-glucosylglycerol to a high level by two screened positive variants.

Fabrication of Versatile Pyrazole Hydrazide Derivatives Bearing a 1,3,4-Oxadiazole Core as Multipurpose Agricultural Chemicals against Plant Fungal, Oomycete, and Bacterial Diseases.

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds a1-a6, b1-b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 µg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 was effective with protective and curative activities of 90.2 and 86.3% at 200 µg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC50 = 3.21 µM, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae with EC50 values of 2.92 and 8.43 µg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (a4) at 200 µg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.

Garcinone-E exhibits anticancer effects in HeLa human cervical carcinoma cells mediated via programmed cell death, cell cycle arrest and suppression of cell migration and invasion.

Xanthones are an important class of natural compounds bearing huge bioactivity profiles. Garcinone-E is one among most active xanthones showing potential anticancer activity against various human cancer cell lines. Therefore, the current study was performed to explore the anticancer potency of naturally occurring garcinone-E xanthone against human HeLa cervical cancer cells. The underlying mechanism of action was also tried to be explored via testifying its induction of programmed cell death, arrest of cell cycle, suppression of cell migration, cell invasion and cell adhesion. MTT assay was implemented to estimate the viability of HeLa cells after garcinone-E exposure and clonogenic assay was used to analyze the effect on clonogenic potential. Acridine orange/ethidium bromine (AO/EB) staining assay was performed for monitoring of programmed cell death along with western blotting. Flow cytometric studies were carried out to analyze cell cycle check points. Transwell chambers assays were carried out for studying the impact of garcinone-E on migration and invasion potency of HeLa cells. Western blotting was used to study the expressions of apoptosis linked proteins in HeLa cells. Results indicated that garcinone-E remarkably decreased the viability to minimum in HeLa cells in both dose and time-reliant manner. The clonogenic capacity of HeLa cells was efficiently reduced by garcinone exposure. AO/EB staining showed that the anti-viability action of garcinone-E was apoptosis allied which was supported by western blotting as well. The cell cycle check points study indicated cell cycle arrest at G2/M-phase. HeLa cell migration and invasion were reduced efficiently after being subjected to garcinone-E treatment in a dose reliant fashion. In conclusion, garcinone-E has a remarkable potential to act as anti-cervical cancer chemopreventive provided further in vivo studies are required.

Activation of BK Channels Prevents Hepatic Stellate Cell Activation and Liver Fibrosis Through the Suppression of TGFß1/SMAD3 and JAK/STAT3 Profibrotic Signaling Pathways.

Large-conductance and Ca2+-activated K+ (BK) channels are expressed in human hepatic stellate cells (HSCs), where they have roles in normal hepatic microcirculation, as well as in portal hypertension in liver cirrhosis through the regulation of contractility in activated HSCs. Nevertheless, whether BK channel activity exerts protective effects against aberrant HSC activation and hepatic fibrosis is unknown. Here, we report that BK channels are expressed in activated primary rat HSCs as well as in a human HSC line. Moreover, whole-cell K+ currents recorded from activated HSCs were markedly increased by exposure to rottlerin, a BK channel-specific activator, but were inhibited by treatment with the BK channel-specific inhibitor, paxilline, suggesting that BK channels are functional in activated HSCs. Overexpression but not downregulation of the BK channel pore-forming alpha subunit, KCNMA1, led to reduced migration and collagen expression in activated HSCs. Consistently, rottlerin treatment suppressed the fibrogenic cell function both in vitro and in CCl4-induced liver fibrosis in vivo. Microarray and pathway analysis, combined with a luciferase reporter assay and western blotting, further showed that rottlerin treatment led to a significant downregulation of the profibrotic TGFß1/SMAD3 and JAK/STAT3 signaling pathways, both in vitro and in vivo. Our findings not only link BK channel function to profibrotic signaling pathways, but also provide evidence that BK channel activation represents a promising therapeutic strategy for the treatment of liver fibrosis.

[A cohort study of serum leptin level in Zhejiang Province middle and old age residents on blood pressure and hypertension from 2014 to 2017].

OBJECTIVE: To investigate the association between serum leptin concentration with blood pressure and hypertension in different gender. METHODS: A total of 343 non-hypertensive residents aged 30 to 65 were randomly selected from Zhejiang Province in 2014. Parameters including height, weight, waist, blood pressure, serum lipid and serum leptin concentration of participants were measured and determined by physical examination and laboratory detection in 2014 and 2017. The differences in serum leptin levels between the new hypertensive and non-hypertensive people were compared after three years. The relationship between serum leptin levels and hypertension was analyzed by Logistic regression. RESULTS: In 2014 and 2017, concentration of serum leptin in females was significantly higher than that in males, and the blood pressure in males was higher than that in females. At the end of follow-up, 26 new cases of hypertension were found. Serum leptin levels were higher in the female hypertensive group than in the non-hypertensive group(P=0. 0289), whereas there was no statistical difference in males(P>0. 01). Regardless of gender, serum leptin was significantly positively correlated with body mass index(BMI) and waist-to-height ratio(WHtR)(P<0. 0001), and also had correlation with blood pressure. However, after adjusting for BMI or WHtR, the correlation between serum leptin and blood pressure disappeared(P>0. 01). Logistic regression also showed the similar result. CONCLUSION: Serum leptin is not directly related to blood pressure and hypertension, and the positive correlation between them may be explained largely by BMI and WHtR.

[Effect of body mass index, waist-to-height ratio and dietary fat on serum leptin level of middle-age adult in Zhejiang Province].

OBJECTIVE: To investigate the association between body mass index(BMI), waist-to-height ratio(WHtR) and dietary fat with serum leptin concentration. METHODS: A three-day 24-h dietary recall method was conducted on 513 participants aged30-65 years who were randomly selected from Zhejiang Province in 2014 to investigate usual fat intake. In addition, parameters including height, weight, waist and serum leptinconcentration of participants were measured and determined by physical examination and laboratory detection. RESULTS: Concentration of serum leptin in women was significantly higher than that in men( P< 0. 001). Both BMI and WHtR were positively correlated with serum leptin level( men: r=0. 488 and 0. 576, women: r =0. 453 and 0. 333, P<0. 0001), but only correlation of WHtR that men(r=0. 354, P<0. 0001) and BMI in women(r=0. 321, P< 0. 0001) remained when BMI and WHtR were controlled respectively. Standardized partial regression coefficient of WHtR(ß =0. 27) was higher than that of BMI(ß=0. 21) in men while in women the coefficient of BMI(ß=0. 26)was higher than that of WHtR(ß = 0. 20). Serum leptin level was negatively correlated with total energy, total fat and MUFA in men(P<0. 05), but the correlation between total energy and leptin was disappeared when WHtR was controlled for. Serum leptin level was positively correlated with the proportion of PUFA from total energy and(PUFA +MUFA) ∶ SFA in women(P<0. 05), while only the correlation between the proportion of PUFA from total energy and leptin remained when BMI was controlled for. CONCLUSION: Obesity degree was gender-specifically positively correlated with serum leptin level, which indicated different obesity indicators should be used for men and women when analyzing serum leptin. Serum leptin was negatively correlated with total fat and MUFA in men, while positively correlated with the proportion of PUFA from total energy in women.

[Effects of marginal zinc deficiency on obesity].

OBJECTIVE: To investigate the influence of marginal zinc deficiency on obesity and provide the theory basis for the prevention and treatment of obesity. METHODS: Thirty two male SPF SD rats were randomly divided into four groups. Four groups were supplied different doses of zinc. All rats were sacrificed after 6 weeks. Serum zinc, serum lipid, leptin, total antioxidant capacity( T-AOC), superoxide dismutase( SOD) and malondialdehyde( MDA) were detected. RESULTS: From the 5th week, the serum zinc in low zinc group was significantly lower than that in low zinc pair-control group and control group( P < 0. 05), and marginal zinc deficiency model was set up. At the 6th week, body fat ratio of rats in low zinc group was significantly higher than that in low zinc paircontrol group and control group( P < 0. 05). The MDA in liver tissue of the rats in low zinc group and middle zinc group was significantly higher than that in control group( P <0. 05). The levels of T-AOC and SOD in the liver tissue in low zinc group and middle zinc group were significantly lower than that in control group( P < 0. 05). The oxidative stressof the rats in low zinc group and middle zinc group increased. CONCLUSION: Marginal zinc deficiency can increase the risk of obesity. Oxidative stress significantly increase in marginal zinc-deficient rats, which may be the main reason that marginal zinc deficiency increase the risk of obesity.

[Effects of isocaloric diets with different percentage energy from fat on blood glucose and lipids in rats].

OBJECTIVE: To investigate the effects of isocaloric diets with different percentage energy from fat on blood glucose and lipids in rats. METHODS: Forty male SD rats were assigned to low fat group, normal fat group, medium fat group and high fat group using randomized blocks method. Rats in four groups were fed with isocaloric diets whose percentage energy from fat were 5%, 15%, 25% and 40% respectively for 10 weeks. Body weight and body length of rats were measured every week. Blood glucose, blood lipids and insulin were determined at 0, 5th and 10 th week. The perirenal fat and epididymal fat pad were separated and weighed at the end of the 10 th week and the body fat rate was calculated. RESULTS: At the end of the 5th and 10 th week, there were no significant differences among four groups in body weight, Lee's index, body fat rate, insulin and low density lipoprotein cholesterol. At the end of the 10 th week, the level of blood glucose was higher for rats in the high fat group than those in the low fat group( P <0. 01). The level of total cholesterol, triglyceride and high density lipoprotein cholesterol were lower for rats in the high fat group than those in the low fat group( P < 0. 01). The level of blood glucose of the 10 th week was higher for rats in the high fat group than the level at the beginning( P < 0. 05). The level of total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol of the 10 th week was higher for rats in the high fat group than the level at the beginning( P < 0. 01). CONCLUSION: When rats were fed with a isocaloric diet and in the condition of normal growth, diet with high proportion of energy derived from fat would not lead to overweight in rats, whereas it may change the metabolism of blood glucose and lipids.

Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation.

Although purinergic signaling is important in regulation of immune responses, the therapeutic potential of it in the tumor microenvironment is little defined. In this study, we demonstrate that UDP/P2Y6 signaling facilitates breast cancer metastasis both in vitro and in vivo. We found that P2Y6 is not only aberrantly expressed and mutated in most tumor types, but also highly correlated with poor prognosis in breast cancer patients. Furthermore, the migration and invasion of breast cancer cells was obviously increased by UDP and blocked by P2Y6 specific inhibitor MRS2578 and P2Y6 shRNA. Similar results was also found in breast cancer cell metastasis mouse model. Interestingly, the endogenous agonist UDP was released significantly by doxorubicin treated cells. In addition, the expression and enzyme activity of MMP-9 were both promoted by UDP and inhibited by MRS2578 or P2Y6 shRNA. Furthermore, UDP-induced cell invasion was blocked by an MMP-9 inhibitor. Mechanistically, the MAPKs and NF-κB signaling pathways, known to be involved in regulation of MMP-9 expression, were both activated by UDP. Taken together, our study reveals a relationship between extracellular danger signals and breast cancer metastasis, which suggests the potential therapeutic significance of UDP/P2Y6 signaling in cancer therapy.

Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations.

Voltage-gated ether à go-go (EAG) K(+) channels are expressed in various types of cancer cells and also in the central nervous system. Aberrant overactivation of human EAG1 (hEAG1) channels is associated with cancer and neuronal disorders such as Zimmermann-Laband and Temple-Baraitser syndromes. Although hEAG1 channels are recognized as potential therapeutic targets, regulation of their functional properties is only poorly understood. Here, we show that the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent inhibitory gating modifier of hEAG1 channels. PIP2 inhibits the channel activity by directly binding to a short N-terminal segment of the channel important for Ca(2+)/calmodulin (CaM) binding as evidenced by bio-layer interferometry measurements. Conversely, depletion of endogenous PIP2 either by serotonin-induced phospholipase C (PLC) activation or by a rapamycin-induced translocation system enhances the channel activity at physiological membrane potentials, suggesting that PIP2 exerts a tonic inhibitory influence. Our study, combining electrophysiological and direct binding assays, demonstrates that hEAG1 channels are subject to potent inhibitory modulation by multiple phospholipids and suggests that manipulations of the PIP2 signaling pathway may represent a strategy to treat hEAG1 channel-associated diseases.

[Construction of P2Y6 constitutive knock down breast cancer cell line and evaluation of its proliferation].

AIM: To construct the constitutive P2Y6 knock down breast cancer cell line with shRNA technology and provide a basis for discovering how P2Y6 regulates tumorigenesis and progression in breast cancer. METHODS: The paired oligo nucleotides targeting human P2Y6 gene were synthesized and annealed into linear PLKO lentiviral vector digested by EcoRI and AgeI. The recombined vector which was identified by double digest with EcoRI and NdeI and DNA sequencing was packaged in 293T cells together with psPAX2 and pMD2.G. Virus in culture supernatant was concentrated, three recombinant vectors were transfected into BT549 cells, and the constitutive P2Y6 knock down cells were selected by puromycin. The efficiency of RNA interference was detected by RT-PCR and Western blotting. MTS assay was used to detect the influence of P2Y6 on breast cancer cells'proliferation. RESULTS: The inserted sequence was proven to be correct by DNA sequencing. After stable transfection of P2Y6 shRNA, the expression of P2Y6 in BT549 cells was decreased obviously in both protein and mRNA level. But no obvious influence on proliferation was found in P2Y6 gene knock down cells. CONCLUSION: The constitutive P2Y6 knock down cell line was successfully constructed in BT549 cells. Whereas, no obvious correlation was found between the expression of P2Y6 and breast cancer cell proliferation.

Evaluation of the expert patient program in a Chinese population with permanent colostomy.

BACKGROUND: A colostomy can negatively impact patients' quality of life. Recent research findings suggest that self-efficacy and psychosocial adjustment are positively associated with quality of life, but there are few research reports about the self-efficacy and psychosocial adjustment of patients with a permanent colostomy. OBJECTIVES: The objective of the study was to evaluate the effect of a 3-week Expert Patient Program (EPP) on colostomy knowledge, stoma care self-efficacy, self-management, and psychosocial adjustment in Chinese patients who had a permanent colostomy. METHODS: Eleven patients with permanent colostomy volunteered to be trained to be expert patients. Eighty-one patients with permanent colostomy were recruited and participated in the 3-week EPP courses. Questionnaires with items about knowledge on colostomy, stoma care self efficacy, self-management, and psychosocial adjustment were administered before and at 4 weeks following the EPP courses. Each EPP participant also completed a verbal interview at the end of the program. RESULTS: The EPP participants demonstrated statistically significant improvement (P < .01) in knowledge, self-efficacy, self-management, and psychosocial adjustment to colostomy (mean [SD]: 51.89 [11.45] vs 89.22 [19.90], 71.56 [5.93] vs 85.61 [14.32], 125.44 [19.27] vs 140.78 [15.34], 47.59 [9.64] vs 53.37 [10.68], respectively). Most participants gave positive ratings to the EPP. CONCLUSIONS: This study showed that the EPP was applied effectively in patients with permanent colostomy. IMPLICATIONS FOR PRACTICE: This study highlights the importance of psychosocial support for patients with permanent colostomy. It offers a model of self-help practice in colostomy patients, supported by community that can benefit more patients with permanent colostomy.

Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway.

Nitidine is a benzophenanthridine alkaloid, which has been shown to have anti-tumor properties. Here, we demonstrated that Nitidine Chloride (NC) could inhibit breast cancer cells migration and invasion both in vitro and in vivo. Meanwhile, the protrusion formation and partial proteolytic activity of MMP-9 and MMP-2 were attenuated by NC in a dose-dependent manner in MDA-MB-231 cells. Furthermore, addition NC to cells significantly decreases PDGF induced phosphorylation of c-Src, FAK, MAPKs, activation of RhoA, Rac1 and AP-1 transcriptional activity. Taken together, our results indicate that NC could have potential as a novel anti-metastasis drug to breast cancer.