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AIMS To evaluate the effectiveness of the hospital-family holistic care model based on the theory of 'Timing It Right' in caregivers of patients with permanent enterostomy. DESIGN A prospective randomized controlled trial. METHODS One hundred and twenty-five caregivers of patients with permanent enterostomy were recruited from 1 May 2017-31 August 2019. They were randomized into either intervention group (N = 62) or control group (N = 63). The control group received routine care and follow-up, while the intervention group received routine care, follow-up, and hospital-family holistic care intervention based on 'Timing It Right'. The care ability, psychological distress, and life quality of the caregivers were evaluated between the groups before the intervention, at discharge, and 3 and 6 months after discharge. RESULTS One hundred and eleven caregivers completed the study (88.8%). At 3 and 6 months after discharge, the care ability and life quality in the intervention group were significantly better than those in the control group (t = 8.506/9.783, t = 22.652/26.179, p

The growth and differentiation of neurons are critical events in the establishment of proper neuron connectivity and function. Planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for neuronal differentiation in vivo. The Wnt/Ca2+ signaling pathway is crucial for cancer development, arousing inflammatory responses, and neurodegeneration. We analyzed the expression patterns and RNAi phenotypes for members of the Wnt/Ca2+ signaling pathway in the planarian, Dugesia japonica. The expression of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln during regeneration was surprisingly similar and revealing in the regenerated brain. RNAi knockdown of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln led to defects in regenerated brains including brain partial deletions, incompact phenotypes at the posterior of the new brain, and lateral branches, which could not regenerate. Furthermore, the expressions of GAD and the number of GABAergic neurons decreased. Together, these results suggest that the Wnt/Ca2+ signaling pathway is required for GABAergic neuron regeneration.

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase‐activating polypeptide (PACAP) suppresses anti‐inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and tumour necrosis factor alpha (TNF‐α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down‐regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up‐regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK‐3β, in the liver of obese mice. However, down‐regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti‐inflammation, glucose regulation and lipid metabolism in obese liver.

A dual-Forster resonance energy transfer (FRET)-based versatile prodrug (V-prodrug), in which the fluorescence of both 5(6)-carboxylfluorescein (FAM) and doxorubicin (DOX) can be quenched by 4-(dimethylaminoazo)benzene-4-carboxylic acid (Dabcyl) with high quenching efficiency, is developed in this paper. The V-prodrug can selectively bind to the αvβ3 integrin overexpressed cancer cells through the Arg-Gly-Asp (RGD) targeting moiety. After that, the acid-mediated DOX release of the V-prodrug can be real-time monitored by the increase of the red fluorescence from DOX. Thereafter, DOX-induced cell apoptosis can also be in situ assessed by the fluorescence recovery of the FAM, due to the caspase-3-mediated Asp-Glu-Val-Asp (DEVD) peptide sequence cleavage. This novel prodrug provides a cascaded imaging of real-time drug release and subsequent cell apoptosis, which enables the in situ detection of the cancer response and the therapeutic efficacy evaluation of the prodrug.

In this study, a pH sensitive chimeric peptide is developed to codeliver a photosensitizer, protoporphyrin IX (PpIX), and plasmid DNA simultaneously. In the presence of matrix metalloproteinase-2 (MMP-2), the chimeric peptide undergoes the process of hydrolysis of PLGVR peptide sequence, exfoliation of PEG, and increase of positive charges. As a result, the chimeric peptide can be preferentially uptaken by MMP-2 rich tumor cells. To realize synergistic effect of drug and gene delivery, a dual-stage light irradiation strategy is developed, i.e., the short time light irradiation can efficiently enhance the endosomal escape of the chimeric peptide/PpIX/DNA complexes by the formation the reactive oxygen species (ROS), resulting in synergistic endosomal escape and improved DNA expression. In addition, due to the screened phototoxicity of PpIX, short time light irradiation does not lead to detectable changes in the cell viability. After the gene transfection, the screened phototoxicity of PpIX is subsequently stimulated by long time irradiation to achieve high synergistic efficacy of photodynamic and gene therapies. Both in vitro and in vivo studies confirm the chimeric peptide-based nanocarrier with a good synergistic effect is a promising nanoplatform for tumor treatments.

This paper reports a drug nanovehicle self-assembled from an amine-functionalized block copolymer poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione)-block-poly(1,3-dioxepan-2-one) (PADMC-b-PTeMC), which is prepared by controlable ring-opening block copolymerization attractively in a "one-shot feeding" pathway. The copolymers display high cell-biocompatibility with no apparent cytotoxicities detected in 293T and HeLa cells. Due to their amphiphilic nature, PADMC-b-PTeMC copolymers can self-assemble into nanosized micelles capable of loading anticancer drugs such as camptothecin (CPT) and doxorubicin (DOX). In particular, the outer PADMC shell endows the PADMC-b-PTeMC nanomicelles with pH-dependent control over the micellar morphology, cell uptake efficiency, and the drug release pattern. Confocal inspection reveals the remarkably enhanced cellular internalization of drug loaded micelles by cancerous HeLa cells at relatively lower pH 5.8 simulating the mildly acid microenvironment in tumors. Along with the acidity-triggered volume expansion of micelles, an accelerated CPT release in vitro occurs. The obtained results adumbrate the possibility of completely biodegradable PADMC-b-PTeMC as pH-sensitive drug carriers for tumor chemotherapy.

Cancer differentiation therapy is an attractive concept and has been clinically used to treat leukemia. However, it is limited to date for solid tumors. In this study, the pH-sensitive nanoparticles based on poly(amidoamine) (PAMAM) dendrimers are synthesized by coupling 3,4,5,6-tetrahydrophthalic anhydride with the first generation PAMAM. The modified dendrimers can self-assemble in aqueous solution to form nanoparticles with a diameter of 125-435 nm. The nanoparticles are relatively stable at physiological pH (pH 7.4) but dissociated in acidic environments (pH 5.0 or 6.0). The present studies show that the proliferation inhibition and albumin secretion of hepatoma carcinoma cells are enhanced with all-trans retinoic acid (ATRA) encapsulated in the nanoparticles. The enhancement of induced differentiation is due to the high internalization of ATRA in the cells by the nanoparticles. These experimental results demonstrate that pH-sensitive nanoparticles may be efficient for improving the differentiation therapy for solid tumor.

Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.

By exploiting boronic acid coupling and host-guest chemistry, a pH-responsive drug/gene co-delivery nanoplatform is designed for cancer treatments with the excellently serum-tolerant transfection activity and the capability to load and release hydrophobic drugs in an acidity-accelerated manner. Via boronate linkage, γ-CD is allowed to spontaneously attach onto phenylboronic-acid-modified oligoethylenimine (PEI1.8K-PB2.9 ) at neutral condition. The formed vehicle/DNA nanoformulation is thus surrounded densely by γ-CD moieties to biomimic the carbohydrate-rich cell surface, providing a novel approach to overcome serum-susceptible drawbacks frequently associated with synthetic gene carriers. PEI1.8K-PB2.9 -γ-CD conjugates demonstrate significantly improved cell-biocompatibility and transfection activity over PEI1.8K-PB2.9 . Noticeably, serum-associated inhibition effect is negligible for PEI1.8K-PB2.9 -γ-CD-mediated transfection whereas marked transfection reduction occurs for PEI25K and PEI1.8K-PB2.9 upon serum exposure. Consequently, PEI1.8K-PB2.9 -γ-CDs afford much higher transfection efficiency, that is, 25-fold higher luciferase expression over PEI25K in presence of 30% serum. An anticancer drug of doxorubicin (DOX) is shown to be readily accommodated into the nanoformulation via host-guest chemistry and intracellularly co-delivered together with plasmid DNA. Due to the acidity-labile feature of boronate linkage, DOX/γ-CD inclusion complexes would be mostly detached from the nanoformulation triggered by acidity, leading to faster drug release. Furthermore, drug inclusion does not alter the serum-compatible transfection efficiency of PEI1.8K-PB2.9 -γ-CD.

OBJECTIVE: To investigate the dynamic progress of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis and fibrosis in rat model. METHODS: In all, 44 Sprague–Dawley rats were randomly divided into the model and control groups. Colitis was induced by intrarectal injection of 10–30 mg TNBS in 50% ethanol enema weekly for 5 cycles. The control group received an equal volume of 50% ethanol. If the rat died during the procedure, necropsy was performed immediately. At the end of the 2nd, 3rd, 4th and 5th week the rats were sacrificed, and histological damage and fibrosis of the colon were examined using HE and Masson trichrome stain. The concentrations of Th1, Th2, Th17 cytokines in colon tissue were detected by ELISA, intestinal fibrosis-relevant cytokine expressions were detected by fluorescent quantification-polymerase chain reaction. RESULTS: Colitis model was successfully induced with a low mortality rate. The microscopic colonic damage score, collagen area, Th1/Th17 cytokines and expressions of intestinal fibrosis-relevant cytokines were significantly higher in the model group than those in the control group. Furthermore, the collagen area, content of interleukin 17 and expressions of intestinal fibrosis-related cytokines in the model group were more elevated in the chronic phase (after 3 to 4 cycles) than in the acute phase (P

To clarify the role of adipocytokine, adiponectin, and leptin in the pathogenesis of pre-eclampsia (PE) and determine the relationships between plasma adiponectin and leptin levels.A total of 73 women in the third trimester of pregnancy were recruited, 53 women with PE (study patients) and 20 age- and BMI-matched normotensive women (healthy controls). They were divided into 3 groups: the 20 normotensive pregnant women (group 1); 32 women with mild pre-eclampsia (group 2); and 21 women with severe pre-eclampsia (group 3). The plasma levels of adiponectin and leptin are measured simultaneously and their correlation and balance were evaluated by enzyme-linked immunosorbent assay.Compared with controls, levels of adiponectin were significantly lower in women with mild or severe PE (P0.01 for both groups) whereas levels of leptin were significantly higher in women with mild or severe PE (P0.05 and P0.01, respectively). There was a negative correlation between plasma levels of adiponectin and leptin in pre-eclamptic women (r=-0.76, P0.01). Moreover, the adiponectin level to leptin level ratio was significantly lower in pre-eclamptic women than that in healthy controls (P0.01). In the pre-eclamptic women serum levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol were significantly increased (P0.01 for all), while high-density lipoprotein cholesterol was significantly decreased compared to levels in normotensive pregnant women (P0.01).These findings suggest that there is an imbalance between adiponectin and leptin in the plasma of pre-eclamptic women. Reduced adiponectin and elevated leptin levels may be involved in the pathogenesis of PE and associated with the development of severe disease.

Aim: To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. Methods: From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. Results: The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). Conclusion: Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer.

Acidosis is one of the important deleterious factors during myocardial ischaemia and reperfusion. The ether-a-go-go-related gene, HERG, is a primary target for blockade by many drugs including dofetilide, quinidine and azimilide. While most drugs lose their efficacy against arrhythmias associated with myocardial ischaemia and reperfusion, dofetilide remains effective. The unique ability of dofetilide to terminate ischaemia-induced arrhythmias is not yet fully explained. The aim of the present study is to elucidate the acidification modulation of antiarrhythmic drugs blockade of HERG channels. The human gene HERG encoding K+ channels were expressed in Xenopus oocytes, and Whole-cell macroscopic currents of Xenopus oocytes were recorded with conventional two-electrode techniques. The inhibitory effects of dofetilide (0.25 microM) were significantly enhanced with decreasing pH (from 7.5 to 6.5). The percent block of dofetilide under pH 6.5 at 0 mV was 69+/-6.1% versus 54+/-3.0% under pH 7.5 (n=7, P

An immunoluminometric assay for plasma lactoferrin has been developed and used to study the levels in children and neonates with viral and bacterial infections. The reference range for plasma lactoferrin was 50–250 μg/l. Lactoferrin levels were significantly higher in patients with bacterial versus viral infections.