As an integral part of worldwide healthcare,nursing still has a big task to make in conducting implementation research.Addressing the pressing challenges of closing the gap between evidence and nursing practice,and effectively disseminating and applying evidence within the nursing discipline,remains a top priority.This paper presents a compilation of the status of evidence implementation in clinical nursing from an implementation science perspective,including the theoretical framework of barriers to evidence implementation,common research methodologies,and research progress of related factors in the field of nursing.The goal of this work is to bring more insights to further advance the implementation of evidence in nursing.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Objective To retrospectively investigate the relapse rates of different duration of extended consolidation after withdrawal of nucleos(t) ide analogues (NAs) treatment in patients with chronic hepatitis B (CHB) who met NAs cessation criteria.Methods 102 CHB patients discontinued treatment according to NAs cessation criteria or extended duration of consolidation therapy after meeting the cessation criteria.30 patients meeting the cessation criteria were Group A.72 patients extending consolidation therapy after meeting the cessation criteria were Group B.Based on different duration of extended consolidation therapy,72 patients were divided into 3 groups.Patients with a duration of extended 12 months after meeting NAs cessation criteria were Group B1.Patients with a duration of extended 24 months were Group B2.Patients with duration of extended 36 months were Group B3.After cessation of NAs treatment,the cumulative relapse of different group was calculated by the Kaplan-Meier method.The cumulative relapses between the selected groups were analyzed with Log-rank test.Results The cumulative relapse rates after 6,12,18,24,36 and 48 months after cessation of NAs treatment were 52.3％,70.0％,74.3％,76.7％,82.4％ and 88.4％ in Group A;24.0％,38.8％,40.6％,43.3％,43.3％ and 43.3％ in Group B;respectively.The relapse rate of Group B was much lower than that of Group A.The cumulative relapse rates after 6,12,18,24,36 and 48 months after cessation of NAs treatment were 35.0％,48.2％,51.9％,57.9％,57.9％ and 57.9％ in Group B1;18.1％,30.7％,30.7％,30.7％,30.7％ in Group B2;7.1％,21.4％,21.4％,21.4％ in group B3;respectively.The relapse rate of Group B1 was the highest,the following was of Group B2,and of Group B3 was the lowest one.The total amount of relapse in Group A,B1,B2 and B3 was 26,21,5 and 3 respectively.Conclusions A longer duration of extended consolidation therapy after meeting NAs cessation criteria may contribute to the lower relapse rates.

OBJECTIVETo investigate the optimal conditions for establishing insulin-resistant 3T3-L1 adipocytes.

METHOSDexamethason (DEX), 3-isobutyl-methylxanthine (IBMX) and different concentrations of insulin (10(-8), 10(-7), and 10(-6) mol·L(-1)) were used to induce 3T3-L1 preadipocytes into mature adipocytes identified by oil red O staining. We established insulin- resistant 3T3-L1 adipocytes cell model (IR-3T3-L1) by exposing the cells to 1µmol·L(-1) DEX, and the changes of glucose concen- tration in the cell culture were determined by glucose oxidase-peroxidase (GOD-POD) assay.

RESULTSTreatment of 3T3-L1 cells with DEX, IBMX and 10(-6) mol·L(-1)) insulin for 9 days resulted in the differentiation of >90% of the cells into mature adipocytes. IR-3T3-L1 cells cultured for 96 h in the culture media containing 1 µmol·L(-1) DEX showed significantly increased glucose consumption (P=0.0003) as compared with the control group at 36 h (P<0.001).

CONCLUSION3T3-L1 cells can be induced into mature adipocytes by exposure to 1 µmol·L(-1) DEX, 0.5 mmol·L(-1) IBMX and 10(-6) mol·L(-1)) insulin. A 96 h exposure to 1 µmol·L(-1) DEX can induce 3T3-L1 adipocytes to acquire insulin resistance that can be maintained for 36 h.

1-Methyl-3-isobutylxanthine ; chemistry ; 3T3-L1 Cells ; Adipocytes ; cytology ; Animals ; Cell Differentiation ; Culture Media ; chemistry ; Dexamethasone ; chemistry ; Glucose ; chemistry ; Insulin ; chemistry ; Insulin Resistance ; Mice

Objective To investigate short-term efficacy and security of transplantation of human umbilical cord mesenchymal stem cells (HUCMSCs)in the course of treatment of decompensated cirrhosis.Methods Ninety-six Hepatitis B patients with decompensated cirrhosis were enrolled,among which 50 were sbject to transplantation of HUCMSCs in addition to routine therapy (the treatment group) and the rest patients were underwent routine therapy(the control group).We observed the efficacy and security at 2,4,6 and 12 week of the treatment course.Results The symptoms of atigue,anorexia,bloating and edema were greatly relieved in both groups after 4 weeks,and sustained remission after 4-12 weeks.The overall survival rate was 96％ after 12 weeks of the treatment group,2 patients were died after 8 and 12 weeks of the HUCMSCs transplantation due to hepatic encephalopathy repecticely.Compared to the baseline,ALT,AST,TBil and ALB(albumin) were improved after 2,4,6 and 12 weeks in both groups(P ＜ 0.05),and the averages of ALB(albumin) of treatment group were higher than the control group.PT(prothrombin time) and PTA(prothrombin time activity) were improved after 4,6,12 weeks in the treatment group (P ＜ 0.05),however,there were no differences in the control group during the 4,6 and 12 weeks(P ＞0.05).During the course of HUCMSCs tranplantation,the security was satisfied and no special side effects were observed.Conclusion The transplantation of HUCMSCs for therapy of Hepatitis B patients with decompensated cirrhosis is a safety and effective therapy,and can improved ALB,PT,PTA,liver function and clinical symptoms within a short period,which is an alternative method of treatment recommended.

It is now well established that inflammation plays an important role in the development of numerous chronic metabolic diseases including insulin resistance (IR) and type 2 diabetes (T2DM). Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Our pre- vious study has shown that rutaecarpine (Rut) can benefit blood lipid profile, mitigate inflammation, and improve kidney, liver, pan- creas pathology status of T2DM rats. However, the effects of Rut on inflammatory cytokines in the development of IR-skeletal muscle cells have not been studied. Thus, our objective was to investigate effects of Rut on inflammatory cytokines interleukiri (IL)-1, IL-6 and tumor necrosis factor (TNF)-α in insulin resistant primary skeletal muscle cells (IR-PSMC). Primary cultures of skeletal muscle cells were prepared from 5 neonate SD rats, and the primary rat skeletal muscle cells were identified by cell morphology, effect of ru- taecarpine on cell proliferation by MTT assay. IR-PSMC cells were induced by palmitic acid (PA), the glucose concentration was measured by glucose oxidase and peroxidase (GOD-POD) method. The effects of Rut on inflammatory cytokines IL-1, IL-6 and TNF-α in IR-PSMC cells were tested by enzyme-linked immunosorbent assay (ELISA) kit. The results show that the primary skeletal muscle cells from neonatal rat cultured for 2-4 days, parallel alignment regularly, and cultured for 7 days, cells fused and myotube formed. It was shown that Rut in concentration 0-180. 0 μmol x L(-1) possessed no cytotoxic effect towards cultured primary skeletal muscle cells. However, after 24 h exposure to 0.6 mmol x L(-1) PA, primary skeletal muscle cells were able to induce a state of insulin resistance. The results obtained indicated significant decrease (P < 0.05 to P < 0.001) IL-1, IL-6 and TNF-α production by cultured IR-PSMC cells when incubating 24 hours with Rut, beginning from 20 to 180.0 μmol x L(-1). IL-1, IL-6 and TNF-α in the Rut treated groups were dose-dependently decreased compared with that in the IR-PSMC control group. Our results demonstrated that the Rut promoted glucose consumption and improved insulin resistance possibly through suppression of inflammatory cytokines in the IR-PSMC cells.
Animals ; Cell Proliferation ; drug effects ; Cytokines ; metabolism ; Female ; Glucose ; metabolism ; Indole Alkaloids ; pharmacology ; Inflammation ; metabolism ; Insulin Resistance ; Male ; Muscle, Skeletal ; cytology ; drug effects ; metabolism ; Quinazolines ; pharmacology ; Rats

Objective To investigate short-term efficacy and security of telbivudine as a sequential therapy in the HBeAg positive chronic hepatitis B (CHB) patients with pegylated IFNα-2a treatment failure.Methods 27 CHB patients with HBeAg positive and HBV DNA detectable after a 48-week pegylated IFNα-2a therapy were enrolled into this study,and were assigned to group A,with telbivudine as a sequential therapy.54 CHB patients with HBeAg positive were assigned to group B,with telbivudine as a naive treatment.To assessment the efficacy and security of telbivudine at week 48.Results At week 12,the rates of aminotransferases normalization,HBeAg seroconversion and HBV DNA undetectable (＜ 100 IU/ ml) among the two groups were 59.3％,14.8％,66.7％ vs 75.9％,5.6％,46.3％ respectively.At week 24,the rates among the two groups were 92.6％,25.9％,70.3％ vs 92.6％,7.4％,85.2％,respectively.At week 48,the rates among the two groups were 88.9％,29.6％,81.5％ vs 98.1％,28.0％,83.3％ respectively.All these were not statistically significant.But the rate of HBeAg seroconversion in group A is higher than that in group B.The virological breakthrough rate of group B at week 48 is 14.8％,no virological breakthrough was observed in group A.During the treatment,38.3％ of patients had creatine kinase(CK) elevation,but there was no case stopping treatment for severe adverse effect.Conclusion CHB patients with HBeAg positive after a 48-week pegylated IFNα-2a treatment failure can also achieve the same efficacy and security as the na(i)ve treatment,after receiving telbivudine as a sequential therapy.

Objective To investigate the efficacy of combined treatment of PEG IFNα-2a and recombinant hepatitis B vaccine in CHB patients with HBeAg positive.Methods 75 CHB patients with HBeAg positive were enrolled into this study.45 patients received the monotherapy of pegylated IFNα-2a (group A),and 30 patients were treated with PEG IFNα-2a combined with recombinant hepatitis B vaccine (group B).The two groups were compared clinical features,such as ALT,HBsAg levels and HBeAg seroconversion rates,HBV DNA suppression,at different time point(At 0,24,48,72 week).Results At week 0,levels of aminotransferases,HBsAg and HBV DNA were not statistically significant between the two groups(P ＞0.05).But the level of HBeAg in group B was much more than that in group A.This diversity show statistical significance(P ＜ 0.05).During week 24 to week 48,rates of aminotransferases normalization HBsAg seroconversion HBeAg seroconversion,and HBV DNA suppression were also not statistically significant between group A and B (P ＞ 0.05).At the 72 week of follow up,levels of aminotransferases,HBeAg seroconversion rate and HBsAg levels were not statistically significant among the two groups (P ＞0.05),but the negative conversion rate of HBV DNA drop in group B was much more than that in group A,the difference was statistically significant (P =0.032).Conclusion The combined treatment of PEG IFNα-2a and recombinant hepatitis B vaccine in CHB patients with HBeAg positive can improve the negative conversion rate of HBV DNA 72 weeks after the end of the 48 week of treatment,but wasn't associated with HBeAg seroconversion and HBsAg levels.

Objective To investigate the efficacy of Telbivudine as sequential therapy for HBeAg positive CHB patients with pegylated IFNα-2a (PEG-IFNα-2a)treatment failure.Methods After a 48-week pegylated IFNα-2a therapy,102 HBeAg positive CHB patients,whose HBeAg expression was positive and HBV DNA load was Detectable,were enrolled.These patients were randomly divided into two groups.Group A,included 52 patients,were treated with Telbivudine as a sequential therapy after a 3 months or longer wash-out period.Group B,included 49 patients,were treated with Telbivudine as a sequential therapy without wash-out period.The rate of ALT normalization,HBeAg seroconversion,the negative rate of HBV DNA and the level of creatine kinase in the two groups were observed and compared,respectively.Results HBeAg seroconversion of Group A at 3,6,12 months was 7.69％,15.3％,21.1％,respectively.HBeAg seroconversion undetectable of Group B at 3,6,12 months was 22.4％,32.6％,38.8％,respectively.Furthermore,there was statistically significant difference in HBeAg seroconversion between the two groups (P ＜ 0.05).However,there were not statistical difference in the rate of ALT normalization,the negative rate of HBV DNA and the level of creatine kinase between the two groups at 3,6,12 months.Conclusion Telbivudine,which was used as a sequential therapy without wash-out period for HBeAg positive CHB patients after PEG-IFNα-2a treatment failure,was secure.Moreover,HBeAg seroconversion of patients treated with Telbivudine as a sequential therapy without wash-out period was higher than those with wash-out period.