Dominant Negative Mutants of Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) Disrupt Core-Binding Factor Beta-Vif Interaction.

Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3s) are host restriction factors that inhibit viral replication. Viral infectivity factor (Vif), a human immunodeficiency virus type 1 (HIV-1) accessory protein, mediates the degradation of APOBEC3s by forming the Vif-E3 complex, in which core-binding factor beta (CBFß) is an essential molecular chaperone. Here, we screened nonfunctional Vif mutants with high affinity for CBFß to inhibit HIV-1 in a dominant negative manner. We applied the yeast surface display technology to express Vif random mutant libraries, and mutants showing high CBFß affinity were screened using flow cytometry. Most of the screened Vif mutants containing random mutations of different frequencies were able to rescue APOBEC3G (A3G). In the subsequent screening, three of the mutants restricted HIV-1, recovered G-to-A hypermutation, and rescued APOBEC3s. Among them, Vif-6M showed a cross-protection effect toward APOBEC3C, APOBEC3F, and African green monkey A3G. Stable expression of Vif-6M in T lymphocytes inhibited the viral replication in newly HIV-1-infected cells and the chronically infected cell line H9/HXB2. Furthermore, the expression of Vif-6M provided a survival advantage to T lymphocytes infected with HIV-1. These results suggest that dominant negative Vif mutants acting on the Vif-CBFß target potently restrict HIV-1. IMPORTANCE Antiviral therapy cannot eliminate HIV and exhibits disadvantages such as drug resistance and toxicity. Therefore, novel strategies for inhibiting viral replication in patients with HIV are urgently needed. APOBEC3s in host cells are able to inhibit viral replication but are antagonized by HIV-1 Vif-mediated degradation. Therefore, we screened nonfunctional Vif mutants with high affinity for CBFß to compete with the wild-type Vif (wtVif) as a potential strategy to assist with HIV-1 treatment. Most screened mutants rescued the expression of A3G in the presence of wtVif, especially Vif-6M, which could protect various APOBEC3s and improve the incorporation of A3G into HIV-1 particles. Transduction of Vif-6M into T lymphocytes inhibited the replication of the newly infected virus and the chronically infected virus. These data suggest that Vif mutants targeting the Vif-CBFß interaction may be promising in the development of a new AIDS therapeutic strategy.

Adsorption and Aggregation Behavior in Aqueous Solution of Tetrasiloxane-based Carboxylate Surfactants via "Thiol-ene" Photochemical Reaction.

Anionic silicone surfactants have long been a neglected field. In this paper three anionic silicone surfactants were synthesized first time from dichloromethylvinylsilane through hydrolysis-condensation, "thiol-ene" photo- chemical and then salting reaction. The critical aggregate concentration (CAC), surface tension, minimum surface area per surfactant molecule and surface pressure at CAC were studied by both surface tension and electrical conductivity. The results showed that they had significant surface activity at the gas/liquid interface and were capable to reduce the surface tension of water to approximately 20 mN m-1 . The results of transmission electron microscopy showed that the three silicone surfactants self-assembled into spherical aggregates of uniform size in aqueous solution above the CAC. The dynamic light scattering results demonstrated that the size of the aggregates was determined to be in the range from 60 to 300 nm at 0.05 mol L-1 and the order of the size of the aggregates is (Me3 SiO)3 SiCO2 Li<(Me3 SiO)3 SiCO2 Na<(Me3 SiO)3 SiCO2 K.

Establishment of a modified Kyoto classification scoring model and its significance in the diagnosis of Helicobacter pylori current infection.

BACKGROUND AND AIMS: We aimed to establish a modified model of the Kyoto classification score and verify its accuracy for predicting Helicobacter pylori (HP) infection during endoscopy. METHODS: Patients who underwent gastroscopy from June 2020 to March 2021 were included in this study. Atrophy, intestinal metaplasia, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, xanthoma, map-like redness, fundic gland polyp, and regular arrangement of collecting venules (RAC) were recorded according to the Kyoto classification of gastritis. The HP infection status of participants was determined by a 13C breath test, anti-HP antibody, and histopathologic hematoxylin and eosin staining. The modified Kyoto classification scoring model was established based on univariate analysis and logistic regression analysis. The modified scoring model was used to judge the status of HP infection in patients undergoing gastroscopy from July to September 2021 and to evaluate the accuracy of the prediction. RESULTS: Of 667 participants in the derivation dataset, 326 cases had HP infection and 341 cases did not. Atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, and spotty redness were associated with HP current infection. Thus, a new scoring model, termed the modified Kyoto classification scoring model, was constructed that included atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, fundic gland polyp, and RAC as indicators. To test the model, 808 subjects, including 251 HP-positive patients, comprised the validation dataset. CONCLUSIONS: The modified Kyoto classification scoring model improved the accuracy of endoscopic determination of HP current infection and has clinical application potential in the Chinese population.

Cerium-Encapsulated SbIII-SeIV-Templating Polyoxotungstate for Electrochemically Sensing Human Multidrug Resistance Gene Segment.

A tower-like SbIII-SeIV-templating polyoxotungstate [H2N(CH3)2]12Na7H3[Ce0.5/Na0.5(H2O)5]2[SbSe2W21O75]2·50H2O (1) was synthesized, whose skeleton is assembled from two prolonged lacunary Dawson [SbSe2W21O75]13- units and two [Ce0.5/Na0.5(H2O)5]2+ linkers. The uncommon [SbSe2W21O75]13- unit can be viewed as a combination of one [SeW6O21]2- group grafted onto a trivacant Dawson [SbSeW15O54]11- subunit. The conductive composite 1-Au@rGO containing 1, gold nanoparticles, and reduced graphene oxide (rGO) was conveniently prepared, using which the 1-Au@rGO-based electrochemical genosensor was constructed for detecting human multidrug resistance gene segment. This work enriches structural types of dual-heteroatom-inserted polyoxometalates and promotes the application of polyoxometalates in genosensors.

Successful Fidaxomicin Hospital Discharges of Adult Patients With Clostridioides difficile Infections Post-2021 Guidelines: Are Economic Barriers Finally Coming Down?

We reviewed Clostridioides difficile-positive patients discharged on fidaxomicin after local adoption of 2021 C. difficile infection (CDI) guidelines. From 14 June to 3 October 2021, 80% (12/15) had copayments of $0-$35 and 27% (4/15) required prior authorization. The 30-day CDI recurrence was 7%.

Two Innovative Fumaric Acid Bridging Lanthanide-Encapsulated Hexameric Selenotungstates Containing Mixed Building Units and Electrochemical Performance for Detecting Mycotoxin.

Two particular fumaric acid bridging lanthanide-encapsulated selenotungstates [H2N(CH3)2]16Na8[Ln3(H2O)7]2 [W4O8(C4H2O4) (C4H3O4)]2[SeW6O25]2[B-α-SeW9O33]4·46H2O [Ln = Ce3+ (1), La3+ (2)] were acquired by the deliberately designed step-by-step synthetic strategy, which are composed of four trilacunary Keggin [B-α-SeW9O33]8- and two original [SeW6O25]10- building units together with one fumaric acid bridging heterometallic [Ln3(H2O)7]2[W4O8(C4H2O4) (C4H3O4)]228+ entity. Particularly, this heterometallic cluster contains four fumaric acid ligands, which play two different roles: one works as the pendant decorating the cluster and the other acts as the linker connecting the whole structure. In addition, the 1@DDA hybrid material was produced through the cation exchange of 1 and dimethyl distearylammonium chloride (DDA·Cl) and its beehive-shaped film of 1@DDA was prepared by the breath figure method, which can be further used to establish an electrochemical biosensor for detecting a kind of mycotoxin-ochratoxin A (OX-A). The 1@DDA beehive-shaped film-based electrochemical biosensor exhibits good reproducibility and specific sensing toward OX-A with a low detection limit of 29.26 pM. These results highlight the huge feasibility of long-chain flexible ligands in building lanthanide-encapsulated selenotungstates with structural complexity and further demonstrate great electrochemical application potentiality of polyoxometalate-involved materials in bioanalysis, tumor diagnosis, and iatrology.

Risk factors and outcomes associated with persistent vancomycin resistant Enterococcal Bacteremia.

BACKGROUND: Prior studies have identified that vancomycin resistant enterococcus (VRE) bacteremia that persists for four days or more is an independent predictor of mortality. Despite this, there is no published data to identify those patients at highest risk of developing persistent VRE bacteremia. METHODS: This was a single center, retrospective, case-control study of adult patients with a VRE bloodstream infection (BSI). Case patients were those with persistent bacteremia (≥ 4 days despite VRE-directed therapy) and control patients were those with non-persistent bacteremia. Logistic regression was used to assess risk factors associated with persistent VRE BSIs. Secondary outcomes included in-hospital mortality, recurrent bacteremia, and breakthrough bacteremia. RESULTS: During the study period, 24/108 (22%) patients had persistently positive blood cultures. Risk factors for persistent bacteremia included severe neutropenia (OR 2.13), 4 out of 4 positive index blood cultures (OR 11.29) and lack of source control (OR 11.88). In an unadjusted analysis, no statistically significant differences in in-hospital mortality (58% versus 40%; p = 0.121), recurrent bacteremia (17% versus 6%; p = 0.090), or breakthrough bacteremia (13% versus 7%; p = 0.402) were observed between groups. CONCLUSION: Patients with severe neutropenia, 4 out of 4 positive index blood culture bottles, and lack of source control were more likely to develop persistent VRE bacteremia despite directed antibiotic treatment.

A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting vif/CBFß interaction.

HIV remains a health challenge worldwide, partly because of the continued development of resistance to drugs. Therefore, it is urgent to find new HIV inhibitors and targets. Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3) are important host restriction factors that inhibit HIV-1 replication by their cytidine deaminase activity. HIV-1 viral infectivity factor (Vif) promotes proteasomal degradation of APOBEC3 proteins by recruiting the E3 ubiquitin ligase complex, in which core-binding factor ß (CBFß) is a necessary molecular chaperone. Interrupting the interaction between Vif and CBFß can release APOBEC3 proteins to inhibit HIV-1 replication and may be useful for developing new drug targets for HIV-1. In this study, we identified a potent small molecule inhibitor CBFß/Vif-3 (CV-3) of HIV-1 replication by employing structure-based virtual screening using the crystal structure of Vif and CBFß (PDB: 4N9F) and validated CV-3's antiviral activity. We found that CV-3 specifically inhibited HIV-1 replication (IC50 = 8.16 µm; 50% cytotoxic concentration >100 µm) in nonpermissive lymphocytes. Furthermore, CV-3 treatment rescued APOBEC3 family members (human APOBEC3G (hA3G), hA3C, and hA3F) in the presence of Vif and enabled hA3G packaging into HIV-1 virions, which resulted in Gly-to-Ala hypermutations in viral genomes. Finally, we used FRET to demonstrate that CV-3 inhibited the interaction between Vif and CBFß by simultaneously forming hydrogen bonds with residues Gln-67, Ile-102, and Arg-131 of CBFß. These findings demonstrate that CV-3 can effectively inhibit HIV-1 by blocking the interaction between Vif and CBFß and that this interaction can serve as a new target for developing HIV-1 inhibitors.

The C-terminal domain of feline and bovine SAMHD1 proteins has a crucial role in lentiviral restriction.

SAM and HD domain-containing protein 1 (SAMHD1) is a host factor that restricts reverse transcription of lentiviruses such as HIV in myeloid cells and resting T cells through its dNTP triphosphohydrolase (dNTPase) activity. Lentiviruses counteract this restriction by expressing the accessory protein Vpx or Vpr, which targets SAMHD1 for proteasomal degradation. SAMHD1 is conserved among mammals, and the feline and bovine SAMHD1 proteins (fSAM and bSAM) restrict lentiviruses by reducing cellular dNTP concentrations. However, the functional regions of fSAM and bSAM that are required for their biological functions are not well-characterized. Here, to establish alternative models to investigate SAMHD1 in vivo, we studied the restriction profile of fSAM and bSAM against different primate lentiviruses. We found that both fSAM and bSAM strongly restrict primate lentiviruses and that Vpx induces the proteasomal degradation of both fSAM and bSAM. Further investigation identified one and five amino acid sites in the C-terminal domain (CTD) of fSAM and bSAM, respectively, that are required for Vpx-mediated degradation. We also found that the CTD of bSAM is directly involved in mediating bSAM's antiviral activity by regulating dNTPase activity, whereas the CTD of fSAM is not. Our results suggest that the CTDs of fSAM and bSAM have important roles in their antiviral functions. These findings advance our understanding of the mechanism of fSAM- and bSAM-mediated viral restriction and might inform strategies for improving HIV animal models.

Impact of Rapid Antimicrobial Susceptibility Testing in Gram-Negative Rod Bacteremia: a Quasi-experimental Study.

Clinical justification for rapid antimicrobial susceptibility testing (AST) in Gram-negative rod (GNR) bacteremia is compelling; however, evidence supporting its value is sparse. We investigated the impact of rapid AST on clinical and antimicrobial stewardship outcomes in real-world practice. We performed a before-and-after quasi-experimental study from February 2018 to July 2019 at a tertiary hospital of the 24-h/day, 7-day/week implementation of the direct Vitek 2 AST method from positive blood culture broth for GNR bacteremia with electronic isolate-specific de-escalation comments and daytime antibiotic stewardship program (ASP) intervention. The primary outcome was time to appropriate antibiotic escalation or de-escalation, and secondary outcomes included time to oral antibiotic stepdown, hospital length of stay (LOS), all-cause 30-day mortality, 7-day incidence of acute kidney injury (AKI), and 30-day incidence of Clostridioides difficile infection (CDI). A total of 671 GNR isolates were included from 643 adult patients. Among patients for whom antibiotic change occurred after rapid AST result, rapid AST was associated with a trend in decreased time to escalation or de-escalation (hazard ratio, 1.22; 95% confidence interval [CI], 0.99 to 1.51; P = 0.06), with median times of 52.3 versus 42.2 h. Secondary outcomes were similar in both groups and include median time to oral antibiotic stepdown, LOS, all-cause mortality, and incidence of AKI and CDI. Rapid AST led to improved stewardship measures but did not impact clinical patient outcomes. These results highlight that multiple variables in addition to the timing of the AST result contribute to clinical outcome and that further intervention may be required to clinically justify rapid AST implementation.

Mica Can Alleviate TNBS-Induced Colitis in Mice by Reducing Angiotensin II and IL-17A and Increasing Angiotensin-Converting Enzyme 2, Angiotensin 1-7, and IL-10.

AIM: To explore the treatment effect of mica on 2,4,6-trinitrobenzenesulfonic acid solution- (TNBS-) induced colitis in mice. MATERIALS AND METHODS: Thirty male BALB/C mice were randomly divided into the control group, the TNBS group, and the mica group. Control mice were treated with saline solution. Experimental colitis was induced by TNBS (250 mg/kg/d) in the TNBS group and the mica group. After modeling, the mica group was treated with mica (180 mg/kg/d) for 3 days, while the TNBS group continued the treatment with TNBS. All solutions were injected intrarectally. During treatment, body weight and mice activity were monitored daily. After treatment, the colon tissues of mice were collected; angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), angiotensin 1-7 (Ang (1-7)), IL-17A, and IL-10 expression was analyzed by ELISA and immunohistochemistry. RESULTS: Food intake, activity, and body weight gradually decreased in the TNBS group compared to the control group and the mica group (all P < 0.05). Also, black stool adhesion in the anus and thin and bloody stool were observed in the TNBS group, but not in the other two groups. Moreover, the expression of Ang II, ACE2, Ang (1-7), IL-17A, and IL-10 in the TNBS group increased compared to that in the control group. Compared to the TNBS group, ACE2, Ang (1-7), and IL-10 in the mica group increased, while Ang II and IL-17A decreased (all P < 0.05). CONCLUSION: Mica can alleviate TNBS-induced colitis in mice by regulating the inflammation process; it reduces Ang II and IL-17A and increases ACE2, IL-10, and Ang (1-7).

The effects of Sea buckthorn seed protein on glucose metabolism in streptozotocin-induced diabetic ICR mice.

In this paper, we investigated the effects of protein from sea buckthorn seed on the expression of genes involved in liver glucose metabolism and on the activation of the AMPK/SIRT1 pathway in streptozotocin (STZ)-induced diabetic ICR mice. The investigated factors included oral glucose tolerance test, insulin resistance, insulin sensitivity index, AMPK and SIRT1 activity and the expression of liver glucose metabolism genes. Seabuckthorn seed protein (SSP) improved the oral glucose tolerance and insulin sensitivity, reduced insulin resistance, suppressed expression of liver glucose metabolism genes and upregulated activation of the AMPK/SIRT1 pathway. Therefore, the results demonstrate that SSP can improve insulin resistance, suppress expression of these genes and upregulate activation on the AMPK /SIRT1 pathway in STZ-induced diabetic ICR mice.

Synthesis, Properties, and Aggregation Behavior of Tetrasiloxane-Based Anionic Surfactants.

Three silicone surfactants, 3-tris(trimethylsiloxy)silylpropyl sulfonate with different alkaline counterions (lithium, sodium, and potassium), were synthesized for the first time. Their chemical structures were confirmed by FT-IR spectra, 1H NMR, and ESI-MS, and their behaviors in aqueous solutions were investigated by surface tensiometry, electrical conductivity, dynamic light scattering, and different transmission electron microscopy techniques. These anionic silicone surfactants exhibited remarkable surface activity and could reduce the surface tension of water to as low as 19.8 mN/m at the critical aggregate concentration (CAC). The adsorption and aggregation behaviors of these surfactants were assessed by determining the adsorption efficiency, minimum average area per surfactant molecule, and thermodynamic parameters. The cryo-TEM results verified that these molecules could form vesicles in water above the CAC. Moreover, the lowest surface tension, the smallest CAC value, and the largest aggregate size have been reached with potassium counterions. Thus, the different behavior of these surfactants in water can be explained by the different sizes of the hydrated ions.

The correlation between histological gastritis staging- 'OLGA/OLGIM' and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China.

BACKGROUND: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years. GOALS: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM. METHODS: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson's χ2 test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test. RESULTS: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7 ± 10.8 years. Patients among OLGA/OLGIM Stage III-IV were presented with a lower level of serum PGI and PGI/PGII (p < .05), especially for Stage IV (p = .01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p = .022; p = .028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p = .036; p = .013). In addition, the percentage of G-17 <1 pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p = .029). The proportion of G-17 > 15 pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p = .023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p < .001, p < .001). CONCLUSIONS: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.

Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

BACKGROUND: Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). RESULTS: Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. CONCLUSION: These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry.

Mediating and/or moderating roles of psychological empowerment.

PURPOSE: The purpose of this study was to explore the mediating and/or moderating effects of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. BACKGROUND: Burnout is prevalent among nurses. Previous studies have found that empowering organizational structures contribute to reduce nurses' burnout. However, little is known about the mediating or moderating role of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. METHODS: A cross-sectional design was conducted. A total of 244 nurses participated in this study. The data were collected in March 2013. Multiple regressions were used to test the hypothesized models. RESULTS: Psychological empowerment was found to be a significant mediator of the relationship between structural empowerment and burnout (standardized ß=-0.553, Sobel test: z=7.79, p<0.001). The moderating effect of psychological empowerment in that relationship was not verified. CONCLUSION: Both structural and psychological empowerment negatively correlated with burnout. The psychological empowerment had a mediating effect on burnout. IMPLICATIONS FOR NURSING MANAGEMENT: It is important for nurse managers to develop strategies to ensure that empowering structures are in place and to facilitate nurses' perception of psychological empowerment.

Evaluation of the Expanded Criteria of Endoscopic Submucosal Dissection for Early Gastric Cancers: A Meta-Analysis.

BACKGROUND: In 2010, undifferentiated early-stage gastric cancers (EGCs; ≤1 cm and confined to the mucosa) were included in the expanded criteria for endoscopic submucosal dissection (ESD), as established by the Japanese Gastric Cancer Association. OBJECTIVE: To evaluate the safety and efficacy of the newly expanded criteria of ESD for EGCs. METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies published between January 1, 2010 and July 10, 2014. These studies were collected by 2 authors and then analyzed with RevMan 5.0. RESULTS: Six studies including 6,687 patients were identified. Compared to the standard group (SG), the expanded group (EG) had higher bleeding (OR 1.66; 95% CI 1.02-2.68), perforation (OR 2.03; 95% CI 1.25-3.31), positive lateral margin rates (OR 16.88; 95% CI 3.83-74.5) and lower en bloc resection rate (OR 0.48; 95% CI 0.34-0.70). The local recurrence (OR 2.46; 95% CI 0.31-19.23) and total survival rates (OR 0.92; 95% CI 0.76-1.12) between the 2 groups were not statistically different. CONCLUSIONS: Considering the similar rates of local recurrence and total survival between the SG and EG, the use of ESD for the management of EGCs that meet the expanded criteria could be considered a safe and effective treatment method.

Relationships among structural empowerment, psychological empowerment, intent to stay and burnout in nursing field in mainland China-based on a cross-sectional questionnaire research.

The aim of the study was to explore the relationship among perceived structural empowerment, psychological empowerment, burnout and intent to stay by nurses in mainland China.With the shortage of nurses in many countries, including China, intent to stay is a dominant factor to influence the quality of care. Also, burnout is identified to negatively affect the quality of care. Empowered clinical nurse practical environment is related to intent to stay and burnout. In the current literature, there is a lack of data based on empowering environment discussing the relationship between burnout and intent to stay. The study used an anonymous questionnaire, filled voluntarily by 219 nurses from different sections in a city in mainland China, 2012.Structural equation modelling (SEM) was used to test the proposed hypotheses. Based on the SEM model, structural empowerment and psychological empowerment had significant positive effects on intent to stay of nurses and negative effects on burnout. Burnout had a significant negative effect on intent to stay. The final modified models yielded χ(2) = 58.580, P > 0.05, χ(2) /df = 1.046, root mean square error of approximation = 0.015, Tucker-Lewis Index = 0.996, comparative fit index = 0.998,which indicated good fit indices. Creating a positive empowering workplace can encourage nurses to stay long and prevent burnout. Therefore, higher level of empowering environment is required.

[Reversal Effect of curcuma wenyujin extract on SGC-7901/VCR induced subcutaneous transplanted tumor in nude mice and its effect on the expression of P-glycoprotein].

OBJECTIVE: To explore the reversal effect of multidrug resistance of Curcuma Wenyujin (CW) and its possible mechanism by establishing Vincristine-resistant gastric cancer SGC-7901 cells (SGC-7901/VCR) induced subcutaneous transplanted tumor in nude mice. METHODS: First we identified the resistance of SGC-7901/VCR by using methyl thiazolyl tetrazolium (MTT). The SGC-7901/VCR induced subcutaneous transplanted tumor model was established in 50 BALB/c nude mice by tissue block method. After 2 -3 weeks 36 mice with similar tumor size were selected and divided into 6 groups by random digit table, i.e., the model group, the Vincristine (VCR) group, the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group, 6 in each group. Normal saline was intraperitoneally injected to mice in the model group at 10 mL/kg, once per 2 days. VCR was intraperitoneally injected to mice in the VCR group at 0.28 mg/kg once per 2 days. CW at 1.4 and 2.8 g/kg was administered to mice in the low and high dose CW groups by gastrogavage, 0.2 mL each time, once daily. CW at 1.4 and 2.8 g/kg was administered by gastrogavage and VCR was intraperitoneally injected at 0.28 mg/kg, once per 2 days to mice in the low dose CW combined VCR group and the high dose CW combined VCR group. All medication lasted for 14 days. The tumor growth was observed. The inhibition rate was calculated. Meanwhile, the positioning and expression of P-glycoprotein (P-gp) were detected by immunohistochemistry and Western blot. RESULTS: SGC-7901/VCR had strong resistance to VCR, Adramycin (ADM), fluorouracil (5-FU), and Cisplatin (DDP), especially to VCR. Proliferation activities of SGC-7901/VCR were significantly enhanced after drug elution. The tumor volume gradually increased as time went by. The tumor volume was the minimum in the high dose CW combined VCR group. The tumor volume was obviously reduced in the high dose CW combined VCR group with obviously reduced with increased inhibition rate of 51.56%, when compared with that of the model group and the VCR group (P < 0.05). Western blot test showed that, when compared with the model group, the gray level of P-gp in the VCR group increased (P < 0.05), and the relative expression of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group significantly decreased (P < 0.05). Compared with the VCR group, the gray level of the P-gp decreased in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05). Results of immunohistochemistry showed that, when compared with the model group, expression scores of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group decreased with statistical difference (P < 0.05). Compared with the VCR group, expression scores of P-gp were obviously lowered in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05). CONCLUSIONS: CW could reverse the drug resistance of SGC-7901/VCR subcutaneous transplanted tumor. And its mechanism might be related to down-regulating the expression of P-gp, suggesting that CW could be used as a kind of multidrug resistance reversal agent based on P-gp.

[Effect of Weifuchun on inhibiting inflammation of Helicobacter pylori-infected GES-1 cells and NF-kappaB signaling pathway].

OBJECTIVE: To study the effect of Weifuchun on inflammation of Helicobacter pylori (Hp)-infected gastric epithelial cells (GES-1) and its correlation with NF-kappaB signaling pathway. METHODS: Hp standard home-made strain (CagA +, VacA +) NCTCI 1637 infected GES-1 cells were used. Weifuchun was used as intervention. Weifuchun of different concentrations (5,10, and 20 microg/mL) were screened by MTT assay. A blank group and the model group were set up. Then the growth inhibition rate of drugs on gastric epithelial GES-1 cells was detected with MTT assay. Cell cycle was detected using flow cytometry. The supernatant liquid was separated to detect the contents of IL-8 and IL-4 by ELISA.The protein expression level of NF-kappaB was detected by Western blot analysis. RESULTS: MTT assay indicated significantly inhibitory effect of Weifuchun on GES-1 cells [5% inhibiting concentration (IC5)] was 10 microg/ml in the Weifuchun group. After GES-1 and Hp were cultured together,the contents of IL-8 in the supernatant were more obviously higher in the model group than in the blank group (P < 0.05), and then gradually decreased. After treatment with different concentrations of Weifuchun, the levels of IL-8 in the supernatant were less when compared with the model group at 12, 24, 48, and 72 h (P < 0.05). The decrement was the most significant in the high dose Weifuchun group. The IL-4 level in the supernatant was obviously lower in the model group than in the blank group. It obviously increased in the high concentration Weifuchun group (P < 0.05). There was no statistical difference in the IL-4 level between middle, low concentration Weifuchun group and the blank group (P > 0.05). The protein expression of intranuclear P65 increased and that of IkBalpha decreased 60 min after Hp infection. But the protein expression of intranuclear P65 decreased and the protein expression of IkBalpha increased after intervention of Weifuchun. CONCLUSIONS: Weifuchun adjusted H. pylori induced IL-8 and IL-4 production by gastric epithelial cells through blocking NF-kappaB pathways. Its mechanisms might possibly lie in inhibiting p65 from entry into nucleus and the degradation of IkBalpha. Weifuchun was an effective drug for treatment of Hp correlated chronic gastritis.