Mechanism of PANoptosis in metabolic dysfunction-associated steatotic liver disease.

In recent years, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been steadily rising, emerging as a major chronic liver disease of global concern. The course of MASLD is varied, spanning from MASLD to metabolic dysfunction associated steatohepatitis (MASH). MASH is an important contributor to cirrhosis, which may subsequently lead to hepatocellular carcinoma. It has been found that PANoptosis, an emerging inflammatory programmed cell death (PCD), is involved in the pathogenesis of MASLD and facilitates the development of NASH, eventually resulting in inflammatory fibrosis and hepatocyte death. This paper reviews the latest research progress on PANoptosis and MASLD to understand the mechanism of MASLD and provide new directions for future treatment and drug development.

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.

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.

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.

Effects of Endoscopic Submucosal Excavation With Non-Submucosal Injection on Stromal Tumors in Stomach.

Background and Aim: Endoscopic submucosal excavation (ESE) is commonly used to treat gastrointestinal stromal tumors (GISTs), especially for tumor sizes within 2 cm; compared with the conventical ESE, the efficacy and safety of the no-submucosal injection (NSI) ESE remains unclear. The aim of this study was to assess the clinical efficacy and safety of NSI-ESE for gastric stromal tumors. Methods: ESE was performed in 102 patients at our hospital between January 2018 and January 2020, and the clinical features, surgical outcomes, complications, cost of performance, pathological diagnosis, and risk classification were evaluated. Results: All tumors were completely resected by endoscopic resection (ER), with a complete resection rate of 100%. It was achieved by ESE/EFTR (endoscopic full-thickness resection) in 49 cases with submucosal injection, and by ESE/EFTR in 53 cases with NSI-ESE. The mean surgical time in cases with submucosal injection was 25.86 ± 4.45 min, compared to the cases without submucosal injection (17.23 ± 3.47 min), and the difference was significant (p < 0.001); the exposure time of tumor, the time of complete excavation of tumor, procedure cost, and hospital stay in the NSI-ESE group were all lower than those cases with submucosal injection (p < 0.05). In the risk classification, 95 (93.1%) cases had a very low risk, 4 (4.0%) cases had a low risk, and 2 (2.0%) cases had a high risk. No recurrence or metastasis was observed during the follow-up period of 18 ± 6 months (range: 13-25 months). Conclusions: NSI-ESE is a feasible, effective, and safe treatment for gastric GISTs; compared to the conventional ESE, NSI-ESE has the following advantages: it decreases procedure time, it lowers the risk of perforation, and it is cost-effective.

Effectiveness of a nurse-led Mindfulness-based Tai Chi Chuan (MTCC) program on Posttraumatic Growth and perceived stress and anxiety of breast cancer survivors.

Background: With the development of positive psychology, posttraumatic growth research on cancer patients has attracted increasing attention from researchers. It is immensely important to effectively increase the posttraumatic growth level of cancer patients and improve their quality of life. Objectives: To investigate the effectiveness of a nurse-led mindfulness-based Tai Chi Chuan (MTCC) programme for increasing posttraumatic growth (PTG) and decreasing the perceived stress and anxiety of breast cancer survivors. Methods: A RCT was conducted. Participants were randomly assigned to either the MTCC group or the control group. The programme included 59 women with stage I-III breast cancer. Participants in the intervention group participated in a nurse-led 8-week, twice a week, one-hour per day mindfulness-based exercise programme. The effectiveness of the intervention was measured three times (T1 - before intervention; T2 - after intervention; T3 - one year after intervention) using validated scales, including the PTG inventory (PTGI), Perceived Stress Scale (PSS), and Self-rating Anxiety Scale (SAS). A repeated-measure analysis of variance model was used to analyse the data. Results: Compared with the wait-list control group, the PTG level in the MTCC group was much higher after the 8-week intervention and the follow-up (F = 374.98, P < .000). The results showed that MTCC increased the level of PTG, and the effect persisted 1 year after intervention. In addition, PSS (F = 55.22, P < .000) and SAS (F = 148.92, P < .000) scores were significantly decreased at T2 and T3. Conclusion: The research preliminarily revealed that the MTCC programme was simple, effective, and more suitable to clinical nurses which should be recommended to cancer survivors to promote their recovery.

Antecedentes: Con el desarrollo de la psicología positiva, la investigación de crecimiento postraumático en pacientes con cáncer ha atraído cada vez más la atención de los investigadores. Es sumamente importante aumentar de manera eficaz el nivel de crecimiento postraumático de los pacientes con cáncer y mejorar su calidad de vida.Objetivos: Investigar la efectividad de un programa de Tai Chi Chuan basado en mindfulness (MTCC en sus siglas en inglés) dirigido por enfermeras para aumentar el crecimiento postraumático (PTG en sus siglas en inglés) y disminuir la percepción de estrés y ansiedad de las sobrevivientes de cáncer de mama.Métodos: Se condujo un ECA. Las participantes fueron asignadas al azar al grupo MTCC o al grupo control. El programa incluyó a cincuenta y nueve mujeres con cáncer de mama en estadio I-III. Las participantes en el grupo de intervención participaron en un programa de ejercicios basados en mindfulness dirigido por enfermeras, de 8 semanas, dos veces por semana, de una hora diaria. La efectividad de la intervención se midió tres veces (T1 ­ antes de la intervención; T2 ­ después de la intervención; T3 ­ un año después de la intervención) usando escalas validadas, incluidas el inventario de PTG (PTGI), la Escala de Estrés Percibida (PSS) y la Escala de Ansiedad Auto-reportada (SAS). Para analizar los datos se utilizó un modelo de análisis de varianza de medidas repetidas.Resultados: En comparación con el grupo control de la lista de espera, el nivel de PTG en el grupo MTCC fue mucho más alto después de intervención de 8 semanas y al seguimiento (F = 374.98, P< 0.000). Los resultados mostraron que la MTCC aumentó los niveles de PTG y el efecto persistió un año después de la intervención. Además, las puntuaciones de PSS (F = 55.22, P< 0.000) y SAS (F = 148.92, P< 0.000) disminuyeron significativamente en T2 y T3.Conclusiones: Las investigaciones preliminares revelaron que el programa de MTCC era simple, efectivo y más adecuado para las enfermeras clínicas, lo que debería recomendarse a las sobrevivientes de cáncer para promover su recuperación.

IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma.

BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.

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.

Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl Alcohol Extract Inhibits AGS Cell Helicobacter pyloriCagA+VacA+ Promoted Invasiveness by Down-Regulating Caudal Type Homeobox Transcription Factor and Claudin-2 Expression.

OBJECTIVE: To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP). METHODS: AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPCagA+VacA+, Group C with HPCagA-VacA-, Group D with HPCagA+VacA+ and CWNAE, and Group E with HPCagA-VacA- and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HPCagA+VacA+ and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells. RESULTS: The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 µg/mL. More AGS cells were elongated after co-culturing with HPCagA+VacA+ than after culturing with HPCagA-VacA-. In tumor invasion assays, HPCagA+VacA+ significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HPCagA+VacA+. HPCagA+VacA+ up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HPCagA+VacA+ (P<0.05), but not by HPCagA-VacA-. CONCLUSION: HPCagA+VacA+ promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HPCagA+VacA+ on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.

Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were adopted to evaluate gastric risk stratification in five biopsy samples. This study aimed to evaluate the degree of gastric atrophy (GA) and intestinal metaplasia (IM) in five locations to detect a more representative biopsy sample in gastric cancer (GC) screening. Our study enrolled 368 patients and 5 biopsy pieces were acquired from them. Gastric risk stratification was calculated by OLGA and OLGIM staging system. The results revealed that the IM score in the incisura angularis was higher than that in the larger and lesser curvature of corpus mucosa (p = 0.037 and p = 0.030, respectively) and the IM score in the lesser curvature of antrum mucosa was higher than that in the incisura angularis mucosa (p = 0.018). IM is more frequently observed in the angulus region than in the lesser curvature of corpus in the mild degree (p = 0.004) and mild IM lesions in the lesser curvature of antrum were more frequently observed than in the incisura angularis mucosa (p = 0.004), Four biopsy pieces protocol (larger curvature and lesser curvature of the antrum, lesser curvature of the corpus and angulus) demonstrated accurate consistency (97.83% and 98.37%, respectively) with a Kendall's tau-b of higher than 0.990, along with low misdiagnosis rates of OLGA and OLGIM (III + IV) (9.76% and 5.00%, respectively). Three biopsy pieces protocol (lesser curvature of the antrum and corpus, angulus biopsy) in OLGA and OLGIM staging system was close to the standard protocol (five biopsy specimens) with a consistency of 94.84% and 94.29% and has a Kendall's tau-b higher than 0.950 and diagnostic omission rates of 9.76% and 5.00%, respectively, which was exactly the same with the four biopsy pieces protocol. Furthermore, it had the second-highest Youden index (0.902 and 0.950, respectively) and area under the ROC curve (0.992 and 0.996, respectively) for the screening of high-risk GC by OLGA and OLGIM stages. Thus, we recommended the angulus and the lesser curvature of antrum as a conventional biopsy and three biopsy pieces for further GC risk screening.

Efficacy and mechanism of acupuncture for ischemic poststroke depression: Study protocol for a multicenter single-blinded randomized sham-controlled trial.

INTRODUCTION: Poststroke depression is a serious and common complication of stroke, especially the ischemic poststroke depression. Antidepressants are used in poststroke depression, and acupuncture may be an alternative approach. However, the efficacy and mechanism of acupuncture for poststroke depression has not been confirmed. METHODS/DESIGN: This is a multicenter, central-randomized, single-blind, sham-controlled clinical trial. We will allocate 208 subjects aged between 40 and 80 years old, diagnosed with initial poststroke depression (PSD) within 6 months to 2 groups randomly in a ratio of 1:1. Patients in the experimental group will be treated with traditional acupuncture and placebo pills, whereas the others in the control group will be treated with sham-acupoints acupuncture and antidepressant (fluoxetine hydrochloride tablets). All will be given acupuncture and/or medication treatment for 12 weeks, and then received 12-week follow-up. Patients will be evaluated with the 17-item Hamilton Depression Scale and Se1f-rating Depression Scale for depression state, National Institute of Health Stroke Scale for neurological deficit, Modified Barthel Index for activities of daily living, Treatment Emergent Symptom Scale for side effects of treatments, diagnosis and evaluation criteria of traditional Chinese medicine for stroke (try out) for curative effects of stroke, and clinical global impression for synthesize effect before and the 2nd, 4th, 8th, and 12th week of treatment, 24th week of follow-up. Study on mechanisms of acupuncture will be revealed through the diversity of brain metabolites (choline-containing compounds [Cho], N-acetylaspartate [NAA], myoinositol, glutamine and glutamate complex, creatine [Cr], Cho/Cr, Cho/NAA, Cr/NAA) in bilateral dorsolateral prefrontal cortex and anterior cingulate cortex monitored by proton magnetic resonance spectroscopy, and serum monoamine neurotransmitters (5-hydroxytryptamine, norepinephrine, dopamine) and cytokines (brain-derived neurotrophic factor [BDNF], interleukin [IL]-4, IL-6, IL-10, IL-18, IL-1ß, tumor necrosis factor alpha) before and the 12th week of treatment. Baseline characteristics of patients will be summarized by groups and compared with chi-square for categorical variables, and 2-sample t tests or Wilcoxon rank-sum test for the continuous variables. Primary and secondary outcomes according to the measurement times are applicable to univariate repetitive measurement deviation analysis or 2-sample t tests, or Wilcoxon rank-sum test. CONCLUSION: The present research is designed to investigate efficacy and mechanism of traditional acupuncture therapy on ischemic PSD, also to explore the correlation between cerebra metabolic and serologic factors, and ischemic PSD. With this research, we are looking forward to find out an appropriate alternative nondrug therapy for PSD people to alleviate the adverse effects and drug dependence caused by antidepressants.

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.

Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury.

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

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.

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats.

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 µg/mL MNNG. Stomach tissues were collected at the end of the 15(th), 25(th) and 40(th) week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Hypoglycemic and anti-inflammatory effects of seabuckthorn seed protein in diabetic ICR mice.

In this paper, we have investigated the hypoglycemic and anti-inflammatory effects of seabuckthorn seed protein (SSP) on streptozocin (STZ)-induced diabetic IRC mice. The effects of SSP on the body weight (BW), fasting blood glucose (FBG) levels, serum lipids, inflammatory factors and insulin (SIN) levels of normal and diabetic mice have been investigated. SSP has been shown to reduce insulin resistance (IR) and control the effects of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor-κ-gene binding (NF-κB). In addition, this paper further validates the hypoglycemic and anti-inflammatory effects of seabuckthorn procyanidins (SPR) and seabuckthorn polysaccharides (SPO) in diabetic mice and the experimental results were consistent with previous studies. Moreover, results from animal experiments showed that SSP has a significant hypoglycemic and anti-inflammatory effect as evidenced by the lower BW, FBG levels, SIN and lipid contents of diabetic mice treated with SSP compared to the diabetic control mice.

Esophageal motility after peroral endoscopic myotomy for achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been introduced as a novel endoscopic treatment for achalasia. The aim of this work is to assess the changes in esophageal motility caused by POEM in patients with achalasia. METHODS: Forty-one patients with achalasia underwent POEM from September 2012 to November 2014. Esophageal motility of all patients was evaluated preoperatively and 1 month after POEM utilizing high-resolution manometry, which was performed with ten water swallows, ten steamed bread swallows, and multiple rapid swallows (MRS). RESULTS: In single swallows, including liquid swallows and bread swallows, all the parameters of lower esophagus sphincter resting pressure (LESP), 4-s integrated relaxation pressure (4sIRP), and intra-bolus pressure (IBP) were decreased between pre- and post-POEM patients (all p < 0.05). Postoperatively, the trend of distal contractile integral (DCI) and distal esophageal peristaltic amplitude declined in subtype II and subtype III (subtype II: p < 0.05; subtype III: p > 0.05), but increased in subtype I (subtype I: p > 0.05). In liquid swallows, the Eckardt score of subtype II patients decreased with DCI, and distal esophageal peristaltic amplitude after POEM was significantly lower compared with those showing increased values of those two parameters (p < 0.05). In MRS, the rate of LES relaxation increased from 66.67 to 95.24%, but without normal response in all achalasia patients. CONCLUSIONS: POEM reduces LES pressure in achalasia, and partly restores esophageal motility. POEM displayed varying effect on esophageal motility in patients with different patterns of swallowing. In addition, the changes in parameters associated with esophageal peristalsis correlated with decreases in Eckardt score.

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.

Effects and mechanisms of transcutaneous electroacupuncture on chemotherapy-induced nausea and vomiting.

Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA) at Neiguan (PC6) and Jianshi (PC5) on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n = 34) and TEA group (n = 38). TEA was performed at PC 6 and PC 5 (1 h, bid) in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1) In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P < 0.01) and reduced the nausea score (P < 0.05), compared with sham-TEA. (2) TEA significantly reduced serum levels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated via mechanisms involving serotonin and dopamine.