Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus: A pilot bioinformatics study.

BACKGROUND: Helicobacter pylori (H. pylori) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown. AIM: To explore potential molecular connections between H. pylori infection and T2DM. METHODS: We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed. RESULTS: A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4, ITGAM, C5AR1, FCER1G, and FCGR2A, were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes. CONCLUSION: We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori-induced onset of T2DM.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Prognostic model of hepatocellular carcinoma based on cancer grade.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. With highly invasive biological characteristics and a lack of obvious clinical manifestations, HCC usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary HCC are still unclear. AIM: To select the characteristic genes that are significantly associated with the prognosis of HCC patients and construct a prognosis model of this malignancy. METHODS: By comparing the gene expression levels of patients with different cancer grades of HCC, we screened out differentially expressed genes associated with tumour grade. By protein-protein interaction (PPI) network analysis, we obtained the top 2 PPI networks and hub genes from these differentially expressed genes. By using least absolute shrinkage and selection operator Cox regression, 13 prognostic genes were selected for feature extraction, and a prognostic risk model of HCC was established. RESULTS: The model had significant prognostic ability in HCC. We also analysed the biological functions of these prognostic genes. CONCLUSION: By comparing the gene profiles of patients with different stages of HCC, We have constructed a prognosis model consisting of 13 genes that have important prognostic value. This model has good application value and can be explained clinically.

Antinociceptive and neuroprotective effect of echinacoside on peripheral neuropathic pain in mice through inhibiting P2X7R/FKN/CX3CR1 pathway.

Clinically, neuropathic pain treatment remains a challenging issue because the major therapy, centred around pharmacological intervention, is not satisfactory enough to patient by reason of low effectiveness and more adverse reaction. Therefore, it is still necessary to find more effective and safe therapy to ameliorate neuropathic pain. The purpose of this study was to explore the antinociceptive effect of Echinacoside (ECH), an active compound of Cistanche deserticola Ma, on peripheral neuropathic pain induced by chronic constriction injury (CCI) in mice, and to demonstrate its potential mechanism in vivo and vitro. In the present study, results showed that intraperitoneal administration of ECH (50, 100, and 200 mg/kg) could alleviate mechanical allodynia, cold allodynia and thermal hyperalgesia via behavioural test. Moreover, the structure and function of injured sciatic nerve by CCI were taken a turn for the better to a certain extent after ECH treatment using histopathological and electrophysiological test. Furthermore, ECH repressed the expression of the P2X7R and FKN and reduced the expression and release of the IL-1ß, IL-6 and TNF-α. Besides, ECH could decrease Ca2+ influx and Cats efflux and inhibit phosphorylation of p38MAPK. To sum up, the present study illustrated that ECH could alleviate peripheral neuropathic pain by inhibiting microglia overactivation and inflammation through P2X7R/FKN/CX3CR1 signalling pathway in spinal cord. This study would provide a new perspective and strategy for the pharmacological treatment on neuropathic pain.

Broadband sensory networks with locally stored responsivities for neuromorphic machine vision.

As the most promising candidates for the implementation of in-sensor computing, retinomorphic vision sensors can constitute built-in neural networks and directly implement multiply-and-accumulation operations using responsivities as the weights. However, existing retinomorphic vision sensors mainly use a sustained gate bias to maintain the responsivity due to its volatile nature. Here, we propose an ion-induced localized-field strategy to develop retinomorphic vision sensors with nonvolatile tunable responsivity in both positive and negative regimes and construct a broadband and reconfigurable sensory network with locally stored weights to implement in-sensor convolutional processing in spectral range of 400 to 1800 nanometers. In addition to in-sensor computing, this retinomorphic device can implement in-memory computing benefiting from the nonvolatile tunable conductance, and a complete neuromorphic visual system involving front-end in-sensor computing and back-end in-memory computing architectures has been constructed, executing supervised and unsupervised learning tasks as demonstrations. This work paves the way for the development of high-speed and low-power neuromorphic machine vision for time-critical and data-intensive applications.

Role of MEG3 in Cellular Physiology of Atherosclerosis.

OBJECTIVE: To investigate the role of the lncRNA MEG3 (MEG3) in opposing the biochemical processes thought to be involved in the development of atherosclerosis (AS). METHODS: Thirty patients with AS and thirty healthy control subjects were enrolled in this study. The expression of MEG3, miR-200b-3p and ABCA1 was analyzed by RT-qPCR in the individuals and the macrophages-derived foam cells. Lipid accumulation was detected by oil red O staining. Cholesterol efflux was measured by ELISA assay in the foam cells. Expression of miR-200b-3p was identified by sequencing. Targeting relationships were determined by dual luciferase assay between MEG3 and miR-200b-3p, miR-200b-3p and ABCA1. RESULTS: In the patients with AS, MEG3 and ABCA1 expression were decreased and miR-200b-3p expression was upregulated. Foam cells transfected with an expression vector (pcDNA3.1) containing MEG3 (pcDNA3.1-MEG3) induced decrease of lipid accumulation and increase of cholesterol efflux compared to cells transfected with control plasmid alone. Foam cells transfected by pcDNA3.1-MEG3 also showed decreased miR-200b-3p and increased ABCA1 expression. Interestingly, co-expression of miR-200b-3p partially prevented these effects of MEG3 expression. CONCLUSION: Expression of MEG3 is downregulated in the patients with AS and foam cells. Overexpressed MEG3 may act as an anti-atherosclerotic factor by reducing lipid accumulation and accelerating cholesterol efflux through the miR-200b-3p/ABCA1 axis.

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma: A real-world retrospective cohort study.

BACKGROUND: Signet-ring cell carcinoma (SRCC) was previously thought to have a worse prognosis than other differentiated gastric cancer (GC), however, recent studies have shown that the prognosis of SRCC is related to pathological type. We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis (LNM). AIM: To establish models to predict LNM in early GC (EGC), including early gastric SRCC. METHODS: Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed. The patients were divided into three groups based on type: Pure SRCC, mixed SRCC, and non-signet ring cell carcinoma (NSRC). The risk factors were identified through statistical tests using SPSS 23.0, R, and Em-powerStats software. RESULTS: A total of 1922 subjects with EGC were enrolled in this study, and included 249 SRCC patients and 1673 NSRC patients, while 278 of the patients (14.46%) presented with LNM. Multivariable analysis showed that gender, tumor size, depth of invasion, lymphovascular invasion, ulceration, and histological subtype were independent risk factors for LNM in EGC. Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy (98.0% vs 58.1%, P = 0.034; 88.4% vs 86.8%, P < 0.001, respectively). Among the 249 SRCC patients, LNM was more common in mixed (35.06%) rather than in pure SRCC (8.42%, P < 0.001). The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760 (95%CI: 0.682-0.843), while the area under the operating characteristic curve of the internal validation set was 0.734 (95%CI: 0.643-0.826). The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size > 2 cm (OR = 5.422, P = 0.038). CONCLUSION: A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC, which can aid in pre-surgical decision making of the best method of treatment for patients.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy as a First-Line Treatment of Helicobacter pylori Infection Compared With Bismuth-Containing Quadruple Therapy.

INTRODUCTION: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. METHODS: A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. RESULTS: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). CONCLUSIONS: The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy.

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions: The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Low-voltage ultrafast nonvolatile memory via direct charge injection through a threshold resistive-switching layer.

The explosion in demand for massive data processing and storage requires revolutionary memory technologies featuring ultrahigh speed, ultralong retention, ultrahigh capacity and ultralow energy consumption. Although a breakthrough in ultrafast floating-gate memory has been achieved very recently, it still suffers a high operation voltage (tens of volts) due to the Fowler-Nordheim tunnelling mechanism. It is still a great challenge to realize ultrafast nonvolatile storage with low operation voltage. Here we propose a floating-gate memory with a structure of MoS2/hBN/MoS2/graphdiyne oxide/WSe2, in which a threshold switching layer, graphdiyne oxide, instead of a dielectric blocking layer in conventional floating-gate memories, is used to connect the floating gate and control gate. The volatile threshold switching characteristic of graphdiyne oxide allows the direct charge injection from control gate to floating gate by applying a nanosecond voltage pulse (20 ns) with low magnitude (2 V), and restricts the injected charges in floating gate for a long-term retention (10 years) after the pulse. The high operation speed and low voltage endow the device with an ultralow energy consumption of 10 fJ. These results demonstrate a new strategy to develop next-generation high-speed low-energy nonvolatile memory.

Endoscopic detection of esophageal low-grade squamous dysplasia: How to predict pathologic upgrades before treatment?

OBJECTIVE: In this study we aimed to predict the risk factors related to histopathologic upgrade after endoscopic submucosal dissection (ESD) in patients with pre-ESD esophageal squamous low-grade intraepithelial neoplasm (LGIN). METHODS: A training cohort of 201 patients with biopsy-confirmed esophageal squamous LGIN and underwent ESD at a tertiary medical center between January 2017 and July 2019 were included. Risk factors for histological upgrade were identified using the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then established. Internal validation was evaluated by discrimination, calibration plot, and decision-curve analysis. Another cohort of 48 patients were prospectively collected from July 2019 to June 2021 for external validation of the nomogram. RESULTS: The rate of histological upgrade was 34.8% (70/201) and 27.1% (13/48) in the training and validation sets, respectively. LASSO regression identified that tumor area (mm2 ) per biopsy, Lugol's staining pattern, background coloration, and the circumferential range of the lesion were significantly associated with histological upgrade. The final nomogram attained favorable prediction efficacy in the training cohort (area under the receiver operating curve [AUROC] 0.96, 95% confidence interval [CI] 0.94-0.98) and validation cohort (AUROC 0.92, 95% CI 0.79 -0.99). This model generated well-fitted calibration and clinical-decision curves in both cohorts. CONCLUSIONS: The nomogram may better guide clinical decision on whether performing EDS or follow-up for suspicious lesions in patients with biopsy-confirmed esophageal squamous LGIN.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Inhibition of miR-200b-3p alleviates lipid accumulation and promotes cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells.

Atherosclerosis (As) is a chronic cardiovascular disease characterized by abnormal of lipid accumulation and cholesterol efflux. The present study aimed to investigate whether the micro-RNA (miR)-200b-3p could exacerbate As by promoting lipid accumulation and inhibiting cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) in macrophage-derived foam cells. Blood samples from 30 patients with As and 30 healthy people were collected at Quanzhou First Hospital. RAW264.7 cells were used to establish foam cells using oxidized low-density lipoprotein. The expression of miR-200b-3p and ABCA1 was evaluated by reverse transcription quantitative PCR and western blotting. Lipid accumulation was analyzed by Oil Red O staining and cholesterol content was assessed by ELISA. A targeting relationship between miR-200b-3p and ABCA1 was demonstrated by luciferase reporter assays. Compared with healthy volunteers and RAW264.7 cells, the expression level of miR-200b-3p was significantly increased whereas the expression level of ABCA1 was significantly decreased in patients with As and foam cells. Furthermore, miR-200b-3p expression was negatively correlated with ABCA1 expression in the blood of the patients with As. Lipid content was significantly decreased and cholesterol efflux was significantly increased in foam cells transfected with the miR-200b-3p inhibitor compared with inhibitor control cells. In addition, ABCA1 was shown to be targeted by miR-200b-3p. Furthermore, the lipid content in foam cells transfected with the miR-200b-3p inhibitor and small interfering-ABCA1 was significantly increased, while the cholesterol efflux was significantly decreased compared with foam cells transfected with the miR-200b-3p inhibitor. In conclusion, the findings from the present study indicated that inhibition of miR-200b-3p may alleviate lipid accumulation and promote cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells.

Influence of Dietary Components and Traditional Chinese Medicine on Hypertension: A Potential Role for Gut Microbiota.

Hypertension (HTN) is an important worldwide public health issue affecting human health. The pathogenesis of HTN involves complex factors such as genetics, external environment, diet, and the gut microbial dysbiosis. The gut microbiota, as a medium of diet and drug metabolism, is closely correlated to host's health and disease (including HTN). Literatures were randomly collected from various databases including PubMed, ScienceDirect, Google Scholar, and China National Knowledge Infrastructure (CNKI). In this review, we elucidate the relationship between HTN and gut microbiota, as well as concerning the effects of different dietary components, diet-derived microbial metabolites, and traditional Chinese medicine (TCM) on intestinal flora. These studies have shown that diet and TCM can regulate and balance the intestinal flora, which are inclined to increasing the abundance of Akkermansia, Bifidobacterium, and Bacteroides and reducing the ratio of Firmicutes and Bacteroidetes. Moreover, monitoring the dynamic change of gut microflora may indicate patient prognosis and personalized response to treatment. This review aims to provide novel perspectives and potential personalized interventions for future HTN management from the perspective of gut microbiota.

miR­212 promotes renal interstitial fibrosis by inhibiting hypoxia­inducible factor 1­α inhibitor.

Renal interstitial fibrosis is one of the common causes, and a major pathological basis for the development of various types of chronic progressive renal to end­stage renal diseases. Therefore, it is important to clarify the underlying mechanisms of disease progression in order to develop effective strategies for the treatment and prevention of these pathologies. The aim of the present study was to investigate the association between microRNA (miR)­212 expression and the development of renal interstitial fibrosis, as well as analyzing the role of miR­212 in the disease. The expression of miR­212 was significantly increased in the peripheral blood of patients with renal interstitial fibrosis and in the kidney tissues of unilateral ureteral obstruction (UUO) mice. Angiotensin (Ang) II, TGF­ß1 and hypoxia were found to increase the expression of miR­212 and α smooth muscle actin (α­SMA) in NRK49F cells. Ang II stimulation induced the expression of miR­212 and α­SMA in NRK49F cells, while transfection of miR­212 mimics further upregulated the expression of α­SMA. miR­212 was also revealed to target hypoxia­inducible factor 1α inhibitor (HIF1AN) and to upregulate the expression of hypoxia­inducible factor 1α, α­SMA, connective tissue growth factor, collagen α­1(I) chain and collagen α­1(III) chain, whereas HIF1AN overexpression reversed the regulatory effects of miR­212. In UUO mice, miR­212 overexpression promoted the progression of renal interstitial fibrosis, whereas inhibiting miR­212 resulted in the opposite effect. These results indicated that high expression of miR­212 was closely associated with the occurrence of renal interstitial fibrosis, and that miR­212 may promote its development by targeting HIF1AN.

New genotypes of Helicobacter Pylori VacA d-region identified from global strains.

BACKGROUND: Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS: We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS: Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.

Anti-inflammatory and analgesic activities of indigo through regulating the IKKß/IκB/NF-κB pathway in mice.

This study investigated the anti-inflammatory and analgesic activities of indigo in mice and explored the possible related mechanisms. Xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeability tests were used in investigating the anti-inflammatory activities. The anti-nociceptive effects of indigo were assessed through acetic acid-induced writhing, hot plate test, and formalin test, and spontaneous locomotor activity and motor performance were evaluated. The mechanisms of activities of indigo were explored by evaluating the expression levels of IκB kinase (IKK)ß, p-IKKß, inhibitor κB (IκB)α, p-IκBα, p65 nuclear factor (NF)-kB, p-p65 NF-κB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) through western blotting and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) through enzyme-linked immunosorbent assay. The results showed that indigo significantly reduced xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeation. In addition, indigo significantly inhibited nociception induced by acetic acid and formalin. However, the level of nociception was not decreased by indigo in the hot plate test, and indigo did not affect spontaneous locomotor activity and motor performance. The expression levels of p-IKKß, p-IκBα, p65 NF-kB, p-p65 NF-κB, COX-2, iNOS, TNF-α, IL-1ß, IL-6, and PGE2 decreased, whereas the expression level of IκBα increased obviously after indigo treatment. In conclusion, indigo exerts significant anti-inflammatory and analgesic activities in mice by inhibiting IKKß phosphorylation and reducing the production of important pain mediators, such as PGE2 and COX-2, via the IKKß/IκB/NF-κB pathway.