MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q-markers in Paris polyphylla var. yunnanensis.

To enhance the quality evaluation and control of traditional Chinese medicine (TCM) and ensure the safety and efficacy of clinical medication, it is imperative to establish a comprehensive quality assessment method aligned with TCM efficacy. This study uses a representative Chinese medicine with multi-origin and multi-efficacy, Paris polyphylla var. yunnanensis (PY), as an illustrative example. Surprisingly, despite the high fingerprint similarity among the 12 batches of PY samples collected from various regions in Yunnan, a notable variation in the composition and content of components was observed. The chromatographic analysis identified seven common peaks, namely, polyphyllin I, polyphyllin II, polyphyllin V, polyphyllin VI, polyphyllin VII, polyphyllin H, and polyphyllin D. In the bioactivity evaluation, an in vitro antiplatelet aggregation model induced by adenosine diphosphate was established, showcasing excellent stability. The maximum antiplatelet aggregation inhibition rate for all PY samples consistently remained stable at 73.1%-99.1%. However, the 50% inhibitory concentration (IC50 ) values exhibited a range from 1.615 to 18.200 mg/mL. This approach not only meets high-throughput screening requirements but also demonstrates remarkable discrimination. The results of chemical and bioactivity evaluations were analyzed using hierarchical cluster analysis and canonical correlation analysis. Polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin H, and polyphyllin D were identified as the Q-markers for antiplatelet aggregation in PY samples. Validation of the bioactivity for these monomer components aligned with the previously mentioned findings. Notably, this study established a spectrum-effect model for PY samples, enhancing the scientific robustness of the quality evaluation method. Furthermore, these findings offer valuable research insights for improving the quality assessment of other TCMs.

Assessment of the quality, diagnosis, and therapeutic recommendations of clinical practice guidelines on patients with Helicobacter pylori infection: A systematic review.

We conducted this study to systematically review and assess the current clinical practice guidelines (CPGs) related to the diagnosis and treatment of Helicobacter pylori (H. pylori) infection. The aim was to evaluate the quality of these included CPGs and provide clinicians with a convenient and comprehensive reference for updating their own CPGs. We searched four databases to identify eligible CPGs focusing on H. pylori diagnosis and treatment recommendations. The results were presented using evidence mappings. Quality and clinical applicability were assessed comprehensively using AGREE-II and AGREE-REX. Statistical tests, specifically Bonferroni tests, were employed to compare the quality between evidence-based guidelines and consensus. A total of 30 eligible CPGs were included, comprising 17 consensuses and 13 guidelines. The quality showed no statistical significance between consensuses and guidelines, mainly within the moderate to low range. Notably, recommendations across CPGs exhibited inconsistency. Nevertheless, concerning diagnosis, the urea breath test emerged as the most frequently recommended method for testing H. pylori. Regarding treatment, bismuth quadruple therapy stood out as the predominantly recommended eradication strategy, with high-dose dual therapy being a newly recommended option. Our findings suggest the need for specific organizations to update their CPGs on H. pylori or refer to recently published CPGs. Specifically, CPGs for pediatric cases require improvement and updating, while a notable absence of CPGs for the elderly was observed. Furthermore, there is a pressing need to improve the overall quality of CPGs related to H. pylori. Regarding recommendations, additional evidence is essential to elucidate the relationship between H. pylori infection and other diseases and refine test indications. Clinicians are encouraged to consider bismuth quadruple or high-dose dual therapy, incorporating locally sensitive antibiotics, as empirical radical therapy. .

High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.

Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice.

CONTEXT: Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury. OBJECTIVE: To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure. MATERIALS AND METHODS: Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups (n = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes. RESULTS: In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 µmol/L and 3.31 ± 0.35 µmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABAA in the cortex decreased. CONCLUSIONS: We speculate that DMY can serve as a novel treatment for HE.

The chloroplast genomes of two medicinal species (Veronica anagallis-aquatica L. and Veronica undulata Wall.) and its comparative analysis with related Veronica species.

Veronica anagallis-aquatica L. and Veronica undulata Wall. are widely used ethnomedicinal plants in China. The two species have different clinical efficacies, while their extremely similar morphology and unclear interspecific relationship make it difficult to accurately identify them, leading to increased instances of mixed usage. This article reports on the complete chloroplast genomes sequence of these two species and their related Veronica species to conduct a comparative genomics analysis and phylogenetic construction. The results showed that the chloroplast (cp) genomes of Veronica exhibited typical circular quadripartite structures, with total lengths of 149,386 to 152,319 base pairs (bp), and GC content of 37.9 to 38.1%, and the number of genes was between 129-134. The total number of simple sequence repeats (SSRs) in V. anagallis-aquatica and V. undulata is 37 and 36, while V. arvensis had the highest total number of 56, predominantly characterized by A/T single bases. The vast majority of long repeat sequence types are forward repeats and palindromic repeats. Selective Ka/Ks values showed that three genes were under positive selection. Sequence differences often occur in the non-coding regions of the large single-copy region (LSC) and small single-copy region (SSC), with the lowest sequence variation in the inverted repeat regions (IR). Seven highly variable regions (trnT-GGU-psbD, rps8-rpl16, trnQ-UUG, trnN-GUU-ndhF, petL, ycf3, and ycf1) were detected, which may be potential molecular markers for identifying V. anagallis-aquatica and V. undulata. The phylogenetic tree indicates that there is a close genetic relationship between the genera Veronica and Neopicrorhiza, and V. anagallis-aquatica and V. undulata are sister groups. The molecular clock analysis results indicate that the divergence time of Veronica may occur at ∼ 9.09 Ma, and the divergence time of these two species occurs at ∼ 0.48 Ma. It is speculated that climate change may be the cause of Veronica species diversity and promote the radiation of the genus. The chloroplast genome data of nine Veronica specie provides important insights into the characteristics and evolution of the chloroplast genome of this genus, as well as the phylogenetic relationships of the genus Veronica.

Integrated management of fruit trees and Bletilla striata: implications for soil nutrient profiles and microbial community structures.

Introduction: Forest medicinal compound systems in agroforestry ecosystems represent a multi-layered cultivation approach that utilizes forest resources efficiently. However, research on how these systems affect soil nutrients and microbial communities is limited. Methods: This study compared the soil chemical properties and microbial communities of Bletilla striata (C) grown alone versus in agroforestry systems with apple (PB), pear (LB), and peach trees (TB), aiming to understand the impact of these systems on soil health and microbial diversity. Results: Soil in the GAB systems showed increased levels of essential nutrients but lower pH and ammonium nitrogen levels compared to the control. Significant improvements in organic matter, total phosphorus, and total potassium were observed in TB, PB, and LB systems, respectively. The bacterial diversity increased in GAB systems, with significant changes in microbial phyla indicative of a healthier soil ecosystem. The correlation between soil properties and bacterial communities was stronger than with fungal communities. Discussion: Integrating B. striata with fruit trees enhances soil nutrients and microbial diversity but may lead to soil acidification. Adjustments such as using controlled-release fertilizers and soil amendments like lime could mitigate negative impacts, improving soil health in GAB systems.

Dihydromyricetin ameliorates experimental ulcerative colitis by inhibiting neutrophil extracellular traps formation via the HIF-1α/VEGFA signaling pathway.

Dihydromyricetin (DHM), which has various biological functions, possesses therapeutic potential for ulcerative colitis (UC). Neutrophil extracellular traps (NETs) and their components play a crucial role in several pathological processes in UC. However, whether DHM alleviates UC by regulating NETs remains unclear. Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with DHM at different concentrations, and the severity of colitis was evaluated by assessing body weight, colon length, histological scores, cytokine production, and epithelial barrier integrity. To quantify and visualize NETs, the expression of cell free-DNA (cf-DNA) in serum and Cit-H3 in colonic tissue was analyzed via western blotting and immunofluorescence analysis. HL-60 cells and mouse bone marrow-derived neutrophils (BMDNs) were used to evaluate the effects of DHM on NETs in vitro. NETs were treated with DHM at varying concentrations or DNase I and used to repair the intestinal epithelial barrier in a Caco-2/HIEC-6 cell monolayer model. Furthermore, the genes targeted by DHM through neutrophils for alleviating UC were identified by screening online databases, and the results of network pharmacological analysis were verified via western blotting and quantitative real-time polymerase chain reaction. DHM alleviated DSS-induced colitis in mice by reversing weight loss, increased DAI score, colon length shortening, enhanced spleen index, colonic pathological damage, cytokine production, and epithelial barrier loss in a dose-dependent manner. In addition, it inhibited the formation of NETs both in vivo and in vitro. Based on the results of network pharmacological analysis, DHM may target HIF-1α and VEGFA through neutrophils to alleviate UC. Treatment with PMA increased the expression of HIF-1α and VEGFA in D-HL-60 cells and BMDNs, whereas treatment with DHM or DNase I reversed this effect. Treatment with DMOG, an inhibitor of HIF prolyl hydroxylase (HIF-PH), counteracted the suppressive effects of DHM on NETs formation in D-HL-60 cells and BMDNs. Accordingly, it partially counteracted the protective effects of DHM on the intestinal epithelial barrier in Caco-2 and HIEC-6 cells. These results indicated that DHM alleviated DSS-induced UC by regulating NETs formation via the HIF-1α/VEGFA signaling pathway, suggesting that DHM is a promising therapeutic candidate for UC.

Focusing on discoidin domain receptors in premalignant and malignant liver diseases.

Discoidin domain receptors (DDRs) are receptor tyrosine kinases on the membrane surface that bind to extracellular collagens, but they are rarely expressed in normal liver tissues. Recent studies have demonstrated that DDRs participate in and influence the processes underlying premalignant and malignant liver diseases. A brief overview of the potential roles of DDR1 and DDR2 in premalignant and malignant liver diseases is presented. DDR1 has proinflammatory and profibrotic benefits and promotes the invasion, migration and liver metastasis of tumour cells. However, DDR2 may play a pathogenic role in early-stage liver injury (prefibrotic stage) and a different role in chronic liver fibrosis and in metastatic liver cancer. These views are critically significant and first described in detail in this review. The main purpose of this review was to describe how DDRs act in premalignant and malignant liver diseases and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for cancer treatment and accelerate translation from bench to bedside.

Focusing on Helicobacter pylori infection in the elderly.

As a confirmed carcinogen, Helicobacter pylori (H. pylori) is the main cause of inflammatory diseases of the upper digestive tract and even gastric cancer. There is a high prevalence of H. pylori infection among the elderly population, which may cause adverse clinical outcomes. Particularly noteworthy is that guidelines or expert consensus presently available on H. pylori infection overlook the management of the elderly population as a special group. A brief overview of H. pylori in the elderly is as follows. The detection of H. pylori infection can be divided into invasive and non-invasive techniques, and each technique has its advantages and shortcomings. There may be more side effects associated with eradication treatment in elderly individuals, especially for the frail population. Physical conditions and risk-benefit assessments of the elderly should be considered when selecting therapeutic strategies for H. pylori eradication. Unless there are competing factors, elderly patients should receive H. pylori eradication regimens to finally reduce the formation of gastric cancer. In this review, we summarize the latest understanding of H. pylori in the elderly population to provide effective managements and treatment measures.

CRISPR-cas technology: A key approach for SARS-CoV-2 detection.

The CRISPR (Clustered Regularly Spaced Short Palindromic Repeats) system was first discovered in prokaryotes as a unique immune mechanism to clear foreign nucleic acids. It has been rapidly and extensively used in basic and applied research owing to its strong ability of gene editing, regulation and detection in eukaryotes. Hererin in this article, we reviewed the biology, mechanisms and relevance of CRISPR-Cas technology and its applications in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. CRISPR-Cas nucleic acid detection tools include CRISPR-Cas9, CRISPR-Cas12, CRISPR-Cas13, CRISPR-Cas14, CRISPR nucleic acid amplification detection technology, and CRISPR colorimetric readout detection system. The above CRISPR technologies have been applied to the nucleic acid detection, including SARS-CoV-2 detection. Common nucleic acid detection based on CRISPR derivation technology include SHERLOCK, DETECTR, and STOPCovid. CRISPR-Cas biosensing technology has been widely applied to point-of-care testing (POCT) by targeting recognition of both DNA molecules and RNA Molecules.

Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer.

BACKGROUND: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. METHODS: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). RESULTS: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. CONCLUSION: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.

The prognostic role and metabolic function of GGPS1 in oral squamous cell carcinoma.

Background: GGPS1(geranylgeranyl diphosphate synthase 1) is a member of the prenyltransferase family. Abnormal expression of GGPS1 can disrupt the balance between protein farnesylation and geranylgeranylation, thereby affecting a variety of cellular physiologic and pathological processes. However, it is still unknown how this gene could contribute to the prognosis of oral squamous cell carcinoma (OSCC). This study aimed to explore the prognostic role of GGPS1 in OSCC and its relationship with clinical features. Methods: The RNA-seq data and clinical data were obtained from TCGA. The survival analyses, Cox regression analyses, ROC curves, nomograms, calibration curves, and gene function enrichments were established by R software. Results: The results showed that the high expression of GGPS1 in OSCC is related to poor prognosis. At the same time, multivariate Cox regression analyses showed that GGPS1 could be an independent prognostic biomarker, and its gene expression level is closely related to the histological stage of cancer. GGPS1 may promote tumorigenesis because of its metabolic function. Conclusion: This study came to a conclusion that GGPS1, whose high expression has a significantly unfavorable meaning toward the prognosis of OSCC, can act as a novel independent biomarker for OSCC.

Insight into increased risk of portal vein thrombosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases with increased morbidity and mortality rates for extrahepatic diseases (including cardiovascular disease, portal vein thrombosis, etc.). There is an increased risk of thrombosis in both the portal and systemic circulation in patients with NAFLD, independent of traditional liver cirrhosis. However, increased portal pressure, the most critical factor, is frequently observed in NAFLD patients, predisposing them to portal vein thrombosis (PVT). It has been reported that there is an 8.5% incidence of PVT among patients with non-cirrhotic NAFLD in a prospective cohort study. Based on the prothrombotic status of NAFLD itself, patients combined with cirrhosis may accelerate the development of PVT and lead to a poor prognosis. Moreover, PVT has been shown to complicate the procedure and adversely affect the outcome during liver transplantation surgery. NAFLD is in a prothrombotic state, and its underlying mechanisms have not been fully understood so far. Particularly noteworthy is that gastroenterologists currently overlook the higher risk of PVT in NAFLD. We investigate the pathogenesis of NAFLD complicated with PVT from the perspective of primary, secondary, and tertiary hemostasis, and also summarize relevant studies in humans. Some treatment options that may affect NAFLD and its PVT are also explored to improve patient-oriented outcomes.

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma.

The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC.

Phylogeny and Genetic Divergence among Sorghum Mosaic Virus Isolates Infecting Sugarcane.

Sorghum mosaic virus (SrMV, the genus Potyvirus of the family Potyviridae) is a causal agent of common mosaic in sugarcane and poses a threat to the global sugar industry. In this study, a total of 901 sugarcane leaf samples with mosaic symptom were collected from eight provinces in China and were detected via RT-PCR using a primer pair specific to the SrMV coat protein (CP). These leaf samples included 839 samples from modern cultivars (Saccharum spp. hybrids) and 62 samples from chewing cane (S. officinarum). Among these, 632 out of 901 (70.1%) samples were tested positive for SrMV. The incidences of SrMV infection were 72.3% and 40.3% in modern cultivars and chewing cane, respectively. Phylogenetic analysis showed that all tested SrMV isolates were clustered into three clades consisting of six phylogenetic groups based on 306 CP sequences (this study = 265 and GenBank database = 41). A total of 10 SrMV isolates from South America (the United States and Argentina) along with 106 isolates from China were clustered in group D, while the remaining 190 SrMV isolates from Asia (China and Vietnam) were dispersed in five groups. The SrMV isolates in group F were limited to Yunnan province in China, and those in group A were spread over eight provinces. A significant genetic heterogeneity was elucidated in the nucleotide sequence identities of all SrMV CPs, ranging from 69.0% to 100%. A potential recombination event was postulated among SrMV isolates based on CP sequences. All tested SrMV CPs underwent dominant negative selection. Geographical isolation (South America vs. Asia) and host types (modern cultivars vs. chewing cane) are important factors promoting the genetic differentiation of SrMV populations. Overall, this study contributes to the global understanding of the genetic evolution of SrMV and provides a valuable resource for the epidemiology and management of the mosaic in sugarcane.

Molecular mechanism and therapeutic significance of dihydromyricetin in nonalcoholic fatty liver disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been steadily increasing, and it has become one of the most prevalent chronic liver diseases worldwide. Recent studies have shown that dihydromyricetin (DHM) is influential in treating NAFLD. The purpose of this review was to describe how DHM prevents and treats NAFLD and its potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. A brief overview of DHM's potential role in NAFLD involves regulation of lipid/glucose metabolism, possibly via anti-inflammatory or sirtuin-dependent mechanisms. For NAFLD, there is currently no effective and approved medication for therapy. DHM has the characteristics of liver protection, antioxidation, anti-inflammatory and apoptosis-regulatory benefits, which provides a new idea for the treatment of NAFLD. With the increasing interest in utilizing natural products to prevent and control liver diseases, our work aims to provide new ideas for the treatment of NAFLD and accelerate its translation from bench to bedside.

Identification of therapeutic targets and prognostic biomarkers among frizzled family genes in glioma.

Background: The biological functions of the Frizzled gene family (FZDs), as the key node of wingless-type MMTV integration site family (Wnt) and mammalian target of rapamycin signaling pathways, have not been fully elucidated in glioma. This study aims to identify novel therapeutic targets and prognostic biomarkers for gliomas, which may help us understand the role of FZDs. Methods: RNA-sequence data were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Survival analyses, Cox regression analyses, nomograms, calibration curves, receiver operating characteristic (ROC) curves, gene function enrichment analyses, and immune cell infiltration analyses were conducted using R. Results: High expressions of FZDs were positively associated with the activation of mTOR signaling. FZD1/2/3/4/5/7/8 was significantly highly expressed in tumor tissues, and the high expression of FZD1/2/5/6/7/8 was significantly positively associated with poorer prognosis. FZD2 and FZD6 positively served as independent predictors of poor prognosis. Gene function analysis showed that FZDs were associated with mTOR signaling, immune response, cytokine-cytokine receptor interaction, extracellular matrix organization, apoptosis, and p53 signaling pathway. Conclusions: Our finding strongly indicated a crucial role of FZDs in glioma. FZD1/2/5/6/7/8 could be an unfavorable prognostic factor in glioma and FZD2 and FZD6 may be novel independent predictors of poor prognosis in glioma.

The efficacy of vonoprazan combined with different dose amoxicillin on eradication of Helicobacter pylori: an open, multicenter, randomized clinical study.

Background: The use of vonoprazan (VPZ) has improved the Helicobacter pylori (H. pylori) eradication therapy in Japan. There is no agreement on the dosage and frequency of amoxicillin administration in the VPZ dual treatment in China. We aimed to investigate the clinical effectiveness and safety of 3 treatment regimens using VPZ as an acid-suppressing medication to eradicate H. pylori. Methods: This experiment involved an open, multicenter, randomized, and parallel controlled clinical investigation. A total of 230 newly diagnosed H. pylori-infected patients were then randomly assigned to 1 of 3 groups: (I) H-VA (high-dose amoxicillin combined with VPZ): VPZ 20 mg b.i.d with amoxicillin 750 mg q.i.d for 7 days; (II) L-VA (low-dose amoxicillin combined with VPZ): VPZ 20 mg b.i.d plus amoxicillin 500 mg q.i.d for 7 days; (III) VAC (amoxicillin combined with VPZ and clarithromycin): VPZ 20 mg b.i.d plus amoxicillin 750 mg plus clarithromycin 500 mg for 7 days. At least 4 weeks after treatment, the urea breath test (UBT) was reexamined. The effectiveness of various regimens was assessed based on compliance, safety, and eradication rate. Results: The regimen effectiveness was 63.5% (54/85) in the H-VA group, 58.3% (49/84) in the L-VA group, and 60.7% (37/61) in the VAC group, according to intention to treat (ITT) analysis. According to per protocol (PP) analysis, the eradication rate of the H-VA group was 65.1% (54/83), that of the L-VA group was 66.2% (49/74), and that of the VAC group was 64.9% (37/57). There was no discernible difference in the eradication rate across the 3 regimens, as shown by the results of ITT analysis (χ2=0.032, P=0.984) and PP analysis (χ2=0.480, P=0.786). The rate of adverse effect was 16.90% in the H-VA group, 13.20% in the L-VA group, and 24.10% in the VAC group. There was no discernible difference in the incidence of adverse effect between the three groups (χ2=2.784, P=0.266). Conclusions: None of the 7-day elimination regimens investigated in this study, which included the acid-suppressing medicine VPZ and either a dual treatment paired with amoxicillin, or a triple treatment combined with amoxicillin and clarithromycin, achieved an acceptable eradication rate of H. pylori. Further research is required to identify an effective and safe treatment regimen. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000040955.