BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

Heme oxygenase-1(HO-1)is an inducible heme oxygenase and a catalytic enzyme for heme decomposition reactions,which can catalyze the heme decomposition into CO,biliverdin and Fe2+.HO-1 and its metabolites have anti-inflammatory,antioxidant and anti-apoptotic effects in human body,and play an important role in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease.This article will review the production,distribution,and gene structure of HO-1,the biological characteristics of its metabolites,and the role and mechanism of HO-1 in neurodegenerative diseases,in order to provide a theoretical basis for the clinical application of HO-1.

OBJECTIVE: To explore the immunological mechanisms underlying spermatogenetic malfunction in patients with non-obstructive azoospermia (NOA) based on bioinformatics and machine learning, and to screen out the key genes associated with spermatogenesis failure. METHODS: NOA-related datasets were obtained from the GEO database, and the differentially expressed genes identified by differential analysis and weighted gene co-expression network analysis (WGCNA). A model of spermatogenesis scoring was established for analysis of the immunological microenvironment and cell interaction networks related to spermatogenesis failure. The key genes were screened out by machine learning, followed by analysis of their correlation with T cells and macrophages. An NOA mouse model was constructed for validation of transcriptome sequencing. RESULTS: Seventy-five differentially expressed genes were identified for the establishment of the spermatogenesis scoring model. The low spermatogenesis score group showed a higher infiltration of the immune cells, with an increased proportion of T cells and macrophages and a correlation of cell interaction signals with immunity. SOX30, KCTD19, ASRGL1 and DRC7 were identified by machine learning as the key genes related to spermatogenesis, with down-regulated expressions in the NOA group, and their expression levels negatively correlated with the infiltration of T cells and macrophages. The accuracy of the spermatogenesis scoring and machine learning models, as well as the trend of the expression levels of the key genes, was successfully validated with the transcriptome sequencing data on the NOA mouse testis. CONCLUSION The development of NOA is closely associated with enhanced immunological microenvironment in the testis. T cells and macrophages may play important roles in spermatogenesis failure. SOX30, KCTD19, ASRGL1 and DRC7 are potential biomarkers for the diagnosis and treatment of NOA.
Male ; Azoospermia/genetics* ; Machine Learning ; Animals ; Computational Biology ; Mice ; Humans ; Spermatogenesis/genetics* ; Gene Expression Profiling ; Macrophages/immunology* ; Gene Regulatory Networks ; T-Lymphocytes/immunology* ; Transcriptome

OBJECTIVETo organize the clinical practice guidelines (CPGs) related to acupuncture included in the National Guideline Clearinghouse (NGC) to systematically summarize the diseases and disorders most commonly treated with acupuncture, the strength of recommendations for acupuncture and the quality of evidence.

METHODSThe NGC database was systematically searched for guidelines that included acupuncture as an intervention. Two independent reviewers studied the summaries and the full texts of the guidelines and included guidelines based on the inclusion and exclusion criteria. Thirty-nine guidelines were collected with 80 recommendations. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used to assess the quality of these guidelines.

RESULTSOf the 80 recommendations on acupuncture, 49 recommendations were clearly for acupuncture, 25 recommendations were against acupuncture and 6 recommendations did not indicate any clear recommendations, 37 recommendations were for painful diseases/disorders, and 12 recommendations were for non-painful diseases/disorders. Locomotor system disorders were the most common in the painful diseases/disorders category. Out of all the recommendations for acupuncture, most recommendations (87.76%) were weak in strength, and most of the evidence (40.84%) was of low quality.

CONCLUSIONSIn the National Guideline Clearinghouse, the recommendations for acupuncture focus on painful diseases/disorders. The recommendations in the guidelines are not high in strength, and most of the evidence is moderate or low in quality.

Objective To investitate the efficacy of cannabinoid-2 receptor (CB2R) activation in preventing liver ischemia-reperfusion (I/R) injury in mice.Methods Forty-eight male C57BL/6J mice,weighing 20-30 g,were divided into 4 groups (n =12 each):sham operation group (group S),group I/R,CB2R agonist JWH133 group (group J),and CB2R agonist JWH133 + CB2R antagonist SR144528 group (group JS).Liver I/ R was produced by blocking the hepatic artery and portal vein for 30 min followed by 45 min of reperfusion in anesthetized mice.At 60 min before ischemia,JWH133 20 mg/kg was injected intraperitoneally in group J,and JWH133 20 mg/kg and SR144528 30 mg/kg were injected intraperitoneally in group JS.The liver was removed at 45 min of reperfusion for determination of tumor necrosis factor-α (TNF-α),macrophage inflammatory protein-1α (MIP-1α) and MIP-2 contents (using ELISA),and expression of TNF-α,MIP-1α,MIP-2 and intercellular adhesion molecule-1 (ICAM-1) mRNA (by RT-PCR) in the liver tissues and for microscopic examination of the pathological changes.Results Compared with group S,the contents of TNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in J and JS groups.Compared with group I/R,the contents of TNF-α,MIP-1α and MIP-2 were significantly decreased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was down-regulated in J group,and no significant change was found in the parameters mentioned above in JS group.Compared with group J,the contents ofTNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in JS group.The pathological changes of liver tissues were significantly attenuated in group J as compared with I/R and JS groups.Conclusion CB2R activation is effective in preventing liver I/R injury in mice and the mechanism is related to inhibitioni of inflammatory responses in liver tissues.