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The Suxiao Jiuxin pill (SJP) is a Chinese medical patent drug on the national essential drug list of China, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been elucidated clearly, especially its relationship with the gut microbiota. This study aimed to investigate the cardioprotective effect of SJP against isoproterenol-induced acute myocardial infarction (AMI) by integrating the gut microbiome and metabolome. A rat model of AMI was generated using isoproterenol. Firstly, the effect of antibiotic (ABX) treatment on the blood absorption and excretion of the main components of SJP were studied. Secondly, 16S rRNA sequencing and untargeted metabolomics were used to discover the improvement of SJP treatment on gut microbiota and host metabolism in AMI rats. Finally, targeted metabolomics was used to verify the effects of SJP treatment on host metabolism in AMI rats. The results showed that ABX treatment could affect the blood absorption and fecal excretion of the main active components of SJP. At the same time, SJP can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Jeotgalicoccus , Lachnospiraceae, and Blautia) are significantly associated with fatty acids. Untargeted metabolomics also found that SJP could restore the levels of various fatty acid metabolites in serum and cecal contents (p < 0.01, FC > 1.5 and VIP >1). Targeted metabolomics further confirmed that 41, 21, and 39 fatty acids were significantly altered in serum, cecal contents, and heart samples, respectively. Interestingly, these fatty acids belong to the class of eicosanoids, and SJP can significantly downregulate these eicosanoids in AMI rats. The results of this study suggest that SJP may exert its cardioprotective effects by remodeling the gut microbiota and host fatty acid metabolism. [Display omitted] • Microbiome-metabolome to reveal the potential therapeutic of SJP for AMI. • SJP improve heart function by remodeling gut microbiota and host metabolism. • Targeted metabolome revealed the mechanism of SJP was related to fatty acids. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the prevalence of laboratory critical results (CRs) and associated risk factors in patients with eye diseases in a tertiary eye hospital. Methods. Blood samples were collected from both inpatients and outpatients at Zhongshan Ophthalmic Center, Guangzhou, China, from June 1, 2012, to May 31, 2014, and samples were sent to the hospital’s clinical laboratory for blood routine, biochemistry, and blood coagulation tests. Laboratory CRs for blood glucose, sodium, potassium, white blood cell count, platelet count, prothrombin time, fibrinogen, international normalized ratio, and activated partial thromboplastin time were included in the current analysis. Results. A total of 60403 subjects were enrolled in the current analysis. CRs were identified in 339 tests from 336 patients with a prevalence of 5.7‰. Age was positively associated with the presence of CRs. Compared to patients with lens diseases, patients with strabismus, oculoplastics, and ocular trauma were less likely to have CRs (P<0.05), while patients with tumors were more likely to have CRs (P<0.001). Conclusions. The prevalence of CRs in eye patients is low but calls for medication attention. It is important for medical personnel, especially ophthalmologists, to increase awareness of the importance, as well as the prevalence and risk factors of CRs. [ABSTRACT FROM AUTHOR]

• The evaluation of columns and software were based on large clinical cohort samples. • XCMS performed the best in the detection of the most reliable peaks. • Progenesis QI showed a clear advantage in metabolic pathway enrichment. • C 18 and amide columns completed each other in terms of metabolic pathways. In untargeted liquid chromatography‒mass spectrometry (LC‒MS) metabolomics studies, data preprocessing and metabolic pathway recognition are crucial for screening important pathways that are disturbed by diseases or restored by drugs. Here, we collected high-resolution mass spectrometry data of serum samples from 221 coronary heart disease (CHD) patients under two different chromatographic columns (BEH amide and C 18 column) and evaluated the three commonly used software programs (XCMS, Progenesis QI, MarkerView) from four aspects (including signal drift, peak number, metabolite annotation and metabolic pathway enrichment). The results showed that the data preprocessed by the three software programs have different degrees of signal drift, but the StatTarget could improve the data quality to meet the data analysis requirement after correction. In addition, XCMS surpassed other software in detection of real chromatographic peaks and Progenesis QI was the best performer in terms of the number of metabolite annotation. XCMS and Progenesis QI showed different performance in pathway enrichment. However, metabolic pathways based on the combination of XCMS and Progenesis QI had a high coincidence with Progenesis QI. In addition, we also reported that C 18 and amide columns were highly complementary and have great potential for cooperation in the context of metabolic pathways. In this study, the effects of different chromatographic columns and software pretreatments on metabolomics data were evaluated based on clinical large cohort samples, which will provide a reference for the metabolomics of clinical samples and guide subsequent mechanistic research. [ABSTRACT FROM AUTHOR]

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma. Methods: A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection. Results: Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05). Conclusions: Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion and angiogenesis are characteristic features of its TME. The role of YTH N6‐methyladenosine RNA binding protein 2 (YTHDF2), as an m6A reader, in regulating HCC TME are not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 and H3 lysine 27 acetylation modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. Animal experiments demonstrated that Ythdf2 depletion inhibited spontaneous HCC formation, while its overexpression promoted xenografted HCC progression. Mechanistically, YTHDF2 recognized the m6A modification in the 5′‐untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Elevated ETV5 expression induced the transcription of programmed death ligand‐1 and vascular endothelial growth factor A, thereby promoting HCC immune evasion and angiogenesis. Targeting YTHDF2 via small interference RNA‐containing aptamer/liposomes successfully both inhibited HCC immune evasion and angiogenesis. Together, this findings reveal the potential application of YTHDF2 in HCC prognosis and targeted treatment. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) still has a very unfavorable prognosis with a very high mortality, which is complicated by a lack of prognostic biomarkers. In this study, CCA patients in the Gene Expression Omnibus (GEO) cohort were categorized into two subtypes. Differentially expressed and methylated genes were identified, and the impact of DNA methylation in the trans‐regulation of gene expression was investigated. Finally, a CIMP‐related methylation signature specific for CCA (CMSC) was trained in GEO and validated in the Tongji cohort. A subset of patients with CIMP‐H was identified, which was correlated with an unfavorable prognosis. Gene enrichment analysis implied the potential mechanism of CIMP as a promoter of carcinogenesis by regulating proliferation. The trans‐regulation among differentially methylated CpG sites and genes with the same change trends was positively correlated, while the converse situation showed a negative correlation. Notably, CMSC based on four genes could significantly classify CCA patients into low‐ and high‐risk groups in the GEO cohort, and the robustness of CMSC was validated in the Tongji cohort. The results of receiver operating characteristic analysis further indicated that CMSC was capable of highly sensitive and specific prediction of the patient outcomes in CCA. In conclusion, our work highlights the clinical significance of CMSC in the prognosis of CCA. [ABSTRACT FROM AUTHOR]

Cold exposure has been suggested to be advantageous for the spread and infection of the coronavirus, and the gut microbiota influences the severity of the infection by modulating host inflammatory and immune responses. However, it remains unclear whether the promotion of viral infection through cold exposure is linked to the gut microbiota. In this study, we performed an unbiased analysis of gut microbiota, serum, and lung tissue metabolome changes in cold-exposed and virus-infected mice, alongside the assessment of immune-inflammatory indicators in serum and lung tissue. The results revealed that both cold exposure and viral infection significantly decreased the percentage of peripheral blood lymphocytes (CD4+ T cells, CD8+ T cells, and B cell) and increased the expression of inflammatory factors (IL-6, IL-1β, TNF-α, and IFN-γ). Meanwhile, cold exposure disrupted the homeostasis of gut microbiota, elevating the abundance of pathogenic bacteria (Staphylococcus) and diminishing the abundance of beneficial bacteria (Alistipes). Notably, in virus-infected mice exposed to a cold environment, the reduction in the abundance of beneficial bacteria Alistipes was more pronounced than in cases of single virus infection and cold exposure. Analysis of altered serum and lung tissue metabolites highlighted glycerophospholipids, fatty acids, and eicosanoids as the most affected metabolites by cold exposure. These metabolites, closely associated with virus infection, exhibited a significant correlation with immune-inflammatory indicators. These findings establish a mechanistic connection between cold exposure and virus infection, suggesting that cold exposure-induced dysregulation of gut microbiota and lipid metabolism diminishes host immunity, promoting virus infection. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the incidence and risk factors of intraocular foreign body- (IOFB-) related endophthalmitis. Methods. A total of 1701 patients diagnosed with IOFB between January 1, 2005 and June 30, 2015 were included. Two groups of patients were defined according to the presence or absence of endophthalmitis, and a comparison of personal information, IOFB characteristics, and wound location were performed. Results. In total, 279 patients (16.4%) developed endophthalmitis, older age (P=0.01) was a risk factor. IOFBs retained in the crystal lens or wall of the eyeball conferred lower risks (P=0.01 and 0.04, respectively) compared to the vitreous chamber. The coexistence of different IOFB types and plant IOFBs conferred higher risks (P=0.02 and 0.03, respectively), while glass/plastic IOFBs conferred a lower risk (P=0.03) compared to metallic IOFBs. Conclusions. Age, IOFB locations, and types were related to development of endophthalmitis, while IOFB number, size, or timing of primary repairs was not related. [ABSTRACT FROM AUTHOR]

E26 transformation-specific (ETS) transcription variant 5 (ETV5), also known as ETS-related molecule (ERM), exerts versatile functions in normal physiological processes, including branching morphogenesis, neural system development, fertility, embryonic development, immune regulation, and cell metabolism. In addition, ETV5 is repeatedly found to be overexpressed in multiple malignant tumors, where it is involved in cancer progression as an oncogenic transcription factor. Its roles in cancer metastasis, proliferation, oxidative stress response and drug resistance indicate that it is a potential prognostic biomarker, as well as a therapeutic target for cancer treatment. Post-translational modifications, gene fusion events, sophisticated cellular signaling crosstalk and non-coding RNAs contribute to the dysregulation and abnormal activities of ETV5. However, few studies to date systematically summarized the role and molecular mechanisms of ETV5 in benign diseases and in oncogenic progression. In this review, we specify the molecular structure and post-translational modifications of ETV5. In addition, its critical roles in benign and malignant diseases are summarized to draw a panorama for specialists and clinicians. The updated molecular mechanisms of ETV5 in cancer biology and tumor progression are delineated. Finally, we prospect the further direction of ETV5 research in oncology and its potential translational applications in the clinic. [ABSTRACT FROM AUTHOR]

This study aimed to identify the microbial etiology of infectious endophthalmitis and to determine the antibacterial susceptibilities of bacterial isolates at an eye hospital in South China. A retrospective analysis was carried out on 330 patients with clinically diagnosed infectious endophthalmitis who underwent microbiological evaluation from January 2010 to December 2014. Of the 330 patients, 193 patients (58.5%) had posttraumatic endophthalmitis, 67 patients (20.3%) had postoperative endophthalmitis, 61 patients (18.5%) had endogenous endophthalmitis, and 9 patients (2.7%) had postcorneal infective endophthalmitis. Of the 105 cases (31.8%) of culture-positive endophthalmitis, 79 cases (75.2%) had bacterial growth and 26 cases (24.8%) had fungal growth. In posttraumatic endophthalmitis, Gram-positive bacteria were the predominant species, followed by Gram-negative bacteria and fungi. In endogenous endophthalmitis, Gram-negative bacteria were the predominant species, followed by fungi and Gram-positive bacteria. In postsurgical endophthalmitis, all infections were bacterial. However, in postcorneal infective endophthalmitis, all infections were fungal. Overall, levofloxacin showed the highest activity against bacterial isolates. There was a significant difference in the susceptibility to tobramycin between the isolates from posttraumatic and postoperative endophthalmitis (p<0.05). The results of this study identify the microbial spectrum of infectious endophthalmitis in this clinical setting. [ABSTRACT FROM AUTHOR]

Background: The hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and treponema pallidum (TP) are blood-borne pathogens. They can lead to nosocomial and occupational infections in health care settings. We aimed to identify the prevalence of and risk factors associated with HBV, HCV, HIV and TP infections among patients with eye diseases at a tertiary eye hospital in Southern China. Methods: From July 2011 to June 2012, a total of 26,386 blood units were collected from eye patients, including inpatients and the day surgery patients at Zhongshan Ophthalmic Center, one of the biggest eye hospitals in China. Based on the primary diagnoses from this period, the subjects were classified into different ocular disease groups. All blood samples were tested for HBsAg, anti-HCV, anti-HIV and anti-TP. Result: The overall prevalence of HBV, HCV, TP and HIV was 9.79%, 0.99%, 2.43% and 0.11%, respectively. The prevalence of HBsAg was much lower among patients younger than 20 years compared to other age groups. In addition, the risk of HBsAg was associated with the male gender, ocular trauma and glaucoma. The prevalence of TP increased with age and the prevalence among patients older than 30 was higher than that in patients younger than 20 years. Conclusions: The prevalence of HBV, HCV, HIV and TP in patients with eye diseases was identified. This information can be utilised to strengthen the health education and implementation of universal safety precautions to prevent the spread of blood-borne pathogens in health care settings. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent common cancer worldwide with high mortality. Transforming growth factor-β (TGF-β) signaling pathway was reported dysregulated during liver cancer formation and progression. As a key component of TGF-β signaling, the role of SMAD2 and its regulatory mechanisms in HCC remain unclear. Methods: SMAD2 expression in paired HCC specimens were determined by western blot and immunohistochemistry (IHC). quantitative real-time PCR (qRT-PCR) was used to measure mRNA and microRNA (miRNA) expression level. Cell migration, invasion and proliferation ability were evaluated by transwell, CCK8 and EdU assay. In silico websites were used to manifest overall survival rates of HCC patients or to predict miRNAs targeting SMAD2. Dual luciferase reporter assay and anti-Ago2 immunoprecipitation assay were performed to confirm the binding between SMAD2 mRNA and miRNA-148a-3p (miR-148a). Tumorigenesis and lung metastasis mouse model were used to explore the role of miR-148a in vivo. In situ hybridization (ISH) was conducted to determine the expression of miR-148a in liver tissues. Results: In this study, we found that SMAD2 was highly expressed in HCC and elevated SMAD2 expression predicted shorter overall survival (OS) time for HCC patients. SMAD2 promoted mobility and proliferation of HCC cells in vitro. We further revealed that the expression of miR-148a was negatively correlated with SMAD2 and found that miR-148a repressed SMAD2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2) in HCC. Transwell, CCK8 and animal experiments exhibited miR-148a inhibited metastasis and proliferation of HCC in vitro and in vivo. Moreover, the phenotype changes caused by miR-148a manipulation were recovered by rescuing SMAD2 expression in HCC cells. ISH assay indicated miR-148a was downregulated in HCC and low expression of miR-148a associated with more aggressive clinic features and poor prognosis. Conclusion: miR-148a was identified as a repressor of HCC progression by downregulating SMAD2 in an Ago2 dependent manner. [ABSTRACT FROM AUTHOR]