Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

[Mechanism of Dabugan Decoction in treatment of generalized anxiety disorder based on network pharmacology and experimental verification].

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

[MicroRNA-22-3p Regulates the Expression of Kruppel-like Factor 6 to Affect the Cardiomyocyte-like Differentiation of Bone Marrow Mesenchymal Stem Cell].

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.

Molecular epidemiology and clinical characteristics of Clostridioides difficile infection in patients with inflammatory bowel disease from a teaching hospital.

BACKGROUND: Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is of increasing concern. This study aimed to investigate the molecular epidemiology and antimicrobial susceptibilities of toxigenic C. difficile isolated from IBD patients and to evaluate the risk factors for CDI in IBD population. METHODS: Loose or watery stools from IBD patients were tested for glutamate dehydrogenase, C. difficile toxins A&B and anaerobic culture. Toxigenic C. difficile isolates were characterized by multi-locus sequence typing, ribotyping and antimicrobial susceptibility testing. RESULTS: The prevalence of CDI in IBD patients was 13.6% (43/317). The dominant sequence types (STs) were ST35 (20.9%), ST2 (18.6%) and ST37 (16.3%). The most common ribotypes (RTs) were RT 017 (18.6%), RT 012 (14.0%), and RT 220 (14.0%), whereas RT 027 and RT 078 were not detected in this study. All the isolates were susceptible to vancomycin and metronidazole. The multidrug resistance rate of C. difficile RT 017 was higher (p < 0.01) than that of other RT strains. Recent hospitalization, use of corticosteroids and proton pump inhibitors were related to increased risk of CDI in IBD patients; of these, recent hospitalization and proton pump inhibitors use were independent risk factors. CONCLUSION: Patients with IBD have a relatively high incidence rate of CDI. C. difficile RT 017 is most frequently isolated from IBD patients in this region and warrants more attention to its high resistance rate. Clinicians should pay greater attention to CDI testing in IBD patients with diarrhea to ensure early diagnosis and initiation of effective treatment.

The Association Between the Use of Antiarrhythmic Drugs in Non-Valvular Atrial Fibrillation and Patient Prognosis Using Data from the China Atrial Fibrillation (China-AF) Registry.

BACKGROUND Results of the landmark Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial comparing rhythm control and rate control strategies has led to dramatic changes in the pharmacological management of non-valvular atrial fibrillation (NVAF) patients. We sought to investigate the effect of antiarrhythmic drugs (AADs) on the clinical outcomes of NVAF patients using "real-world" data from China. MATERIAL AND METHODS We evaluated the association between AAD usage and clinical outcomes using clinical data of 8161 NVAF patients who were AAD-naive before enrollment in the China Atrial Fibrillation Registry, recruited between August 2011 and February 2017. The primary outcome was all-cause mortality. RESULTS Compared with 6167 patients who never used any AADs, 1994 patients in the AAD group had lower incidence (per 100 person-years) of all-cause mortality (1.44 versus 3.91), cardiovascular death (0.45 versus 2.31), ischemic stroke (1.36 versus 2.03), and cardiovascular hospitalization (9.83 versus 10.22) over a mean follow-up duration of 316.7±90.4 days. After adjusting for potential confounders, AAD usage was associated with a lower risk of all-cause mortality [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.31-0.81] and decreased risk of cardiovascular death (HR: 0.30, 95% CI: 0.13-0.68). Subgroup analysis revealed AAD was associated with higher risk of cardiovascular hospitalization among female patients. CONCLUSIONS AAD usage was associated with lower risk of 1-year all-cause mortality and cardiovascular death in "real-world" patients with NVAF.

Sex Differences in Presentation, Quality of Life, and Treatment in Chinese Atrial Fibrillation Patients: Insights from the China Atrial Fibrillation Registry Study.

BACKGROUND There is a growing recognition of sex-related disparities in atrial fibrillation (AF). However, limited data is available in Chinese AF patients. MATERIAL AND METHODS We compared symptoms, quality of life (QoL), and treatment of AF according to sex from the China AF Registry study. RESULTS We studied 14 723 patients with non-valvular AF, of whom 5645 patients (38.3%) were female. Women were older than men (67.5±10.6 vs. 62.2±12.2). Compared to men, women had more comorbidities and a higher proportion of CHA2DS2-VASC score ≥2. Women with AF experienced more severe or disabling symptoms than men (33.7% vs. 22.9% in age <75 group; 40.3% vs. 28.7% in age ≥75 group; both P<0.0001). After multivariate analysis, women with AF still had lower QoL (OR 0.69; 95%CI, 0.63-0.76; P<0.0001). Women tended to have lower rates of ablation and rhythm-control drug use in those aged <75 years. Oral anticoagulant use was low and had no sex difference in AF patients with a CHA2DS2-VASC score ≥2. CONCLUSIONS In Chinese AF patients, women were older and more symptomatic, and had worse QoL. Despite all these differences, women tended to receive less rhythm-control treatment in those aged <75 years. Oral anticoagulant was substantially underused in high stroke risk patients, regardless of sex.

The mechanism and clinical significance of long noncoding RNA-mediated gene expression via nuclear architecture.

Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts exceeding 200 nucleotides in length. Accumulating evidence achieved by several sophisticated techniques such as chromatin conformation capture and RNA-seq has led to new questions concerning correlations between lncRNAs and chromatin structures. Many studies have revealed that lncRNAs exert great influences on gene expression through regulating chromatin 3D structures. In addition, lncRNAs play a crucial role in tumorigenesis and therefore hold great promises in disease diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs regulate gene expression by modulating nuclear architecture and discussing clinical values of lncRNAs in oncotherapy.

Research progress on liquid biopsy in oncology and its clinical applications.

Liquid biopsy is an emerging and promising detection tool for cancer, with the benefit of being non-invasive and convenient. It analyzes tumor-derived information in the blood or other body fluids including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion of liquid biopsy research contents and the development of capture and detection technologies, liquid biopsy is increasingly utilized in clinical applications, promoting the development of tumor precision medicine. Here, we mainly focus on reviewing the objects and technologies about liquid biopsy, as well as its applications, development and challenges in clinical practices.

Prevalence and Antimicrobial Susceptibility of Mycobacterium abscessus in a General Hospital, China.

OBJECTIVE: To gain greater insight into the prevalence drug resistant profiles of M. abscessus from a general hospital in Beijing, China. METHODS: Partial gene sequencing of 16S, hsp65, and rpoB were used to distinguish the species of NTM isolates. All strains identified as M. abscessus were further enrolled in the drug susceptibility testing by using broth microdilution method. RESULTS: We found that M. avium complex was the most frequent NTM organism, accounting for 54.1% (33/61) of all isolates. Behind MAC, the second most common organisms were M. abscessus (22 out of 61, 36.1%). Average rates of resistance were 4.5% for AMK, 9.1% for LZD, and 13.6% for CLA, respectively. In contrast, resistance to LEV (17/22, 77.3%), IMI (9/22, 40.9%), and SMX (10/22, 45.5%) was noted in more than 40% of M. abscessus isolates. DNA sequencing revealed that all the CLA-resistant isolates harbored nucleotide substitutions in position 2058 (1/3, 33.3%) or 2059 (2/3, 66.7%) of 23S rRNA. CONCLUSION: In conclusion, our data demonstrated that M. intracellulare and M. abscessus were the most common NTM species in the general hospital of Beijing. CLA, AMK, LZD showed promising activity, where as LEV, IMI, and SMX exhibited poor activity against M. abscessus in vitro.

Emergence and spread of O16-ST131 and O25b-ST131 clones among faecal CTX-M-producing Escherichia coli in healthy individuals in Hunan Province, China.

OBJECTIVES: The objectives of this study were to determine CTX-M-producing Escherichia coli ST131 strain prevalence in stool specimens from healthy subjects in central China and to molecularly characterize clonal groups. METHODS: From November 2013 to January 2014, stool specimens from healthy individuals in Hunan Province were screened for ESBL-producing E. coli using chromogenic medium and CTX-M genotypes and phylogenetic groups were determined. ST131 clonal groups were detected by PCR and characterized for antibiotic resistance, fimH, gyrA and parC alleles, plasmid-mediated quinolone resistance determinants, virulence genotypes and PFGE patterns. RESULTS: Among 563 subjects, 287 (51.0%) exhibited the presence of faecal ESBL-producing E. coli, all of which produced CTX-M enzymes. The most common CTX-M genotypes were CTX-M-14 (48.4%), CTX-M-15 (27.5%) and CTX-M-27 (15.0%). Of the 287 CTX-M-producing isolates, 32 (11.1%) belonged to the ST131 clone. O16-ST131 isolates were dominant (75%) and contained the fimH41 allele. The remaining eight (25%) ST131 isolates were of the O25b subgroup and contained fimH30 or fimH41. Ciprofloxacin resistance was found in 100% of the O25b-ST131 isolates, whereas only 8% of the O16-ST131 isolates were resistant. All of the O25b-ST131 isolates except one showed gyrA1AB and parC1aAB mutations; most of the O16-ST131 isolates had gyrA1A and parC1b mutations. The virulence genotypes of O16-ST131 resembled those of the O25b-ST131 isolates. The 32 ST131 isolates formed one large group at the 64% similarity level. They comprised 15 PFGE groups (defined at ≥85% similarity). CONCLUSIONS: O16-ST131 isolates have emerged as the predominant type of ST131 isolate in faecal CTX-M-producing E. coli in healthy individuals in China.

[Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line].

Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

[Analysis of clinical features among severe or critical pregnant women in different trimesters with 2009 pandemic H1N1 infection].

OBJECTIVE: To explore the disease course and outcomes of severe or critical pregnant women with 2009 pandemic H1N1 (pH1N1) infection in China. METHODS: A retrospective observational study was conducted for 394 severe or critical pregnant women with pH1N1 influenza admitted into hospital in 27 Chinese provinces from September 1, 2009 to December 31, 2009. Their clinical features in different trimesters were analyzed. The viral infection of pH1N1 was verified by real-time reverse transcription (rRT)-PCR. Severe and critical cases were defined according to the 2009 H1N1 clinical guidelines. RESULTS: Among them, 374 (94.9%) were infected in the second or third trimester. Fever and cough were the most common symptoms in all trimesters. However, hemoptysis, dyspnea and associated pneumonia were likely to occur in the second or third trimester. The ratio of required mechanical ventilation in the second or third trimester (44.7%, 167/374) was significantly higher than that in the first trimester (3/20). Among 77 mortality cases, 72.7% (56/77) died in the third trimester. Pregnancy was terminated after the onset of pH1N1 symptoms in 52.5%(207/394) pregnant women. And 57.0%(118/207) of them had delivery < 37 weeks and 29.0%(60/207) fetuses deceased. CONCLUSION: A clinician should be on a high alert for pH1N1 infection in pregnant women, particularly in the second or third trimester.

Effect of oral pre-emptive analgesia on pain management after total knee arthroplasty: a protocol for systematic review and meta-analysis.

INTRODUCTION: Total knee arthroplasty (TKA) is currently regarded as an effective treatment for knee osteoarthritis, relieving patients' pain and significantly enhancing their quality of life and activity levels, allowing them to return to work and daily life after surgery. However, some TKA patients suffer from varying degrees of postoperative residual pain and opioid abuse, which negatively impacts their recovery and quality of life. It has been reported that preoperative treatment with multimodal analgesics improves postoperative pain and reduces opioid consumption. However, there is no conclusive evidence that pre-emptive analgesia provides the same benefits in TKA. In order to inform future research, this protocol focuses on the efficacy and safety of oral analgesics used in TKA pre-emptive analgesia. METHODS AND ANALYSIS: We will search the literature on the involvement of pre-emptive analgesia in the management of pain in TKA from the PubMed, EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, from their inception to 1 February 2023. Additionally, clinical registry platforms will be investigated to collect data for ongoing studies. Using the Cochrane Risk of Bias Tool, the quality assessment will be conducted. RevMan V.5.4 will be used for the meta-analysis. The statistic I 2 will be used to measure the percentage of total variability due to heterogeneity between studies. Where appropriate, subgroup and sensitivity analyses, assessment of evidence quality and publication bias will be conducted. ETHICS AND DISSEMINATION: No ethical approval and consent is required for this systematic review. Moreover, the results of this systematic review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022380782.

[Adult hospital acquired pneumonia: a multicenter study on microbiology and clinical characteristics of patients from 9 Chinese cities].

OBJECTIVE: To investigate the etiology and clinical characteristics of hospital-acquired pneumonia (HAP) in China and to provide evidence for appropriate therapy. METHODS: We performed a prospective multicenter study in 13 Chinese urban tertiary hospitals. All HAP cases diagnosed at respiratory general ward and respiratory intensive care unit (RICU) from August 2008 to December 2010 were studied. Epidemiological data, etiology and clinical characteristics of enrolled patients were collected. Sputum or tracheal aspirate and blood cultures, Legionella antibodies and Streptococcus pneumoniae urinary antigen tests were performed. Bacteria to antimicrobial susceptibility test was performed. RESULTS: A total of 610 cases of HAP were diagnosed during the study, with an overall incidence of 1.4% among 42 877 hospitalized patients, while the incidence was 0.9% (362/41 261) in respiratory general ward and 15.4% (248/1616) in RICU. 93.9% (573 cases) of patients had at least one underlying disease, and 91.0% (555 cases) had exposure to at least one antimicrobial agent within 90 days prior to HAP diagnosis. Pathogens were identified in 487 patients, with Acinetobacter baumannii [30.0% (183/610)], Pseudomonas aeruginosa [22.0% (134/610)], Staphylococcus aureus [13.4% (82/610)] and Klebsiella pneumonia [9.7% (59/610)] being the most common pathogens. Eighteen patients (3.0%) had infection with fastidious bacteria. A. baumannii and S. aureus were the more frequent pathogens in the ventilator-associated pneumonia (VAP) cases [50.5% (97/192) and 21.4% (41/192)] as compared to non-VAP cases [20.6% (86/418) and 9.8% (41/418), P < 0.01]. A. baumannii and S. aureus were also frequent pathogens in cases with a score of more than 20 by the acute physiology and chronic health evaluation II (APACHEII) scoring [45.7% (69/151) and 20.5% (31/151)], as compared to cases with a score of less than 20 of APACHE II [24.8% (114/459) and 11.1% (51/459), P < 0.01]. A. baumannii showed high resistance rates to carbapenems [more than 70% (109/142)], and the susceptibility to cefoperazone/sulbactam, polymyxin B and tigecycline were 40.8% (58/142), 99.3% (141/142) and 95.8% (136/142) respectively. Resistance rates of P. aeruginosa to meropenem and imipenem were 48.8% (40/82) and 70.7% (58/82) respectively. Methicillin-resistant S. aureus (MRSA) accounted for 87.8% (43/49) in all strains of S. aureus. Mortality rate of VAP cases was 34.5% (61/177), significantly more than that of HAP patients [22.3% (135/605), P < 0.05]. The average hospital stay of patients with HAP was (23.8 ± 20.5) days, significantly more than that of the average for inpatients [(13.2 ± 13.6) days, P < 0.01] during the study period. Mean costs of HAP were (108 950 ± 116 608) yuan, significantly higher than the average hospital costs of respiratory inpatients (17 999 ± 33 364) yuan. CONCLUSIONS: Among Chinese patients hospitalized in urban tertiary medical centers, HAP incidence and mortality rate were high, which increased the patients' hospital stay and the medical costs. Common pathogens were A. baumannii, P. aeruginosa, S. aureus and K. pneumonia. The common bacteria of HAP in China showed high resistance rates to antibiotics.

Oral Chinese patent medicines for acute myocardial infarction after percutaneous coronary intervention: A protocol for systematic review and network meta-analysis.

BACKGROUND: Acute myocardial infarction (AMI) is a serious and fatal heart disease with one of the highest mortality rates in the world. In some countries, percutaneous coronary intervention (PCI) is the preferred reperfusion strategy after AMI, but it cannot achieve safe and effective treatment of AMI after PCI remains a challenging clinical problem. The potential of oral Chinese patent medicines to treat AMI after PCI has been demonstrated, but which type of oral Chinese patent medicines may be preferred remains controversial. The aim of this network meta-analysis was to investigate the efficacy and safety of multiple oral Chinese patent medicines in the treatment of AMI after PCI. METHODS: We will conduct a literature search from China National Knowledge Infrastructure, formerly Chinese Biomedical Database (SinoMed), Wanfang Data, Chongqing VIP, PubMed, Embase, Web of Science and Cochrane Library (The Cochrane Database of Systematic Reviews) from their inception until to November 1, 2022, with language restricted to Chinese and English. Then, the study selection process will follow the Preferred Reporting Items for Meta-Analyses guideline, and the quality assessment will be conducted with Cochrane Collaboration's tool. Pairwise and network meta-analysis will be conducted using the WinBUGS V.1.4.3.37 and STATA V.13. Additionally, sensitivity analysis, subgroup analysis, quality assessment, Small-study effects and publication bias will be performed. ETHICS AND DISSEMINATION: This work is based on published research and therefore does not require ethical approval. This review will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020188065.

Identification of the Diagnostic Biomarker VIPR1 in Hepatocellular Carcinoma Based on Machine Learning Algorithm.

The purpose of this study was to identify the potential diagnostic biomarkers in hepatocellular carcinoma (HCC) by machine learning (ML) and to explore the significance of immune cell infiltration in HCC. From GEO datasets, the microarray datasets of HCC patients were obtained and downloaded. Differentially expressed genes (DEGs) were screened from five datasets of GSE57957, GSE84402, GSE112790, GSE113996, and GSE121248, totalling 125 normal liver tissues and 326 HCC tissues. In order to find the diagnostic indicators of HCC, the LASSO regression and the SVM-RFE algorithms were utilized. The prognostic value of VIPR1 was analyzed. Finally, the difference of immune cell infiltration between HCC tissues and normal liver tissues was evaluated by CIBERSORT algorithm. In this study, a total of 232 DEGs were identified in 125 normal liver tissues and 326 HCC tissues. 11 diagnostic markers were identified by LASSO regression and SVM-RFE algorithms. FCN2, ECM1, VIRP1, IGFALS, and ASPG genes with AUC>0.85 were regarded as candidate biomarkers with high diagnostic value, and the above results were verified in GSE36376. Survival analyses showed that VIPR1 and IGFALS were significantly correlated with the OS, while ASPG, ECM1, and FCN2 had no statistical significance with the OS. Multivariate assays indicated that VIPR1 gene could be used as an independent prognostic factor for HCC, while FCN2, ECM1, IGFALS, and ASPG could not be used as independent prognostic factors for HCC. Immune cell infiltration analyses showed that the expression of VIPR1 in HCC was positively correlated with the levels of several immune cells. Overall, VIPR1 gene can be used as a diagnostic feature marker of HCC and may be a potential target for the diagnosis and treatment of liver cancer in the future.

Community Fecal Carriage and Molecular Epidemiology of Extended-Spectrum ß-Lactamase- and Carbapenemase-Producing Escherichia coli from Healthy Children in the Central South China.

Background: Fecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) and carbapenemase-producing E. coli (CP-EC) is well reported among hospitalized adults and children. However, there are few studies on the carriage prevalence and ESBL-EC and CP-EC genotypes among healthy children in China. Patients and Methods: Stool samples were collected from 330 students in 2021 from three randomly selected primary schools in Changsha, China. ESBL-EC and CP-EC were screened using CHROMagarTM chromogenic plates. ESBL and carbapenemase production was confirmed using the double-disc synergy test and a modified carbapenem inactivation method, respectively. Antimicrobial susceptibility was tested using the broth microdilution method. Resistance determinants, virulence factors, and phylogenetic groups were determined by PCR and sequencing. Multi-locus sequence typing (MLST) was performed (seven housekeeping genes were amplified and sequenced) on the phylogenic group B2 E. coli to detect high-risk clonal strains such as ST131 E. coli. Then, ST131 E. coli were characterized based on ST131 clades, O-type, and fimH alleles. Results: In total, 118 (35.8%) ESBL-EC and 3 (0.9%) CP-EC were isolated. bla CTX-M was the most common genotype (27.1%), identified in all ESBL-EC, except one, which carried bla SHV-12. One isolate with mcr-1 was found amongst ESBL-EC, whereas all three CP-EC carried bla NDM-1. The predominant sequence type (ST) clones in group B2 were ST131 and ST1193. The prevalence of ST131 E. coli was 9.9%, displaying serotypes O16 and O25b, fimH alleles 30, 41, and 89, and ST131 clades A and C1-M27. Conclusion: In this study, high carriage rate of ESBL-EC was found among healthy children, and the dominant ESBL was CTX-M-14. In addition, high-risk clones (ST131 and ST1193) were also detected. This emphasizes the importance of monitoring ESBL-EC in community settings.

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of Mycobacterium tuberculosis.

OBJECTIVE: To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the rpoB, katG, and inhA genes at the Chinese Center for Disease Control and Prevention. METHODS: MDR-LAMP assay was evaluated using 100 Mycobacterium tuberculosis ( Mtb) isolates obtained from the National Reference Laboratory for Tuberculosis in China. Phenotypic resistance to isoniazid and rifampicin and whole-genome sequencing served as reference standards. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of Mtb cultured from smear-positive sputum samples, respectively. When DNA sequencing was used as the reference standard, the sensitivity, specificity, PPV, and NPV of MDR-LAMP were 93.1%, 92.3%, 97.2%, and 82.8% for the detection of katG and inhA gene mutations, respectively, and 89.1%, 88.9%, 93.4%, and 81.1% for the detection of rpoB gene mutation, respectively. CONCLUSION: MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of Mtb isolates.

Nontuberculous mycobacteria in China: incidence and antimicrobial resistance spectrum from a nationwide survey.

BACKGROUND: Information on the prevalence and resistance spectrum of nontuberculous mycobacteria (NTM) in China is mainly based on regional or local data. To estimate the proportion of NTM cases in China, a national survey of NTM pulmonary disease was carried out based on acid-fast positive sputum samples collected in 2013. METHODS: Sputum samples collected from enrolled presumptive cases in 72 nationwide tuberculosis surveillance sites from the 31 provinces in the mainland of China were cultured using L-J medium at the National tuberculosis reference laboratory (NTRL). MALDI-TOF MS identified the species of re-cultured strains, and minimal inhibitory concentrations (MICs) were determined to evaluate the drug susceptibility of NTM isolates. Data analysis used statistical software SPSS version 22.0 for Windows statistical package. RESULTS: Of 4917 mycobacterial isolates cultured, 6.4% [317/4917, 95% confidence interval (CI) 5.8%-7.2%] were confirmed as NTM, among which 7.7% (287/3709, 95% CI 6.9%-8.6%) were from the southern region. In inland and coastal China, 87.7% (95% CI 78.7%-93.2%) and 50.0% (95% CI 43.7%-56.3%) of isolates, respectively, were slow-growing mycobacteria (SGM), with the remaining rapid growing mycobacteria (RGM). A total of 29 species were detected, Mycobacterium abscessus had higher clarithromycin-inducible resistance rates than M. massiliense (65.67% vs 2.22%). M. kansasii presented lower resistance rates in linezolid and moxifloxacin than M. avium-intracellulare complex (3.23% vs 66.67%, 0 vs 47.22%) and other SGM (3.23% vs 38%, 0 vs 26%). CONCLUSIONS: More NTM pulmonary disease was observed in the south and coastal China (P < 0.01). SGM was widely distributed, and more RGM are present in southern and coastal China (P < 0.01). The antimicrobial resistance spectrum of different NTM species was significantly different and accurate species identification would be facilitated to NTM pulmonary disease treatment.

Effects of Persimmon Tannin-Aloe vera Composite on Cytotoxic Activities, and Radioprotection Against X-rays Irradiated in Human Hepatoma and Hepatic Cells.

A persimmon tannin-Aloe vera composite powder (PT-A) was investigated for its capacity to protect against ionizing radiation. Human hepatic cells (L02 cells) and human hepatoma cells (HepG2 cells) were pretreated with different concentrations of PT-A or the single compounds (PT or Aloe vera) and radiated with X-rays. After radiation and post-incubation for 12 h or 24 h, the cell viability, apoptosis, and reactive oxygen species (ROS) production were analyzed by Cell Counting Kit 8 (CCK-8), 2',7'-dichlorfluorescein diacetate (DCFH-DA) staining, and Hoechst 33258 staining/flow cytometry, respectively. CCK-8 results illustrated that the optimal radiation dose L02 cells was 8 Gy for L02 cells, and the cell activity was 71.72% (IC50 = 412.1 µg/mL) after post-radiation incubation of 12 h. For HepG2 cells, the optimal radiation dose was 8 Gy, and the cell activity was 62.37% (IC50 = 213.0 µg/mL). The cell apoptotic rate was the lowest at a PT-A concentration of 200 µg/mL in L02 cells (4.32%, P < 0.05), and at 100 µg/mL in HepG2 cells (9.80%, P < 0.05). ROS production induced by radiation could be effectively inhibited by 200 µg/mL of PT-A in L02 cells, and by 100 µg/mL of PT-A in HepG2 cells. The PT-A composite has good radioprotective effects on cell vitality and apoptosis of X-rays radiation exposure towards L02 cells and HepG2 cells compared to the persimmon tannin or Aloe vera. Therefore, PT-A composite might be useful as a natural, harmless anti-ionizing radiation agent, and has various clinical application prospects in future.