[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.

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.

[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.

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.

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.

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.

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.

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.

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.

Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles.

BACKGROUND: Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis. MAIN TEXT: We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020. Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries. CONCLUSIONS: It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.

[Heavy Metal Contents in Animal Manure in China and the Related Soil Accumulation Risks].

The environmental risks posed by heavy metals (HMs) in animal manure are increasing because of the use of trace metals as additives in feedstuffs. Manure samples were collected, and published literature was reviewed in this study to systematically analyze the HMs content in animal manure and compare the results to different sources of animal manures. Results show that the distribution of HMs content in animal manure was skewed. The ranges were between not detected (ND)-147 mg·kg-1 for Cd, ND-1919 mg·kg-1 for Pb, 0.003-2278 mg·kg-1 for Cr, ND-978 mg·kg-1 for As, ND-103 mg·kg-1 for Hg, ND-1747 mg·kg-1 for Cu, ND-11547 mg·kg-1 for Zn, and 1.22-1140 mg·kg-1 for Ni. The means (medians) of those elements were 2.31(0.72) mg·kg-1, 13.5(8.96) mg·kg-1, 36.3(12.0) mg·kg-1, 14.0(3.52) mg·kg-1, 0.97(0.07) mg·kg-1, 282(115) mg·kg-1, 656(366) mg·kg-1, and 21.8 (13.1) mg·kg-1 for Cd, Pb, Cr, As, Hg, Cu, Zn, and Ni, respectively. Means were significantly higher (1-13 times) than the medians. According to maximum limits of Cd, Pb, Cr, As, and Hg for organic fertilizers NY 525-2012, about 12.3% (for Cd), 2.58% (for Pb), 2.76% (for Cr), 20.6% (for As), and 3.69% (for Hg) of the data were above the limits. According to the composting regulations of Germany, about 53.9% (for Cu), 45.7% (for Zn), and 0.59% (for Ni) exceeded the maximum limits. The heavy metal contents in animal manure of different regions differs significantly. As and Cd contents in animal manure in the Shandong Province tend to be higher with their average values at 1.7 times and 10.1 times of the mean contents for national scale, respectively; the heavy metal contents in eastern China tend to be higher. Cd and As contents in animal manure tend to be higher in Northeast and Eastern China, while Cu and Zn contents were higher in Eastern and South China. After comparing HMs content in different sources of manures, we found that Cd, As, Hg, Cu, Zn, and Ni mean contents in pig manure were 1.0-3.0 times, 1.8-6.8 times, 1.1-15.8 times, 4.9-17.5 times, 2.7-12.0 times, and 1.7-2.1 times that of cattle manure, sheep manure, and poultry manure. The Pb content in poultry manure was the highest, with the mean being 2.8, 2.5, and 2.2 times higher than pig manure, cattle manure, and sheep manure, respectively. When recycling animal manure into the crop field, the accumulation rates for Cd were under 0.02 mg·(kg·a)-1 in over 90% of the circumstances and the accumulation rates for Pb were all below 0.15 mg·(kg·a)-1. When applying poultry manure, Cr in soil is easily accumulated with the maximum accumulation rate of 0.28 mg·(kg·a)-1.

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 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.

Identification of Frailty and Its Risk Factors in Elderly Hospitalized Patients from Different Wards: A Cross-Sectional Study in China.

OBJECTIVES: To survey the difference of frailty prevalence in elderly inpatients amongdifferent wards; to compare the diagnostic performance of five frailty measurements (Clinical Frailty Scale [CFS], FRAIL, Fried, Edmonton, Frailty Index [FI]) in identifying frailty; and to explore the risk factors of frailty in elderly inpatients. PARTICIPANTS AND METHODS: This was a cross-sectional study including 1000 inpatients (mean age 75.2±6.7 years, 51.5% male; 542, 229, and 229 patients from cardiology, non-surgical, and surgical wards, respectively) in a tertiary hospital from September 2018 to February 2019. We applied the combined index to integrate the five frailty measurements mentioned above as the gold standard of frailty diagnosis. Multivariate logistic regression models were used to determine the independent risk factors of frailty. RESULTS: Frailty prevalence was 32.3% (Fried), 36.2% (CFS), 19.2% (FRAIL), 25.2% (Edmonton), 35.1% (FI) in all patients. The frailty was more common in non-surgical wards, regardless of the frailty assessment tools used (non-surgical wards: 27.5% to 51.5%; cardiology ward: 14.9% to 29.3%; surgical wards: 18.8% to 41.9%). CFS≥5 showed a sensitivity of 94.1% and a specificity of 85.2% for all patients. FI≥0.25 showed a sensitivity of 94.8% and a specificity of 87.0% for all patients. Age [odds ratio (OR) = 1.089, P<0.001], education level (OR = 0.782, P=0.001), heart rate (OR = 1.025, P<0.001), albumin (OR = 0.911, P=0.002), log D-dimer (OR = 2.940, P<0.001), ≥5 comorbidities (OR = 2.164, P=0.002), and ≥5 medications (OR = 2.819, P<0.001) were independently associated with frailty in all participants. CONCLUSION: Frailty is common among elderly inpatients, especially in non-surgical wards. CFS is a preferred screening tool and FI may be an optimal assessment tool. Old age, low educational level, fast heart rate, low albumin, high D-dimer, ≥5 comorbidities, and polypharmacy are independent risk factors of frailty in elderly hospitalized patients.

Fabrication and Characterization of Graphene Microcrystal Prepared from Lignin Refined from Sugarcane Bagasse.

Graphene microcrystal (GMC) is a type of glassy carbon fabricated from lignin, in which the microcrystals of graphene are chemically bonded by sp³ carbon atoms, forming a glass-like microcrystal structure. The lignin is refined from sugarcane bagasse using an ethanol-based organosolv technique which is used for the fabrication of GMC by two technical schemes: The pyrolysis reaction of lignin in a tubular furnace at atmospheric pressure; and the hydrothermal carbonization (HTC) of lignin at lower temperature, followed by pyrolysis at higher temperature. The existence of graphene nanofragments in GMC is proven by Raman spectra and XRD patterns; the ratio of sp² carbon atoms to sp³ carbon atoms is demonstrated by XPS spectra; and the microcrystal structure is observed in the high-resolution transmission electron microscope (HRTEM) images. Temperature and pressure have an important impact on the quality of GMC samples. With the elevation of temperature, the fraction of carbon increases, while the fraction of oxygen decreases, and the ratio of sp² to sp³ carbon atoms increases. In contrast to the pyrolysis techniques, the HTC technique needs lower temperatures because of the high vapor pressure of water. In general, with the help of biorefinery, the biomass material, lignin, is found to be qualified and sustainable material for the manufacture of GMC. Lignin acts as a renewable substitute for the traditional raw materials of glassy carbon, copolymer resins of phenol formaldehyde, and furfuryl alcohol-phenol.

A comparative study for the organic byproducts from hydrothermal carbonizations of sugarcane bagasse and its bio-refined components cellulose and lignin.

Sugarcane bagasse was refined into cellulose, hemicellulose, and lignin using an ethanol-based organosolv technique. The hydrothermal carbonization (HTC) reactions were applied for bagasse and its two components cellulose and lignin. Based on GC-MS analysis, 32 (13+19) organic byproducts were derived from cellulose and lignin, more than the 22 byproducts from bagasse. Particularly, more valuable catechol products were obtained from lignin with 56.8% share in the total GC-MS integral area, much higher than the 2.263% share in the GC-MS integral areas of bagasse. The organic byproducts from lignin make up more than half of the total mass of lignin, indicating that lignin is a chemical treasure storage. In general, bio-refinery and HTC are two effective techniques for the valorization of bagasse and other biomass materials from agriculture and forest industry. HTC could convert the inferior biomass to superior biofuel with higher energy quantity of combustion, at the same time many valuable organic byproducts are produced. Bio-refinery could promote the HTC reaction of biomass more effective. With the help of bio-refinery and HTC, bagasse and other biomass materials are not only the sustainable energy resource, but also the renewable and environment friendly chemical materials, the best alternatives for petroleum, coal and natural gas.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.

BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. MATERIALS AND METHODS: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. RESULTS: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). CONCLUSION: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.