Characterization of Three Polysaccharide-Based Hydrogels Derived from Laminaria japonica and Their Hemostatic Properties.

Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based polysaccharide hydrogels exhibited better swelling properties (14 times their original weight) and the absorption ability of simulated body fluid (first 2 h: 6-10%). They also demonstrated better rigidity and mechanical strength. Young's modulus of LJP-E was 4 times that of the blank. In terms of hemostatic properties, all three polysaccharide hydrogels did not show significant cytotoxic and hemolytic properties. The enzyme- and acid-extracted hydrogels (LJP-Gel-A and LJP-Gel-E) demonstrated better whole-blood coagulant ability compared with the water-extracted hydrogel (LJP-Gel-W), as evidenced by the whole blood coagulation index being half that of LJP-Gel-W. Additionally, the lactate dehydrogenase viabilities of LJP-Gel-A and LJP-Gel-E were significantly higher, at about four and three times those of water extraction, respectively. The above results suggested that LJP-Gel-A and LJP-Gel-E exhibited better blood coagulation capabilities than LJP-Gel-W, due to their enhanced platelet enrichment and adhesion properties. Consequently, these hydrogels are more conducive to promoting coagulation and have good potential for wound hemostasis.

Bivalirudin vs. heparin in paediatric and adult patients on extracorporeal membrane oxygenation: A meta-analysis.

AIMS: Unfractionated heparin (UFH) has been the primary anticoagulant of choice on extracorporeal membrane oxygenation (ECMO). However, it is debatable whether bivalirudin (BIV), a direct thrombin inhibitor, may be considered a better alternative anticoagulant option. METHODS: We searched Embase, Pubmed, Cochrane library, Clinicaltrials.gov, CNKI and Wanfang databases up to 15 June 2021. Randomized controlled trials and observational studies were considered eligible for inclusion. Random-effects meta-analyses, including subgroup analyses, were conducted. RESULTS: A total of 9 studies containing 994 patients were enrolled. All articles were retrospective cohort studies. Compared with UFH, BIV was associated with lower risks of major bleeding (risk ratio [RR]: 0.32, 95% confidence interval [CI] 0.22-0.49), ECMO in-circuit thrombosis (RR: 0.57, 95% CI 0.43-0.74), stroke (RR: 0.52, 95% CI 0.29-0.95) and in-hospital mortality (RR: 0.82, 95% CI 0.69-0.99), and higher rates of survival to ECMO decannulation (RR: 1.18, 95% CI 1.03-1.34). Pooled risk estimates did not show a significant association with clinical thrombotic events (RR: 0.69, 95% CI 0.45-1.07). Moreover, BIV was associated with a lower risk of ECMO in-circuit thrombosis and in-hospital mortality in the adult subgroup but not in the paediatric subgroup. However, leave-one-out sensitivity analyses indicated that the results of stroke, survival to ECMO decannulation and in-hospital mortality should be interpreted with caution. CONCLUSION: BIV appears to be a potential alternative to UFH in paediatric and adult patients requiring ECMO.

Characteristics of viral pneumonia in non-HIV immunocompromised and immunocompetent patients: a retrospective cohort study.

BACKGROUND: Concerning viral pneumonia, few large-scale comparative studies have been published describing non-HIV immunocompromised and immunocompetent patients, but the epidemiological characteristics of different viruses or underlying diseases in immunocompromised hosts are lacking. METHODS: We retrospectively recruited patients hospitalised with viral pneumonia from six academic hospitals in China between August 2016 and December 2019. We measured the prevalence of comorbidities, coinfections, nosocomial infections, and in-hospital mortalities. RESULTS: Of the 806 patients, 370 were immunocompromised and 436 were immunocompetent. The disease severity and in-hospital mortality of immunocompromised patients were higher than those of immunocompetent patients. During the influenza season, an increased number of cases of influenza virus (IFV) infection were found in the immunocompromised group, followed by cases of cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. During the non-influenza season, CMV was the main virus detected in the immunocompromised group, while RSV, adenovirus (AdV), parainfluenza virus (PIV), and rhinovirus (HRV) were the main viruses detected in the immunocompetent group. Pneumonia caused by Pneumocystis jirovecii (22.4%), Aspergillus spp. (14.1%), and bacteria (13.8%) were the most frequently observed coinfections in immunocompromised patients but not in immunocompetent patients (Aspergillus spp. [10.8%], bacteria [7.1%], and Mycoplasma spp. [5.3%]). CMV infection and infection with two-or-more viruses were associated with a higher in-hospital mortality rate than non-IFV infection. However, patients with IFV and non-IFV infection in immunocompromised patients had similar disease severity and prognosis. CONCLUSIONS: Immunocompromised patients have a high frequency of coinfections, and a higher mortality rate was observed among those infected with CMV and two-or-more viruses. In addition, patients with IFV and non-IFV infection in immunocompromised patients had similar same disease severity and prognosis. The type of viral infection varied with seasons.

Effect of Genotype on the Pharmacokinetics and Bleeding Events of Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

This meta-analysis aimed to investigate the effect of the genotype on the pharmacokinetics and bleeding events of direct oral anticoagulants (DOACs) and comprehensively searched electronic databases. Weighted mean difference (WMD) was used to assess the kinetic indicators, odds ratio, and 95% confidence interval (CI) were used to calculate the clinical outcomes. Thirteen articles with 1543 participants were finally included in this study. The peak concentration (Cmax ) and area under the plasma concentration-time curve from time 0 to infinity of individuals with the ABCB1 rs 1045642 CT + TT were higher than that of the CC (WMD = -31.9, 95% CI [-49.94, -12.24], P = .02; WMD = -79.97, 95%CI [-152.38 to -7.56], P = .03, I2 = 0). The Cmax of individuals with mutated genes in ABCB1 2677-3435 is higher than that the wild type (WMD = -19.20, 95%CI [36.62 to -1.79], P = .03, I2 = 0). Carriers of the CYP3A5 rs776746 GG genotype had a higher Cmax than the GA gene (WMD = -51.22, 95%CI [-92.26 to -10.19], P = .01, I2 = 0). Bleeding events were more common in the CES1 rs 2244613 AA + AC than in the CC (odds ratio, 2.62, 95%CI [1.06, 6.47], P = .04; I2 = 0). The Cmax of DOACs was affected by individuals with ABCB1 rs 1045642, ABCB1 2677-343, and cytochrome P450 3A5 rs 776746. Carriers of the ABCB1 rs 1045642 affected the change of area under the plasma concentration-time curve from time 0 to infinity of DOACs. Bleeding events were affected by CES1 rs 2244613.

Distribution Patterns of Pathogens Causing Lower Respiratory Tract Infection Based on Metagenomic Next-Generation Sequencing.

Purpose: Lower Respiratory Tract Infection (LRTI) is a leading cause of morbidity and mortality worldwide. In this study, the distribution patterns of causative pathogens in LRTI were evaluated within a city-level hospital by combining conventional microbiological tests (CMT) with metagenomic next-generation sequencing (mNGS). Patients and Methods: This retrospective cohort study involved 160 patients suspected of having LRTI in a single center. Specimens, including bronchoalveolar lavage fluid (BALF), blood, tissue, sputum, and pus were utilized to identify pathogens. The seasonal prevalence of pathogens and co-pathogens involved in multiple infections was analyzed. Results: A total of 137 patients with 156 samples were included in this study. Pseudomonas aeruginosa, Corynebacterium striatum, Klebsiella pneumoniae, Candida, and human herpesvirus were the top prevalent pathogens. We observed seasonal dynamic variation in the top prevalent bacteria (Pseudomonas aeruginosa and Klebsiella pneumoniae) and herpesvirus (Epstein-Barr virus and Human herpesvirus-7). The majority of patients had single bacterial infections, followed by instances of bacterial-viral co-infections, as well as mixed infections involving bacteria, fungi, and viruses. Notably, the spectrum of co-infecting pathogens was broader among the elderly population, and positive Spearman correlations were observed among these co-infecting pathogens. Conclusion: Co-infections were prevalent among patients with LRTI, and the pathogens displayed distinct seasonal distribution patterns. The findings underscored the significance of comprehending pathogen distribution and epidemic patterns, which can serve as a basis for early etiological identification.

Diffusion tensor imaging techniques show that parkin gene S/N167 polymorphism is responsible for extensive brain white matter damage in patients with Parkinson's disease.

Objective: To explore the influence of disease and genetic factors on the white matter microstructure in patients with PD. The white matter microstructural changes in the substantia nigra-striatum system were detected by diffusion tensor imaging (DTI) using the region of interest (ROI) and diffusion tensor tracer (DTT) methods. Methods: Patients with primary Parkinson's disease (PD) without a family history of PD were selected and divided into PD-G/G and PD-G/A groups according to their parkin S/N167 polymorphism. Control groups matched for age, sex, and gene type (G/G and G/A) were also included. Three-dimensional brain volume imaging (3D-BRAVO) and DTI were performed. The microstructural changes in the substantia nigra-striatum system were evaluated by the ROI and DTT methods. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hoehn-Yahr (H-Y) staging, and the third part of the Unified Parkinson's Disease Rating (UPDRS-III) scales evaluated the cognitive and motor function impairment in patients with PD. Independent samples t-test compared normally-distributed data, and the Wilcoxon rank sum test compared measurement or categorical non-normally distributed data. Multiple regression analysis was used to analyze the correlation between various DTI indicators and the MMSE, MoCA, UPDRS-III, and H-Y scores in the PD-G/G and PD-G/A groups. P < 0.05 was considered statistically significant. Results: The white matter microstructural changes in the nigrostriatal pathway differed significantly between the PD or PD-G/A and the control group (P < 0.05)The ROI method showed that the left globus pallidus radial diffusivity (RD) value was negatively correlated with the MMSE score (r = -0.404, P = 0.040), and the left substantia nigra (LSN) fractional anisotropy (FA) value was positively correlated with the MoCA score (r = 0.405, P = 0.040) and negatively with the H-Y stage (r = -0.479, P = 0.013).The DTT method showed that the MMSE score was positively correlated with the right substantia nigra (RSN) FA value (r = 0.592, P = 0.001) and negatively with its RD value (r = -0.439, P = 0.025). The H-Y grade was negatively correlated with the number of fibers in the RSN (r = -0.406, P = 0.040). The UPDRS-Ⅲ score was positively correlated with the mean diffusivity (r = 0.420, P = 0.033) and RD (r = 0.396, P = 0.045) values of the LSN, and the AD value of the RSN (r = 0.439, P = 0.025). Conclusion: The DTI technique detected extensive white matter fiber damage in patients with PD, primarily in those with the G/A genotype, that led to motor and cognitivesymptoms.

Prediction of Alzheimer's Disease Using Patterns of Methylation Levels in Key Immunologic-Related Genes.

BACKGROUND: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer's disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD. OBJECTIVE: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD. METHODS: Methylation levels were obtained from 222 participants (101 AD, 72 MCI, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity. RESULTS: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7 1040077, CNR1 88166293, CX3CR1 39322324, LRRK2 40618505, LRRK2 40618493, NGFR 49496745, TARDBP 11070956, TARDBP 11070840 area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7 1040077 and CX3CR1 39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively). CONCLUSION: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD.