The sudden outbreak of coronavirus disease 2019 (COVID-19) has deep and wide negative mental impacts on the public, and studies on the impact of COVID-19 on social and mental well-being are ...necessary. This study aimed to evaluate mental distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), and its related risk factors in Chinese adults in the early stages of the COVID-19 pandemic. This study used a large-scale cross-sectional design. A total of 2067 adult participants completed the online survey via REDcap from 1st to 15th of March 2020 during the COVID-19 outbreak in China. Anxiety, depression, PTSD, and related risk factors, including self-efficacy, coping style, and social support, were measured using valid and reliable instruments. The data were analyzed using multiple linear regression. We found that 201 (9.7%) participants reported moderate-to-severe anxiety, 669 (33.8%) reported depression, and 368 (17.8%) reported symptoms of PTSD. Self-efficacy, coping style, and social support significantly affected anxiety, depression, and PTSD symptoms. Participants' sociodemographic characteristics, COVID-19 pandemic-related factors, low self-efficacy, low social support, and negative coping were predictors of mental distress during the COVID-19 pandemic. Our study will help healthcare professionals carry out early predictions and identification of high-risk groups and provide appropriate interventions to target groups during public health emergencies that plague the world.
Our study aimed to investigate the pharmacogenetics of cytochrome P3A4 (CYP3A4), CYP3A5, CYP2C8, and CYP2C19 and their influence on TAC Pharmacokinetics (PKs) in short-term renal transplant ...recipients.
A total of 105 renal transplant recipients were enrolled. Target Sequencing (TS) based on next-generation sequencing technology was used to detect all exons, exon/intron boundaries, and flanking regions of CYP3A4, CYP3A5, CYP2C8, and CYP2C19. After adjustment of Minor Allele Frequencies (MAF) and Hardy-Weinberg Equilibrium (HWE) analysis, tagger Single-nucleotide Polymorphisms (SNPs) and haplotypes were identified. Influence of tagger SNPs on TAC concentrations was analyzed.
A total of 94 SNPs were identified in TS analysis. Nine tagger SNPs were selected, and two SNPs (rs15524 and rs4646453) were noted to be significantly associated with TAC PKs in short-term post-transplant follow-up. Measurement time points of TAC, body mass index (BMI), usage of sirolimus, and incidence of Delayed Graft Function (DGF) were observed to be significantly associated with TAC PKs. Three haplotypes were identified, and rs15524-rs4646453 was found to remarkably contribute to TAC PKs. Recipients carrying H2/H2 (GG-AA) haplotype also showed significantly high weight- and dose-adjusted TAC concentrations in posttransplant periods of 7, 14, and 30 days and 3 and 6 months.
Two tagger SNPs, namely, rs15524 and rs4646453, are significantly related to the variability of TAC disposition, and TAC measurement time points, BMI, usage of sirolimus, and incidence of DGF contribute to this influence. Recipients carrying H2/H2 (GG-AA) haplotype in rs15524-rs4646453 may require a low dosage of TAC during 1-year follow-up posttransplant.
This study aimed to evaluate the predictive value of procalcitonin (PCT) in ventilator-associated pneumonia (VAP) after cardiac valve replacement. A total of 80 patients who underwent cardiac valve ...replacement in our department were enrolled in this study. Of these patients,40 were diagnosed with VAP and assigned to the observation group, while the other 40 patients not diagnosed with VAP were assigned to the control group. The changes in serum PCT, white blood cell count and C-reactive protein (CRP) were observed before each operation (T0), on the first day after the operation (T1), the second day after the operation (T2) and the third day after the operation (T3). After the operation, the serum PCT in the observation group was significantly higher than those at different time points after the operation, and also significantly higher than those in the control group (p < .05). In the control group, PCT was significantly higher after the operation than before the operation (p < .05), but the differences among the different postoperative time points were not statistically significant (p > .05). In the two groups, the white blood cell count and CRP were significantly higher after the operation than before the operation (p < .05), but the differences between the two groups were not statistically significant (p > .05). Serum PCT is an early, sensitive and highly specific high-risk monitoring index and has an early prediction value for VAP after cardiac valve replacement.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Acute rejection (AR) is a common complication of kidney transplantation. Nuclear factors of activated T cells (NFATs) are transcription factors involved in the activation of T lymphocytes, ...but their association with AR is unclear.
Methods
This retrospective, case–control study included 200 renal transplant recipients who were divided into the AR group (
n
= 69) and stable group (
n
= 131). Their blood samples were collected, and DNA was extracted from the whole blood. High-throughput next-generation sequencing was used to identify single nucleotide polymorphisms (SNPs) of the
NFATC2
and
NFATC4
genes. The correlation of these SNPs with AR was determined by logistic analysis.
Results
Seventy-one SNPs of the
NFATC2
and
NFATC4
genes were identified by the sequencing and Hardy–Weinberg equilibrium analyses. After adjusting for age, gender and immunosuppressive protocols, 27 SNPs were correlated with AR, of which the SNP rs2426295 of the
NFATC2
gene showed a significant correlation with AR in the HET model (AA vs. AC: OR = 0.43, 95% CI = 0.19–0.98,
P
= 0.045), but no significant
NFATC4
SNPs were identified.
Conclusions
Our study shows that the rs2426295 variant of the
NFATC2
gene is significantly associated with the occurrence of AR following kidney transplantation. And patients with AA genotypes in rs2426295 are inclined to suffer from AR pathogenesis.
Prussian blue analogues (PBA) possess a high theoretical specific capacity for sodium ion batteries. However, cycling PBA to a high current density causes severe capacity fading. Here, we develop a ...selective edge-etching approach to tackle this long-standing issue of poor rate capability. Well-crystallized PBA particles were produced by hydrothermal treatment of a sodium hexacyanoferrate precursor dissolved in muriatic acid solution, which were then eroded in hydrochloric acid solution to promote selective etching along the edges of the PBA crystals. The defect concentration (Fe(CN)
6
4−
) on the edge is denser than that at the face or corner, which stimulates the preferred etching of edges
via
the defect-induced heterogeneous mechanism. Due to the increasing exposed surface area and active sites, the etched PBA display much improved electrochemical performance with a capacity of 167 mA h g
−1
at a current density of 5 mA g
−1
and a capacity retention of 82.7% when the current density was increased to 40 mA g
−1
, demonstrating fast sodium ion transfer and high rate capability.
Prussian blue analogues prefer to be etched along the edge in HCl solution, resulting in much enhanced ionic diffusions and thus rate capability.
The purpose of this research was to prepare a novel type of Tat tagged and folate modified N-succinyl-chitosan (Tat-Suc-FA) self-assembly nanoparticles, to provide a new vector for tumor gene ...therapy. In this study, Tat-Suc-FA polymers was synthesized and characterized using (1)H NMR and FT-IR. The copolymer had a mean diameter of 65 ± 22.6 nm, a zeta potential of 40 ± 0.2 mV. The cytotoxicity assay showed that Tat-Suc-FA polymers were less toxic than chitosan in the tested concentration range (from 2 to 500 μg/ml). Tat-Suc-FA/DNA complexes at various weight ratios were formulated and characterized. Particle sizes of Tat-Suc-FA/DNA complexes were between 54 and 106 nm as determined by dynamic light scattering. Accordingly, Transmission electron microscope photo of Tat-Suc-FA/DNA complexes exhibited a spherical and compact morphology. Zeta potentials of these complexes changed as the weight ratio varied (from 3 to 44 mV). Agarose gel electrophoresis assay showed that Tat-Suc-FA could efficiently condense the DNA, when the weight ratio was above 1.5/1. Together, these results suggest that the low toxic Tat-Suc-FA cationic polymers could be considered for use as a novel type of gene delivery vectors.
The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behavior underlying ...imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of tumor immune microenvironment (TIME) underpinning patient-specific imaging traits.
Between January 2009 and December 2019, a total of 322 patients who underwent dynamic CT/MRI and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n=193) and validation (n=129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative and one integrating pre-and postoperative variables, were developed using Cox regression analysis. We then prospectively analyzed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence.
Pre-and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumor number, radiological/pathological nodal status, pathological necrosis and three radiological traits (arterial enhancement pattern, tumor boundary and capsular retraction), demonstrated good performance in predicting disease-specific (C-statistic＞0.80) and disease-free (C-statistic＞0.75) survival that outperformed rival models and staging systems across study cohorts (P＜0.05 for all). Patients with MICC-RACS score of 0-2 (low-risk), 3-5 (medium-risk) and ≥6 (high-risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive Tregs and M2-like macrophages at invasive margin were noted in tumors with distinct boundary and capsular retraction, respectively.
Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach.
The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behavior of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumor boundary and capsular retraction) were highly correlated with heterogeneous tumor-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease.
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●We proposed novel and simple but powerful prognostic tools for MICC.●MICC-RACS systems can predict the prognosis either before or after surgery.●MICC-RACS systems outperform rival models and staging systems.●Radiological traits integrated into systems are highly correlated with TIMEs.●MICC-RACS systems may facilitate patient-tailored immunotherapy approach.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton. Early and accurate diagnosis is necessary for the timely and effective treatment of this disease and its common ...complications. Lipid metabolites form various kinds of bioactive molecules that regulate the initiation and progression of inflammation. However, there are currently few studies that investigate the alteration of serum lipid in AS patients.
Blood samples were collected from 115 AS patients and 108 healthy controls (HCs). Serum-untargeted lipidomics were performed using ultrahigh-performance liquid chromatography coupled with Q-Exactive spectrometry, and the data were determined by multivariate statistical methods to explore potential lipid biomarkers.
Lipid phenotypes associated with disease activity were detected in the serum of patients with AS. Of all 586 identified lipids, there are 297 differential lipid metabolites between the AS and HC groups, of which 15 lipid metabolites are significant. In the AS groups, the levels of triacylglycerol (TAG) (18:0/18:1/20:0) were increased, and the levels of phosphatidylcholine (PC) (16:0e/26:4) and PC (18:1/22:6) were decreased. The areas under the receiver operating characteristic curve (AUC) of TAG (18:0/18:1/20:0), PC (16:0e/26:4), and PC (18:1/22:6) were 0.919, 0.843, and 0.907, respectively.
Our findings uncovered that lipid deregulation is a crucial hallmark of AS, thereby providing new insights into the early diagnosis of AS.
Ritter reaction has been recognized as an elegant strategy to construct the C−N bond. Its key feature is forming the carbocation for nucleophilic attack by nitriles. Herein, we report a complementary ...visible-light-induced three-component Ritter reaction of alkenes, nitriles, and α-bromo nitriles/esters, thereby providing mild and rapid access to various γ-amino nitriles/acids. Mechanistic studies indicated that traceless fluoride relay, transforming KF into imidoyl fluoride intermediate, is critical for the efficient reaction switch from atom transfer radical addition (ATRA) to the Ritter reaction. This approach to amino-alkylation of alkenes is chemoselective and operationally simple.
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•Using light irradiation to promote amino-alkylation of alkenes•Using KF to facilitate three-component Ritter reaction•Access functionalized amides under mild conditions
Chemistry; Organic chemistry; Organic synthesis
Natalizumab (NAT), a humanized monoclonal antibody, which binds in both α4β1 integrins and α4β7 integrins, is approved for the treatment of multiple sclerosis (MS) and Crohn's disease (CD). An ...uncommon but serious adverse event from NAT treatment is known as progressive multifocal leukoencephalopathy (PML). However, clinical comprehensive safety evidence of NAT is limited.
We will search Medline, Embase, Cochrane library, and ClinicalTrials.gov website from inception to May 9, 2018. Double-blind, randomized placebo-controlled trials reporting safety data of NAT will be eligible for inclusion. Outcome variables will include adverse events (AEs) varying degrees and AEs occurring in ≥ 5% patients with NAT or placebo. STATA software (version 12, Statacorp, College Station, TX) will be utilized to assess risk of bias and synthesize data. Outcomes will be reported by weight mean difference (WMD), risk ratios (RRs), and their 95% confidence intervals (95% CIs). I statistic will be used to evaluate heterogeneity among studies.
This systemic review and meta-analysis will evaluate serious AEs and AEs of NAT as compared to placebo.
Our study will provide a comprehensive picture of AEs of NAT.
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