Search

Background: Ground-glass Opacity (GGO) and Consolidation Opacity (CLO) are the common CT lung opacities, and their heterogeneity may have potential for prognosis ofcoronavirus disease-19 (COVID-19) patients. Objective: This study aimed to estimate clinical outcomes in individual COVID-19 patients using histogram heterogeneity analysis based on CT opacities. Methods: 71 COVID-19 cases’ medical records were retrospectively reviewed from a designated hospital in Wuhan, China, from January 24th to February 28th at the early stage of the pandemic. Two characteristic lung abnormity opacities, GGO and CLO, were drawn on CT images to identify the heterogeneity using quantitative histogram analysis. The parameters (mean, mode, kurtosis, and skewness) were derived from histograms to evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. Results: A total of 57 COVID-19 cases were eligible for the study cohort after excluding 14 cases. The highest lung abnormalities were GGO mixed with CLO in both the survival populations (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as follows: GGO_skewness: specificity= 66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity= 76.92%, and AUC=0.746. Nomogram based on histogram parameters can predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively. Conclusion: Histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.

The transparent conductive CuCr1–xNixO2 (0 ≤ x ≤ 8%) films were prepared by sol–gel method with two-step annealing process. The structure, morphology, phonon modes, chemical composition, optical ba...

Background: The role of aberrant DNA methylation in allopurinol-induced severe cutaneous adverse reactions (SCARs) is incompletely understood. To fill the gap, we analyze the DNA methylation profiling in allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients and identify the DNA methylation signature for predisposing allopurinol hypersensitivity. Methods: Genome-scale methylation analysis was conducted using the Illumina® HumanMethylation450 BeadChip. Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to analyze the data. Results: A total of 21,497 annotated promoter regions were analyzed. Ten modules were identified between allopurinol hypersensitivity and tolerance, with turquoise and yellow modules being the most significant correlation. ATG13, EPM2AIP1, and SRSF11 were the top three hub genes in the turquoise module. MIR412, MIR369, and MIR409 were the top three hub genes in the yellow module. Gene Ontology (GO) analysis revealed that the turquoise module was related to the metabolic process in intracellular organelles and the binding of various compounds, proteins, or nucleotides. The yellow module, however, was related to stimulus sensory perception in cytoskeletal elements and the activity of the receptor or transducer. Conclusion: DNA methylation plays a vital role in allopurinol-induced SCARs. DNA methylation profiling of SJS/TEN is significantly related to autophagy and microRNAs (miRNAs).

Isoliensinine is a bis-benzylisoquinoline alkaloid that can be isolated from the lotus Nelumbo nucifera Gaertn. It has been reported to exert a variety of anti-cancer properties. In the present study, the potential effects of isoliensinine on cervical cancer Siha, HeLa, Caski and C33A cell lines were investigated by using Cell Counting Kit-8 (CCK-8), flow cytometry, western blotting and reverse transcription-PCR (RT-PCR) to measure cell proliferation, the cell cycle and apoptosis, in addition to elucidating the underlying molecular mechanism. Protein levels of p21, CDK2, Cyclin E, Mcl-1, cleaved Caspase-9, AKT, phosphorylated-AKT, glycogen synthase kinase (Gsk)3α, PTEN, and mRNA levels of p21, p15, p27, CDK2, CDK4, Cyclin E, Cyclin D, Gsk3α, Gsk3β and PTEN were measured. Molecular docking assays were used to calculate the strength of binding of isoliensinine to AKT using AutoDock 4.0. Isoliensinine was found to induce cell cycle arrest at the G0/G1 phase by upregulating p21 expression and downregulating CDK2 and cyclin E in breast cancer cells. In addition, in previous research, isoliensinine promoted cell apoptosis by downregulating myeloid-cell leukemia 1 expression and activating caspase-9. Upstream, isoliensinine significantly downregulated AKT (S473) phosphorylation and GSK3α expression in a dose- and time-dependent manner. The AKT inhibitor AKTi-1/2 enhanced the function of isoliensinine on cell cycle arrest and apoptosis through the AKT/GSK3α pathway. AutoDock analysis showed that isoliensinine can bind to the AKT protein. These findings suggest that isoliensinine can induce cervical cancer cell cycle arrest and apoptosis by inhibiting the AKT/GSK3α pathway, which represents a novel strategy for the treatment of cervical cancer.

Background Reports regarding the causative drugs of drug-induced cutaneous adverse reactions in China are indistinct, such that different regions have reported the spectrum of drugs differs substantially in different clinical conditions. Objective To explore the causative drugs that led to cutaneous reactions. Methods Adverse drug reaction reports from central China were collected and divided into cutaneous adverse reactions and severe cutaneous adverse reactions groups. Cases were reviewed retrospectively for causative drugs. Results The male:female ratio was equal in both cutaneous adverse reactions and severe cutaneous adverse reactions. In cutaneous adverse reactions (n = 482), the highest incidence happened between 51 and 60 years of age and the top three causative drugs were antibiotics (48%), Chinese medicine (16%), and allopurinol (9%). In severe cutaneous adverse reactions (n = 126), the highest incidence happened between 41 and 50 years of age and the top three causative drugs were sedative-hypnotics and antiepileptics (39%), antibiotics (22%), and allopurinol (15%). Carbamazepine was the most frequently used single-drug (16/18) in sedative-hypnotics and antiepileptics. β-lactams were the most frequently used antibiotics that induced both cutaneous adverse reactions and severe cutaneous adverse reactions. Study limitations The small sample size, retrospective design, collection of cutaneous adverse reactions and severe cutaneous adverse reactions at different time frames and locations, and exclusion of patients taking more than five medications are limitations of the study. Conclusions Gender does not affect cutaneous adverse reactions and severe cutaneous adverse reactions. The top three drugs to induce cutaneous adverse reactions are antibiotics, Chinese medicine, and allopurinol, while those that triggered severe cutaneous adverse reactions are sedative-hypnotics and antiepileptics, antibiotics, and allopurinol. Carbamazepine is the most frequent single drug that induces severe cutaneous adverse reactions. β-lactams are the most frequently used antibiotics that induce both cutaneous adverse reactions and severe cutaneous adverse reactions.

This study aimed to estimate clinical outcome in individual COVID-19 patient by using histogram heterogeneity analysis based on CT opacities. 57 COVID-19 cases’ medical records were retrospectively reviewed from a designated hospital in Wuhan, China. Two characteristic lung abnormity opacities, ground-glass opacity (GGO) and consolidation opacity (CLO) were drawn on CT images to identify the heterogeneity by using quantitative histogram analysis. The parameters (mean, mode, kurtosis, skewness) derived from histograms evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. The most highly frequency of lung abnormalities was GGO mixed with CLO in both survival population (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as following: GGO_skewness: specificity=66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity=76.92%, AUC=0.746. Nomogram based on histogram parameters can predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively. The histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA) is a novel alternative compound for perfluorooctane sulfonate (PFOS), with its environmental risk not well known. The bioaccumulation and toxic effects of Cl-PFESA in the freshwater alga is crucial for the understanding of its potential hazards to the aquatic environment. Scenedesmus obliquus was exposed to Cl-PFESA at ng L−1 to mg L−1, with the exposure regime beginning at the environmentally relevant level. The total log BAF of Cl-PFESA in S. obliquus was 4.66, higher than the reported log BAF of PFOS in the freshwater plankton (2.2–3.2). Cl-PFESA adsorbed to the cell surface accounted for 33.5–68.3% of the total concentrations. The IC50 of Cl-PFESA to algal growth was estimated to be 40.3 mg L−1. Significant changes in algal growth rate and chlorophyll a/b contents were observed at 11.6 mg L−1 and 13.4 mg L−1 of Cl-PFESA, respectively. The sample cell membrane permeability, measured by the fluorescein diacetate hydrolyzation, was increased by Cl-PFESA at 5.42 mg L−1. The mitochondrial membrane potential, measured by Rh123 staining, was also increased, indicating the hyperpolarization induced by Cl-PFESA. The increasing ROS and MDA contents, along with the enhanced SOD, CAT activity, and GSH contents, suggested that Cl-PFESA caused oxidative damage in the algal cells. It is less possible that current Cl-PFESA pollution in surface water posed obvious toxic effects on the green algae. However, the bioaccumulation of Cl-PFESA in algae would contribute to its biomagnification in the aquatic food chain and its effects on membrane property could potentially increase the accessibility and toxicity of other coexisting pollutants.

Two-dimensional (2D) crystalline carbonitride C3N, as a very attractive material, has received extensive attention. By using the first-principles calculations, we systematically studied the electronic properties of antimonene/C3N van der Waals (vdW) heterojunction. The results show that the heterostructure has an inherent type-II band alignment with an indirect band gap. Moreover, the band gap of the C3N/antimonene heterojunction can be adjusted linearly within a certain range by applying vertical strain and electric field. The calculated absorption curve shows that the antimonene/C3N heterostructure can exhibit good visible-light absorption performance, and the optical properties of the C3N/antimonene heterojunction can be changed by applying biaxial and vertical strain, which can be expected to have potential applications in photovoltaic devices.

The aim of the present study is to investigate if rapamycin is a radiosensitizer of nasopharyngeal carcinoma (NPC), and to identify which pathways are involved in radiation sensitization. In vitro, using untreated cells as the control, NPC cells were treated with rapamycin, ionizing radiation (IR) or both. Differences in the phosphorylation of ribosomal protein S6 and glycogen synthase kinase (GSK) 3β, expression of cyclin D1, clonogenic survival, number of phosphorylated histone subunit 2AX (γH2AX) foci, and cell cycle status between the study groups were compared. The results indicated that rapamycin alone decreased the phosphorylation of S6 and GSK3β, as well as the expression of cyclin D1, in NPC cells. Thus, rapamycin-treated NPC cells had lower cell viability, and higher DNA damage and G1 arrest than control cells. In addition, the combination of rapamycin and IR caused the highest cell death, DNA damage and G1 arrest when compared with the effects caused by either treatment alone. In conclusion, rapamycin improves the anti-tumor effect of IR for treating NPC through inhibiting the Akt/mechanistic target of rapamycin/S6 and Akt/GSK3β/cyclin D1 signaling pathways.

Background Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia by greatly improving its solubility. Results This system (size 23.50 ± 1.67 nm, zeta potential − 3.35 ± 0.03 mV) was prepared with RH40 (surfactant), 1,2-propanediol (co-surfactant), squalene (oil) and BBR using low-energy emulsification methods. The system loaded BBR successfully according to thermal gravimetric, differential scanning calorimetry, and Fourier transform infrared spectroscopy analyses. The release profile results showed that BBR SNE released BBR more slowly than BBR solution. The relative oral bioavailability of this novel system in rabbits was significantly enhanced by 3.41-fold over that of BBR. Furthermore, Caco-2 cell monolayer transport studies showed that this system could help enhance permeation and prevent efflux of BBR. Importantly, mice with BBR SNE treatment had significantly longer survival time than BBR-treated mice (P

Additional file 1: Figure S1. Effect of a series of berberine and cytarabine solutions on the Jurkat cell line at (A) 24 h and (B) 48 h. The data are expressed as the mean ± S.D. (n = 3); ***P

A fluorescent assay for oxytetracycline (OTC) detection was presented based on an indirectly fluorescein-labelled aptamer probe, which was fabricated through the partial hybridization of an OTC long-chain aptamer with a FAM-labelled short-chain ssDNA (S1). Upon combination of the target OTC and its aptamer, S1 with quenched fluorescein was released from the probe to the graphene sheet freely. Subsequently, it was hybridized with the complementary ssDNA (C1) and escaped from the quencher graphene to the solution, resulting in the restoration of fluorescence. Benefiting from the labelling of S1 instead of the OTC aptamer directly, the restoration of fluorescence was independent of the long-chain aptamer, perfectly avoiding the negative effects of the intrinsically existing secondary structure. Together with the high affinity of the aptamer for its target, this assay exhibited excellent sensitivity and selectivity. The linear response for OTC was found to be 0.01–0.2 μM with a limit of quantitation of 0.01 μM. Furthermore, the feasibility of the developed assay in a fresh water system and a milk sample was verified through the recovery experiments using spiked samples. This achievement based on such an indirect labelling method is also expected to lay a foundation to realize effective analysis of small molecule pollutants in the environment, for which the specific aptamers are long-chain nucleotide sequences.

Objectives A new method of HLA-B*5801 genotyping was compared with sequence-based typing (SBT) to find an accurate and prompt method in genotyping HLA-B*5801. Methods Two groups of patients from allopurinol-induced cutaneous adverse reactions (SCARs) and allopurinol-tolerant were both genotyped with PG5801 kit and SBT method. The genotyping results of HLA-B*5801 were compared between the two groups. Results The PG5801 detection kit results were 100% (79/79) in agreement with the SBT genotyping results for identifying the HLA-B*5801 (+) patients. No false-positive or false-negative errors were found. The sensitivity, specificity, rate of adherence, positive predictive value (PPV) and negative predictive value (NPV) were 100%. Conclusion The potential fast screening method is an ideal tool to rule out the high-risk allopurinol-induced SCARs patients. Clin Trans Sci 2015; Volume #: 1–3

The purpose of this study is to evaluate the association between variants in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin F (2α) receptor (PTGFR), and multidrug resistance protein 4 (MRP4) genes and intraocular pressure (IOP) response to latanoprost in Chinese patients with primary open-angle glaucoma (POAG).The IOP response to latanoprost was evaluated by percent IOP reduction (%ΔIOP) in the treated eye with the formula %ΔIOP = (Baseline IOP values - IOP values posttreatment) / Baseline IOP values × 100 %. Polymorphisms in PTGS1 (rs3842787 and rs10306114), PTGFR (rs3753380 and rs3766355), and MRP4 (rs11568658 and rs11568668) genes were detected by direct DNA sequencing. The differences among %ΔIOP of genotypes or haplotypes were obtained by use of the Mann-Whitney U test. Association analyses were performed by multiple linear regression analysis.Latanoprost were prescribed to 63 subjects, 60 of which met the inclusion/exclusion criteria for the current study. Notably, the %ΔIOP in the rs11568658 GT heterozygous genotype was 10.4 %ΔIOP lower than that of GG homozygous wild-type on day 7 (15.7 ± 2.52 vs. 26.1 ± 2.88, P=0.003), and the corresponding results in the rs10306114 AG heterozygous genotype and AT haplotype constructed by rs3753380 and rs3766355 on day 7 were 7.2 and 10.3 %ΔIOP (P0.05). Interestingly, similar results were also observed on day 30 (P=0.008, P=0.006, and P=0.002, respectively). Multiple regression analysis showed that heterozygous genotypes of rs10306114, rs11568658, and carrier of AT haplotype were significantly correlated with the lower %ΔIOP. On day 30, the above variations explained 9.9, 10.7, and 17.7 % of the total variability of %ΔIOP in the Chinese POAG patients, respectively.rs10306114, rs3753380, rs3766355, and rs11568658 single-nucleotide polymorphisms (SNPs) correlate with a response to latanoprost treatment in patients with POAG. These SNPs may be important determinants of variability in response to latanoprost.

To investigate whether single-nucleotide polymorphisms (SNPs) in the P450 oxidoreductase (POR) gene were correlated with interindividual variations in cytochrome P450 (CYP) 2B6 activity. Thirty-six healthy volunteers who tested CYP2B6 and POR polymorphisms were enrolled in the study. CYP2B6 activity was measured by bupropion hydroxylation with LC/MS/MS. The ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup) in terms of area under the time-concentration curve (AUC) was used to represent the CYP2B6 activity. The volunteers carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/ AUC_bup than those CYP2B6*1/*6 and CYP2B6*6/*6 variants (15.66 ± 1.65 vs. 9.25 ± 1.92, P = 0.008 and 15.66 ± 1.65 vs. 8.21 ± 1.74, P = 0.006, respectively). POR rs2868177 (6593 A > G) AA homozygotes showed a significantly lower mean AUC_hyd/ AUC_bup than that of POR rs2868177 AG heterozygotes or GG homozygotes (8.13 ± 1.37 vs. 12.15 ± 2.97, P = 0.005 and 8.13 ± 1.37 vs. 17.59 ± 3.25, P = 0.001, respectively). Moreover, POR rs2868177 AG heterozygotes and GG homozygotes showed a significantly increased mean AUC_hyd/AUC_bup than AA homozygotes in the CYP2B6*1/*1 and CYP2B6*6 carriers (16.40 ± 2.01 vs. 12.40 ± 1.45, P = 0.006 and 10.65 ± 1.47 vs. 6.54 ± 1.25, P = 0.004, respectively). Meanwhile, a strong correlation between the genetic variations (POR rs2868177 and CYP2B6*6) and AUC_hyd/ AUC_bup was found (P = 0.009 and P = 0.001, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR *28 genotypes (P > 0.05). POR rs2868177 and CYP2B6*6 variants contribute to the interindividual variability in human CYP2B6 activity, which may affect the disposition and interaction of other CYP2B6 substrate drugs.

To explore the relationship between allogeneic transfusion and hospital infections in patients with closed traumatic brain injury in the perioperative period. The clinical data of 181 patients with open brain surgery suffering closed brain injury in Changsha Central Hospital from February, 2012 to December, 2013 were retrospectively collected. The patients were divided into a mild and moderate brain injury group (n=83) and a severe brain injury group (n=98) according to evaluation system of Glasgow coma scale (GCS). They were also divided into a autologous transfusion plus mild and moderate brain injury group (n=14), a autologous transfusion plus severe brain injury group (n=10); an allogeneic transfusion plus mild and moderate brain injury group (n=31), an allogeneic transfustion plus severe brain injury group (n=70); a non-transfusion plus mild and moderate brain injury group (n=38) and a non-transfusion plus severe brain injury group (n=18) according to the transfusion styles. The hospital infection of all the patients was examined. The rate of hospital infection was significantly higher in the severe brain injury group than that in the mild and moderate brain injury group (P0.05). The rate of post-operative hospital infection in the allogeneic transfusion plus severe brain injury group was also significantly higher than that in the autologous transfusion plus severe brain injury group (P0.05). Similarly, the rate of post-operative hospital infection in the allogeneic transfusion plus mild and moderate brain injury group is higher than that in the non-transfusion plus mild and moderate brain injury group (P0.05). The allogeneic transfusion at perioperative period may be one of the risk factors for post-operative hospital infection in the closed brain injury patients. The more severe the injury is, the higher risk the hospital infection will be.目的：探讨闭合性颅脑外伤患者围手术期输注异体血液与其发生院内感染是否存在相关性。方法：回顾性选择长沙市中心医院神经外科2012年2月至2013年12月因创伤所致闭合性颅脑外伤行开放性颅脑手术患者181例，依据入院时患者的格拉斯哥评分将患者分为轻、中型颅脑外伤组(n=83)与重型颅脑外伤组(n=98)；依据不同的输血情况，将上述入组患者又分为轻、中型颅脑外伤自体输血组(n=14)和重型颅脑外伤自体输血组(n=10)，轻、中型颅脑外伤异体输血组(n=31)和重型颅脑外伤异体输血组(n=70)，以及轻、中型颅脑外伤未输血组(n=38)和重型颅脑外伤未输血组(n=18)，并分析各组院内感染的发生情况。结果：重型颅脑外伤组的院内感染率显著高于轻、中型颅脑外伤组(P0.05)；重型颅脑外伤组中的异体输血组术后院内感染率明显高于自体输血组(P0.05)；轻、中型颅脑外伤组中异体输血组的术后院内感染率与未输血组相比，差异有统计学意义(P0.05)。结论：闭合性颅脑外伤患者围术期异体输血是术后发生院内感染的危险因素之一。伤情越重，院内感染的风险越高。.

The relationship of structural and functional brain damage and disorders of consciousness (DOC) for diffuse axonal injury (DAI) is still not fully explored. We employed diffusion tensor imaging (DTI) and resting-state fMRI (RS-fMRI) to examine the changes of resting activations and white matter (WM) integrity for DAI with DOC. WM damages were observed in the body and genu of the corpus callosum, right external capsule (EC) and superior corona radiate (SCR), left superior cerebellar peduncle (SCP) and posterior thalamic radiation (PTR). The RS-fMRI revealed augmented amplitude of low-frequency fluctuation (ALFF) in the anterior cingulate cortex, hippocampus, insula, amygdala and putamen, and reduced ALFF in the precuneus, thalamus, pre-central and post-central gyri. Correlation analysis identified positive associations between the Glasgow Coma Scale (GCS) and activation of the precuneus and between GCS and DTI measurements in the left PTR and SCP, but a negative correlation was found between GCS and activation of the thalamus. Cross modality association analyses indicated that activations of the amygdala and postcentral gyrus were correlated with DTI measurements of the right EC and left PTR respectively. These results implicate that the WM damages in thalamocortical sensorimotor circuit and aberrant brain activity responding to self-awareness and sensation are critical factors to DOC, which expand the current understanding of the neural mechanisms underlying DAI.

This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value

Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI).Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated.Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses.Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs.