Identification of shared and distinct patterns of brain network abnormality across mental disorders through individualized structural covariance network analysis.

BACKGROUND: Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders. METHODS: Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed. RESULTS: Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network. CONCLUSIONS: These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

LncRNA MEG3 promotes neuronal apoptosis in rats with ischemic cerebral infarction via the TGF-ß1 pathway.

To study the influence of long non-coding ribonucleic acid maternally expressed gene 3 (lncRNA MEG3) on the neuronal apoptosis in rats with ischemic cerebral infarction, and to analyze its regulatory effect on the transforming growth factor-beta 1 (TGF-ß1) pathway. A total of 36 Sprague-Dawley rats were randomly assigned into sham group, model group and low expression group. Ischemic cerebral infarction modeling was constructed in rats of the model group and low expression group. Corresponding adenoviruses were intracranially injected in rats of low expression group to knock down lncRNA MEG3 expression. At 24 h after the operation, the neurological function of rats was evaluated in each group, and the expression level of lncRNA MEG3 in cerebral tissues was determined using quantitative polymerase chain reaction (qPCR). The infarct size was measured via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The apoptosis level of neurons in cerebral tissues was determined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Besides, enzyme-linked immunosorbent assay (ELISA) was performed to determine the contents of inflammatory factors in cerebral tissues. Expression levels of apoptosis-associated proteins and vital genes in the TGF-ß1 signaling pathway in rat cerebral tissues were measured using Western blotting. Compared with the sham group, rats in the model group exhibited substantial increases in the neurological score and apoptosis level of neurons (p<0.01). Relative levels of lncRNA MEG3, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), Caspase-3, TGF-ß1, small mothers against decapentaplegic homolog 2 (Smad2) and Smad3 (p<0.01) were higher in a model group than those in sham group. Notable declines in the content of IL-10 (p<0.01) and the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl associated X protein (Bax) (p<0.01) were seen in the model group compared with the sham group. The abovementioned changes in the model group were partially abolished in the low expression group. LncRNA MEG3 is upregulated in the cerebral tissues of rats with ischemic cerebral infarction. It induces an inflammatory response, expands cerebral infarct size, and promotes neuronal apoptosis and impairment by activating the TGF-ß1 pathway.

Altered time-varying local spontaneous brain activity pattern in patients with high myopia: a dynamic amplitude of low-frequency fluctuations study.

PURPOSE: To investigate the abnormal time-varying local spontaneous brain activity in patients with high myopia (HM) on the basis of the dynamic amplitude of low-frequency fluctuations (dALFF) approach. METHODS: Age and gender matching were performed based on resting-state functional magnetic resonance imaging data from 86 HM patients and 87 healthy controls (HCs). Local spontaneous brain activities were evaluated using the time-varying dALFF method. Support vector machine combined with the radial basis function kernel was used for pattern classification analysis. RESULTS: Inter-group comparison between HCs and HM patients has demonstrated that dALFF variability in the left inferior frontal gyrus (orbital part), left lingual gyrus, right anterior cingulate and paracingulate gyri, and right calcarine fissure and surrounding cortex was decreased in HM patients, while increased in the left thalamus, left paracentral lobule, and left inferior parietal (except supramarginal and angular gyri). Pattern classification between HM patients and HCs displayed a classification accuracy of 85.5%. CONCLUSION: In this study, the findings mentioned above have suggested the association between local brain activities of HM patients and abnormal variability in brain regions performing visual sensorimotor and attentional control functions. Several useful information has been provided to elucidate the mechanism-related alterations of the myopic nervous system. In addition, the significant role of abnormal dALFF variability has been highlighted to achieve an in-depth comprehension of the pathological alterations and neuroimaging mechanisms in the field of HM.

Prognostic roles of hematological indicators for the efficacy and prognosis of immune checkpoint inhibitors in patients with advanced tumors: a retrospective cohort study.

BACKGROUND: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy. METHODS: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis. RESULTS: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively. CONCLUSIONS: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy.

Nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity: A fMRI study of interaction effects.

BACKGROUND: Nicotine addiction and overweight often co-exist, but the neurobiological mechanism of their co-morbidity remains to be clarified. In this study, we explore how nicotine addiction and overweight affect intrinsic neural activity and neurotransmitter activity. METHODS: This study included 54 overweight people and 54 age-, sex-, and handedness-matched normal-weight individuals, who were further divided into four groups based on nicotine addiction. We used a two-way factorial design to compare intrinsic neural activity (calculated by the fALFF method) in four groups based on resting-state functional magnetic resonance images (rs-fMRI). Furthermore, the correlation between fALFF values and PET- and SPECT-derived maps to examine specific neurotransmitter system changes underlying nicotine addiction and overweight. RESULTS: Nicotine addiction and overweight affect intrinsic neural activity by themselves. In combination, they showed antagonistic effects in the interactive brain regions (left insula and right precuneus). Cross-modal correlations displayed that intrinsic neural activity changes in the interactive brain regions were related to the noradrenaline system (NAT). CONCLUSION: Due to the existence of interaction, nicotine partially restored the changes of spontaneous activity in the interactive brain regions of overweight people. Therefore, when studying one factor alone, the other should be used as a control variable. Besides, this work links the noradrenaline system with intrinsic neural activity in overweight nicotine addicts. By examining the interactions between nicotine addiction and overweight from neuroimaging and molecular perspectives, this study provides some ideas for the treatment of both co-morbidities.

Abnormal interhemispheric and intrahemispheric functional connectivity dynamics in drug-naïve first-episode schizophrenia patients with auditory verbal hallucinations.

Numerous studies indicate altered static local and long-range functional connectivity of multiple brain regions in schizophrenia patients with auditory verbal hallucinations (AVHs). However, the temporal dynamics of interhemispheric and intrahemispheric functional connectivity patterns remain unknown in schizophrenia patients with AVHs. We analyzed resting-state functional magnetic resonance imaging data for drug-naïve first-episode schizophrenia patients, 50 with AVHs and 50 without AVH (NAVH), and 50 age- and sex-matched healthy controls. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral parts, and sliding-window analysis was used to calculate voxel-wise interhemispheric and intrahemispheric dynamic functional connectivity density (dFCD). Finally, the correlation analysis was performed between abnormal dFCD variance and clinical measures in the AVH and NAVH groups. Compared with the NAVH group and healthy controls, the AVH group showed weaker interhemispheric dFCD variability in the left middle temporal gyrus (p < .01; p < .001), as well as stronger interhemispheric dFCD variability in the right thalamus (p < .001; p < .001) and right inferior temporal gyrus (p < .01; p < .001) and stronger intrahemispheric dFCD variability in the left inferior frontal gyrus (p < .001; p < .01). Moreover, abnormal contralateral dFCD variability of the left middle temporal gyrus correlated with the severity of AVHs in the AVH group (r = -.319, p = .024). The findings demonstrate that abnormal temporal variability of interhemispheric and intrahemispheric dFCD in schizophrenia patients with AVHs mainly focus on the temporal and frontal cortices and thalamus that are pivotal components of auditory and language pathways.

Unexpected favorable outcome to sintilimab monotherapy in a relapse pancreatic ductal adenocarcinoma patient with high tumor mutational burden: a case report.

The reason that immune checkpoint inhibitors have not been widely applied to pancreatic cancer treatment is probably because of low immunogenicity or dense stromal fibrosis. Recently, only pembrolizumab was recommended for DNA mismatch repair deficiency or high microsatellite instability by National Comprehensive Cancer Network guideline. Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer, with a poor overall survival rate, the value of immunotherapy for PDAC needs more research. Here, we report a 56-year-old man suffered from PDAC with liver metastasis after radical surgery. The next-generation sequencing result demonstrated that it had remarkably high tumor mutational burden (TMB) of 49.92 Muts/Mb and microsatellite stability. Sintilimab (anti-PD-1) monotherapy was continuously administrated after failure of combined chemotherapy in second line, achieving stable disease within 22 months and few immunotherapy-related adverse events. To our knowledge, this is the first time to report a good outcome achieving 22 months with progression-free survival after PDAC metastasis with monotherapy of sintilimab. TMB may serve as a potential efficacy-related predictor in PDAC patients with sintilimab and help physicians make optimum clinical strategy.

Multi-marker approach using C-reactive protein, procalcitonin, neutrophil CD64 index for the prognosis of sepsis in intensive care unit: a retrospective cohort study.

BACKGROUND: We aimed to explore the prognostic utilities of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 (nCD64) index, in combination or alone, in septic patients. METHODS: We retrospectively included 349 septic patients (based on Sepsis 3.0 definition). The primary outcome was 28-day all-cause mortality. Cox regression model, receiver-operating characteristic (ROC) curve, reclassification analysis, Kaplan-Meier survival curves were performed to evaluate the predictive efficacy of the above parameters. RESULTS: CRP, nCD64 index were independent predictors of 28-day mortality for sepsis in the Cox regression model [CRP, HR 1.004 (95% CI 1.002-1.006), P < 0.001; nCD64 index, HR 1.263 (95% CI 1.187-1.345, P < 0.001]. Area under the ROC curve (AUC) of CRP, PCT, nCD64 index, nCD64 index plus PCT, nCD64 index plus CRP, were 0.798 (95% CI 0.752-0.839), 0.833 (95% CI 0.790-0.871), 0.906 (95% CI 0.870-0.935), 0.910 (95% CI 0.875-0.938), 0.916 (95% CI 0.881-0.943), respectively. nCD64 plus CRP performed best in prediction, discrimination, and reclassification of the 28-day mortality risk in sepsis. The risk of 28-day mortality increased stepwise as the number of data exceeding optimal cut-off values increased. CONCLUSIONS: nCD64 index combined with CRP was superior to CRP, PCT, nCD64 index and nCD64 index plus PCT in predicting 28-day mortality in sepsis. Multi-marker approach could improve the predictive accuracy and be beneficial for septic patients.

Genome-wide identification and characterization of small auxin-up RNA (SAUR) gene family in plants: evolution and expression profiles during normal growth and stress response.

BACKGROUND: Auxin is critical to plant growth and development, as well as stress responses. Small auxin-up RNA (SAUR) is the largest family of early auxin responsive genes in higher plants. However, the function of few SAUR genes is known owing to functional redundancy among the many family members. RESULTS: In this study, we conducted a phylogenetic analysis using protein sequences of 795 SAURs from Anthoceros angustus, Marchantia polymorpha, Physcomitrella patens, Selaginella moellendorffii, Ginkgo biloba, Gnetum montanum, Amborella trichopoda, Arabidopsis thaliana, Oryza sativa, Zea mays, Glycine max, Medicago truncatula and Setaria italica. The phylogenetic trees showed that the SAUR proteins could be divided into 10 clades and three subfamilies, and that SAUR proteins of three bryophyte species were only located in subfamily III, which suggested that they may be ancestral. From bryophyta to anthophyta, SAUR family have appeared very large expansion. The number of SAUR gene in Fabaceae species was considerably higher than that in other plants, which may be associated with independent whole genome duplication event in the Fabaceae lineages. The phylogenetic trees also showed that SAUR genes had expanded independently monocotyledons and dicotyledons in angiosperms. Conserved motif and protein structure prediction revealed that SAUR proteins were highly conserved among higher plants, and two leucine residues in motif I were observed in almost all SAUR proteins, which suggests the residues plays a critical role in the stability and function of SAUR proteins. Expression analysis of SAUR genes using publicly available RNA-seq data from rice and soybean indicated functional similarity of members in the same clade, which was also further confirmed by qRT-PCR. Summarization of SAUR functions also showed that SAUR functions were usually consistent within a subclade. CONCLUSIONS: This study provides insights into the evolution and function of the SAUR gene family from bryophyta to anthophyta, particularly in Fabaceae plants. Future investigation to understand the functions of SAUR family members should employ a clade as the study unit.

SPLICING FACTOR1 Is Important in Chloroplast Development under Cold Stress.

RNA SPLICING FACTOR1 (SF1) is responsible for recognizing the branch point site (BPS) sequence in introns and is critical for pre-mRNA splicing. In Arabidopsis (Arabidopsis thaliana), splicing factor1 (AtSF1) has been shown to retain the conserved function, but it is unexpected that null atsf1 mutants are viable. Here, we identified an allele of atsf1, named suppressor of thf1-4 (sot4), from suppressor screening for leaf variegation of thylakoid formation1 The sot4 mutant resulting from the G-to-R mutation at the highly conserved 198th amino acid residue within the functionally unknown domain exhibits leaf virescence associated with less accumulation of mature plastid ribosomal RNA, particularly under cold stress. Interestingly, the same point mutation in yeast Saccharomyces cerevisiae MUD synthetic-lethal 5p (SF1/Msl5p) also causes hypersensitivity to coldness and a low splicing activity for the introns with suboptimal BPS sequences. Transcriptomic profiling and reverse-transcription quantitative PCR analyses showed that expression of many genes were up- or downregulated in atsf1 via insufficient intron splicing. Our search for a BPS consensus from the retained introns in atsf1 transcriptomes, combined with RNA electrophoresis mobility shift assays, revealed that AtSF1 directly binds to the BPS consensus containing 5'-CU(U/A)AU-3'. Taken together, our data provide insight into a role for AtSF1 in regulating intron splicing efficiency, which helps plants acclimate to coldness.

Sevoflurane inhibits the migration, invasion and induces apoptosis by regulating the expression of WNT1 via miR-637 in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy. Sevoflurane has been reported to involve in the progression in several cancers. However, the molecular mechanism of sevoflurane in CRC progression remains unclear. Quantitative real-time PCR and western blot was used to detect the expression of miR-637 and WNT1. Cell migration, invasion and apoptosis were detected by transwell assay, flow cytometry or western blot, respectively. The interaction between WNT1 and miR-637 was confirmed by luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. We found sevoflurane could inhibit cell migration and invasion but induced apoptosis in CRC. Besides, the miR-637 level was decreased in CRC tissues and cells but could be rescued by sevoflurane. MiR-637 overexpression enhanced the anticancer functions of sevoflurane in CRC cells, while miR-637 inhibition showed opposite effects. WNT1 was confirmed to be a target of miR-637 and was inhibited by sevoflurane or miR-637. Importantly, knockdown of WNT1 reversed the carcinogenic effects mediated by miR-637 inhibitor in CRC cells treated with sevoflurane. Collectively, sevoflurane inhibited cell migration, invasion and induced apoptosis by regulating the miR-637/WNT1 axis in colorectal cancer, indicating a novel insight into the effective clinical implication for the anesthetic in CRC treatment.

The pentatricopeptide repeat protein EMB1270 interacts with CFM2 to splice specific group II introns in Arabidopsis chloroplasts.

Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes. Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat (PPR) protein, is required for chloroplast biogenesis in Arabidopsis thaliana. Knockout of EMB1270 led to embryo arrest, whereas a mild knockdown mutant of EMB1270 displayed a virescent phenotype. Almost no photosynthetic proteins accumulated in the albino emb1270 knockout mutant. By contrast, in the emb1270 knockdown mutant, the levels of ClpP1 and photosystem I (PSI) subunits were significantly reduced, whereas the levels of photosystem II (PSII) subunits were normal. Furthermore, the splicing efficiencies of the clpP1.2, ycf3.1, ndhA, and ndhB plastid introns were dramatically reduced in both emb1270 mutants. RNA immunoprecipitation revealed that EMB1270 associated with these introns in vivo. In an RNA electrophoretic mobility shift assay (REMSA), a truncated EMB1270 protein containing the 11 N-terminal PPR motifs bound to the predicted sequences of the clpP1.2, ycf3.1, and ndhA introns. In addition, EMB1270 specifically interacted with CRM Family Member 2 (CFM2). Given that CFM2 is known to be required for splicing the same plastid RNAs, our results suggest that EMB1270 associates with CFM2 to facilitate the splicing of specific group II introns in Arabidopsis.

[Identification of critical influencing factors in dropping process of Xuesaitong Dropping Pills].

With the dropping process of Xuesaitong Dropping Pills(XDP) as the study object, critical factors affecting the quality indicators of pill pass rate, average weight of drop pills and roundness were screened out, so as to deepen the understanding of the dropping process. The critical process units, critical quality attributes and potential critical process influencing factors of XDP were determined by risk analysis and prior knowledge, and then the critical influencing factors were screened out by Plackett-Burman design. First, according to the risk assessment, the critical technique of XDP preparation process was dropping, and then the critical quality attributes of dropping process were pill pass rate, average weight of drop pills and roundness. Then, according to fishbone diagram and failure mode and effects analysis(FMEA), potential critical influencing factors were determined as flow rate, matrix ratio, solid-liquid ratio, feed-liquid temperature, top temperature of condensate, bottom temperature of condensate and dropping distance. Finally, among these seven potential factors, the critical influencing factors were determined as material liquid ratio, dropping distance, top temperature of condensate, bottom temperature of condensate. This study revealed the potential of Plackett-Burman design in screening and understanding the influence of selected factors on XDP dropping process, which could provide a reference for studying the dropping process.

Oxycodone stimulates normal and malignant hematopoietic progenitors via opioid-receptor-independent-ß-catenin activation.

Oxycodone is a common type of opioid used for the treatment of moderate to severe pain. Besides its analgesic effects on neuron cells, the effects of oxycodone on other cell types are yet to be elucidated. We previously demonstrated that oxycodone displayed both pro- and anti-cancer effects on bulk cancer cells. This work further investigated the effects of oxycodone on normal and malignant hematopoietic stem cells. Using hematopoietic CD34+ cells isolated from normal bone marrow (NBM) or patients with acute myeloid leukemia (AML), we showed that oxycodone activates hematopoietic cells regardless of cell development stage and malignant status. Oxycodone dose-dependently increases colony formation and self-renewal capacity of NBM and AML stem/progenitor cells, and promotes proliferation of AML bulk cells. NBM stem/progenitor cells are more sensitive to oxycodone than AML counterparts. In addition, oxycodone alleviates chemotherapy drug-induced toxicity in AML stem/progenitor cells. Mechanism studies demonstrate that oxycodone acts on hematopoietic cells in an opioid-receptor-independent manner. Oxycodone did not affect epithelial growth factor receptor (EGFR) signaling neither but stimulated Wnt/ß-catenin signaling. Rescue studies via depleting ß-catenin using genetic and pharmacological approaches confirmed that ß-catenin was required for the activation of hematopoietic cells induced by oxycodone. Our work demonstrates 1) the protective role of oxycodone in malignant hematopoietic cells from chemotherapy; 2) stimulatory effects of oxycodone in normal hematopoietic stem cells; and 3) ability of oxycodone in Wnt signaling activation.

Anesthetic management of gigantic pheochromocytoma resection with inferior vena cava and right atrium tumor thrombosis: a case report.

BACKGROUND: This report describes one case of anesthetic management about surgical resection of a malignant phaeochromocytoma with tumor extension into vena cava and right atrium in a patient. Report for anesthetic management is limited in these patients under surgical resection until now. CASE PRESENTATION: In September 2015, a 24-year-old male presented to the department of cardiology with right flank pain and hypertensive urgency in our hospital. Contrast-enhanced CT abdomen and MRI abdomen revealed a mass phaeochromocytoma in right adrenal, which invaded the right inferior vena cava(IVC)wall along with IVC thrombus. Echocardiography shown no abnormal detection. Finally, this patient gave up the surgical resection of phaeochromocytoma and chose the expectant treatment. In April 2018, this patient once again presented to the emergence department in our hospital, he had experienced persistent cough and intermittent wheezing for 5 h. Contrast-enhanced CT and echocardiography shown existing IVC thrombus had extended into the right atrium. After the careful preoperative preparation, adrenalectomy with complete thrombus excision by inferior vena cava exploration and right atriotomy were performed successfully by a multidisciplinary team. After one month post-operation care, this patient healthily left our hospital. CONCLUSION: To the best of our knowledge, the occurrence of pheochromocytoma with IVC and right atrium thrombosis has not been reported in mainland China so far. This clinical case may supply a rare reference experience for surgical treatment and anesthetic management in the group of phaeochromocytoma patient with distance vascular extension.

Procoagulant Activity of Blood and Endothelial Cells via Phosphatidylserine Exposure and Microparticle Delivery in Patients with Diabetic Retinopathy.

BACKGROUND/AIMS: The mechanisms for thrombosis in diabetic retinopathy (DR) are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS) exposure on microparticles (MPs) and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA) in DR patients. METHODS: PS-positive MPs and cells from healthy controls (n = 20) and diabetic patients (n = 60) were analyzed by flow cytometry and confocal microscopy. Clotting time and purified coagulation complex assays were used to measure PCA. RESULTS: PS exposure on platelets and monocytes was higher in proliferative DR (PDR) patients than in non-PDR patients or controls. The highest levels of MPs (derived from platelets [30%], erythrocytes [13%], leukocytes [28%], and endothelial cells [10%]) were found in patients with PDR. In addition, PS exposure on blood cells and shed MPs in DR patients led to significantly increased FXa and FIIa generation, fibrin formation, and markedly shortened coagulation time. Moreover, lactadherin reduced 70% of PCA by blocking PS, while an anti-tissue factor antibody had a smaller effect. CONCLUSION: Our results confirmed that PCA in DR patients may be partly ascribed to PS exposure and MP release from blood and endothelial cells. Lactadherin may act as an efficient anticoagulant factor in this process.

Neonatal ICU System Safety: A Pilot Test for Medication Error by Using Fuzzy Grey Relational Analysis.

This study analyzed risk factors for medication/near-miss errors in the neonatal intensive care unit by using Grey Relational Analysis based on self-incident reports from staff nurses. The ASSESS-ERR Medication System Worksheet was used. A total of 156 medication/near-miss errors were found across 5 stages of the medication use process. The order prescribing stage had the most errors. The highest systemic risk factors were critical drug information missing; environmental, staffing, and workflow problems; and lack of staff education.

Identification of miRNAs and their targets through high-throughput sequencing and degradome analysis in male and female Asparagus officinalis.

BACKGROUND: MicroRNAs (miRNAs), a class of non-coding small RNAs (sRNAs), regulate various biological processes. Although miRNAs have been identified and characterized in several plant species, miRNAs in Asparagus officinalis have not been reported. As a dioecious plant with homomorphic sex chromosomes, asparagus is regarded as an important model system for studying mechanisms of plant sex determination. RESULTS: Two independent sRNA libraries from male and female asparagus plants were sequenced with Illumina sequencing, thereby generating 4.13 and 5.88 million final clean reads, respectively. Both libraries predominantly contained 24-nt sRNAs, followed by 21-nt sRNAs. Further analysis identified 154 conserved miRNAs, which belong to 26 families, and 39 novel miRNA candidates seemed to be specific to asparagus. Comparative profiling revealed that 63 miRNAs exhibited significant differential expression between male and female plants, which was confirmed by real-time quantitative PCR analysis. Among them, 37 miRNAs were significantly up-regulated in the female library, whereas the others were preferentially expressed in the male library. Furthermore, 40 target mRNAs representing 44 conserved and seven novel miRNAs were identified in asparagus through high-throughput degradome sequencing. Functional annotation showed that these target mRNAs were involved in a wide range of developmental and metabolic processes. CONCLUSIONS: We identified a large set of conserved and specific miRNAs and compared their expression levels between male and female asparagus plants. Several asparagus miRNAs, which belong to the miR159, miR167, and miR172 families involved in reproductive organ development, were differentially expressed between male and female plants, as well as during flower development. Consistently, several predicted targets of asparagus miRNAs were associated with floral organ development. These findings suggest the potential roles of miRNAs in sex determination and reproductive developmental processes in asparagus.

External Magnetic Field-Induced Targeted Delivery of Highly Sensitive Iron Oxide Nanocubes for MRI of Myocardial Infarction.

Magnetic field responsive nanocubes (MFRFs) are synthesized as nanoplatforms for external magnetic field-induced selective targeting of macrophages in the infarcted tissue and magnetic resonance imaging (MRI) monitoring. MFRFs have uniform size, favorable colloidal stability, and high magnetic properties. Under the influence of external magnetic field, MFRFs perform qualitative and quantitative MRI of myocardial infarction.

[Effect of CCM3 gene defect on lead-induced cell genotoxicity in mouse embryonic fibroblasts].

OBJECTIVE: To investigate the effect of CCM3 gene defection on lead induced cell genotoxicity in mouse embryonic fibroblasts. METHODS: C57 female mice were mated with CCM3 gene heterozygous male mice. E13.5 embryos were taken to isolate primary mouse embryonic fibroblasts. After genotyping, wild type and heterozygous cells were treated with different doses of lead acetate. Cell viability, genotoxicity and protein expression were detected by MTS assay, CB micronucleus method and Western blot, respectively. RESULTS: Mouse embryonic fibroblasts with lead acetate treatment for 24 h, wild-type cells 100.00 µmol/L lead acetate-treated group (69.16±1.36) and the control group (100.00±2.33) compared to cells decreased by 30%, CCM3 heterozygous type cell 100.00 µmol/L lead acetate-treated group (87.16±5.50) and the control group (100.00±2.06) compared to cells decreased by 13%, the difference was statistically significant (F values were 98.59, 82.63, P<0.001). Lead acetate treatment after 48 h, wild-type cells 100.00 µmol/L lead acetate-treated group (51.99±5.62) and the control group (100.00±3.11) compared to cells decreased by 50%, heterozygous type cells 100.00 µmol/L lead acetate treatment group (66.33±4.06) and the control group (100.00±5.72) compared to cells decreased by 35%, the differences were statistically significant (F values were 82.63, 36.86, P < 0.001). The results of CBMN test showed that with increased dose, micronucleus cell rate of two genotypes showed an increasing trend, in the wild-type cells, the micronucleus cell rate (/1 000) for the control group, 29.6±2.2, 6.25 µmol/L dose group 47.3±6.6, 25 µmol/L dose group 55.5±9.1, 100.00 µmol/L dose group 66.8±3.5; heterozygous cells micronucleus cell rate (/1 000) for the control group, 35.3±5.6, 6.25 µmol/L dose of 50.0±8.3, 25.00 µmol/L dose group 57.0±8.5, 100.00 µmol/L dose group 58.8±2.1. Micronucleus cell rates (/1 000) were significant differences, in 100.00 µmol/L dose groups of two genotypes. Western blot results showed that wild-type cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.70±0.03) was 1.32 times higher than the control group (0.53±0.07), heterozygous cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.48±0.02) was 1.77 times higher than control group that of 0.27±0.04, there was statistically significant difference (F values were 14.77, 25.74, P < 0.001); wild-type cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.69±0.03) was 1.06 times higher than the control group (0.65±0.07), heterozygous cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.99±0.04) was 1.55 times higher than the control group CCM3 expression levels (0.64±0.06), there was statistically significant difference (wild-type cells: F = 7.08, P = 0.012, heterozygous type cell: F = 13.49, P = 0.002). CONCLUSION: CCM3 gene may play a role in lead-induced genetic toxicity of mouse embryonic fibroblasts, CCM3 gene-lead interactions effects on mouse embryonic fibroblasts cell toxicity.