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Background: Caudal epidural block (CEB) may be beneficial in anorectal surgery because its use may extend postoperative analgesia. This dose-finding study aimed to estimate the minimum effective anesthetic concentrations for 95% patients(MEC95) of 20 ml or 25 ml of ropivacaine in with CEB. Patients and methods: In this double-blind, prospective study, the concentration of ropivacaine administered in 20 ml and 25 ml for ultrasound-guided CEB were determined using the sample up-and-down sequential allocation study design of binary response variables. The first participant was given 0.5% ropivacaine. Depending on whether a block was successful or unsuccessful, the concentration of local anesthesia was decreased or increased by 0.025% in the next patient. Every five minutes for 30 min, the sensory blockade using a pin-prick sensation at S3 dermatome compared to at T6 dermatome were evaluated every 5 min within 30 min. An effective CEB was defined as a a reduction of sensation at S3 dermatome and the existence of flaccid anal sphincter. Anesthesia was considered successful if the surgeon could perform the surgery without additional anesthesia. We determined the MEC50 using the Dixon and Massey up-and-down method and estimated the MEC95 using probit regression. Results: The concentration of ropivacaine administered in 20 ml for CEB ranged from 0.2% to 0.5%. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC 50 of ropivacaine for anorectal surgical anesthesia were 0.27% (95% CI, 0.24 to 0.31) and 0.36%(95% CI, 0.32 to 0.61). The concentration of ropivacaine administered in 25 ml for CEB ranged from 0.175 to 0.5. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC95 for CEB were 0.24% (95% CI, 0.19 to 0.27) and 0.32% (95% CI, 0.28 to 0.54). Conclusion: With ultrasound-guided CEB, the MEC95 of 0.36% ropivacaine at 20 ml and 0.32% ropivacaine at 25 ml provide adequate surgical anesthesia/analgesia 95% of patients undergoing anorectoal surgery. Trial registration: Clinicaltrails.gov: Retrospectively registered (ChiCTR2100042954; Registration date:1/2, 2021). [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy of risk management in the nursing of critically ill patients on continuous renal replacement therapy (CRRT). Methods. In this retrospective study, 80 critically ill patients on continuous renal replacement therapy in our hospital from February 2020 to February 2021 were recruited. They were randomly assigned to receive either the risk management treatment (risk management group) or the conventional management treatment (conventional management group) via the random number table method. Outcome measurements included the occurrence of adverse events, complications, psychological status, quality of life, treatment compliance, duration of CRRT, and nursing satisfaction. Results. Risk management treatment was associated with lower incidence of adverse events compared to conventional management treatment (P value < 0.05). The risk management group also resulted in a lower incidence of complications compared to the conventional management group (P value < 0.05). Patients who received risk management treatments demonstrated a significantly lower anxiety/depression level and a higher World Health Organization Quality of Life Brief Version (WHOQOL-BREF) (P value < 0.05). The risk management group resulted in more cases with high compliance and fewer cases with moderate and poor compliance (P < 0.05). Risk management was associated with more cases with a CRRT duration less than 36 hours and 36–48 hours and fewer cases with a duration longer than 48 h (X2 = 2.999, P value < 0.05). Patients who were given a risk management treatment had a higher nursing satisfaction compared to conventional management treatment (X2 = 4.501, P value < 0.05). Conclusion. Risk management treatment in caring of critically ill patients on CRRT shows better efficacy than conventional management treatments. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly used to treat patients with biliary/pancreatic duct obstruction or stricture outside the operating room. Effective and safe sedation techniques are needed because of painful stimuli and the long duration of the ERCP procedure.Nalbuphine has been shown to cause less respiratory depression during sedation than similar cases without nalbuphine. This study compared the effects of propofol-nalbuphine (PN) and propofol-fentanyl (PF) sedation in patients undergoing ERCP. Methods: Four hundred patients scheduled for ERCP procedures were divided into two groups: the PF group (receiving PF sedation,n = 199) and the PN group (receiving PN sedation,n = 201). Vital signs, adverse events during surgery, patient movement scores, pain scores, and adverse events one day post-ERCP were recorded. Results: Stable haemodynamics were observed in both groups.Compared to the PF group, the PN group showed significantly decreased respiratory depression (P < 0.0001) and surgical interruptions (P = 0.048).Nalbuphine decreased patient movement by reducing pain from ERCP. Conclusion: Nalbuphine, instead of fentanyl, precipitated less respiratory depression while permitting adequate/equivalent sedation for ERCP and therefore provides more efficient and safer sedation. Trial registration ChiCTR, ChiCTR1800016018, Registered 7 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27085 [ABSTRACT FROM AUTHOR]

Bcl2-associated athanogene 4 (BAG4) has been found to be aberrantly expressed in several types of human cancers. However, little is known about its expression, role, and clinical significance in gastric cancer (GC). In this study, we aimed to address these issues and to explore the underlying mechanisms. The expression level of BAG4, measured by immunohistochemistry, was significantly higher in GC tissues than in paired normal tissues. Elevated BAG4 expression was positively correlated with T stage, lymph node metastasis, and tumor size of GC and was associated with unfavorable outcomes of the patients. The overexpression of BAG4 promoted the in vitro invasion and in vivo metastasis of GC cells, and opposite results were observed after silencing of BAG4. Silencing of BAG4 significantly reduced the phosphorylation of PI3K, AKT, and p65, whereas overexpression of BAG4 markedly enhanced the phosphorylation of these molecules. At the same time, manipulating BAG4 expression resulted in the corresponding changes in p65 nuclear translocation and ZEB1 expression. Luciferase reporter and chromatin immunoprecipitation assays verified that p65 binds to the promoter of ZEB1 to upregulate its transcription. Our results demonstrate that BAG4 plays an oncogenic role in the invasion and metastasis of GC cells by activating the PI3K/AKT/NF-κB/ZEB1 axis to induce epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)?Summary Answer: Pregnant women with hereditary thrombophilia have an increased risk of RPL, especially for pregnant women with the G1691A mutation of the factor V Leiden (FVL) gene, the G20210A mutation of the prothrombin gene (PGM), and deficiency of protein S (PS).What Is Known Already: Prior studies have suggested that pregnant women with hereditary thrombophilia have a higher risk of RPL, however, the results are inconsistent; furthermore, a complete overview is missing. This lack of information is an obstacle to the risk assessment of RPL in pregnant women with hereditary thrombophilia. A comprehensive meta-analysis on the relation between hereditary thrombophilia and the risk of RPL is needed.Study Design, Size, Duration: A systematic review and meta-analysis was performed using observational studies published in English before 1 April 2020 to evaluate the relation between hereditary thrombophilia and risk of RPL.Participants/materials, Setting, Methods: Relevant studies were identified from PubMed, Web of Science, and EMBASE searches and complemented with perusal of bibliographies of retrieved articles. The exposure of interest was hereditary thrombophilia, including FVL mutation, PGM, deficiency of antithrombin (AT), deficiency of protein C (PC), and deficiency of PS. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were carried out to explore possible sources of heterogeneity and assess the robustness of the results.Main Results and the Role Of Chance: A total of 89 studies involving 30 254 individuals were included. Results showed that women with FVL mutation (odds ratio (OR): 2.44, 95% CI: 1.96-3.03), PGM (OR: 2.08, 95% CI: 1.61-2.68), or deficiency of PS (OR: 3.45, 95% CI: 1.15-10.35) had higher risks of developing RPL. Compared with the reference group, there was no observed relation between a deficiency in AT or PC and RPL (all P > 0.05). Heterogeneity in the risk estimates of RPL was partially explained by geographic region, definitions of RPL, types of RPL, and controlled confounders. Sensitivity analyses validated the robustness of the findings.Limitations, Reasons For Caution: Only 39 of the included studies controlled for one or more confounders, and the heterogeneity across all included studies was high. Based on the data available, we cannot determine whether this association is confounded by other potential risk factors of RPL.Wider Implications Of the Findings: This systematic review and meta-analysis show a possible association between hereditary thrombophilia and an increased risk of RPL, suggesting that testing for hereditary thrombophilia should be considered in individuals with RPL.Study Funding/competing Interest(s): The study was funded by the Hunan Provincial Key Research and Development Program (Grant number: 2018SK2062) and National Natural Science Foundation Program (Grant number: 81973137). There are no conflicts of interest.Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs).Methods: All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs.Results: A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52-2.28, P < 0.01). For disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS), lower miR-34a expression was related to worse DFS/PFS/RFS with a pooled HR of 1.86 (95% CI: 1.31-2.63, P  <  0.01). A significant relation of differentiation/TNM stage/lymphatic metastasis and the expression level of miR-34a was identified.Conclusion: This meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs. [ABSTRACT FROM AUTHOR]

With the aging of the population and the extension of life expectancy, osteoporosis is becoming a global epidemic. Although there are several drugs used to treat osteoporosis in clinical practice, such as parathyroid hormone or bisphosphonates, they all have some serious side effects. Therefore, a safer drug is called for osteoporosis, especially for the prevention in the early stage of the disease, not only the treatment in the later stage. Panax notoginseng saponin (PNS), a traditional Chinese herb, has been used as anti-ischemic drug due to its function on improving vascular circulation. In order to verify whether Panax notoginseng saponins (PNS) could be used to prevent osteoporosis, ovariectomy (OVX) was induced in female C57BL/C6J mice, followed by orally administration with 40 mg/kg/d, 80 mg/kg/d, and 160 mg/kg/d of three different dosages of PNS for 9 weeks. Serum biochemical analysis, micro-CT, histological evaluation, and immunostaining of markers of osteogenesis and angiogenesis were performed in the sham, osteoporotic (OVX), and treatment (OVX+PNS) groups. Micro-CT and histological evaluation showed that compared to sham group, the bone mass of OVX group reduced significantly, while it was significantly restored in the moderate-dose PNS (40 mg/kg and 80 mg/kg) treatment groups. The expression of CD31 and osteocalcin (OCN) in the bone tissue of treatment group also increased, suggesting that PNS activated osteogenesis and angiogenesis, which subsequently increased the bone mass. These results confirmed the potential function of PNS on the prevention of osteoporosis. However, in the high dose of PNS (160 mg/kg) group, the antiosteoportic effect had been eliminated, which also suggested the importance of proper dose of PNS for the prevention and treatment of osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

The hub-and-spoke semantic representation theory posits that semantic knowledge is processed in a neural network, which contains an amodal hub, the sensorimotor modality-specific regions, and the connections between them. The exact neural basis of the hub, regions and connectivity remains unclear. Semantic dementia could be an ideal lesion model to construct the semantic network as this disease presents both amodal and modality-specific semantic processing (e.g. colour) deficits. The goal of the present study was to identify, using an unbiased data-driven approach, the semantic hub and its general and modality-specific semantic white matter connections by investigating the relationship between the lesion degree of the network and the severity of semantic deficits in 33 patients with semantic dementia. Data of diffusion-weighted imaging and behavioural performance in processing knowledge of general semantic and six sensorimotor modalities (i.e. object form, colour, motion, sound, manipulation and function) were collected from each subject. Specifically, to identify the semantic hub, we mapped the white matter nodal degree value (a graph theoretical index) of the 90 regions in the automated anatomical labelling atlas with the general semantic abilities of the patients. Of the regions, only the left fusiform gyrus was identified as the hub because its structural connectivity strength (i.e. nodal degree value) could significantly predict the general semantic processing of the patients. To identify the general and modality-specific semantic connections of the semantic hub, we separately correlated the white matter integrity values of each tract connected with the left fusiform gyrus, with the performance for general semantic processing and each of six semantic modality processing. The results showed that the hub region worked in concert with nine other regions in the semantic memory network for general semantic processing. Moreover, the connection between the hub and the left calcarine was associated with colour-specific semantic processing. The observed effects could not be accounted for by potential confounding variables (e.g. total grey matter volume, regional grey matter volume and performance on non-semantic control tasks). Our findings refine the neuroanatomical structure of the semantic network and underline the critical role of the left fusiform gyrus and its connectivity in the network. [ABSTRACT FROM AUTHOR]

Background: Vancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.Objectives: To determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.Methods: Fifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT-PCR.Results: Twenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.Conclusions: This study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure. [ABSTRACT FROM AUTHOR]

Purpose: The interferon regulatory factor 2 (IRF-2) acted as a tumor suppressor. We inspected IRF-2 as a predictor of prognosis in gastric cancer (GC) patients and tried to find out the potential molecular mechanism.Methods: In this study, the association between IRF-2 expression and clinical or prognosis significance was investigated in 86 pairs of tumor and the adjacent normal gastric tissues from GC patients. After establishing the stable cell lines, the Transwell assays were deduced to evaluate the malignancy of tumor. Then, microarray assay was carried out and the GO/KEGG pathway analyses were conducted to identify IRF-2's target gene. The relationship between IRF-2 and matrix metalloproteinases 1 (MMP-1) was also investigated by the immunohistochemistry in 15 pairs of tumor and adjacent normal gastric tissues.Results: We found that IRF-2 expression level in GC was significantly correlated with the prognosis of the patients. Transwell assays suggested an impaired ability of invasion and migration in IRF-2-overexpressed GC cells and a progressive malignant phenotype in IRF-2-knockdown GC cells. Ninety differentially expressed genes were found between IRF-2-overexpressed GC cells and its normal control sets by microarray. We demonstrated that MMP-1 was canonical in the network of differentially expressed genes by GO and KEGG pathway analysis and its expression level was markedly decreased in IRF-2-overexpressed cells of MKN-45 and increased in IRF-2-knockdown cells of SGC-7901. The expression of MMP-1 was inversely correlated with IRF-2 in GAC TMA specimens.Conclusion: IRF-2 may inhibit GC progression by down-regulating MMP-1 level. [ABSTRACT FROM AUTHOR]

Background: The relationship between an increasing elderly population and wide-ranging neurological conditions has led to heightened rates of cognitive function impairment. Some researchers have found that health literacy risk may be associated with cognitive impairment in older adults. Objectives: The purpose of this study was to delineate the difference in health literacy risk between older adults with mild cognitive impairment and those with normal cognitive function. Methods: We conducted a survey study to explore the health literacy risk in older adults with and without mild cognitive impairment. Data were collected from 412 subjects between 60 and 91 years of age (260 without and 152 with mild cognitive impairment) between June and December 2016 in China. Cognitive function was measured using the Mini-Mental Status Examination, Montreal Cognitive Assessment, Global Deterioration Scale, Activities of Daily Living, and Hamilton Depression Rating Scale. Health literacy was measured using the Chinese Citizen Health Literacy Questionnaire. Results: The scores of total health literacy and its three dimensions (basic health knowledge and mind, basic skills, and health lifestyle and behavior) were lower in those with mild cognitive impairment. Older adults with normal cognitive function had adequate or marginal health literacy levels, whereas those with mild cognitive impairment had marginal or inadequate health literacy levels. Using multiple logistic regression analysis, we found that health literacy risk, education level, age, marital status, and body mass index were independent risk factors for mild cognitive impairment. Discussion: These results suggest that low health literacy may be a predictor of mild cognitive impairment. Screening for lower health literacy risk should be included in multidimensional geriatric evaluation. [ABSTRACT FROM AUTHOR]

Sorghum comprises 31 species that exhibit considerable morphological and ecological diversity. The phylogenetic relationships among Sorghum species still remain unresolved due to lower information on the traditional DNA markers, which provides a limited resolution for identifying Sorghum species. In this study, we sequenced the complete chloroplast genomes of Sorghum sudanense and S. propinquum and analyzed the published chloroplast genomes of S. bicolor and S. timorense to retrieve valuable chloroplast molecular resources for Sorghum. The chloroplast genomes ranged in length from 140,629 to 140,755 bp, and their gene contents, gene orders, and GC contents were similar to those for other Poaceae species but were slightly different in the number of SSRs. Comparative analyses among the four chloroplast genomes revealed 651 variable sites, 137 indels, and nine small inversions. Four highly divergent DNA regions (rps16-trnQ, trnG-trnM, rbcL-psaI, and rps15-ndhF), which were suitable for phylogenetic and species identification, were detected in the Sorghum chloroplast genomes. A phylogenetic analysis strongly supported that Sorghum is a monophyletic group in the tribe Andropogoneae. Overall, the genomic resources in this study could provide potential molecular markers for phylogeny and species identification in Sorghum. [ABSTRACT FROM AUTHOR]

Objective: To identify whether whole-tumour histogram analysis of pharmacokinetic parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could predict T-stage and regional lymph node metastasis (LNM) of resectable oesophageal squamous cell carcinoma (SCC).Materials and Methods: Forty-two consecutive patients with confirmed oesophageal SCC underwent thoracic DCE-MRI. Histogram metrics (median, mean, standard deviation [SD], skewness, kurtosis and entropy) of whole-tumour pharmacokinetic parameters including endothelial transfer constant (Ktrans), reflux rate (Kep) and fractional extravascular extracellular space volume (Ve) were generated by the Omni-Kinetics software. Histogram datasets were interpreted using the Mann-Whitney U test and receiver operating characteristic (ROC) statistical analyses.Results: The Mann-Whitney U tests revealed that the median, mean and SD of Ktrans, the SD and entropy of Kep, and the median, mean and entropy of Ve of T1-2 stage oesophageal SCC were lower when compared with T3 stage (all Ps < 0.05); and the ROC analysis showed that the entropy of Ve could reliably distinguish T1-2 stage from T3 stage with an area under ROC (AUC) of 0.773. The Mann-Whitney U tests illustrated that the entropy of Ktrans, and the median, mean, SD and entropy of Kep were higher while the skewness of Kep was lower in tumours with LNM than without LNM (all Ps < 0.05); and the ROC analysis demonstrated that the SD of Kep could best identify tumours with LNM with an AUC of 0.702.Conclusion: Whole-tumour histogram analysis of pharmacokinetic parameters of oesophageal SCC on DCE-MRI could be used to predict T-stage and regional LNM. [ABSTRACT FROM AUTHOR]

Although hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) cause a sever health problem worldwide, the underlying mechanisms are still elusive. This study aimed to investigate the responses of different cell types isolated from HBV transgenic mice. A cross-sectional set of hepatocytes and oval cells were obtained from HBV transgenic and control mice. Flow cytometry, immunohistochemistry and microarray were applied to investigate the cell biology of the hepatocytes and oval cells. Our results showed that HBV induced the proliferation of both cell oval cells and hepatocytes, and induced cell death of HBV hepatocytes while had minimal effects on oval cells. Further molecular and pathways analysis identified some genes and signaling pathways may be responsible for the different responses between oval cells and hepatocytes. In addition, analyses of selectively ten genes by IHC staining in human samples were consistent with microarray data. In summary, HBV transgenic mice is a useful model for studying the biological behaviors of oval cells affected by HBV and HBV-cirrhosis. Also, our results help better understand the mechanisms of HBV induced cirrhosis, and provide novel progenitor markers or prognostic/therapeutic markers. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the efficacy and safety of combined vitrectomy with tumor resection in the treatment of retinal vasoproliferative tumors (RVPT). Methods. Retrospective study. RVPT patients who underwent vitreous surgery at the Eye Hospital of Wenzhou Medical University from January 2011 to July 2017 were included. The main outcomes included treatment type, tumor activity, and best-corrected visual acuity (BCVA). Results. Altogether, 16 patients with 17 eyes were enrolled with follow-up of no less than 6 months. Eight eyes were in the resection treatment group (Group R) and 9 eyes were in the conservative treatment group (Group C). Female (69%) were more common. The mean age was 50 (49.72 ± 12.92) years. Fifteen patients got unilateral onset and only one patient suffered bilaterally. The common symptoms were decreased visual acuity, floaters, and visual distortion. The preoperative BCVA ranged from hand movement to 20/20, with an average of 0.82 ± 0.75 LogMAR. Patients were all not high myopia, with a mean axial length of 23.27 ± 0.27 mm (21.61 mm to 24.67 mm). Of the retinal diseases, the epiretinal membrane was the most common, followed by vitreous hemorrhage, uveitis, subretinal fluid, and so on. Compared with the baseline BCVA, it improved more at postoperative 6 months and the last visit in Group R than in Group C (P=0.006 and P=0.033). The BCVA-improved 0.2 LogMAR or above in 6 months was 2 eyes in Group C and 7 eyes in Group R. All tumors in Group R were completely resected, whereas three in Group C (33.3%) had definite activity (P=0.008). In all samples, tumors were located on the inner side of the retina and had small vessel wall thickening and hyaline degeneration. The degree of astrocyte proliferation varies widely among different tumors. Conclusions. RVPT was more likely to occur in nonhigh myopia patients. Epiretinal membrane and vitreous hemorrhage were the main causes for vitreous surgery in RVPT patients. Compared with conservative treatment, surgical resection of the tumor is more beneficial to patients on visual acuity recovery and preventing tumor relapse. It is a safe and effective way to treat RVPT. [ABSTRACT FROM AUTHOR]

This paper mainly does research and analysis on anti-dispersive performance and anti-nonlinear performance for intensity modulation formats such as NRZ, RZ, CS-RZ, DRZ, MD-RZ in 40 Gbps high-speed single-channel optical transmission system. It compares the five pattern modulation formats in dispersion tolerance, nonlinear tolerance, and advantages and disadvantages in transmission distance. Anti-nonlinear effect ability of CSRZ and RZ are stronger than that of NRZ code; in the single-channel transmission system, DRZ and improved modulation format MDRZ have better resistance for anti-nonlinear performance, so they are suitable for long-distance transmission. RZ has the minimum dispersion tolerance. NRZ has higher spectrum efficiency than RZ, and thus have a better dispersion tolerance. CSRZ code has higher spectral efficiency, higher dispersion tolerance and nonlinear tolerance than RZ code, making it more suitable for long distance transmission. [ABSTRACT FROM AUTHOR]

To compare the proliferation and osteogenic differentiation of osteoblasts between newborn rats (1d group) and two-week-old rats (14d group) and to clarify the mechanism underlying these effects. The endogenous expression of osteogenic marker genes was detected by qPCR, including ALP, OCN, Col1a1, and Runx2. The osteoblasts proliferation was evaluated by EdU assay and Western Blotting [PCNA and Cyclin D1]. ALP activities in osteoblasts were detected using a PNPP kit, ALP staining and qPCR. Mineralized nodule formation and intracellular calcium levels were assessed by Alizarin Red staining and calcium colorimetric assay respectively while OCN, Col1a1 and Runx2 levels in osteoblasts were analyzed by immunostaining. Osteogenesis-associated pathways including Wnt/β-Catenin, Akt/PPAR and Smad were analyzed via Western Blotting. Endogenous ALP, OCN, Col1a1, and Runx2 expression levels were significantly higher in osteoblasts from 14d group than those from 1d group. After treatment with osteogenic induction medium, osteoblast proliferation, ALP activity, mineralized nodule formation, and intracellular calcium levels were markedly increased in osteoblasts from 1d group, with similar results also being observed for the expression of OCN, Col1a1, and Runx2. Wnt3a, β-catenin, p-Akt, p-Smad1/5/8, and p-Smad5 protein levels were also higher in osteoblasts from 1d group relative to those from 14d group, while the expression of PPARγ was lower. The superior osteogenic differentiation capacity in osteoblasts was associated with the higher activation levels of Wnt/β-Catenin, Akt/PPAR and Smad signaling pathways, and the enhanced proliferative activity in osteoblasts from 1d group. [ABSTRACT FROM AUTHOR]

Abstract: We investigate gender differences and menstrual cycle effects in first-price and second-price sealed-bid auctions with independent private values in a laboratory setting. We find that women bid significantly higher and earn significantly less than men do in the first-price auction, while we find no evidence of a gender difference in bidding or earnings in the second-price auction. Focusing on the first-price auction, we find that, while the gender gap in bidding and earnings persists over the entire course of the menstrual cycle, bidding of contraceptive pill users follows a sine-like pattern throughout the menstrual cycle, with higher than average bidding in the follicular phase and lower than average bidding in the luteal phase. In comparison, pill non-users have a flat bidding profile throughout the cycle. [Copyright &y& Elsevier]

Abstract: We study the spiral wave in an unbounded excitable medium from the wave front interaction model derived by Zykov in 2009. This model consists of two systems of ordinary differential equations that describe the wave front and the wave back, respectively. First, we derive some properties of the back by the shooting argument and the comparison principle. Next we show the global existence of the solution of the back. Then we study its asymptotic behavior at infinity. Finally, we prove the uniqueness of the solution. [Copyright &y& Elsevier]

Abstract: The health risks of heavy metals to local residents via consumption of food crops cultivated in the reclaimed soils of the Pearl River Estuary (PRE) were investigated. Soils in the river estuary were found to be significantly contaminated with heavy metals, with mean concentrations of Cd, 0.858; Pb, 48.7; Cr, 112.4; Cu, 57.3; Zn, 210.8; and Ni, 40.0mgkg−1. Rice and root vegetables were also polluted severely. The percentages of rice samples that exceeded the maximum allowable levels were 94.3, 91.4, 88.6, and 17.1% for Pb, Cr, Cd, and Cu, respectively. The accumulation factor (AF) of Cd was the highest compared with the other five metals. The total values of the health risk index (HRI) of Cd and Cu from all the crops were 3.683 and 1.665, respectively. They exceeded considerably the allowable level 1.0. The HRI values of all the metals were mostly from rice consumption. These results suggest that more attention should be directed to the potential health risks of heavy metals to residents living in the tidal flat reclaimed areas. [Copyright &y& Elsevier]

As the output power of photovoltaic (PV) array changes with the change of external environment and load, the maximum power point tracking (MPPT) technology is needed to bring the efficiency of PV device into full play. In this paper, the chaos search theory is first applied on the MPPT technology of PV system; the chaos search algorithm based on dual carrier increases the adequacy of chaos search and overcomes the blindness of traditional chaos search, thus improves the search efficiency and solves the problem of multiple MPP under partially shadowing conditions. Comparative tests show that the proposed method can track the step response quickly and accurately; at the same time get better optimization result. Simulation and experimental results showed the effectiveness and good performance of the proposed method. [ABSTRACT FROM AUTHOR]

Abstract: Sulfonated polybenzothiazoles with benzimidazole moieties were successfully prepared by polycondensation. For comparison purpose, sulfonated polybenzothiazoles were also synthesized. Rigid-rod sulfonated polybenzothiazoles generally show poor solubility in organic solvents, whereas these sulfonated polybenzothiazoles with high sulfonation degree are soluble, but the membranes cast from them swell excessively in water. Thus they could not be used as proton exchange membranes (PEMs). The comparison study demonstrates that the incorporation of benzimidazole moieties to sulfonated polybenzothiazoles greatly enhances the solubility of products. The resulting copolymers thus could be cast into the membranes as PEMs. The benzimidazole moieties in the resulting polymers improve thermal properties, dimensional stability, tensile strength, Young''s modulus, and oxidative stability, but they decrease proton conductivity and the elongation at break, due to the ionic cross-linking and hydrogen bonds. Even so, sulfonated polybenzothiazoles with appropriate content of benzimidazole moieties (10mol%) could still display a high proton conductivity of 0.094Scm−1 at 80°C and an elongation at break of 26.1%. These ionomers exhibited excellent overall properties such as excellent mechanical properties, high thermal and oxidative stability, low swelling, and high proton conductivity, thus they might be a candidate for proton exchange membranes. [Copyright &y& Elsevier]

Background: Plasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients. Methods: We analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders. Results: A total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00–4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68–1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008). Conclusions: In HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions. Trial registration: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020. [ABSTRACT FROM AUTHOR]

High-throughput detection of nascent RNA is critical for studies of transcription and much more challenging than that of mRNA. Recently, several massively parallel nascent RNA sequencing methods were established in eukaryotic cells. Here, we systematically compared 3 classes of methods on the same pure or crude nuclei preparations: GRO-seq for sequence nuclear run-on RNAs, pNET-seq for sequence RNA polymerase II-associated RNAs, and CB RNA-seq for sequence chromatin-bound (CB) RNAs in Arabidopsis (Arabidopsis thaliana). To improve the resolution of CB RNAs, 3′CB RNA-seq was established to sequence the 3′ ends of CB RNAs. In addition, we modified pNET-seq to establish the Chromatin Native Elongation Transcript sequencing (ChrNET) method using chromatin as the starting material for RNA immunoprecipitation. Reproducibility, sensitivity and accuracy in detecting nascent transcripts, experimental procedures, and costs were analyzed, which revealed the strengths and weaknesses of each method. We found that pNET and GRO methods best detected active RNA polymerase II. CB RNA-seq is a simple and cost-effective alternative for nascent RNA studies, due to its high correlation with pNET-seq and GRO-seq. Compared with pNET, ChrNET has higher specificity for nascent RNA capture and lower sequencing cost. 3′CB is sensitive to transcription-coupled splicing. Using these methods, we identified 1,404 unknown transcripts, 4,482 unannotated splicing events, and 60 potential recursive splicing events. This comprehensive comparison of different nascent/chromatin RNA sequencing methods highlights the strengths of each method and serves as a guide for researchers aiming to select a method that best meets their study goals. The strengths and weaknesses of 7 nascent RNA sequencing methods were experimentally and systematically compared in Arabidopsis. [ABSTRACT FROM AUTHOR]

Simple Summary: A considerable number of patients with colorectal cancer (CRC) do not have elevated serum carcinoembryonic antigen (CEA) levels before undergoing radical surgery for colorectal cancer, but they may still have a poor prognosis. It is imperative to find sensitive and dependable prognostic markers to quickly identify high-risk populations who are susceptible to adverse outcomes in order to offer timely interventions to improve prognosis. In this real-world study of more than 1000 samples, a nomogram based on serum tumor markers and other clinicopathological features was used to accurately forecast the 3-year and 5-year overall survival rates of stage I–III CRC patients after radical resection with normal preoperative CEA, and its predictive power and clinical applicability markedly exceed those of the AJCC 8th TNM stage. In addition, we found the potential prognostic values of carbohydrate antigen 125 (CA125) and carbohydrate antigen 242 (CA242) as supplementary tumor markers in CRC patients who have normal preoperative CEA. We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA. [ABSTRACT FROM AUTHOR]

Background: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer's disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia.Objective: To unravel mutual and divergent functional alterations in Alzheimer's disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer's disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17).Methods: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis.Results: Apart from differing connections between Alzheimer's disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes.Conclusion: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain's functional disconnectivity in Alzheimer's disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures. [ABSTRACT FROM AUTHOR]

microRNA (miRNA) play important roles in drug addiction and act as a post-transcriptional regulator of gene expression. We previously reported extensive downregulation of miRNAs in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice. However, the regulatory mechanism of this METH-induced downregulation of miRNAs has yet to be elucidated. Thus, we examined METH-induced changes in the expression of miRNAs and their precursors, as well as the expression levels of mRNA and the proteins involved in miRNA biogenesis such as Dicer1 and Ago2, in the nucleus accumbens of METH-induced locomotor sensitized mice. miRNAs and Ago2 were significantly downregulated, while the expression of miRNA precursors remained unchanged or upregulated, which suggests that the downregulation of miRNAs was likely due to a reduction in Ago2-mediated splicing but unlikely to be regulated at the transcription level. Interestingly, the expression level of Dicer1, which is a potential target of METH-induced decreased miRNAs, such as miR-124, miR-212 and miR-29b, was significantly increased. In conclusion, this study indicates that miRNA biogenesis (such as Ago2 and Dicer1) and their miRNA products may have a role in the development of METH addiction. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the potential of various metrics derived from mono-exponential model (MEM), bi-exponential model (BEM) and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in diagnosing and differentiating the pathological subtypes and grades of uterine cervical carcinoma.Methods: 71 newly diagnosed patients with cervical carcinoma (50 cases of squamous cell carcinoma [SCC] and 21 cases of adenocarcinoma [AC]) and 32 healthy volunteers received DWI with multiple b values. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between tumour and normal cervix, among different pathological subtypes and grades.Results: All of the parameters were significantly lower in cervical carcinoma than normal cervical stroma except alpha. SCC showed lower ADC, D, f and DDC values and higher D* value than AC; D and DDC values of SCC and ADC and D values of AC were lower in the poorly differentiated group than those in the well-moderately differentiated group.Conclusion: Compared with MEM, diffusion parameters from BEM and SEM may offer additional information in cervical carcinoma diagnosis, predicting pathological tumour subtypes and grades, while f and D showed promising significance.Key Points: • DWI-derived parameters by different models are related but provide diversified information. • Commonly used ADC by MEM of DWI overestimates the tissue water diffusivity. • DWI processed by BEM could separate blood perfusion from true diffusion effects. • The derived diffusion-related and perfusion-related parameters by BEM are superior to ADC. [ABSTRACT FROM AUTHOR]

Background: Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources.Objectives: The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD.Methods: A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography-quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics.Results: We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305).Conclusions: Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression. [ABSTRACT FROM AUTHOR]

Objectives: To find out the reasons why patients still need to use rescue analgesics frequently after gastrointestinal tumor surgery under the patient-controlled intravenous analgesia (IV-PCA), and the different abdominal surgery patients using the difference of analgesics. Methods: A total of 970 patients underwent abdominal operation for gastrointestinal tumors were included. According whether patients used dezocine frequently for rescue analgesics within 2 days after surgery, they assigned into two groups: RAN group (Patients who did not frequently use rescue analgesia, 406 cases) and RAY group (Patients who frequently used rescue analgesia, 564 cases). The data collected included patient's characteristics, postoperative visual analogue scale (VAS), nausea and vomiting (PONV), and postoperative activity recovery time. Results: No differences were observed in the baseline characteristics. Compared with the RAN group, patients in the RAY group had a higher proportion of open surgery, upper abdominal surgery, VAS score at rest on the first 2 days after surgery and PONV, and a slower recovery of most postoperative activities. Under the current use of IV-PCA background, the proportion of rescue analgesics used by patients undergoing laparotomy and upper abdominal surgery was as high as 64.33% and 72.8%, respectively. Regression analysis showed that open surgery (vs laparoscopic surgery: OR: 2.288, 95% CI: 1.650–3.172) and the location of the tumor in the upper abdomen (vs lower abdominal tumor: OR: 2.738, 95% CI: 2.034–3.686) were influential factors for frequent salvage administration. Conclusions: In our patient population, with our IV-PCA prescription for postoperative pain control, patient who underwent open upper abdominal surgery required more rescue postoperative analgesia. [ABSTRACT FROM AUTHOR]

Background: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). Results: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. Conclusions: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle. [ABSTRACT FROM AUTHOR]

Numerous evidence indicates that inflammation in adipose tissue is the primary cause of systemic insulin resistance induced by obesity. Obesity-associated changes in circulating LPS level and hypoxia/HIF-1α activation have been proposed to be involved in boosting obesity-induced inflammation. However, there is poor understanding of what triggers obesity-induced inflammation. In this study, we pinpoint lactate as a key trigger to mediate obesity-induced inflammation and systemic insulin resistance. Specific deletion of Slc16a1 that encodes MCT1, the primary lactate transporter in adipose tissues, robustly elevates blood levels of proinflammatory cytokines and aggravates systemic insulin resistance without alteration of adiposity in mice fed high-fat diet. Slc16a1 deletion in adipocytes elevates intracellular lactate level while reducing circulating lactate concentration. Mechanistically, lactate retention due to Slc16a1 deletion initiates adipocyte apoptosis and cytokine release. The locally recruited macrophages amplify the inflammation by release of proinflammatory cytokines to the circulation, leading to insulin resistance in peripheral tissues. This study, therefore, indicates that lactate within adipocytes has a key biological function linking obesity to insulin resistance, and harnessing lactate in adipocytes can be a promising strategy to break this link. [ABSTRACT FROM AUTHOR]

Background: Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs.Methods: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS).Results: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103).Conclusions: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression.Clinical Trials Registration: NCT01965418. [ABSTRACT FROM AUTHOR]

Objectives Medical terminologies vary in the amount of concept information (the “density”) represented, even in the same sub-domains. This causes problems in terminology mapping, semantic harmonization and terminology integration. Moreover, complex clinical scenarios need to be encoded by a medical terminology with comprehensive content. SNOMED Clinical Terms (SNOMED CT), a leading clinical terminology, was reported to lack concepts and synonyms, problems that cannot be fully alleviated by using post-coordination. Therefore, a scalable solution is needed to enrich the conceptual content of SNOMED CT. We are developing a structure-based, algorithmic method to identify potential concepts for enriching the conceptual content of SNOMED CT and to support semantic harmonization of SNOMED CT with selected other Unified Medical Language System (UMLS) terminologies. Methods We first identified a subset of English terminologies in the UMLS that have ‘PAR’ relationship labeled with ‘IS_A’ and over 10% overlap with one or more of the 19 hierarchies of SNOMED CT. We call these “reference terminologies” and we note that our use of this name is different from the standard use. Next, we defined a set of topological patterns across pairs of terminologies, with SNOMED CT being one terminology in each pair and the other being one of the reference terminologies. We then explored how often these topological patterns appear between SNOMED CT and each reference terminology, and how to interpret them. Results Four viable reference terminologies were identified. Large density differences between terminologies were found. Expected interpretations of these differences were indeed observed, as follows. A random sample of 299 instances of special topological patterns (“2:3 and 3:2 trapezoids”) showed that 39.1% and 59.5% of analyzed concepts in SNOMED CT and in a reference terminology, respectively, were deemed to be alternative classifications of the same conceptual content. In 30.5% and 17.6% of the cases, it was found that intermediate concepts could be imported into SNOMED CT or into the reference terminology, respectively, to enhance their conceptual content, if approved by a human curator. Other cases included synonymy and errors in one of the terminologies. Conclusion These results show that structure-based algorithmic methods can be used to identify potential concepts to enrich SNOMED CT and the four reference terminologies. The comparative analysis has the future potential of supporting terminology authoring by suggesting new content to improve content coverage and semantic harmonization between terminologies. [ABSTRACT FROM AUTHOR]

Choline metabolite trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found that the TMAO levels in peripheral and cord plasma were increased in women with GDM and that TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion, and angiogenesis of HTR-8/Svneo cells. However, TMAO not only could inhibit the formation of NETs but also could enhance the biological function of HTR-8/Svneo cells. With induction of GDM in NETs-deficient PAD4-/- and wild-type mice, the placental weight of PAD4-/- mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicate that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO not only could promote the development of the placenta and fetuses but also could inhibit the formation of NETs. [ABSTRACT FROM AUTHOR]

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition. [ABSTRACT FROM AUTHOR]

Purpose: Few studies explored the relationship between the family doctor contract services (FDCS) and health-related quality of life (HRQOL) among patients with chronic diseases in rural China. This study aims to explore the relationship between the status of signing on FDCS and HRQOL among patients with chronic diseases and examine whether there are differences in the relationship between different socioeconomic status (SES). Methods: A total of 1,210 respondents were included in this study. HRQOL was measured by EQ-5D-3L. The contracting status was divided into uncontracted and contracted. Tobit regression and Logistic regression were employed to explore the association between contracting status and HRQOL. The interaction terms were included to explore the differences in the association among different SES. Results: Contracting with family doctors was associated with HRQOL (coefficient = 0.042; 95%CI 0.008 to 0.075). The association was different among different socioeconomic levels that the contracting status was only associated with HRQOL in sub-high-income (P < 0.01) and highly educated patients (P < 0.05). Compared with uncontracted patients, contracted patients reported higher ED-5D-3L utility value in the sub-high-income group (coefficient = 0.078; 95%CI 0.017 to 0.140) and high educational attainment (coefficient = 0.266; 95%CI 0.119 to 0.413). Conclusions: This study found a significant association between FDCS and HRQOL among chronic patients in rural Shandong, China. This relationship varied by income levels and educational attainment. The government should take efforts to formulate a variety of measures to encourage chronic patients to contract with family doctors, with special attention to people with low SES. [ABSTRACT FROM AUTHOR]

Background: Macrosomia has been defined in various ways by obstetricians and researchers. The purpose of the present study was to search for a definition of macrosomia through an outcome-based approach. Methods: In a study of 30,831,694 singleton term live births and 38,053 stillbirths in the U.S. Linked Birth-Infant Death Cohort datasets (1995–2004), we compared the occurrence of stillbirth, neonatal death, and 5-min Apgar score less than four in subgroups of birthweight (4000–4099 g, 4100–4199 g, 4200–4299 g, 4300–4399 g, 4400–4499 g, 4500–4999 g vs. reference group 3500–4000 g) and birthweight percentile for gestational age (90th–94th percentile, 95th-96th, and ≥97th percentile, vs. reference group 75th–90th percentile). Results: There was no significant increase in adverse perinatal outcomes until birthweight exceeded the 97th percentile. Weight-specific odds ratios (ORs) elevated substantially to 2 when birthweight exceeded 4500 g in Whites. In Blacks and Hispanics, the aORs exceeded 2 for 5-min Apgar less than four when birthweight exceeded 4300 g. For vaginal deliveries, the aORs of perinatal morbidity and mortality were larger for most of the subgroups, but the patterns remained the same. Conclusions: A birthweight greater than 4500 g in Whites, or 4300 g in Blacks and Hispanics regardless of gestational age is the optimal threshold to define macrosomia. A birthweight greater than the 97th percentile for a given gestational age, irrespective of race is also reasonable to define macrosomia. The former may be more clinically useful and simpler to apply. [ABSTRACT FROM AUTHOR]

Background: In China, some previous studies have investigated the signing rate and willingness of residents to sign the family doctor contract services (FDCS). Few studies have explored residents' willingness to renew the FDCS. This study is designed to understand the family characteristics difference towards rural households' willingness of maintaining the FDCS.Methods: A total of 823 rural households were included in the analysis. A descriptive analysis was conducted to describe the sample characteristics. The binary logistic regression model was used to explore the family characteristics that influence the renewal willingness for FDCS among rural households in Shandong province, China.Results: Our study found that about 95.5% rural households had willingness to maintain the FDCS in Shandong, China. Those households with catastrophic health expenditures (CHE) (OR = 0.328, 95%CI = 0.153-0.703), with highest level of education at graduate or above (OR = 0.303, 95%CI = 0.123-0.747) were less willing to maintain the FDCS. Those whose households have more than half of the labor force (OR = 0.403, 95%CI = 0.173-0.941) and those households living in economically higher condition were less willing to maintain the FDCS.Conclusions: This study demonstrates a significant association between family characteristics (CHE, highest education in households, proportion of the household labor force) and willingness to maintain FDCS among rural households in Shandong, China. Targeted policies should be made for rural residents of identified at-risk families. [ABSTRACT FROM AUTHOR]

Cloud properties were retrieved by applying the Clouds and Earth's Radiant Energy System (CERES) project Edition-2 algorithms to 3.5 years of Tropical Rainfall Measuring Mission Visible and Infrared Scanner data and 5.5 and 8 years of MODerate Resolution Imaging Spectroradiometer (MODIS) data from Aqua and Terra, respectively. The cloud products are consistent quantitatively from all three imagers; the greatest discrepancies occur over ice-covered surfaces. The retrieved cloud cover (\sim59%) is divided equally between liquid and ice clouds. Global mean cloud effective heights, optical depth, effective particle sizes, and water paths are 2.5 km, 9.9, 12.9 \mu\m, and 80 \g\cdot \m^-2, respectively, for liquid clouds and 8.3 km, 12.7, 52.2 \mu\m, and 230 \g\cdot \m^-2 for ice clouds. Cloud droplet effective radius is greater over ocean than land and has a pronounced seasonal cycle over southern oceans. Comparisons with independent measurements from surface sites, the Ice Cloud and Land Elevation Satellite, and the Aqua Advanced Microwave Scanning Radiometer–Earth Observing System are used to evaluate the results. The mean CERES and MODIS Atmosphere Science Team cloud properties have many similarities but exhibit large discrepancies in certain parameters due to differences in the algorithms and the number of unretrieved cloud pixels. Problem areas in the CERES algorithms are identified and discussed. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure are unknown.Methods: Serum IgE levels and cardiac FcεR1 expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone marrow transplantation. The roles of the IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes and cardiac fibroblasts (CFs). RNA sequencing and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1.Results: Serum IgE levels were significantly elevated in patients with heart failure as well as in 2 mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin II infusion. Interestingly, FcεR1 expression levels were also significantly upregulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated transverse aortic constriction- or angiotensin II-induced pathological cardiac remodeling or dysfunction. Anti-IgE antibodies (including the clinical drug omalizumab) also significantly alleviated angiotensin II-induced cardiac remodeling. Bone marrow transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-bone marrow-derived cells. FcεR1 was found to be expressed in both cardiomyocytes and CFs. In cultured rat cardiomyocytes, IgE-induced cardiomyocyte hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA sequencing and signaling pathway analyses revealed that transforming growth factor-β may be a critical mediator, and blocking transforming growth factor-β indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro.Conclusions: Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in cardiomyocytes and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling. [ABSTRACT FROM AUTHOR]

Objective: We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution of ARDS.Design: Retrospective analysis of archived samples.Setting: Adult intensive care unit of a postgraduate teaching hospital.Patients: Patients admitted to the adult intensive care unit who fulfilled the American-European Consensus Conference criteria for ARDS.Interventions: Biochemical and immunohistochemical studies using bronchoalveolar lavage fluid or lung tissue were performed in patients with established ARDS and in those undergoing lung resection (controls).Measurements and Main Results: Concentrations of heme oxygenase protein were significantly elevated in lung tissue (193.7 +/- 13.27 vs. 81.0 +/- 16.0%, p < .01) and in bronchoalveolar lavage fluid (2.4 x 10(5) vs. 1.4 x 10(5) densitometric units, p = .047) taken from patients with ARDS compared with controls. Concentrations of heme oxygenase protein in bronchoalveolar lavage fluid from patients with ARDS correlated positively and significantly with changes in the concentrations of ferritin (r = .697, p = .02) and the iron saturation of transferrin (r = .8, p = .014) but correlated negatively and significantly with concentrations of bleomycin-detectable (redox-active) iron (r = -.73, p = .031). Significantly elevated (p < .05) concentrations of heme oxygenase staining in cell types expressing this protein were detected in patients with ARDS, compared with concentrations in the same cells taken from controls undergoing lung resection.Conclusions: Heme oxygenase protein is elevated in the lungs of patients with ARDS and may contribute to the changes in iron mobilization, signaling, and regulation seen in this condition. [ABSTRACT FROM AUTHOR]

Objectives: Decreased cerebrospinal fluid (CSF) orexin levels are one of the diagnostic and classification criteria for narcolepsy. Because of the difficulty in obtaining CSF, its clinical application is limited. Here, we aimed to confirm the significance of determining plasma orexin levels in the diagnosis and treatment of narcolepsy by comparing the differences in these levels between narcolepsy patients and healthy controls and analyzing related factors.Methods: Twenty-four patients with type I narcolepsy who visited our hospital from October 2017 to January 2020 and who met the relevant inclusion and exclusion criteria were selected. Simultaneously, healthy controls with matched basic characteristics were selected at a 1:1 proportion. Patient basic information was collected, the Epworth Sleepiness Scale was recorded, the nocturnal polysomnogram and multiple sleep latency test were performed, and the patients' electrophysiological characteristics were analyzed. The blood samples of the patient and control groups were collected and stored at -80°Caftercentrifugation. Plasma orexin levels were determined by ELISA, following which the results of the two groups were compared, and the relevant factors were analyzed.Results: Our results revealed significantly lower plasma orexin levels in the narcolepsy patients compared to in healthy subjects. There were no correlations between plasma orexin levels and sex, age, body mass index, disease duration, and the severity of sleepiness, and between plasma orexin levels and electrophysiological indicators, including mean sleep latency and sleep-onset rapid eye movement periods.Conclusions: Determining plasma orexin levels has the potential to replace the detection of CSF orexin levels. [ABSTRACT FROM AUTHOR]

Background: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population.Methods: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18-60 years) had FLT3-ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290; the trial is complete.Findings: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0-37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1-13·1) in the sorafenib group and 24·5% (16·6-33·2) in the control group (hazard ratio 0·25, 95% CI 0·11-0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths.Interpretation: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia.Funding: None. [ABSTRACT FROM AUTHOR]

Background Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. Methods Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. Results There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). Conclusions The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week. [ABSTRACT FROM AUTHOR]

Background: As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women.Methods and Findings: In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children's Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups.Conclusions: In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study). [ABSTRACT FROM AUTHOR]

Background: Some reports assert that there is a risk that laparoscopy might worsen the prognosis of incidental gallbladder carcinoma (IGBC) after laparoscopic cholecystectomy (LC) compared with open reoperation. The purpose of this study was to evaluate whether the surgical approach influences outcomes in patients with IGBC after LC. Methods: We retrospectively reviewed the medical records of 106 patients diagnosed with IGBC who had undergone LC for benign gallbladder disease such as cholecystolithiasis at our hospital between April 2010 and February 2018. We included patients with incidentally diagnosed GBC after routine pathology: 45 patients (16 men and 29 women; age: 45-76 years [mean: 62.6 years]) who underwent laparoscopic surgery and 61 patients (24 men and 37 women; age: 51-82 years [mean: 62.6 years]) who underwent open surgery. We evaluated outcomes in each group regarding tumor stage and operative time, time of reoperation after first operation, blood loss volume, number of lymph nodes in pathological specimens, hospital stay, and complication and survival rates. Results: Reoperation time after first operation, number of lymph nodes in pathological specimens, and operative time showed no statistical significance between laparoscopy and open reoperation. During follow-up, 3-year survival between laparoscopy (48.89%) and open reoperation (42.62%) showed no statistical significance, but laparoscopy had better 1-year survival (95.56% versus 86.89%, laparoscopy versus open, respectively; not significant [NS] <0.01) and 5-year survival (44.44% versus 29.51%, laparoscopy versus open, respectively; NS <0.05). However, comparing laparoscopy versus open surgery, respectively, blood -loss volume (100 ± 25.4 mL versus 200 ± 45.6 mL; NS <0.01), hospital stay (3.5 ± 1.9 days versus 5.6 ± 2.7 days, NS <0.01), and complication rates (6.7% versus 13.1%; NS <0.01) were lower, indicating better recovery and better patient experience. Conclusions: Laparoscopic radical reoperation for IGBC after LC is a feasible, effective, and safe procedure and is associated with less bleeding, low morbidity, and shorter hospital stay. [ABSTRACT FROM AUTHOR]

Background and Objectives: To investigate the effect of accelerated rehabilitation combined with enteral nutrition on surgically treated lung cancer patients.Methods and Study Design: In total, 150 lung cancer patients treated in our hospital from January 2017 to January 2018 were retrospectively analysed. Sixty-six patients were randomly divided into a control group with conventional nutrition (Con group) and an accelerated rehabilitation combined with enteral nutrition group (EN group). Postoperative drainage; total hospitalization time; total hospitalization expenses; and albumin, haemoglobin and total lymphocyte counts (TLC) before and after treatment were compared.Results: The serum albumin, prealbumin and haemoglobin in both groups were decreased after operation and were significantly higher in the EN group (p<0.05) than in the Con group. The TLC decreased in both groups after operation and were significantly higher in the EN group than in the con group. The postoperative drainage volume, total hospitalization time and total hospitalization expenses were significantly lower in the EN group than in the Con group (p<0.05).Conclusions: The effect of accelerated rehabilitation combined with enteral nutrition in lung cancer surgery patients is clear. Surgery leads to stress, which enhances catabolism and reduces the synthesis of carbohydrates, protein, and fat, increasing patients' nutritional risk. Nutritional support combined with fast-track minimally invasive thoracic surgery for at-risk lung cancer patients who undergo preoperative nutritional screening and assessment can reduce postoperative complications and hospitalization time and improve nutritional indicators, immunity, respiratory function recovery and clinical outcomes, leading to socioeconomic benefits. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the genetic environment of the carbapenem resistance determinant in Proteus vulgaris of swine origin.Methods: The carbapenem-resistant P. vulgaris strain BC22 was isolated from a faecal swab from a diseased pig with diarrhoea in Sichuan Province of China in 2018. The presence of carbapenemase genes was screened by PCR. WGS and bioinformatics analysis were performed to analyse the genetic environment of the carbapenem resistance determinant.Results: P. vulgaris strain BC22 was found to harbour the carbapenemase gene blaNDM-1. WGS data revealed that blaNDM-1 was located in a truncated ISAba125 composite transposon. The carbapenem resistance gene blaNDM-1 and 20 other resistance genes, including the multiresistance gene cfr and the bifunctional aminoglycoside/quinolone resistance gene aac(6')-lb-cr, were located in a novel SXT/R391 integrative and conjugative element (ICE). This new SXT/R391 ICE of 148.7 kb was chromosomally located, and could be transferred to Escherichia coli.Conclusions: Here, we report a carbapenemase gene, blaNDM-1, integrated into an SXT/R391 ICE. Our study highlights that this SXT/R391 ICE may facilitate the dissemination of clinically important resistance genes such as blaNDM-1, cfr and aac(6')-lb-cr. [ABSTRACT FROM AUTHOR]

Background: Daptomycin is considered an important alternative for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). However, treatment failures associated with daptomycin nonsusceptibility isolates have been reported in recent years.Methods: In this study, we investigated serial MRSA strains from 3 endocarditis patients who had breakthrough bacteremia, despite treatment with daptomycin. The strains were analyzed by whole-genome sequencing, molecular typing, and mutation screening. Population analysis and growth curves were also applied to evaluate heteroresistance and fitness cost.Results: This series of MRSA strains belonged to ST5, ST59, and ST4513. The daptomycin minimum inhibitory concentrations for these MRSA strains increased after daptomycin exposure, whereas daptomycin-resistant strains emerged with mutations in mprF and yycH. Population analysis profiling results demonstrated the presence of a daptomycin-heteroresistant subpopulation among daptomycin-susceptible MRSA strains, and no significant fitness cost was observed within these heteroresistant MRSA clones.Conclusions: We confirmed that daptomycin heteroresistance and resistance could emerge rapidly in MRSA strains of different lineages after daptomycin exposure. Further studies to fully understand the mechanism(s) underlying daptomycin resistance in MRSA are required. [ABSTRACT FROM AUTHOR]