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Background: Gastric cancer (GC), one of the common clinical malignant tumors of the digestive system, is the fourth most commonly diagnosed cancer and the second lethal cancer worldwide and has the characteristics of high metastasis, fatality, and recurrence rate. This research was conducted to investigate the role and mechanism of miR-4295 in gastric cancer. Methods: The expression capacity of miR-4295 was determined in gastric cancer tissues and its normal tissues by qRT-PCR. PTEN expression level was detected by western blot. SGC-7901 and MGC-803 cell lines were cultured and transfected with miR-4295 or its inhibitor. The effects of miR-4295 on cell proliferation, colony formation, migration, and invasion in vitro were investigated. The mutual effect between miR-4295 and PTEN in 293T cells was explored by luciferase reporter gene assays. Results: The results showed that miR-4295 expression was higher in gastric cancer tissues and cell lines, and the miR-4295 level was significantly negatively associated with the tumor size and distal metastasis of gastric cancer. Notably, up-regulated miR-4295 promoted cell proliferation, migration and invasion in vitro, whereas it led to contrary effects while down-regulating miR-4295 expression. Further mechanism studies displayed that miR-4295 could directly fasten the PTEN 3’UTR and dramatically decrease the level of PTEN in vitro. Conclusion: The findings revealed that miR-4295 could promote gastric cancer cell proliferation, migration and invasion, which might be attributed to targeting PTEN. Our study suggested that miR-4295 might be a potential therapeutic target for gastric cancer.

Objectives To develop and validate a general radiomics nomogram capable of identifying EGFR mutation status in non-small cell lung cancer (NSCLC) patients, regardless of patient with either contrast-enhanced CT (CE-CT) or non-contrast-enhanced CT (NE-CT). Methods A total of 412 NSCLC patients were retrospectively enrolled in this study. Patients’ radiomics features not significantly different between NE-CT and CE-CT were defined as general features, and were further used to construct the general radiomics signature. Fivefold cross-validation was used to select the best machine learning algorithm. Finally, a general radiomics nomogram was developed using general radiomics signature, and clinical and radiological characteristics. Two groups of data collected at different time periods were used as two test sets to access the discrimination and clinical usefulness. Area under the receiver operating characteristic curve (ROC-AUC) was applied to performance evaluation. Result The general radiomics signature yielded the highest AUC of 0.756 and 0.739 in the two test sets, respectively. When applying to same type of CT, the performance of general radiomics signature was always similar to or higher than that of models built using only NE-CT or CE-CT features. The general radiomics nomogram combining general radiomics signature, smoking history, emphysema, and ILD achieved higher performance whether applying to NE-CT or CE-CT (test set 1, AUC = 0.833 and 0.842; test set 2, AUC = 0.839 and 0.850). Conclusions Our work demonstrated that using general features to construct radiomics signature and nomogram could help identify EGFR mutation status of NSCLC patients and expand its scope of clinical application. Key Points • General features were proposed to construct general radiomics signature using different types of CT of different patients at the same time to identify EGFR mutation status of NSCLC patients. • The general radiomics nomogram based on general radiomics signature, and clinical and radiological characteristics could identify EGFR mutation status of patients with NSCLC and outperformed the general radiomics signature. • The general radiomics nomogram had a wider scope of clinical application; no matter which of NE-CT and CE-CT the patient has, its EGFR mutation status could be predicted.

We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1β, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV1, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1β, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.

Background: Hepatocellular carcinoma (HCC) is a common type of cancer with a high mortality rate and is usually detected at the middle or late stage, missing the optimal treatment period. The current study aims to identify potential long non-coding RNA (lncRNAs) biomarkers that contribute to the diagnosis and prognosis of HCC. Methods: The differentially expressed lncRNAs (DElncRNAs) in HCC patientsThe differentially expressed lncRNAs (DElncRNAs) in HCC patients were detected from the Cancer Genome Atlas (TCGA) dataset. LncRNAs signature was screened by LASSO regression, univariate, and multivariate Cox regression. The models for predicting diagnosis and prognosis were established, respectively. The prognostic model was evaluated by Kaplan-Meier survival curve receiver operating characteristic (ROC) curve and stratified analysis. The diagnostic model was validated by ROC. The lncRNAs signature was further demonstrated by functional enrichment analysis. were detected from the Cancer Genome Atlas (TCGA) dataset. LncRNAs signature was screened by LASSO regression, univariate and multivariate Cox regression. The models for predicting diagnosis and prognosis were established respectively. The prognostic model was evaluated by Kaplan-Meier survival curve receiver operating characteristic (ROC) curve and stratified analysis. The diagnostic model was validated by ROC. The lncRNAs signature was further demonstrated by functional enrichment analysis. Results: We found the 13-lncRNAs signature that had a good performance in predicting prognosis and could help to improve the value of diagnosis. In the training set, testing set, and entire cohort, the low-risk group had longer survival than the high-risk group (median OS: 3124 vs. 649 days, 2456 vs. 770 days and 3124 vs. 755 days). It performed well in 1-, 3-, and 5-year survival prediction. 13-lncRNAs-based risk score, age, and race were good predictors of prognosis. The AUC of diagnosis was 0.9487, 0.9265, and 0.9376, respectively. Meanwhile, the 13-lncRNAs were involved in important pathways, including the cell cycle and multiple metabolic pathways. Conclusion: In our study, the 13-lncRNAs signature may be a potential marker for the prognosis of HCC and improve the diagnosis.

The consumption of saturated lipids in combination with a sedentary lifestyle increases the risk of obesity and metabolic syndrome. However, the distribution of endogenous fatty acids (FA) after the consumption of saturated lipids and the connection between FA distribution and lipid metabolism-related genes relative expression have not been fully elucidated to date. In this study, we characterized FA profiles in the liver and visceral fats of Sprague Dawley (SD) rats fed with a high-palm-oil diet. The investigation showed that the levels of C16:0 and C18:1 (n-9) increased significantly (P < 0.05) in the liver of the high-palm-oil group (POG), while C16:1 (n-7) and C18:2 (n-6) accumulated markedly (P < 0.05) in the visceral fats of the control group (CN). A correlation analysis indicated a negative correlation between C16:0 and C16:1 (n-7) in the epididymal fat of POG. Our study also demonstrated that the intake of saturated lipids caused changes in lipid metabolism-related gene expression, especially stearoyl-CoA desaturase (SCD), which was upregulated at the third week but was inhibited in the subsequent weeks in the POG liver and perirenal fat. The SCD had a notable positive correlation with C16:1 (n-7) in the POG liver and perirenal fat but a significant negative correlation with C16:0 in the POG epididymal fat. In conclusion, the results of this study indicate that a high-C16:0 diet may result in adaptive SCD expression, and these findings may help to elucidate the effects of dietary fat on lipid metabolism.

Preoperative immune-nutritional status is correlated with postoperative outcomes. The Controlling Nutritional Status (CONUT) score is a useful tool for predicting the postoperative outcomes of cancer surgery. This study aimed to evaluate whether the CONUT score could predict postoperative complications in Crohn’s disease (CD) patients. In total, 202 CD patients were eligible. Univariate and multivariate analyses were performed to identify risk factors for postoperative complications. Receiver operating characteristic (ROC) curves were generated to examine the cutoff value for predictors of postoperative complications. Among all the patients, 66 developed postoperative complications. The cut-off value of the CONUT score was 3.5 for complications. Eighty-one patients had a low CONUT score ( 3.5). There was a significant difference in postoperative complications between the groups with low and high CONUT score (17.3% vs. 43.0%, p

We conducted a systematic review and meta-analysis to evaluate the association between parental diabetes mellitus and the risk of ADHD in offspring. The PubMed, EMBASE, Cochrane, and Web of Science databases were searched from inception to May 31, 2019. Thirteen observational studies containing 5,052,736 participants were included. Two reviewers independently extracted data and assessed the quality of the studies using predefined standard procedures. Random-effects model were used. We found that maternal pregestational diabetes mellitus (PGDM) was associated with an increased risk of ADHD in offspring (odds ratio [OR]: 1.40; 95% confidence interval [CI]:1.31-1.50) in adjusted analyses. Increased risks of ADHD in offspring were also observed among those with maternal preexisting type 1 diabetes (T1D) (OR: 1.39; 95% CI: 1.27-1.52) and paternal T1D (OR: 1.20; 95% CI: 1.13-1.28) in adjusted analyses. Sensitivity analyses supported the robustness of our findings. Future studies should use robust designs to address whether the association with parental diabetes mellitus is causal.

BACKGROUND Extremely premature infants have poor vascular conditions. Operators often choose deep veins such as the femoral vein and axillary vein to peripherally insert central catheters, and these vessels are often accompanied by arteries; thus, it is easy to mistakenly enter the artery. CASE SUMMARY The case of an extremely premature infant (born at gestational age 28+3) in whom the left upper extremity artery was accidentally entered during peripheral puncture of the central venous catheter is reported. On the 19th day of hospitalization, the index finger, middle finger and ring finger of the left hand were rosy, the left radial artery and brachial artery pulse were palpable, the recovery was 95%, and the improvement was obvious. At discharge 42 d after admission, there was no abnormality in fingertip activity during the follow-up period. CONCLUSION Arterial embolization in preterm infants requires an individualized treatment strategy combined with local anticoagulation and 2% nitroglycerin ointment for local tissue damage caused by arterial embolism in the upper limb. Continuous visualization of disease changes using image visualization increases the likelihood of a good outcome.

To quantify the spatial distribution of relative corneal refractive power shift (RCRPS) to investigate its association with axial length growth.Eighty myopic children were randomly assigned for fitting with type A or B lenses. Axial lengths and corneal topographies were measured at baseline and the 1-, 6-, and 12-months follow-up visits. Treatment-zone decentrations and sizes were derived from tangential maps. RCRPSs were computed by taking the difference between after-treatment and baseline axial maps and then subtracting the apex value. Values at the same radius were averaged to obtain an RCRPS profile, from which four distributional parameters were extracted: the peak value (Rmax), the location where the profile first reached its half peak (X50), and the powers summed within 4- and 8-mm diameter areas (Sum4 and Sum8, respectively). Linear mixed models were used to analyse the correlation between the AL growth and the distributional parameters.At baseline, no significant differences were observed between the two groups. After treatment, Axial length growth was significantly smaller in subjects fitted with type-B lenses (0.15 ± 0.16 vs 0.25 ± 0.22 mm,The spatial distribution of RCRPS is critical in retarding AL growth, and the ones reaching peak within a shorter distance from the apex may provide better myopia control.

Long non-coding RNAs (lncRNAs) constitute a group of >200-nucleotide ncRNA molecules. lncRNAs regulate several cell functions, such as proliferation, apoptosis, invasion and metastasis. Meanwhile, lncRNAs are abnormally expressed in human malignancies, where they suppress or promote tumor growth. The present study focused on growth arrest-specific transcript 5 (GAS5), a well-known lncRNA that acts as a tumor suppressor but is suppressed in multiple types of cancer, including mammary carcinoma, prostate cancer, colorectal cancer, gastric cancer, melanoma, esophageal squamous cell carcinoma, lung cancer, ovarian cancer, cervical cancer, gliomas, osteosarcoma, pancreatic cancer, bladder cancer, kidney cancer, papillary thyroid carcinoma, neuroblastoma, endometrial cancer and liver cancer. Notably, GAS5 is overexpressed in liver cancer, potentially functioning as an oncogene. In the present study, the diagnostic and therapeutic roles of GAS5 in different tumors were reviewed, with a summary of the potential clinical application of the lncRNA, which may help identify novel study directions for GAS5.

The development of Ti3C2Tx-based high performance electrode materials has been proposed to meet the practical requirements of supercapacitors. In this study, transition metal complexes decorated MXene Ti3C2Tx hybrid electrode nanocomposites are fabricated by a facile polyvinylpyrrolidone (PVP)-assisted liquid impregnation strategy (abbreviated as PVP-M/akTi3C2Tx (M = Mn or Ni)). The intercalated Ti3C2Tx is observed to possess a distinct layered structure wrapped by cloud-like Mn/Ni complexes, which form a heterojunction to help the charge transfer of PVP-M/akTi3C2Tx in aqueous electrolytes such as KOH, LiOH, Li2SO4 and Na2SO4. The electrochemical performance of pristine and modified MXene in the above electrolytes changes greatly, mainly due to the difference of electrolytes’ ionic radius and conductivity. Typically, the PVP-Mn/akTi3C2Tx and PVP-Ni/akTi3C2Tx nanocomposites exhibit superior specific capacitances of 154.6 F g−1 and 167.65 F g−1 at 0.3 A g−1 current density in 1 M KOH electrolyte, respectively. Moreover, due to the complete progressive activation process of the electrode materials, the specific capacitance further increased by 25% and 56% after thousands of cycles, and finally kept at 95.70% and 96.21% of the maximum value respectively, indicating the superstability of these electrode materials. This study provides a new perspective to tailor the microstructures of Ti3C2Tx electrode materials for energy applications.

STUDY QUESTION Does the endometrial preparation protocol for frozen embryo transfer (FET) have an impact on perinatal outcomes? SUMMARY ANSWER Singleton newborns from conceptions after an artificial FET cycle had a higher risk of being large for gestational age (LGA). WHAT IS KNOWN ALREADY Most previous studies have concentrated on the clinical pregnancy, miscarriage and live birth rates of different endometrial preparation protocols for FET. However, the impacts of these cycle regimens on perinatal outcomes including birthweight, gestational age (GA) and related outcomes require more investigation. STUDY DESIGN, SIZE, DURATION We retrospectively analysed all singletons conceived by women who underwent non-donor FET cycles between July 2014 and July 2017. The propensity score matching (PSM) method using nearest neighbour matching at a proportion of 1:1 was established to adjust for factors that influence the probability of receiving different FET cycle regimens. The main outcomes of the study included birthweight and its related outcomes, Z-score, low birthweight (LBW, 4000 g). The study outcomes also included GA at birth, preterm delivery ( PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 9267 cycles with live-born singletons were included in the analysis in our centre between July 2014 and July 2017. Of these, 2224, 4299 and 2744 live-born singletons were conceived by natural cycle FET, stimulated cycle FET and artificial cycle FET, respectively. After PSM, 1947 cycles of natural cycle FET versus stimulated cycle FET, 1682 cycles of stimulated cycle FET versus artificial cycle FET and 2333 cycles of natural cycle FET versus artificial cycle FET were included in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE A higher mean birthweight and Z-score were observed in the artificial cycle FET group than in the stimulated cycle FET group (P = 0.005; P = 0.004, respectively). Singleton newborns conceived after artificial cycle FET were more likely to be LGA than those born after natural cycle FET or stimulated cycle FET (19.92% versus 16.94% and 19.29% versus 16.12%, respectively). The adjusted ORs (95% CIs) were 1.25 (1.05, 1.49) for artificial cycle FET compared with natural cycle FET (P = 0.014) and 1.26 (1.08, 1.46) for artificial cycle FET compared with stimulated cycle FET (P = 0.003). Newborns conceived after stimulated cycle FET had a lower mean GA at birth and a lower mean birthweight than those born after natural cycle FET or artificial cycle FET. The stimulated cycle FET group had lower adjusted odds of being macrosomia than the natural cycle FET group. No significant differences between natural cycle FET and stimulated cycle FET were found for any of the other outcomes. LIMITATIONS, REASONS FOR CAUTION This study had the disadvantage of being retrospective, and some cases were excluded due to missing data. The original allocation process was not randomized, which may have introduced bias. We have chosen not to account for multiple comparisons in our statistical analysis. WIDER IMPLICATIONS OF THE FINDINGS LGA can have long-term consequences in terms of risk for disease, which means that the influences of artificial cycle FET are of clinical significance and deserve more attention. Furthermore, these findings are critical for clinicians to be able to make an informed decision when choosing an endometrial preparation method. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth People’s Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare.

Autophagy, an evolutionarily conserved catabolic process, is the most important pathogenic events in the development and progression of liver diseases. Deregulation of Nrf2 is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC). Under certain pathophysiological conditions, such as oxidative stress, impaired autophagy is accompanied by the Nrf2 activation that leads to the detrimental effects favoring the proliferation and survival of HCC. Elucidating its role and potential mechanism is essential for understanding tumorigenesis and the development of effective clinical application. Nrf2 is participated in HCC proliferation, migration and invasion through autophagy pathways. These includes the negatively regulated-Nrf2 by Keap1 that participates in HCC tumorigenesis via regulating ROS production, in which autophagy may contribute to oxidant metabolic reprogramming of HCC cells. Post-transcriptional modifications, such as phosphorylation and ubiquitination of Nrf2, can be positively or negatively induced by multiple transcription factors. Nrf2 exhibits chemoresistance through its binding sites in the promoter region of the target genes. Nrf2 may be a valuable potential biomarker and therapeutic strategy for diagnostics, prognostics and treatment of HCC.

Photo-induced self-healing materials, which can be controlled remotely, instantly and precisely, are attracting increasing attention in various fields. However, it still remains challenging to modulate the self-healing materials with integrated functionalities possessing multiple-wavelength photo-responsiveness. Herein, we report a strategy of building a photo-responsive self-healing system capable of performing ultraviolet (UV) and near-infrared (NIR) two-wavelength induced double-repair. The strategy is based on azobenzene-functionalized multiwalled carbon nanotubes (MWCNTs) via a two-step method. Oxidized MWCNTs were first reacted subsequently with thionyl chloride, glycol, and 2-bromoisobutyryl bromide to yield MWCNT-Br macroinitiators. Then atom transfer radical polymerization (ATRP) of azobenzene monomer, 6-(4-butyl-4′-oxyazobenzene) hexyl methacrylate (Azo), was directly initiated by MWCNT-Br, affording MWCNT-PAzo nanocomposites. The MWCNT-PAzo system can undergo photothermal- and photochemical-induced solid-liquid phase transition to manipulate the self-healing behavior while MWCNTs act as photo-absorbers/heat sources and azobenzene moieties serve on glass transition temperatures (Tg) switchers, in response to NIR and UV light stimuli, respectively. To our best of knowledge, this is the first-time that MWCNT-PAzo nanocomposites possess two-wavelength photo-responsiveness and exhibit excellent self-healing performance through the irradiation of two-wavelength bands (365 and 808 nm) of UV/NIR light.

STUDY QUESTION Does the quality of a single transferred blastocyst affect singleton birthweight in frozen-embryo transfer (FET) cycles? SUMMARY ANSWER The transfer of a poor-quality blastocyst was associated with lower mean birthweight and gestation-adjusted birthweight (Z-scores) when compared with the transfer of an excellent-quality blastocyst during FET cycles. WHAT IS KNOWN ALREADY Embryo quality is a strong predictor of IVF success rates. However, very few studies have examined the effect of embryo quality on singleton birthweight. STUDY DESIGN, SIZE, DURATION This retrospective study involved singleton live births born to women undergoing frozen-thawed single blastocyst transfers during the period from January 2010 to December 2017 at a tertiary care centre. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1207 women who fulfilled the inclusion criteria were included and were grouped into four groups depending on the blastocyst quality: excellent, good, average and poor. The primary outcome measure was singleton birthweight. The Z-score was employed to calculate the birthweight adjusted for gestational age and newborn gender. Multiple linear regression analysis was performed to investigate the relationship between embryo quality and neonatal birthweight after adjustment for some potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In the primary multivariable model, singletons from the poor-quality blastocyst group weighed 183.5 g less than those from the excellent-quality blastocyst group (95% CI: −295.1 to −71.9 g, P = 0.001) in terms of mean birthweight after accounting for patient characteristics, IVF treatment parameters, the year of treatment and newborn gender. Likewise, poor-quality blastocyst transfer was associated with lower gestation-adjusted Z-scores than the transfer of excellent-quality blastocysts (β = −0.35, 95% CI: −0.59 to −0.12, P = 0.003). LIMITATIONS AND REASONS FOR CAUTION The current study was limited by its retrospective design and the fact that our analysis was restricted to women with singleton births from single blastocyst transfers. Future prospective studies are required to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS Our findings provide new insight into the relationship between embryo quality and neonatal outcomes by showing that poor-quality blastocyst transfer was associated with a decrease in singleton birthweight. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (grant no. 2018YFC1003000), the National Natural Science Foundation of China (grant nos. 81771533, 81571397 and 31770989), and the China Postdoctoral Science Foundation (Grant no. 2018M630456). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

Previous research focused on the qualitative discussion of the correlation between surgical time and mortality in acute pancreatitis (AP). Recommendations for surgical timing of necrotizing pancreatitis are delayed as far as possible, without recommendations for individuals. The aim of this article is to predict timing of surgical intervention in necrotizing pancreatitis with recurrent neural network (RNN). Time series data in AP were retrospectively extracted from a hospital in China (n = 15,813) to develop model, and the Cerner Health Facts database in the United States (n = 142,650) was used to externally validate. The developed model, time-aware Phased-Decay long short-term memory (LSTM), was used to predict timing of surgical intervention and critical clinical features in necrotizing pancreatitis based on laboratory tests, compared to other machine learning models. Area under the ROC curve (AUC) of RNN-based models was more than 0.70. The AUC of time-aware Phased-Decay LSTM (0.75) with more explanatory was similar to that (0.76) of Phased-Decay LSTM to predict surgical timing. The developed model visualized the specific surgical process and laboratory indicators changes for the patients with AP from the onset to discharge. Different clinical features had different contribution modes with time to the specific surgical event in AP. Heart function contributed the most to the prediction of surgical intervention at the onset and in the first week. Our developed model could monitor the specific surgical process from the onset of AP to discharge and extract the contribution modes of clinical features with time in necrotizing pancreatitis.

Ginkgo biloba L. is an ancient relict plant with rich pharmacological activity and nutritional value, and its main physiologically active components are flavonoids and terpene lactones. The bZIP gene family is one of the largest gene families in plants and regulates many processes including pathogen defense, secondary metabolism, stress response, seed maturation, and flower development. In this study, genome-wide distribution of the bZIP transcription factors was screened from G. biloba database in silico analysis. A total of 40 bZIP genes were identified in G. biloba and were divided into 10 subclasses. GbbZIP members in the same group share a similar gene structure, number of introns and exons, and motif distribution. Analysis of tissue expression pattern based on transcriptome indicated that GbbZIP08 and GbbZIP15 were most highly expressed in mature leaf. And the expression level of GbbZIP13 was high in all eight tissues. Correlation analysis and phylogenetic tree analysis suggested that GbbZIP08 and GbbZIP15 might be involved in the flavonoid biosynthesis. The transcriptional levels of 20 GbbZIP genes after SA, MeJA, and low temperature treatment were analyzed by qRT-PCR. The expression level of GbbZIP08 was significantly upregulated under 4°C. Protein–protein interaction network analysis indicated that GbbZIP09 might participate in seed germination by interacting with GbbZIP32. Based on transcriptome and degradome data, we found that 32 out of 117 miRNAs were annotated to 17 miRNA families. The results of this study may provide a theoretical foundation for the functional validation of GbbZIP genes in the future.

Background The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown. Methods A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People’s Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization. Results A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153–313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35–326.82) pmol/L versus 92.90 (61.50–123.20) pmol/L, P 2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001–1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003–1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409–8.065, P Conclusion HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM.

Object formation is considered the aim of perceptual organization, but such a proposition has been neglected in empirical studies. In the current study, we investigated the role of object formation in configural superiority. Essentially, discrimination on bar orientations was enhanced by adding a right angle to each of the bars. Such facilitation is due to the emergent feature (EF) of closure formed by combining the bars with right angles. To study object formation, visual stimuli were generated by random dot stereograms to form objects or holes in 3D. Behaviorally, we found that the EF of closure facilitated oddball discrimination on objects, as demonstrated by previous studies, but did not facilitate oddball discrimination on holes with the same shape as objects. Multivariate pattern analysis of functional magnetic resonance imaging (fMRI) data showed that the EF of closure increased the object classification accuracy compared to the holes in the lateral occipital cortex (LOC), where object information is encoded, but not in the early visual cortex (EVC). The neural representations of objects and holes with and without EFs were further investigated using representational similarity analysis. The results demonstrate that in the LOC, the neural representations of objects with EFs showed a greater difference than those of the other three, that is, objects without EFs and holes with or without EFs. However, the uniqueness of objects with EFs was not observed in the EVC. Thus, our results suggest that the EF of closure, which leads to the configural superiority effect, only emerges for objects but not for holes, and only in the LOC but not the EVC. Our study provides the first empirical evidence suggesting that object formation plays an indispensable role in perceptual organization.

BackgroundNeuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory diseases mediated mainly by humoral and cellular immunity. Circulating follicular helper T (Tfh) cells are thought to be involved in the pathogenesis of NMOSD, and serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of Tfh cells on B-cell-mediated humoral immunity. Immune cell and cytokine changes during the dynamic relapsing and remitting processes in NMOSD require further exploration.Patients and methodsBlood samples were collected from 36 patients in acute and recovery phases of NMOSD, 20 patients with other noninflammatory neurological diseases (ONND) and 20 age- and sex-matched healthy volunteers. CD4+CXCR5+PD-1+ Tfh cells were detected by flow cytometry, and serum CXCL13 levels were assessed by enzyme-linked immunosorbent assay (ELISA).ResultsThe percentage of CD4+CXCR5+PD-1+ Tfh cells was significantly higher during the acute phase than during the recovery phase, and serum CXCL13 levels were significantly higher in patients in the acute and recovery phases of NMOSD than in the ONND and control groups. The Tfh cell percentage was positively correlated with CXCL13 levels, and both were positively correlated with Expanded Disability Status Scale (EDSS) scores and cerebrospinal fluid protein levels in patients with acute NMOSD.ConclusionCirculating Tfh cells level has the potential to be a biomarker of disease severity.

OBJECTIVE To determine the relationship between ATP7B mutations and diabetes in Wilson disease (WD). RESEARCH DESIGN AND METHODS A total of 21 exons and exon-intron boundaries of ATP7B were identified by Sanger sequencing. RESULTS Two novel compound heterozygous mutations (c.525 dupA/ Val176Serfs*28 and c.2930 C>T/ p.Thr977Met) were detected in ATP7B. After d-penicillamine (D-PCA) therapy, serum aminotransferase and ceruloplasmin levels in this patient were normalized and levels of HbA1c decreased. However, when the patient ceased to use D-PCA due to an itchy skin, serum levels of fasting blood glucose increased. Dimercaptosuccinic acid capsules were prescribed and memory recovered to some extent, which was accompanied by decreased insulin dosage for glucose control by 5 units. CONCLUSIONS This is the first report of diabetes caused by WD.

Endometritis is a postnatal reproductive disorder disease, which leads to great economic losses for the modern dairy industry. Emerging evidence indicates that microRNAs (miRNAs) play a pivotal role in a variety of diseases and have been identified as critical regulators of the innate immune response. Recent miRNome profile analysis revealed an altered expression level of miR‐148a in cows with endometritis. Therefore, the present study aims to investigate the regulatory role of miR‐148a in the innate immune response involved in endometritis and estimate its potential therapeutic value. Here, we found that miR‐148a expression in lipopolysaccharide (LPS)‐stimulated endometrial epithelial cells was significantly decreased. Our results also showed that overexpression of miR‐148a using agomiR markedly reduced the production of pro‐inflammatory cytokines, such as IL‐1β and TNF‐α. Moreover, overexpression of miR‐148a also suppressed NF‐κB p65 activation by targeting the TLR4‐mediated pathway. Subsequently, we further verified that miR‐148a repressed TLR4 expression by binding to the 3′‐UTR of TLR4 mRNA. Additionally, an experimental mouse endometritis model was employed to evaluate the therapeutic value of miR‐148a. In vivo studies suggested that up‐regulation of miR‐148a alleviated the inflammatory conditions in the uterus as evidenced by H&E staining, qPCR and Western blot assays, while inhibition of miR‐148a had inverse effects. Collectively, pharmacologic stabilization of miR‐148a represents a novel therapy for endometritis and other inflammation‐related diseases.

Study question Is there any association between the number of oocytes retrieved and neonatal outcomes following IVF/ICSI treatment for patients using a freeze-all strategy? Summary answer There was no increased risk of adverse neonatal outcomes in cycles with high number of oocytes retrieved (≥ 16) compared to those with 10–15 oocytes retrieved in freeze-all cycles. What is known already Recent studies have found that there is an increased risk of preterm birth (PTB, 20) of oocytes retrieved in fresh embryo transfer (ET) cycles. Other studies have found that there is an association between the number of oocytes retrieved and placenta praevia. However, the association between the number of oocytes retrieved and neonatal outcomes when using a freeze-all strategy is unknown. Study design, size, duration This retrospective cohort study included 14 170 women with singleton deliveries achieved by a freeze-all strategy performed between November 2006 and December 2017 in China. Only the first delivery from one episode of ovarian stimulation was included. Participants/materials, setting, methods Only cycles using a freeze-all strategy performed during the study period and resulting in singleton live births were included. Patients were categorized into five groups according to the number of oocytes retrieved: 1–3, 4–9, 10–15, 16–20 or >20 oocytes. In univariate and multivariate logistic regression analysis of the association between ovarian response and the outcomes of PTB, early PTB, LBW and other neonatal outcomes, the 10 to 15 oocyte category was used as a reference and other four groups were analysed as dummy variables. Multiple linear regression analysis was used to evaluate possible associations of birth weight z-scores and the number of oocytes retrieved (analysed as a continuous variable) with other confounding factors. Main results and the role of chance After adjusted for confounding factors, no significant differences were observed in the risk of PTB (P = 0.837), LBW (P = 0.974), early PTB (P = 0.341), very LBW (P = 0.848), congenital malformation (P = 0.916) and other adverse neonatal outcome among patients with different number of oocytes retrieved. There was a higher risk of early PTB among women with a poor ovarian response (1–3 oocytes) compared with women with a normal response (10–15 oocytes) (1.5% vs 0.8%), crude odds ratio (OR): 2.001, 95% CI: 1.159–3.465, P = 0.013. However, the difference was not significant after adjusting for confounders, adjusted OR: 1.753, 95% CI: 0.997–3.081, P = 0.051. Limitations, reasons for caution Data on some known confounders such as smoking and medical history of gestational diabetes mellitus and preeclampsia were lacking. As with any retrospective study, unknown confounders may affect outcomes. Wider implications of the findings In the freeze-all cycles, there was no association between number of oocytes retrieved and adverse neonatal outcomes. This is a reassuring finding for both clinicians and patients who are planning to use freeze-all cycles for a variety of indications. Study funding/competing interest(S) Grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth People’s Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non‐HF patients as controls. A total of 771 proteins were identified in liquid chromatography‐tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF‐related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up‐regulated in HF, with HF/non‐HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.

There were conflictions and differences among the results of cross-sectional studies association between PM2.5 and COPD prevalence. We aimed to explore the real association between outdoor PM2.5 and COPD prevalence, analyze the possible cause to the differences and conflictions in previous cross-sectional studies. Cross-sectional literatures about the association between outdoor PM2.5 and COPD prevalence were selected up to 12 September 2018. Subgroup analysis was performed to explore the source of the heterogeneity. Publication bias was tested via funnel plot. Leave-one-out method was used to conduct influential analysis. Variance analysis was used to analyze the influence of concentration, literature quality and age (over 60 or not) on the ln (aOR) values. The initial search revealed 230 studies, of which 8 were selected. The heterogeneity in this study was significant (I2=62, P

The memory dysfunction is one of the disastrous outcomes for perinatal hypoxia ischemia. Erythropoietin (EPO) has been demonstrated as a neuroprotective agent with multiple effects in a series of neurological diseases. We hypothesized that disruption of neural network including synapses and neurites would contribute to memory dysfunction induced by hypoxia ischemia. The aim of the present study was to elucidate the involvement of EPO on synaptogenesis and neurite repair following perinatal hypoxia ischemia. Using a neonatal hypoxia ischemia rat model, we found that EPO rescued hypoxia ischemia-induced decrease of synaptic proteins including Synapsin1 and PSD95 rather than GluR1 in the cortex and hippocampus. In addition, EPO reduced the expression of APP (an axonal injury marker), induced the expression of microtubule-associated protein MAP-2 (a dendritic marker), and restored axonal density after hypoxia ischemia. These changes contributed to improving electrophysiological properties of synapses and spatial memory performance. In summary, our data revealed an important role of EPO in synaptogenesis and neurite repair, providing a new insight into cellular mechanisms underlying cognitive and memory dysfunction associated with perinatal hypoxia ischemia.

Macrophages’ function play a vital role in the progression of atherosclerosis (AS), and miRNAs can modulate inflammatory cytokine secretion, lipid uptake and apoptosis of macrophages. miR-152 is down-regulated in the serum samples of AS patients and inhibits the migration of human umbilical vein endothelial cell, suggesting that miR-152 exerts a role in the atherogenesis. Nevertheless, the function of miR-152 in the inflammatory reaction of macrophages remains unexplored. Besides, bioinformatics shows that KLF5 is a direct target of miR-152. As a result, the objective of this study is to investigate the effects and mechanism of miR-152/KLF5 in the inflammatory reaction of macrophages. ApoE knockdown mouse (ApoE-/-) fed with high fat diet (HFD) was used as animal AS models. Ox-LDL treated RAW264.7 cell was used as cell model. Results showed that miR-152 expression was reduced, while KLF5 expression was elevated in the aortic tissues of AS mice, as compared with that of the control mice. Up-regulation of miR-152 significantly reduced the elevated expression of IL-1, IL-6 and TNF-α mediated by ox-LDL in the cultural supernatant of RAW264.7 cells and reduced β-catenin expression, whereas these effects were all neutralized when KLF5 was up-regulated in the base of miR-152 up-regulation. In conclusion, this study illustrates that miR-152 alleviates the pathogenesis of AS through inhibiting inflammatory responses by targeting KLF5, in which β-catenin might involves in. Our study provides a possibility of consideration of miR-152/KLF5 as a target for AS treatment.

Background Most infants infected with Toxoplasma gondii are completely asymptomatic at birth, yet they may develop ocular and neurological sequelae in the first few months of life. Cases of congenital toxoplasmosis with severe jaundice early after birth combined with pancytopenia and splenomegaly are extremely rare. Here, we report on a rare case of congenital toxoplasmosis presenting with severe jaundice and hemolysis early after birth combined with pancytopenia and splenomegaly. Case presentation A male preterm infant with severe jaundice and splenomegaly was admitted to our department. Laboratory examinations revealed severe hyperbilirubinemia, increased reticulocytes, and pancytopenia. After comprehensive analysis and examination, the final diagnosis was congenital toxoplasmosis, and the infant was treated with azithromycin and subsequently trimethoprim-sulfamethoxazole. Regular follow-up revealed congenital toxoplasmosis in both eyes, which was surgically treated, while neurofunctional assessment results were unremarkable. In this case of congenital toxoplasmosis combined with severe jaundice, we treated the infant with two courses of azithromycin, followed by trimethoprim-sulfamethoxazole after the jaundice resolved. Clinical follow-up indicated that this treatment was effective with few side effects; thus, this report may serve as a valuable clinical reference. Conclusions Timely diagnosis and adequate treatment are closely associated with congenital toxoplasmosis-related prognosis. Infants with congenital toxoplasmosis require long-term follow-up, focusing on nervous system development and ophthalmology.