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Abstract Objective Colorectal cancer (CRC) is a major global health concern, necessitating the identification of biomarkers and molecular subtypes for improved clinical management. This study aims to evaluate the clinical value of adipogenesis-related genes and molecular subtypes in CRC. Methods A comprehensive analysis of adipogenesis-related genes in CRC was performed using publicly available datasets (TCGA and GEO database) and bioinformatics tools. Unsupervised cluster analysis was employed to identify the molecular subtypes of CRC, while LASSO regression analysis was utilized to develop a risk prognostic model. The immunogenomic patterns and immunotherapy analysis were used to predict patient response to immunotherapy. Furthermore, qPCR analysis was conducted to confirm the expression of the identified key genes in vitro. Results Through the analysis of RNAseq data from normal and tumor tissues, we identified 50 differentially expressed genes. Unsupervised cluster analysis identified two subtypes (Cluster A and Cluster B) with significantly different survival outcomes. Cluster A and B displayed differential immune cell compositions and enrichment in specific biological pathways, providing insights into potential therapeutic targets. A risk-scoring model was developed using five ARGs, which successfully classified patients into high and low-risk groups, showing distinct survival outcomes. The model was validated and showed robust predictive performance. High-risk patients exhibited altered immune cell proportions and gene expression patterns compared to low-risk patients. In qPCR validation, four out of the five key genes were consistent with the results of bioinformatics analysis. Conclusion Overall, the findings of our investigation offer valuable understanding regarding the clinical relevance of ARGs and molecular subtypes in CRC, laying the groundwork for improved precision medicine applications and personalized treatment modalities.

Abstract Background 2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain. Methods This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes. Results The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (μg/ml): low group (

Abstract Background The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples from lung adenocarcinoma (LAC) patients with leptomeningeal metastases (LM). Methods Paired CSF cell free DNA (cfDNA), CSF cells, plasma and formalin-fixed and paraffin-embedded (FFPE) samples of primary tumors were collected from 29 LAC patients with LM to detect the mutations by different NGS pipelines. Results DNA libraries were generated successfully for 79 various samples in total for NGS sequencing, of which mutations were detected in 7 plasma samples (24.14%), 12 CSF cfDNA samples (66.67%), and 10 CSF cells (76.9%) samples. For the 26 patients with detected mutations, 8/26(30.77%) had mutations in plasma, which was significantly lower than that those from CSF cfDNA (12/15, 80.00%), CSF cells (10/11, 90.91%) and FFPE samples (13/17, 76.47%). When the input DNA of CSF cells was less than 20 ng, the cHOPE pipeline of NGS identified the most mutations for epidermal growth factor receptor (EGFR). Conclusions NGS-based detection of mutations in cfDNA or cells from CSF provided more information than from plasma samples from LAC patients with LM. In addition, the cHOPE pipeline performed better than the other three NGS pipelines when input DNA from CSF cells was low.

Abstract Background Brain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China. Methods First, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan–Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort. Results BS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs. Conclusions The new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice.

Abstract Background Hemoconcentration has been proposed as surrogate for changes in volume status among patients hospitalized with acute heart failure (AHF) and is associated with a favorable outcome. However, there is a dearth of research assessing the clinical outcomes of hospitalized patients with hemoconcentration, hemodilution and unchanged volume status. Methods We enrolled 510 consecutive patients hospitalized for AHF from April 2011 to July 2015. Hematocrit (HCT) levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients were stratified by delta HCT tertitles into hemodilution (ΔHCT ≤ − 1.6%), no change (NC, −1.6% 1.5%) groups. The endpoint was all-cause death, with a median follow-up duration of 18.9 months. Results Hemoconcentration was associated with lower left ventricle ejection fraction, as compared with NC and hemodilution groups, while renal function at entry, New York Heart Association class IV, and in-hospital worsening renal function (WRF) were not significantly different across the three groups. After multivariable adjustment, hemoconcentration had a lower risk of mortality as compared with hemodilution [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.24–0.63, P

Abstract Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to proinflammatory stimulation, which plays an important role in valvular fibrosis and calcification. Thus, suppression of AVIC proinflammatory response may have therapeutic utility for the prevention of CAVD progression. Interleukin (IL)-37, an antiinflammatory cytokine, reduces tissue inflammation. This study aimed to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists. Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor-inducing interferon-β differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain. Activation of TLR2, TLR3 or TLR4 upregulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This antiinflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling.

Abstract Background There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a comprehensive and up-to-date meta-analysis is lacking. Before clinical translation, it is crucial to thoroughly understand the overall impact of stem cell-derived EVs on POF. Methods PubMed, EMBASE, Cochrane Library, Web of Science were searched up to February 18, 2024. The risk of bias was evaluated according to Cochrane Handbook criteria, while quality of evidence was assessed using the SYRCLE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and sensitivity analysis and publication bias analysis were performed using Stata 14. Results Data from 25 studies involving 339 animals were extracted and analyzed. The analysis revealed significant findings: stem cell-derived EVs increase ovary weight (SMD = 3.88; 95% CI: 2.50 ~ 5.25; P

Abstract Study objectives To assess whether preoperative dexmedetomidine (DEX) nasal drips combined with conventional treatment could mitigate the occurrence of postoperative delirium (POD). Design A prospective randomised controlled study. Setting The cardiac surgery intensive care unit (CSICU) and patient hospitalisation ward at a university hospital. Participants A total of 100 patients (aged ≥60 years) undergoing cardiac surgery at a university hospital between 7 January 2022, and 30 November 2022 met the eligibility criteria and were included in the study. Interventions Patients with sleep disorders (Pittsburgh Sleep Quality Index ≥8) were divided into two groups: Group A (the placebo group, n=50), receiving a short-term preoperative placebo combined with conventional treatment and Group B (the DEX group, n=50), receiving short-term preoperative DEX combined with conventional treatment. Measurements and results The Confusion Assessment Method for the ICU (CAM-ICU) was used for POD assessment in the CSICU, while the CAM was employed to assess delirium in the patient ward. Group B demonstrated a reduced incidence of POD compared to Group A (12% vs. 30%, odds ratio: 0.318, 95% confidence interval: 0.112–0.905, p=0.027). Conclusion The combined treatment involving DEX demonstrated a decreased incidence of POD in elderly individuals with sleep disorders undergoing cardiac surgery compared to the placebo combination treatment. Trial registration URL: www.chictr.org.cn with registration number ChiCTR 2100043968, registered on 06/03/2021.

Abstract Background This study aimed to investigate the effects of perioperative dexmedetomidine (DEX) infusion rates on the postoperative short-term cognitive function. Methods A total of 88 patients aged ≥ 60 years who underwent cardiac surgery from January 2022 to November 2022 at the First Affiliated Hospital of The University of Science and Technology of China (USTC) were included. Based on a single-center pilot analysis, patients were divided into two groups according to the rate of intraoperative DEX infusion, which started after tracheal intubation and continued until 1 h before extubation in the cardiac surgery intensive care unit. In Group L (n = 44), the infusion rate was 0.1–0.5 µg/kg/h (low-dose group), whereas in Group H (n = 44), the infusion rate was 0.5–0.9 µg/kg/h (high-dose group). Clinical outcomes were then compared between the groups. The Mini–Mental State Evaluation (abbreviated as MMSE1, MMSE2, MMSE3, and MMSE4) scale was used for the assessment of cognitive function, which was conducted on postoperative Days 2 (T1), 7 (T2), 14 (T3), and 28 (T4), with the score from postoperative Day 2 (MMSE1) considered as the primary observation. Results Patients in Group L had higher MMSE1 scores compared to those in Group H (26.0 [24.0, 27.0] vs. 24.5 [22.0, 26.0], p = 0.046), and there was no significant difference in the scores between the groups at all subsequent time points. Group H exhibited a higher incidence of hypotension and bradycardia compared to Group L (p = 0.044 and p = 0.047, respectively). Conclusions Compared to a high dose (0.5–0.9 µg/kg/h) of DEX infusion, a low-dose (0.1–0.5 µg/kg/h) infusion started after induction of anesthesia and continued until 1 h before extubation improved postoperative cognitive function scores on postoperative Day 2 in patients aged 60 years and older. Trial registration URL: www.chictr.org.cn with registration number ChiCTR2100055093, registered on 31/12/2021.

Abstract Background The development and maintenance of normal bone tissue is maintained by balanced communication between osteoblasts and osteoclasts. The invasion of cancer cells disrupts this balance, leading to osteolysis. As the only bone resorbing cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. However, the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in osteoclast resorption remains unclear. Methods In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter‐driven Cre‐LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. We observed the effect of osteoclast‐specific knockout of PDK1 on prostate cancer-induced osteolysis. Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to explore the role of PDK1 in osteoclasts. Results In this study, we found that PDK1 conditional knockout (cKO) mice exhibited smaller body sizes when compared to the wild-type (WT) mice. Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and rPDK1educed bone resorption markers in the murine model of prostate cancer-induced osteolysis. In vivo, we discovered that osteoclast‐specific knockout of suppressed RANKL-induced osteoclastogenesis, bone resorption function, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. Conclusion These findings demonstrated that PDK1 performs an important role in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway.

Abstract Background Thin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments. Methods This prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(

Abstract Objective This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs). Methods PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR). Results Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = − 0.331, 95% CI − 0.424 to − 0.238, P effect

Abstract Research question To explore whether prolonged hCG-ovum pickup interval improves assisted reproductive technology outcomes. Design CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science up to May 13 2023 were searched for studies reporting associations between hCG-ovum pickup intervals and assisted reproductive technology outcomes. Intervention types included short (≤ 36 h) and long (> 36 h) hCG-ovum pickup intervals in assisted reproductive technology cycles. All outcomes were based upon only fresh embryo transfers. Primary outcome is defined as the clinical pregnancy rate. Data were pooled using random-effects models. Heterogeneity was assessed using the I 2 statistics. Results Twelve studies were included in the meta-analysis, including five retrospective cohort studies, one prospective cohort study, and six randomized or quasi-randomized controlled trials. The short and long interval groups had similar oocyte maturation rates, fertilization rate and high-quality embryo rate (OR, 0.69; 95% CI, 0.45–1.06; I 2 = 91.1%, OR, 0.88; 95% CI, 0.77–1.0; I 2 = 44.4% and OR, 1.05; 95% CI, 0.95–1.17; I 2 = 8.6%, respectively). The clinical pregnancy rates in the long retrieval group were significantly higher than in the short retrieval group (OR, 0.66; 95% CI, 0.45–0.95; I 2 = 35.4%). The groups had similar miscarriage and live birth rates (OR, 1.92; 95% CI, 0.66–5.60; I 2 = 0.0% and OR, 0.50; 95% CI, 0.24–1.04; I 2 = 0.0%, respectively). Conclusions The clinical pregnancy rates can be increased by prolonging the hCG-ovum pickup interval, which would help us develop more reasonable time schedules for fertility centers and patients. Meta-analysis registration PROSPERO CRD42022310006 (28 Apr 2022).

Abstract Objective Osteoporosis (OP) and periodontal disease (PD) are two common health issues that threaten the older population and potentially connected each other in the context of type 2 diabetes mellitus (T2DM). Dysregulated expression of microRNAs (miRNAs) may contribute to the development and progression of both OP and PD among elderly T2DM patients. The present study aimed to evaluate the accuracy of miR-25-3p expression for the detection of OP and PD when compared to a mixed group of patients with T2DM. Methods The study recruited 45 T2DM patients with normal bone mineral density (BMD) and healthy periodontium, 40 type 2 diabetic osteoporosis patients coexistent with PD, 50 type 2 diabetic osteoporosis patients with healthy periodontium, and 52 periodontally healthy individuals. miRNA expression measurements in the saliva were determined by real-time PCR. Results The salivary expression of miR-25-3p was higher in type 2 diabetic osteoporosis patients than patients with T2DM only and healthy individuals (P

Abstract Background Embryo implantation in a receptive endometrium is crucial for successful pregnancy. Endometrial receptivity (ER) prediction tools based on endometrial transcriptome biomarkers by endometrial biopsy have been used to guide successful embryo implantation in in vitro fertilization (IVF) patients. However, no reliable noninvasive ER prediction method has been established, and one is greatly needed. We aimed to identify biomarkers from uterine fluid transcriptomic sequencing data for establishing noninvasive ER prediction tool and to evaluate its clinical application potential in patients undergoing IVF. Methods The non-invasive RNA-seq based endometrial receptivity test (nirsERT) was established by analyzing transcriptomic profile of 144 uterine fluid specimens (LH + 5, LH + 7, and LH + 9) at three different receptive status from 48 IVF patients with normal ER in combination with random forest algorithm. Subsequently, 22 IVF patients who underwent frozen-thaw blastocyst transfer were recruited and analyzed the correlation between the predicted results of nirsERT and pregnancy outcomes. Results A total of 864 ER-associated differentially expressed genes (DEGs) involved in biological processes associated with endometrium-embryo crosstalk, including protein binding, signal reception and transduction, biomacromolecule transport and cell-cell adherens junctions, were selected. Subsequently, a nirsERT model consisting of 87 markers and 3 hub genes was established using a random forest algorithm. 10-fold cross-validation resulted in a mean accuracy of 93.0%. A small cohort (n = 22) retrospective observation shows that 77.8% (14/18) of IVF patients predicted with a normal WOI had successful intrauterine pregnancies, while none of the 3 patients with a displaced WOI had successful pregnancies. One patient failed due to poor sequencing data quality. Conclusions NirsERT based on uterine fluid transcriptome biomarkers can predict the WOI period relatively accurately and may serve as a noninvasive, reliable and same cycle test for ER in reproductive clinics. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx .

Abstract Background To retrospectively investigate the success rate of primary-molar pulpectomy performed under general anaesthesia and the potential risk factors that affect the 24-month success rate. Methods The case data and two-year follow-up records of children (aged 3–6 years) who received pulpectomy in primary molars performed under general anaesthesia were reviewed and assessed. Potential risk factors included age, gender, decayed-missing-filled teeth, endodontic diagnosis, tooth location, and postobturation sealing of the pulp chamber floor with MTA. With a two-year follow-up period, the outcomes of all the primary molars were classified into success and failure. Survival analysis was used to assess the outcomes. The Kaplan–Meier method was used to analyse the success rate. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the potential risk factors associated with the overall survival of primary molars. Results A total of 410 teeth from 163 children (88 boys and 75 girls) were included in this study. The overall two-year success rate was 66.1% for all primary molars. The mean overall survival time for this study was 22.1 (95% CI, 21.73‒22.48) months. Multivariate Cox regression analysis demonstrated that endodontic diagnosis (irreversible pulpitis or periapical periodontitis), tooth location (maxillary or mandibular primary molar), and postobturation sealing of the pulp chamber floor (MTA or no-MTA) were significant risk factors for overall survival in this study (P .05). Conclusions When compared to teeth diagnosed with irreversible pulpitis, those with periapical periodontitis failed more frequently. Postobturation sealing of the pulp chamber floor with MTA improved the success rate of pulpectomy in primary molars, especially when the inflammation did not spread to the periradicular area.

Abstract Background Previous studies of left ventricular diastolic function (LVDF) have focused on the decrease in active and passive diastolic function due to ischemic factors but have not investigated if the decrease in compliance of the coronary arteries that bypass the surface of the heart and travel between the myocardium could cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis. Methods and Results 581 patients diagnosed with coronary heart disease (CHD) were divided into A group (patients are the control group), B group (patients with less than 50% coronary artery stenosis), C group (patients with coronary artery stenosis between 50 and 75%), D group (patients with coronary artery stenosis greater than 75%) according to the degree of coronary stenosis. The diastolic function of the ventricle is reflected by applying the relaxation time constant T value, which refers to the time between peak dp/dt and end-diastolic pressure in the left ventricle. It was concluded that there was a statistical difference in Gensini scores between patients in groups B, C and D (P

Abstract Background Diabetic nephropathy (DN) involves various structural and functional changes because of chronic glycemic assault and kidney failure. Proteinuria is an early clinical manifestation of DN, but the associated pathogenesis remains elusive. This study aimed to investigate the role of microtubule associated protein 4 (MAP4) phosphorylation (p-MAP4) in proteinuria in DN and its possible mechanisms. Methods In this study, the urine samples of diabetic patients and kidney tissues of streptozotocin (STZ)-induced diabetic mice were obtained to detect changes of p-MAP4. A murine model of hyperphosphorylated MAP4 was established to examine the effect of MAP4 phosphorylation in DN. Podocyte was applied to explore changes of kidney phenotypes and potential mechanisms with multiple methods. Results Our results demonstrated elevated content of p-MAP4 in diabetic patients’ urine samples, and increased kidney p-MAP4 in streptozocin (STZ)-induced diabetic mice. Moreover, p-MAP4 triggered proteinuria with aging in mice, and induced epithelial-to-mesenchymal transition (EMT) and apoptosis in podocytes. Additionally, p-MAP4 mice were much more susceptible to STZ treatment and showed robust DN pathology as compared to wild-type mice. In vitro study revealed high glucose (HG) triggered elevation of p-MAP4, rearrangement of microtubules and F-actin filaments with enhanced cell permeability, accompanied with dedifferentiation and apoptosis of podocytes. These effects were significantly reinforced by MAP4 hyperphosphorylation, and were rectified by MAP4 dephosphorylation. Notably, pretreatment of p38/MAPK inhibitor SB203580 reinstated all HG-induced pathological alterations. Conclusions The findings indicated a novel role for p-MAP4 in causing proteinuria in DN. Our results indicated the therapeutic potential of MAP4 in protecting against proteinuria and related diseases. Video Abstract

Abstract The current kiwifruit industry is mainly based on the cultivars derived from the species Actinidia chinensis (Ac) which may bring risks such as canker disease. Introgression of desired traits from wild relatives is an important method for improving kiwifruit cultivars. Actinidia eriantha (Ae) is a particularly important taxon used for hybridization or introgressive breeding of new kiwifruit cultivars because of its valued species-specific traits. Here, we assembled a chromosome-scale high-quality genome of a Ae sample which was directly collected from its wild populations. Our analysis revealed that 41.3% of the genome consists of repetitive elements, comparable to the percentage in Ac and Ae cultivar “White” genomes. The genomic structural variation, including the presence/absence-variation (PAV) of genes, is distinct between Ae and Ac, despite both sharing the same two kiwifruit-specific whole genome duplication (WGD) events. This suggests that a post-WGD divergence mechanism occurred during their evolution. We further investigated genes involved in ascorbic acid biosynthesis and disease-resistance of Ae, and we found introgressive genome could contribute to the complex relationship between Ae and other representative kiwifruit taxa. Collectively, the Ae genome offers valuable genetic resource to accelerate kiwifruit breeding applications.

Abstract Objectives Limited information is known about preventive dental visits (PDVs) before seven years of age among children in China. This study aimed to examine the early PDV rate, identify the impact of PDV on dental caries and untreated dental caries, and explore the factors related to PDV among Chinese sampled children under seven years old. Methods A cross-sectional survey was conducted in five selected primary health care facilities in Chengdu, China, from May to August 2021. Parent–child dyads during regular systematic medical management were recruited to participate. Children's dental caries were identified through dental examinations and documented as decayed, missing and filled teeth index (dmft) by trained primary care physicians. Dental-related information was collected through a questionnaire. Zero-inflated negative binomial (ZINB) regression was used to test the effect of early PDV on the dmft value, and logistic regression was used to analyse impact factors on the early PDV. Results A total of 2028 out of 2377 parent–child dyads were qualified for analysis. Half of the children (50.4%) were male, with a mean age of 4.8 years. Among all the children, 12.1% had their first dental visit for preventive purposes, 34.4% had their first dental visit for symptomatic purposes, and more than half had never visited a dentist. The results showed that a lower dmft value (adjusted OR: 0.69, 95% CI: 0.48–0.84), a higher rate of caries-free (aOR: 6.5, 95% CI: 3.93–10.58), and a lower rate of untreated dental caries (aOR: 0.40, 95% CI: 0.21–0.76) were associated with early PDV utilization. Children who had a higher rate of PDV were positively associated with living in a family with better parental behaviours (aOR: 2.30, 95% CI: 1.71–3.08), better parental oral health perception (aOR: 1.23, 95% CI: 1.06–1.32), fathers who had no untreated caries (aOR: 0.68, 95% CI: 0.47–0.97), families with higher socioeconomic status (aOR: 1.09, 95% CI: 1.04–1.16), and dental health advice received from well-child care physicians (aOR: 1.47, 95% CI: 1.08–2.00). Conclusions Early PDV was associated with a lower rate of dental caries prevalence and untreated dental caries among sampled children younger than seven in Western China. Underutilization and social inequities existed in PDV utilization. Public health strategies should be developed to increase preventive dental visits and eliminate social disparities that prevent dental care utilization.

Abstract Background Mutation processes leave different signatures in genes. For single-base substitutions, previous studies have suggested that mutation signatures are not only reflected in mutation bases but also in neighboring bases. However, because of the lack of a method to identify features of long sequences next to mutation bases, the understanding of how flanking sequences influence mutation signatures is limited. Methods We constructed a long short-term memory-self organizing map (LSTM-SOM) unsupervised neural network. By extracting mutated sequence features via LSTM and clustering similar features with the SOM, single-base substitutions in The Cancer Genome Atlas database were clustered according to both their mutation site and flanking sequences. The relationship between mutation sequence signatures and clinical features was then analyzed. Finally, we clustered patients into different classes according to the composition of the mutation sequence signatures by the K-means method and then studied the differences in clinical features and survival between classes. Results Ten classes of mutant sequence signatures (mutation blots, MBs) were obtained from 2,141,527 single-base substitutions via LSTM-SOM machine learning approach. Different features in mutation bases and flanking sequences were revealed among MBs. MBs reflect both the site and pathological features of cancers. MBs were related to clinical features, including age, sex, and cancer stage. The class of an MB in a given gene was associated with survival. Finally, patients were clustered into 7 classes according to the MB composition. Significant differences in survival and clinical features were observed among different patient classes. Conclusions We provided a method for analyzing the characteristics of mutant sequences. Result of this study showed that flanking sequences, together with mutation bases, shape the signatures of SBSs. MBs were shown related to clinical features and survival of cancer patients. Composition of MBs is a feasible predictive factor of clinical prognosis. Further study of the mechanism of MBs related to cancer characteristics is suggested.

Abstract Dental general anesthesia (DGA) is an effective treatment for very young children or those who have severe dental fear and mental or physical disabilities. However, the long-term impacts of DGA on oral health-related quality of life (OHRQoL) and parents’ anxiety in China are still questionable. This study aimed to assess the influence of DGA on OHRQoL in Chinese children and their parents’ psychological status. A total of 204 children and their parents participated in this study. The ECOHIS was applied to evaluate OHRQoL in children. The parents’ anxiety was analyzed using the Chinese version of the Kessler 10 scale. The internal consistency was evaluated with Cronbach’s alpha coefficient, and Wilcoxon signed-rank test was used for statistical analyses. The scores of each section of ECOHIS decreased one month after the procedure except for the self-image and social sections (P

Abstract Background Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation. Methods A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing. Conclusions As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions.

Abstract Background Since the outbreak of coronavirus disease 2019 in December 2019, more than 8 million cases have occurred worldwide as of June 16, 2020. However, it is important to distinguish COVID-19 from other respiratory infectious diseases, such as influenza. Here, we comparatively described the clinical characteristics of children with COVID-19 and paediatric patients with influenza. Methods In this retrospective, single-centre study, we reviewed the electronic medical records of 585 paediatric patients with COVID-19 or influenza in Wuhan Children’s Hospital, China. Clinical and epidemiological characteristics, laboratory findings, and clinical outcomes were comparatively analysed. Results The median ages were 6.96 years (IQR, 2–10.81) for children with confirmed COVID-19, 2.67 years (IQR, 1.03–15.25) for those with influenza A and 3.67 years (IQR, 1.62–5.54) for those with influenza B. Fever was a symptom in 84 (34.7%) COVID-19 cases, 132 (70.21%) influenza A cases and 111 (74.50%) influenza B cases. The median length of stay (LOS) was 11 (8–15) days for paediatric COVID-19 patients, 4 (3–6) days for influenza A patients and 5 (3–6) days for influenza B patients. Twenty-six (13.98%) influenza A patients and 18 (12.59%) influenza B patients presented with decreased white blood cell counts, while 13 (5.33%) COVID-19 patients presented with decreased white blood cell counts. Eight (3.28%) COVID-19 patients, 23 (12.71%) influenza A patients and 21 (14.79%) influenza B patients experienced lymphocytopenia. Acute cardiac injury occurred in 18 (7.29%) COVID-19 patients, while 37 (19.68%) influenza A and 27 (18.12%) influenza B patients had acute cardiac injury. Conclusion In this study, the illnesses of children with COVID-19 were demonstrated to be less severe than those of paediatric patients with influenza, and COVID-19 patients had milder illness and fewer complications.

Abstract Background The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. Methods We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. Results The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. Conclusions Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.

Abstract Background To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students. Methods An epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome. Results Twenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects. Conclusions The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.

Abstract Background Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. Methods This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. Results The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. Conclusions The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Surgeon suturing technology plays a pivotal role in patient recovery after laparoscopic surgery. Intracorporal suturing and knot tying in minimally invasive surgery are particularly challenging and represent a key skill for advanced procedures. In this study, we compared the application of multidirectional stitching technology with application of the traditional method in a laparoscopic suturing instructional program. Methods We selected forty residents within two years of graduation to assess the specialized teaching of laparoscopic suturing with laparoscopic simulators. The forty students were randomly divided into two groups, a control group and an experimental group, with twenty students in each group. The control group was scheduled to learn the traditional suture method, and the experimental group applied multidirectional stitching technology. The grades for suturing time, thread length, accuracy of needle entry, stability of the knot, tissue integrity, and tightness of the tissue before and after the training program were calculated. Results There was no significant difference between the two groups before the learning intervention. After the program, both groups significantly improved in each subject. There were significant differences between the control group and the experimental group in suture time (P = 0.001), accuracy of needle entry and exit (P = 0.035), and whether the suture tissue had cracks (P = 0.030). However, the two groups showed non-significant differences in thread length (P = 0.093), stablity of the knot (P = 0.241), or tightness of the tissue (P = 0.367). Conclusions Multidirectional stitching technology improves the efficiency and effectiveness of traditional laparoscopic suture instructional programs. It might be a practicable, novel training method for acquiring proficiency in manual laparoscopic skills in a training setting.

Abstract Background We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. Methods (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of E2 in KGN cell culture medium were measured. Results (a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p

Abstract Background Studies have shown that poor sleep could result in many unpleasant consequences and is prevalent in nurses. Considering the fact of high stress, overwhelming workload and many night shifts in the emergency department in China, this study aimed to evaluate the current status of emergency nurses’ sleep quality in public hospitals in Shandong, China and explored its influencing factors. Methods A self-administered questionnaire incorporating the Job Content Questionnaire and Pittsburgh Sleep Quality Index (PSQI) was conducted among 4856 emergency nurses in five randomly selected city emergency command systems in Shandong, China. The association of potential influencing factors, including occupational, psychosocial and individual factors, with poor sleep (PSQI> 5) was quantified by multivariate logistic regression analysis. Results The average PSQI score of 4730 emergency nurses in public hospitals was 8.2 ± 3.9, including 3114 (65.8%) subjects with PSQI > 5 and 2905 (61.4%) > 8; these figures were found highest for 337 emergency nurses in 14 tertiary hospitals with 11.8 ± 4.3, 257 (76.3%) and 232 (68.8%), followed by 1044 emergency nurses in 43 secondary hospitals with 9.5 ± 3.9, 725 (69.4%) and 675 (64.7%) and 3349 emergency nurses in 167 primary hospitals with 7.4 ± 3.5, 2132 (63.7%) and 1998 (59.7%). The following factors were associated with poor sleep: hospital level (tertiary vs. primary, secondary vs. primary), female sex, less of exercise, long work hours per week, many patients in the charge of at night, high monthly night shift frequency (4–6 vs. never, ≥7 vs. never) and high occupational stress. Conclusions The sleep quality of emergency nurses in public hospitals in China was poor, especially in tertiary hospitals. Many factors as listed above, especially occupational stress, night shift taking and workload at night, should be considered when improving emergency nurses’ sleep quality.

Abstract Silicon (Si) has been widely employed in agriculture to enhance resistance against pathogens in many crop plants. However, the underlying molecular mechanisms of Si-mediated resistance remain elusive. In this study, the Arabidopsis-powdery mildew pathosystem was employed to investigate possible defense mechanisms of Si-mediated resistance. Because Arabidopsis lacks efficient Si transporters and thus is a low Si-accumulator, two heterologous Si influx transporters (from barley and muskmelon) were individually expressed in wild-type Arabidopsis Col-0 and a panel of mutants defective in different immune signaling pathways. Results from infection tests showed that while very low leaf Si content slightly induced salicylic acid (SA)-dependent resistance, high Si promoted PAD4-dependent but largely EDS1- and SA-independent resistance against the adapted powdery mildew isolate Golovinomyces cichoracearum UCSC1. Intriguingly, our results also showed that high Si could largely reboot non-host resistance in an immune-compromised eds1/pad4/sid2 triple mutant background against a non-adapted powdery mildew isolate G. cichoracearum UMSG1. Taken together, our results suggest that assimilated Si modulates distinct, multi-layered defense mechanisms to enhance plant resistance against adapted and no-adapted powdery mildew pathogens, possibly via synergistic interaction with defense-induced callose.

Abstract Background Extrinsic black stain (EBS) is characterized by discrete dark dots or lines on the tooth surface. The relationship between EBS and oral microbiota in children remains elusive. The aim of this study was to compare dental plaque microbiome in EBS children with that in EBS-free children in the primary dentition. Methods The Illumina MiSeq sequencing technique was utilized in the cross-sectional pilot study to investigate the diversity and composition of the supragingival plaque microbiota from 10 EBS-positive and 10 EBS-free children. The results were analysed with nonparametric Mann-Whitney U test, Pearson Chi-Square test, Fisher’s Exact test and one-way ANOVA tests. Results We identified 13 different phyla, 22 classes, 33 orders, 54 families, 105 genera, and 227 species from a total of 52,646 high-quality sequences. Between two groups, no statistical differences were observed in the estimators of community richness and diversity at 97% similarity, as well as in the Unweighted Unifrac principal co-ordinates analysis (PCoA). At the species level, higher level of relative abundance of Actinomyces naeslundii and lower level of relative abundance of a species belonging to Candidate_division_TM7 was observed in dental plaque of EBS-positive subjects, compared to dental plaque of EBS-free subjects (P

Abstract Background There is much value in identifying non-invasive ways of measuring endometrial receptivity, as it has the potential to improve outcomes following in vitro fertilization (IVF). It has been suggested that endometrial echogenicity on the day of hCG administration was a good marker of endometrial receptivity. In the daily practice, we notice that patients with non-homogeneous hyperechoic endometrium on the embryo transfer day usually have lower pregnancy rates. We therefore extended the research onward transformation of echo pattern after hCG trigger to analyze the relationship between endometrial echogenicity transformation and IVF outcomes. Methods A total of 146 infertile women undergoing their first IVF cycle were recruited in the prospective cohort study from August 2017 through August 2018. A series of endometrial echo pattern monitoring was carried out in these patients after hCG trigger: hCG day, from 1 through 3 days after ovum pick-up (OPU + 1, OPU + 2, OPU + 3). Results The endometrial echogenicity value was calculated as the ratio of the hyperechogenic endometrial area over the whole endometrial area. Clinical pregnancy rate and embryo implantation rate had positive relationship with echogenicity value. The ROC curve analysis of endometrial echogenicity showed the area under curve was greatest on the second day after oocyte retrieval (OPU + 1, 2, 3 were 0.738, 0.765, 0.714 respectively) versus pregnancy. Endometrial echogenicity value on OPU + 2 had a higher predictive efficiency, and the cutoff value was 76.5%. The sensitivity was 61.3% and specificity was 82.0%. When putting the cut-off at

Abstract Background This systematic review aimed to assess the clinical effects of laser preparation compared to other types of chemical or mechanical preparation of tooth surfaces used in fissure sealant placement. Methods A systematic literature search was conducted up to January 2019, through Pubmed, Scopus, Medline/EMBASE via OVID and the Cochrane library. Only randomized clinical trials were included. Results Five studies were included in the systematic review and three were included in the meta-analysis. All the studies used acid-etching as a comparator to lasers. All the included studies were rated as having an overall high risk of bias introduced by performance bias. Three studies assessed the clinical effects of fissure sealants placed by acid or laser etching, one compared acid etching versus laser combined with acid etching and one investigated the influence of lasers on the objective and subjective parameters of stress during sealant application in children. The meta-analysis showed no significant difference between laser preparation and conventional acid-etching preparation at 3- (P = 0.08), 6- (P = 0.49), and 12-month (P = 0.87) follow-ups. One study reported that laser preparation as an adjunct to acid-etching enhanced the retention rate. No significant difference in the incidence of caries was reported. And no significant differences were found in heart rates, oxygen saturation or degree of the patient dental anxiety between acid-etching and laser preparation. Conclusion The present limited evidence suggests that lasers could be an effective pretreatment method. The retention rate was similar to that of conventional acid etching. However, the included studies had an overall high risk of bias and more rigorously designed research is needed.

Abstract Background Musculoskeletal disorders (MSDs) are prevalent in working populations and could result in a number of detrimental consequences. In China, healthcare professionals (HCP) in large hospitals may be likely to suffer from MSDs considering the facts of shortages in medical staff, the large Chinese population base, the aging of the population and patients’ inclination to go to large hospitals. This study aimed to determine the prevalence and factors associated with MSDs among HCP working in tertiary hospitals. Methods A self-administered questionnaire incorporating the Nordic Musculoskeletal Questionnaire and the Dutch Musculoskeletal Questionnaire was conducted among 14,720 HCP in eight tertiary hospitals selected by random cluster sampling in Shandong, China. Multivariable logistic regression analysis was used to quantify the association of psychological, ergonomic, organizational and individual factors with MSDs. Results The 12-month period prevalence rate of experiencing an MSD in at least one body region for at least 24 h, experiencing an MSD for at least three months, and seeking health care for this condition were 91.2, 17.1 and 68.3%, respectively; these rates were highest for the lower back (72.8, 14.3, 60.3%) and knees (65.7, 8.1, 46.7%), followed by the shoulders (52.1, 6.2, 38.9%), neck (47.6, 4.8, 32.6%), wrists/hands (31.1, 3.2, 23.1%), ankles/feet (23.6, 1.9, 13.4%), upper back, hips/thighs and elbows. MSDs were associated with workload (work hours per week, break times during workday), psychological factors (psychological fatigue, mental stress), employment status and ergonomic factors. Regarding the ergonomic factors, lower back MSDs were associated with bending the trunk frequently, heavy or awkward lifting, and bending or twisting the neck; knee MSDs were associated with walking or standing for long periods of time; and shoulder MSDs were associated with maintaining shoulder abduction for long periods of time and bending or twisting the neck. Conclusions MSDs among HCP in tertiary hospitals in Mainland China were highly prevalent. The many factors listed above should be considered in the prevention of MSDs in HCP.

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Aberrant expressed genes contribute to the development and progression of T-ALL. However, the regulation underlying their aberrant expression remains elusive. Dysregulated expression of transcription factors and miRNAs played important regulatory roles in the pathogenesis of T-ALL. Methods In this study, we analyzed the alteration of transcriptome profiling and regulatory networks between T-ALL sample and normal T cell samples at transcriptional and post-transcriptional levels. Results Our results demonstrated that genes related to cell cycle and cell proliferation processes were significantly upregulated in T-ALL comparing to normal samples. Meanwhile, regulatory network analyses revealed that FOXM1, MYB, SOX4 and miR-21/19b as core regulators played vital roles in the development of T-ALL. FOXM1-miR-21-5p-CDC25A and MYB/SOX4-miR-19b-3p-RBBP8 were identified as important feed-forward loops involved in the oncogenesis of T-ALL. Drug-specific analyses showed that GSK-J4 may be an effective drug, and CDC25A/CAPN2/MCM2 could serve as potential therapeutic targets for T-ALL. Conclusions This study may provide novel insights for the regulatory mechanisms underlying the development of T-ALL and potential therapeutic targets.

Abstract Background There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm. Case presentation Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects. Conclusions Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.

Abstract Background Lipopolysaccharide (LPS) from Helicobacter pylori (HP) plays an important role in gastric cancer occurrence and development. Toll-like receptor 4 (TLR4) and myeloid differential protein-2 (MD-2) are also reported to be involved in gastric cancer cell proliferation and invasion. CXC chemokine receptor 7 (CXCR7), a second receptor for CXCL12, has been detected in multiple types of tumor tissues. Nevertheless, the biological function and regulation of CXCR7 and its relationship with TLR4 and MD-2 in gastric cancer are not completely understood and therefore warrant further study. Methods CXCR7 expression was examined in 150 gastric cancer tissues using immunohistochemistry (IHC). RT-PCR and western blotting were used to detect CXCR7 expression in several gastric cancer cell lines (SGC7901, AGS, MGC-803, MKN-45 and BGC823). shRNAs were designed using a pGPU6/GFP/Neo vector. A CCK-8 assay was used to assess cell proliferation, and transwell assays were performed to assess cell migration. In addition, a gastric cancer xenograft model was generated. Results The LPS-TLR4-MD-2 pathway elevates CXCR7 expression in SGC7901 cells, and TLR4/MD-2-mediated increases in CXCR7 levels modulate the proliferation and migration of tumor cells. Knockdown of TLR4 and MD-2 demonstrated that both are essential for LPS-induced CXCR7 expression, which in turn is responsible for LPS-induced SGC7901 cell proliferation and migration. Moreover, higher TLR4, MD-2 and CXCR7 expression was detected in gastric cancer tissues than in paracancerous normal control tissues. The expression levels of TLR4, MD-2 and CXCR7 were closely related to gastric cancer TNM stage and lymph node metastasis. In an animal model, significant differences in CXCR7 expression in tumor masses were observed between the control group and experimental group. Conclusions The results of this study indicate that CXCR7 plays an important role in gastric cancer progression via inflammatory mechanisms, suggesting that CXCR7 could provide a basis for the development and clinical application of a targeted drug for gastric cancer.

Abstract Background Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery that influences the clinical outcomes and quality of life of patients. This study aimed to evaluate the effects of Shenmai injection (SMI) on POCD of patients who underwent cardiac valve replacement under cardiopulmonary bypass (CPB). Methods This prospective, randomized, controlled trial was conducted from September 2014 to January 2017. Eighty-eight patients receiving cardiac valve replacement under CPB were randomized into the control (C) or the SMI (S) group. SMI (0.6 mL/kg) was administered intravenously from the time of anesthesia induction to the beginning of CPB. Cognitive function was assessed at 3 days before surgery and 3 days, 7 days, and 1 month after surgery using the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) score. The serum levels of neuroglobin (Ngb), hypoxia-inducible factor-1α (HIF-1α), and neuron-specific enolase (NSE) were measured at 30 min after induction (T0), immediately after the endonasal temperature rewarmed to 36 °C (T1), and 1 h (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after CPB. Results Compared with the baseline values at T0, the serum Ngb levels in group C were significantly decreased at T1–2 and then increased at T3–6, while the levels in group S were decreased at T1–2 and increased at T4–6, compared to group C (p

Abstract Background Powdery mildew (PM) is one of the most important and widespread plant diseases caused by biotrophic fungi. Notably, while monocot (grass) PM fungi exhibit high-level of host-specialization, many dicot PM fungi display a broad host range. To understand such distinct modes of host-adaptation, we sequenced the genomes of four dicot PM biotypes belonging to Golovinomyces cichoracearum or Oidium neolycopersici. Results We compared genomes of the four dicot PM together with those of Blumeria graminis f.sp. hordei (both DH14 and RACE1 isolates), B. graminis f.sp. tritici, and Erysiphe necator infectious on barley, wheat and grapevine, respectively. We found that despite having a similar gene number (6620–6961), the PM genomes vary from 120 to 222 Mb in size. This high-level of genome size variation is indicative of highly differential transposon activities in the PM genomes. While the total number of genes in any given PM genome is only about half of that in the genomes of closely related ascomycete fungi, most (~ 93%) of the ascomycete core genes (ACGs) can be found in the PM genomes. Yet, 186 ACGs were found absent in at least two of the eight PM genomes, of which 35 are missing in some dicot PM biotypes, but present in the three monocot PM genomes, indicating remarkable, independent and perhaps ongoing gene loss in different PM lineages. Consistent with this, we found that only 4192 (3819 singleton) genes are shared by all the eight PM genomes, the remaining genes are lineage- or biotype-specific. Strikingly, whereas the three monocot PM genomes possess up to 661 genes encoding candidate secreted effector proteins (CSEPs) with families containing up to 38 members, all the five dicot PM fungi have only 116–175 genes encoding CSEPs with limited gene amplification. Conclusions Compared to monocot (grass) PM fungi, dicot PM fungi have a much smaller effectorome. This is consistent with their contrasting modes of host-adaption: while the monocot PM fungi show a high-level of host specialization, which may reflect an advanced host-pathogen arms race, the dicot PM fungi tend to practice polyphagy, which might have lessened selective pressure for escalating an with a particular host.

Abstract Background In China, cervical cancer is the fifth most commonly diagnosed cancer, and the outcomes for patients with advanced or recurrent disease are poor. Apatinib, a small molecule inhibitor of vascular endothelial growth factor receptor (VEGFR-2), is an orally bioavailable agent, which has shown survival benefit in multiple solid tumors. Based on previous research, this phase II clinical trial aims to verify apatinib’s efficacy and safety in patients with advanced or recurrent cervical cancer. Methods/design This randomized, parallel arm, open-label, interventional trial will be carried out to evaluate the efficacy and the safety of apatinib for advanced or recurrent cervical cancer. A total of 60 eligible patients will be allocated by intention, in a ratio of 1:1, to either the experimental group or the control group. The primary endpoint is progression-free survival, the secondary endpoints include overall survival, disease control rate, objective response rate, quality of life, and adverse events. Assessments will be carried out before enrolment (baseline) and every 4 weeks after treatment. Discussion The aim of this trial is to demonstrate the clinical effect, safety, and side effects of apatinib in the treatment of advanced or recurrent cervical cancer. This study will clarify the efficacy and safety of this regimen. Trial registration Chinese Clinical Trials Registry, ChiCTR-OIN-17012164. Registered on 24 July 2017.

Abstract Background Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) ‘Hongyang’ draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. Results A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within ‘Hongyang’ The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned ‘Hort16A’ cDNAs and comparing with the predicted protein models for Red5 and both the original ‘Hongyang’ assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised ‘Hongyang’ annotation, respectively, compared with 90.9% to the Red5 models. Conclusions Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.

Abstract Background There exist contradictive views on whether the vitamin D has association with clinical outcome of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). The present meta-analysis aim to establish whether vitamin D was associated with clinical outcomes of IVF/ICSI. Methods MEDLINE, Google Scholar and the Cochrane Library from database inception to March 2017 were searched. Clinical studies, which evaluated the association of vitamin D level and the clinical outcomes after IVF/ICSI, were included. The Main Outcome Measures were clinical pregnancy, ongoing pregnancy, and live birth. Results In the analysis of clinical pregnancy, 9 cohort studies were included. Of which, 2 studies and 3 studies were identified in analyzing ongoing pregnancy and live birth, respectively. Meta-analysis showed trends toward lower clinical pregnancy [RR 0.91, (95% CI 0.77–1.07)] and higher ongoing pregnancy [RR 1.06, (95% CI 0.95–1.19)] for women with deficient level of vitamin D. The probability of live birth for women with deficient level of vitamin D was significantly lower than cases with sufficient level of vitamin D [RR 0.74, (95% CI 0.58–0.90)]. Conclusions Deficient vitamin D was associated with decreased probability of live birth after IVF/ICSI. So vitamin D should be supplied to women with deficient level vitamin D.

Abstract Background Retinoblastoma is the most common intraocular malignancy occurring in children. It can metastasize to the regional lymph nodes, central nervous system and distant organs usually the bones and bone marrow and very rarely to the soft tissue. Here, we report a case of unilateral retinoblastoma in a 4-year-old girl accompanied by a large metastasis of the parotid and submandibular glands that developed about 6 months previously and gradually increased in size 5 months after enucleation of the left eye. Case presentation A 4-year-old girl with a history of unilateral retinoblastoma presented with a large, painful and worsening mass (about 20 × 23 cm) of the left side of the neck. Following surgery, the orbital tumour was completely resected, and the large tumour invasion range in the left side of the neck was not resected completely. Histopathological examination revealed retinoblastoma of the orbit and the parotid and submandibular glands. After chemotherapy and additional local radiotherapy on the parotid and submandibular glands, the tumour was inactive and stable. Conclusions Delayed detection and inappropriate management contribute to poor outcomes. Fundus examinations, education regarding the early signs of RB, and optimization of the therapeutic strategy for RB may play important roles in ocular health.

Abstract Background Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality. Chemical and virus induction are two major risk factors, however, the potential molecular mechanisms of their differences remain elusive. In this study, to identify the similarities and differences between chemical and virus induced HCC models, we compared the gene expression profiles between DEN and HBx mice models, as well as the differences among tumor, para-tumor and normal tissues. Methods We sequenced both gene and microRNA (miRNA) expression for HCC tumor tissues, para-tumor and normal liver tissues from DEN model mice (30-week-old) and downloaded the corresponding microarray expression data of HBx model from GEO database. Then differentially expressed genes (DEGs), miRNAs and transcription factors (TFs) were detected by R packages and performed functional enrichment analysis. To explore the gene regulatory network in HCC models, miRNA and TF regulatory networks were constructed by target prediction. Results For model comparison, although DEGs between tumor and normal tissues in DEN and HBx models only had a small part of overlapping, they shared common pathways including lipid metabolism, oxidation-reduction process and immune process. For tissue comparisons in each model, genes in oxidation-reduction process were down-regulated in tumor tissues and genes in inflammatory response showed the highest expression level in para-tumor tissues. Genes highly expressed in both tumor and para-tumor tissues in two models mainly participated in immune and inflammatory response. Genes expressed in HBx model were also involved in cell proliferation and cell migration etc. Network analysis revealed that several miRNAs such as miR-381-3p, miR-142a-3p, miR-214-3p and TFs such as Egr1, Atf3 and Klf4 were the core regulators in HCC. Conclusions Through the comparative analyses, we found that para-tumor tissue is a highly inflammatory tissue while the tumor tissue is specific with both inflammatory and cancer signaling pathways. The DEN and HBx mice models have different gene expression pattern but shared pathways. This work will help to elucidate the molecular mechanisms underlying different HCC models.