Search

Abstract Background Good gastric preparation is indispensable for Magnetic-controlled Capsule Endoscopy (MCE) examination, but there is no consensus yet. We aim to explore the clinical application value of positioning exercises in improving the quality of MCE examination. Methods Clinical data of 326 patients who underwent MCE examination from January 2020 to December 2023 were collected. The included patients were divided into two groups: the conventional medication preparation group (CMP group, accepted mucosal cleansing medication only) and the positioning exercises group (PE group, accepted mucosal cleansing medication plus positioning exercises). A comparison was made between the two groups in terms of gastric cavity cleanliness score, visibility score, and detection rate of positive lesions. Results The examination time was (21.29 ± 5.82) minutes in the PE group and (30.54 ± 6.37) minutes in the CMP group, showing a significant difference between the two groups (P 0.05). Conclusion Positioning exercises before MCE examination can improve the quality of gastric mucosal images and reduce the duration of the examination for patients.

Abstract It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.

Abstract With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications. Graphical Abstract

Abstract Background Studies has suggested that receiving social support improves the professional identity of health professional students. According to the two-way social support theory, social support includes receiving social support and giving social support. However, the effect of the two-way social support on health professional students’ professional identity has not been clarified yet. Methods To explore the mechanism of how two-way social support affects health professional students’ professional identity, an observational, cross-sectional study was conducted among a convenience and cluster sample of 1449 health professional students from two medical schools in western China. Measures included a short version of the two-way social support scale, a health professional students’ professional identity questionnaire, an achievement motivation scale, and a meaning in life scale. (Data were analyzed by use of SPSS26.0 software, Amos 28.0 software, and PROCESSv4.0 plug-in.). Results Receiving social support, giving social support, achievement motivation, meaning in life, and professional identity were positively correlated with each other. Receiving and giving social support not only directly predicted health professional students’ professional identity, but also indirectly predicted health professional students’ professional identity through the mediating roles of achievement motivation and meaning in life, and the chain mediating roles of achievement motivation and meaning in life, respectively. The effectiveness of predicting health professional students’ professional identity varied among different types of two-way social support, which could be depicted as two-way social support > mainly giving social support > mainly receiving social support > low two-way social support. Conclusion In the medical education, the awareness and ability of health professional students to receive and give social support should be strengthened. More attention should be drawn on the chain mediating effect of achievement motivation and meaning in life between two-way social support and professional identity. The current results shed new light on exploring effective ways of improving health professional students’ professional identity, which suggested that more attention should be paid to the positive effects of mainly giving social support and two-way social support rather than only on the effects of receiving social support.

Background: Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori ( H. pylori ) treatment interventions or provide adjunctive therapy. The objective of this meta-analysis was to evaluate whether Lactobacillus reuteri ( L. reuteri ) could improve H. pylori eradication rate, reduce the incidence of adverse events (AEs), and alleviate gastrointestinal symptoms. Design: A meta-analysis of randomized controlled trials (RCTs) comparing L. reuteri supplementation therapy with placebo was conducted. Sources and methods: We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate, and the scores on the Gastrointestinal Symptom Rating Scale and AEs were secondary outcomes. Results: Eight RCTs including 1087 patients were included in this analysis. The L. reuteri supplementation group showed significantly higher H. pylori eradication rates in both intention-to-treat (ITT) and per-protocol (PP) analysis [ITT: 80.0% versus 72.6%; p = 0.005, relative risk (RR): 1.10; 95% confidence interval (CI): 1.03–1.17; number needed to treat (NNT) = 14; PP: 81.8% versus 75.0%; p = 0.006, RR: 1.09; 95% CI: 1.03–1.16; NNT = 15]. Patients treated with L. reuteri showed greater improvements in gastrointestinal symptoms (pooled mean difference: −2.43, 95% CI: −4.56 to −0.29, p = 0.03). The incidence of AEs was significantly reduced in the L. reuteri supplementation group based on ITT and PP analysis (ITT: p

Iconic memory and short-term memory are not only crucial for perception and cognition, but also of great importance to mental health. Here, we first showed that both types of memory could be improved by improving limiting processes in visual processing through perceptual learning. Normal adults were trained in a contrast detection task for ten days, with their higher-order aberrations (HOA) corrected in real-time. We found that the training improved not only their contrast sensitivity function (CSF), but also their iconic memory and baseline information maintenance for short-term memory, and the relationship between memory and CSF improvements could be well-predicted by an observer model. These results suggest that training the limiting component of a cognitive task with visual perceptual learning could improve visual cognition. They may also provide an empirical foundation for new therapies to treat people with poor sensory memory.

Abstract Purpose Anxiety is a common emotion experienced by patients with prostate cancer (PCa), and can be exacerbated by testing the prostate-specific antigen (PSA) index. The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) was developed to assess the cancer-specific anxiety of these patients, but lack of appropriate thresholds for this scale limits its use. This study aimed to utilize ROC curve analysis to identify the best cut-off values for the Chinese version of the MAX-PC scale. Methods A cross-sectional survey was conducted using the Chinese version of the MAX-PC scale and the Generalized Anxiety Disorder Scale (GAD). ROC curve analysis, Youden index, Kappa consistency test and McNemar test were used for the optimal cutoff points for screening mild, moderate, and severe cancer-specific anxiety levels in patients with PCa, on the Chinese version of the MAX-PC scale. Results Two hundred eighty-seven patients with PCa completed the survey. The appropriate cut-off values for the MAX-PC scale for screening patients with PCa for cancer-specific anxiety were 20, 28, and 38 for mild, moderate, and severe anxiety, respectively with the highest Youden indices. The Kappa and McNemar’s test showed the best level of consistency with values of 0.627, 0.580, and 0.606 for screening mild, moderate, and severe anxiety, respectively. Conclusions The scores 20, 28, and 38 are the best cut-off values for the Chinese version of the MAX-PC scale. This scale should be used for screening cancer-specific anxiety for patients with PCa to assess and evaluate their anxiety levels and provide targeted interventions.

Multimodal knowledge graph completion necessitates the integration of information from multiple modalities (such as images and text) into the structural representation of entities to improve link prediction. However, most existing studies have overlooked the interaction between different modalities and the symmetry in the modal fusion process. To address this issue, this paper proposed a Transformer-based knowledge graph link prediction model (MM-Transformer) that fuses multimodal features. Different modal encoders are employed to extract structural, visual, and textual features, and symmetrical hybrid key-value calculations are performed on features from different modalities based on the Transformer architecture. The similarities of textual tags to structural tags and visual tags are calculated and aggregated, respectively, and multimodal entity representations are modeled and optimized to reduce the heterogeneity of the representations. The experimental results show that compared with the current multimodal SOTA method, MKGformer, MM-Transformer improves the Hits@1 and Hits@10 evaluation indicators by 1.17% and 1.39%, respectively, proving that the proposed method can effectively solve the problem of multimodal feature fusion in the knowledge graph link prediction task.

Combination immunotherapy of cancer vaccines with immune checkpoint inhibitors (ICIs) represents a promising therapeutic strategy for immunosuppressed and cold tumors. However, this strategy still faces challenges, including the limited therapeutic efficacy of cancer vaccines and immune-related adverse events associated with systematic delivery of ICIs. Herein, we demonstrate the antitumor immune response induced by outer membrane vesicle from Akkermansia muciniphila (Akk-OMV), which exhibites a favorable safety profile, highlighting the potential application as a natural and biocompatible self-adjuvanting vesicle. Utilizing tumor cell-derived exosome as an antigen source and Akk-OMV as a natural adjuvant, we construct a cancer vaccine formulation of extracellular vesicles hybrid lipid nanovesicles (Lipo@HEV) for enhanced prophylactic and therapeutic vaccination by promoting dendritic cell (DC) maturation in lymph node and activating cytotoxic T cell (CTL) response. The Lipo@HEV is further loaded with plasmid to enable gene therapy-mediated PD-L1 blockade upon peritumoral injection. Meanwhile, it penetrates into lymph node to initiate DC maturation and CTL activation, synergistically inhibiting the established tumor. The fabrication of extracellular vesicles hybrid plasmid-loaded lipid nanovesicles reveals a promising gene therapy-guided and vesicle-based hybrid system for therapeutic cancer vaccination and synergistic immunotherapy strategy.

Abstract. Background:. Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. Methods:. This cross-sectional study enrolled all infants born at 24+0 to 31+6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. Results:. A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks’ gestation to 3120/3960 (78.8%) at 30 to 31 weeks’ gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. Conclusions:. The use rate of ACS remained low for infants at 24 to 31 weeks’ gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

The nonuniform distribution of interference spectrum in wavenumber k-space is a key issue to limit the imaging quality of Fourier-domain optical coherence tomography (FD-OCT). At present, the reconstruction quality at different depths among a variety of processing methods in k-space is still uncertain. Using simulated and experimental interference spectra at different depths, the effects of common six processing methods including uniform resampling (linear interpolation (LI), cubic spline interpolation (CSI), time-domain interpolation (TDI), and K-B window convolution) and nonuniform sampling direct-reconstruction (Lomb periodogram (LP) and nonuniform discrete Fourier transform (NDFT)) on the reconstruction quality of FD-OCT were quantitatively analyzed and compared in this work. The results obtained by using simulated and experimental data were coincident. From the experimental results, the averaged peak intensity, axial resolution, and signal-to-noise ratio (SNR) of NDFT at depth from 0.5 to 3.0[Formula: see text]mm were improved by about 1.9[Formula: see text]dB, 1.4 times, and 11.8[Formula: see text]dB, respectively, compared to the averaged indices of all the uniform resampling methods at all depths. Similarly, the improvements of the above three indices of LP were 2.0[Formula: see text]dB, 1.4 times, and 11.7[Formula: see text]dB, respectively. The analysis method and the results obtained in this work are helpful to select an appropriate processing method in k-space, so as to improve the imaging quality of FD-OCT.

Nitrogen self-doped hierarchical porous carbon for electrical double-layer capacitors was synthesized by direct carbonization of bean dregs-based tar with potassium acetate as the template agent. The pore structure parameters and chemical element composition were adjusted by varying the heating rate during the carbonization process. The electrochemical properties of the electrode materials were evaluated in a three electrode system with 6 M KOH as the electrolyte. The resultant bean dregs-based porous carbons (BDPCs) exhibited high specific surface area, unique hierarchical architecture (consisting of supermicro- and mesopores), and medium nitrogen content (0.66 to 0.78%). The BDPC-10 sample had the highest specific surface area of 1610 m2/g and reasonable pore size distribution, and consequently exhibited an excellent specific capacitance of 363.7 F/g at the current density of 1 A/g. Nevertheless, the capacitance was reduced to 280.5 F/g at 3 A/g, giving a capacitance retention ratio of 77.1%. This study suggests a facile and environmentally friendly template synthesis process for supercapacitor electrode materials preparation, but it also faces challenges to increase the rate capability.

Background: With the increase in antibiotic resistance, the success rate of Helicobacter pylori ( H. pylori ) eradication therapy has declined in recent years. Vonoprazan–amoxicillin (VA) dual therapy has been reported to be a promising regimen. Objectives: To compare the efficacy and safety of VA dual therapy and bismuth quadruple therapy containing amoxicillin and clarithromycin for H. pylori first-line eradication, and to further analyze the effects of clarithromycin resistance on eradication rate. Design: This study was a single-center, open-label, randomized controlled trial. Methods: Treatment-naïve H. pylori -infected patients were randomly allocated 1:1 to the VA group (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily, for 14 days) or the RBAC group (rabeprazole 10 mg, bismuth potassium citrate 220 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily, for 14 days). H. pylori clarithromycin resistance and CYP2C19 gene polymorphisms were detected with real-time polymerase chain reaction (PCR) technique. The eradication rates and adverse events were analyzed. Results: A total of 151 patients were enrolled. The intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) eradication rates and their 95% confidence intervals (95% CIs) were 94.6% (86.0–98.3%), 98.6% (91.3–99.9%), and 98.5% (90.9–99.9%) for VA group and 87.0% (77.0–93.3%), 91.8% (82.3–96.6%), and 93% (83.7–97.4%) for RBAC group. The eradication rate of the VA group was noninferior to the RBAC group in ITT, mITT, and PP analyses ( p

Background: The eradication rate of Helicobacter pylori infection with empirical therapy has decreased due to increased drug resistance. The latest guidelines recommend genotypic resistance-guided therapy, but its clinical efficacy remains unclear. Objectives: The purpose of our study was to evaluate whether tailored therapy based on genotypic resistance is superior to empirical therapy for H. pylori infection. Design: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing tailored therapy based on genotypic resistance with empirical therapy was performed. Sources and methods: We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate and the adverse events (AEs) was the secondary outcome. A random-effect model was applied to compare pooled risk ratios (RRs) with related 95% confidence intervals (CIs). Results: A total of 12 qualified RCTs containing 3940 patients were identified in our systematic review and meta-analysis. The pooled eradication rates of tailored therapy based on the detection of genotypic resistance were consistently higher than those in the empirical treatment group, with no statistical significance. In triple therapy, the eradication rate was significantly higher in the tailored group than in the empirical group by intention-to-treat analysis (ITT) and per-protocol analysis (PP) analysis ( p

Vernalization plays a crucial role in the flowering and yield of Chinese cabbage, a process intricately influenced by long non-coding RNAs (lncRNAs). Our research focused on lncFLC1, lncFLC2a, and lncFLC2b, which emerged as key players in this process. These lncRNAs exhibited an inverse expression pattern to the flowering repressor genes FLOWERING LOCUS C 1 (BrFLC1) and FLOWERING LOCUS C 2 (BrFLC2) during vernalization, suggesting a complex regulatory mechanism. Notably, their expression in the shoot apex and leaves was confirmed through in fluorescent in situ hybridization (FISH). Furthermore, when these lncRNAs were overexpressed in Arabidopsis, a noticeable acceleration in flowering was observed, unveiling functional similarities to Arabidopsis’s COLD ASSISTED INTRONIC NONCODING RNA (COOLAIR). This resemblance suggests a potentially conserved regulatory mechanism across species. This study not only enhances our understanding of lncRNAs in flowering regulation, but also opens up new possibilities for their application in agricultural practices.

Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one of the hotspots in the field of cancer research. Whereas aerobic glycolysis (known as the Warburg effect) has long been considered a dominant form of energy metabolism in cancer cells, emerging evidence indicates that other metabolic forms, especially oxidative phosphorylation (OXPHOS), may play a critical role at least in some types of cancer. Of note, women with metabolic syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, and hypertension, have an increased risk of developing endometrial carcinoma (EC), suggesting a close link between metabolism and EC. Interestingly, the metabolic preferences vary among EC cell types, particularly cancer stem cells and chemotherapy-resistant cells. Currently, it is commonly accepted that glycolysis is the main energy provider in EC cells, while OXPHOS is reduced or impaired. Moreover, agents specifically targeting the glycolysis and/or OXPHOS pathways can inhibit tumor cell growth and promote chemosensitization. For example, metformin and weight control not only reduce the incidence of EC but also improve the prognosis of EC patients. In this review, we comprehensively overview the current in-depth understanding of the relationship between metabolism and EC and provide up-to-date insights into the development of novel therapies targeting energy metabolism for auxiliary treatment in combination with chemotherapy for EC, especially those resistant to conventional chemotherapy.

Vernalization is a phenomenon in which plants must undergo a period of continuous low temperatures to change from the vegetative growth stage to the reproductive growth stage. Chinese cabbage is a heading vegetable, and flowering time is an essential developmental trait. Premature vernalization leads to premature bolting, which causes a loss of product value and yield. While research into vernalization has provided a wealth of information, a complete understanding of the molecular mechanism for controlling vernalization requirements has not yet been elucidated. In this study, using high-throughput RNA sequencing, we analyzed the plumule-vernalization response of mRNA and long noncoding RNA in the bolting-resistant Chinese cabbage double haploid (DH) line ‘Ju Hongxin’ (JHX). A total of 3382 lncRNAs were identified, of which 1553 differentially expressed (DE) lncRNAs were characterized as plumule-vernalization responses. The ceRNA network revealed that 280 ceRNA pairs participated in the plumule-vernalization reaction of Chinese cabbage. Through identifying DE lncRNAs in Chinese cabbage and analyzing anti-, cis-, and trans-functional analysis, some candidate lncRNAs related to vernalization promoting flowering of Chinese cabbage and their regulated mRNA genes were found. Moreover, the expression of several critical lncRNAs and their targets was verified using qRT-PCR. Furthermore, we identified the candidate plumule-vernalization-related long noncoding RNAs that regulate BrFLCs in Chinese cabbage, which was interesting and different from previous studies and was a new discovery. Our findings expand the knowledge of lncRNAs in the vernalization of Chinese cabbage, and the identified lncRNAs provide rich resources for future comparative and functional studies.

Keypoints Fermentation medium with high antagonistic activity of HR10 strain was determined. Antagonistic crude protein of HR10 strain purified by Ion-Exchange Chromatography. Composition of the antagonist protein of HR10 strain was analyzed using LC-MS-MS.

Abstract Chinese cabbage that prefers cold conditions is also affected by low-temperature stress, such as the accumulation of leaf anthocyanins. Research on anthocyanin biosynthesis and regulation mechanisms has made great progress. However, research on anthocyanin accumulation for resistance to biological and non-biological stress is still lacking. To study the relationship between anthocyanin accumulation of Chinese cabbage and resistance under low-temperature conditions, RNA sequencing (RNA-seq) was performed on Chinese cabbage ‘Xiao Baojian’ grown at a low temperature for four time periods and at a control temperature for five time periods. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 7954 differentially expressed genes (DEGs) were enriched, of which 587 DEGs belonged to "biosynthesis of other secondary metabolites." Gene temporal expression patterns were used to discover enriched genes related to phenylpropanoid biosynthesis; flavonoid biosynthesis and anthocyanin biosynthesis pathways were found in cluster 1. The interaction networks were constructed, and hub genes were selected, showing that flavonoid biosynthesis pathway genes (DFR, ANS, F3H, FLS1, CHS1, CHS3, and TT8) and defense mechanisms-related genes (DFR, SNL6, and TKPR1) interact with each other. Anthocyanin biosynthesis DEGs in Chinese cabbage were evaluated under low-temperature conditions to map the relevant pathways, and expression maps of transcription factors in the flavonoid pathway were created at various periods. Low temperature upregulated the expression of genes related to anthocyanin biosynthesis. Taken together, our results provide further analysis of the relationship between plant anthocyanin synthesis and stress resistance and may also provide further insights for the future development of high-quality color and cold-tolerant Chinese cabbage germplasm resources.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

BackgroundRetinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The purpose of our study was to analyze the association between the use of probiotics and retinopathy of prematurity.MethodsThis study retrospectively collected clinical data of premature infants with gestational age

Poly-ADP-ribose polymerase (PARP) plays an important role in DNA damage detection and repair. PARP inhibitors (PARPi) are a novel class of targeted agents used widely in the treatment of female cancer patients with BRCA mutations, including younger patients. However, the impact of PARPi on ovarian function remains a considerable problem in clinical practice. In this review article, we summarize the current understanding of PARPi's effects on the function of ovary and discuss their potential underlying mechanisms, highlighting the significance of further investigation on the criterion for ovarian failure and its preventive approaches during PARPi treatment.

Objective To assess the experiences and emotional reactions of men prior to receiving a prostate needle biopsy (PNB).Design This was a qualitative study involving (1) material research and filter, (2) interviewer training, (3) cognitive semistructured interviews with open-ended questions, (4) data analysis, including translation and back translation and (5) group discussions to determine common themes in the data. All interviews were digitally audio-recorded. The thematic analysis was conducted by repeatedly reading the data manuscript and engaging in group discussion.Setting and participants A total of 30 participants with suspected prostate cancer (PC) who were scheduled to receive a PNB were interviewed. Eligible participants were Chinese native men aged 51–77 years, and the study was conducted in China between September and December 2020. All participants were informed about the purpose of the study and provided written informed consent.Results Four main themes were identified based on the interview content: (1) fear (of pain, adverse effects and bad results), (2) impact of lower urinary tract symptoms (on emotional impact, work and sleeping), (3) inner struggles (relating to hesitation, regret and embarrassment) and (4) lifestyle change (including diet, exercise and receipt of traditional Chinese medicine).Conclusions This patient cohort had a low level of knowledge about PC and PNB. Providing additional education about these topics would help to reduce patient fear and anxiety and improve experiences of the procedure.

The non-invasive measurement of hemoglobin oxygen saturation (SO2) in retinal vessels is based on spectrophotometry and the absorption spectral characteristics of the tissue. The dual-wavelength retinal images are simultaneously captured via retinal oximetry. SO2 is calculated by processing a series of images and by calculating the optic density ratio of two images. However, existing SO2 research is focused on the thick vessels in the high-clarity region of retinal images. However, the thin vessels in the low-clarity region could provide significant information for the detection and diagnosis of neovascular diseases. To this end, we proposed a novel hybrid vessel segmentation algorithm. Firstly, a median filter was employed for image denoising. Secondly, high- and low-clarity region segmentation was carried out based on a clarity histogram. The vessels in the high-clarity areas were segmented after implementing a Gaussian filter, a matched filter, and morphological segmentation. Additionally, the vessels in the low-clarity areas were segmented using a guided filter, matched filtering, and dynamic threshold segmentation. Finally, the results were obtained through image merger and morphological operations. The experimental results and analysis show that the proposed method can effectively segment thick and thin vessels and can extend the measuring range of dual-wavelength retinal oximetry.

Artificial Intelligence (AI) is increasingly popular, and educators are paying increasing attention to it. For students, learning AI helps them better cope with emerging societal, technological, and environmental challenges. This theory of planned behavior (TPB)-based study developed a survey questionnaire to measure behavioral intention to learn AI (n = 682) among primary school students. The questionnaire was administered online, and it measured responses to five TPB factors. The five factors were (1) self-efficacy in learning AI, (2) AI readiness, (3) perceptions of the use of AI for social good, (4) AI literacy, and (5) behavioral intention. Exploratory factor analysis and a subsequent confirmatory factor analysis were used to validate this five-factor survey. Both analyses indicated satisfactory construct validity. A structural equation model (SEM) was constructed to elucidate the factors’ influence on intention to learn AI. According to the SEM, all factors could predict intention to learn AI, whether directly or indirectly. This study provides new insights for researchers and instructors who are promoting AI education in schools.

The mental health problems have been increasingly threatening the development of adolescence in China, it is very necessary to explore the protective factors preventing adolescents' negative mental health. Previous studies suggested that growth mindset benefits mental health. However, the internal psychological mechanism underlying this relationship is still unclear. This study investigated the relation between growth mindset and negative mental health among Chinese adolescence, and simultaneously tested the mediating effect of psychological resilience and the moderating role of gender in the mediation process of this relation. A total of 1204 middle school students (624 male students and 580 female students) in China completed measures on growth mindset, psychological resilience, and negative mental health. The results revealed that growth mindset not only directly predicted negative mental health, but also indirectly predicted negative mental health through the mediating path of psychological resilience. Moreover, the mediating effect of psychological resilience in the relationship between growth mindset and negative mental health was moderated for females and not males. These findings indicated that intervention focus on growth mindset could improve psychological resilience and prevent negative mental health among middle school students.

Abstract Background Vernalization is a type of low temperature stress used to promote rapid bolting and flowering in plants. Although rapid bolting and flowering promote the reproduction of Chinese cabbages (Brassica rapa L. ssp. pekinensis), this process causes their commercial value to decline. Clarifying the mechanisms of vernalization is essential for its further application. We performed RNA sequencing of gradient-vernalization in order to explore the reasons for the different bolting process of two Chinese cabbage accessions during vernalization. Results There was considerable variation in gene expression between different-bolting Chinese cabbage accessions during vernalization. Comparative transcriptome analysis and weighted gene co-expression network analysis (WGCNA) were performed for different-bolting Chinese cabbage during different vernalization periods. The biological function analysis and hub gene annotation of highly relevant modules revealed that shoot system morphogenesis and polysaccharide and sugar metabolism caused early-bolting ‘XBJ’ to bolt and flower faster; chitin, ABA and ethylene-activated signaling pathways were enriched in late-bolting ‘JWW’; and leaf senescence and carbohydrate metabolism enrichment were found in the two Chinese cabbage-related modules, indicating that these pathways may be related to bolting and flowering. The high connectivity of hub genes regulated vernalization, including MTHFR2, CPRD49, AAP8, endoglucanase 10, BXLs, GATLs, and WRKYs. Additionally, five genes related to flower development, BBX32 (binds to the FT promoter), SUS1 (increases FT expression), TSF (the closest homologue of FT), PAO and NAC029 (plays a role in leaf senescence), were expressed in the two Chinese cabbage accessions. Conclusion The present work provides a comprehensive overview of vernalization-related gene networks in two different-bolting Chinese cabbages during vernalization. In addition, the candidate pathways and hub genes related to vernalization identified here will serve as a reference for breeders in the regulation of Chinese cabbage production.

Dysregulated mucosal immunity plays an essential role in the pathophysiology of inflammatory bowel disease (IBD). Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable ion channel that is implicated in modulating immune responses. However, its role in the pathogenesis of intestinal inflammation remains elusive. Here, we found that TRPV1 gain of function significantly increased the susceptibility of mice to experimental colitis, and that was associated with excessive recruitment of dendritic cells and enhanced Th17 immune responses in the lamina propria of colon. TRPV1 gain of function promoted dendritic cell activation and cytokine production upon inflammatory stimuli, and consequently enhanced dendritic cell-mediated Th17 cell differentiation. Further mechanistic studies showed that TRPV1 gain of function in dendritic cells enhanced activation of calcineurin/nuclear factor of activated T cells (NFATc2) signaling induced by inflammatory stimuli. Moreover, in patients with IBD, TRPV1 expression was increased in lamina propria cells of inflamed colon compared with healthy controls. Our findings identify an important role for TRPV1 in modulating dendritic cell activation and sustaining Th17 responses to inflammatory stimuli, which suggest that TRPV1 might be a potential therapeutic target in controlling mucosal immunity and IBD.

Abstract Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial–mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.

High temperatures have a serious impact on the quality and yield of cold-loving Chinese cabbage, which has evolved to have a unique set of stress mechanisms. To explore the relationship between these mechanisms and the heat-tolerance of Chinese cabbage, the physiological indicators of the heat-tolerant ‘268’ line and heat-sensitive ‘334’ line were measured. Under heat stress, the proline (Pro), soluble sugar (SS), and superoxide dismutase (SOD) indexes of the ‘268’ line increased significantly. When additionally using transcriptome analysis, we found that the identified 3,360 DEGs were abundantly enriched in many metabolic pathways including ‘plant hormone signal transduction’, ‘carbon metabolism’, and ‘glycolysis/gluconeogenesis’. Dynamic gene expression patterns showed that HKL1 in Cluster 15 may be a key factor in the regulation of sugar homeostasis. The interaction network screened four ABA-related genes in Cluster 15, suggesting that high temperatures lead to changes in hormonal signaling, especially an increase in ABA signaling. Compared with the ‘334’ line, the expressions of Prx50, Prx52, Prx54, SOD1, and SOD2 in the ‘268’ line were significantly upregulated, and these genes were actively involved in the reactive oxygen species (ROS) scavenging process. In summary, our results revealed the relationship between plant heat tolerance, physiology, and biochemistry and may also provide ideas for the future development of high-quality and heat-tolerant Chinese cabbage germplasm resources.

Intestinal mucosal inflammation and epithelial barrier dysfunction have been implicated as pathological factors in inflammatory bowel disease (IBD). An emerging area of IBD research focuses on probiotics. The probiotic Escherichia coli Nissle 1917 (EcN) is an excellent choice for engineering therapeutic microbes. Elafin is an endogenous specific inhibitor of neutrophil elastase (NE) and proteinase 3, and we previously found Elafin can effectively suppress the development of colitis. Here, we genetically engineered EcN to deliver Elafin (EcN-Elafin) directly to the colonic mucosa and explored the protective effects of EcN-Elafin against colitis in mice. EcN-Elafin significantly alleviated dextran sodium sulfate (DSS) induced colitis. Compared with wild-type EcN, oral administration of EcN-Elafin displayed better effects on loss of weight, colon length shortening, elevated expression of myeloperoxidase (MPO), and proinflammatory cytokines and chemokine in colonic tissues. In addition, EcN-Elafin restored the expression and distribution of tight junction protein ZO-1 in colonic tissues back to normal. In a damaged colonic epithelial model utilizing Caco-2 cells stimulated with TNF-α, EcN-Elafin efficiently downregulated the activation level of NF-κB signaling. EcN-Elafin was also found to have restored the dysbiosis in gut caused by DSS administration. Moreover, EcN-Elafin significantly enhanced the concentrations of butyrate and valerate in the gut lumen. Thus, our findings demonstrated that EcN-Elafin enhanced the colonic epithelial barrier, promoted the resolution of inflammation, modulated the gut microbiota, and elevated concentrations of short-chain fatty acids (SCFAs) in the gut. EcN-Elafin may be a potential therapeutic method for IBD.

The introduction of various targeted agents into the armamentarium of cancer treatment has revolutionized the standard care of patients with cancer. However, like conventional chemotherapy, drug resistance, either preexisting (primary or intrinsic resistance) or developed following treatment (secondary or acquired resistance), remains the Achilles heel of all targeted agents with no exception, via either genetic or non-genetic mechanisms. In the latter, emerging evidence supports the notion that intracellular signaling pathways for tumor cell survival act as a mutually interdependent network via extensive cross-talks and feedback loops. Thus, dysregulations of multiple signaling pathways usually join forces to drive oncogenesis, tumor progression, invasion, metastasis, and drug resistance, thereby providing a basis for so-called “bypass” mechanisms underlying non-genetic resistance in response to targeted agents. In this context, simultaneous interruption of two or more related targets or pathways (an approach called dual-targeted therapy, DTT), via either linear or parallel inhibition, is required to deal with such a form of drug resistance to targeted agents that specifically inhibit a single oncoprotein or oncogenic pathway. Together, while most types of tumor cells are often addicted to two or more targets or pathways or can switch their dependency between them, DTT targeting either intrinsically activated or drug-induced compensatory targets/pathways would efficiently overcome drug resistance caused by non-genetic events, with a great opportunity that those resistant cells might be particularly more vulnerable. In this review article, we discuss, with our experience, diverse mechanisms for non-genetic resistance to targeted agents and the rationales to circumvent them in the treatment of cancer, emphasizing hematologic malignancies.

There are complex interactions between mycorrhizal helper bacteria (MHBs) and ectomycorrhizal (ECM) fungi, with MHBs promoting mycorrhizal synthesis and ECM fungi regulating plant rhizobacterial colonization, diversity, and function. In this study, to investigate whether the ECM fungus Hymenochaete sp. Rl affects the survival and colonization of the MHB strain Bacillus pumilus HR10 in the rhizosphere, the biomass of B. pumilus HR10 was measured in the rhizosphere and mycorrhizosphere. In addition, extracts of Hymenochaete sp. Rl and Pinus thunbergii were evaluated for their effect on B. pumilus HR10 colonization (growth, sporulation, biofilm formation, extracellular polysaccharide and extracellular protein contents, flagellar motility, and expression of colonization-related genes). The results showed that inoculation of Hymenochaete sp. Rl significantly increased the biomass of B. pumilus HR10 in the rhizosphere; however, while extracts of Hymenochaete sp. Rl and P. thunbergii did not affect the biomass or spore formation of HR10, they did affect its biofilm formation, extracellular polysaccharide and extracellular protein production, and flagellar motility. Furthermore, the addition of symbiont extracts affected the expression of chemotaxis-related genes in HR10. When the extracts were added separately, the expression of srf genes in HR10 increased; when the extracts were added simultaneously, the expression of the flagellin gene fliG in HR10 increased, but there was no significant effect on the expression of srf genes, consistent with the results on biofilm production. Thus, Hymenochaete sp. Rl and P. thunbergii roots had a positive effect on colonization by B. pumilus HR10 at the rhizosphere level through their secretions.

Cervical cancer is the most prevalent gynecologic malignancy, especially in women of low- and middle-income countries (LMICs). With a better understanding of the etiology and pathogenesis of cervical cancer, it has been well accepted that this type of cancer can be prevented and treated via early screening. Due to its higher sensitivity than cytology to identify precursor lesions of cervical cancer, detection of high-risk human papillomavirus (HR-HPV) DNA has been implemented as the primary screening approach. However, a high referral rate for colposcopy after HR-HPV DNA detection due to its low specificity in HR-HPV screening often leads to overtreatment and thus increases the healthcare burden. Emerging evidence has demonstrated that detection of host cell gene and/or HPV DNA methylation represents a promising approach for the early triage of cervical cancer in HR-HPV-positive women owing to its convenience and comparable performance to cytology, particularly in LMICs with limited healthcare resources. While numerous potential markers involving DNA methylation of host cell genes and the HPV genome have been identified thus far, it is crucial to define which genes or panels involving host and/or HPV are feasible and appropriate for large-scale screening and triage. An ideal approach for screening and triage of CIN/ICC requires high sensitivity and adequate specificity and is suitable for self-sampling and inexpensive to allow population-based screening, particularly in LMICs. In this review, we summarize the markers of host cell gene/HR-HPV DNA methylation and discuss their triage performance and feasibility for high-grade precancerous cervical intraepithelial neoplasia or worse (CIN2+ and CIN3+) in HR-HPV-positive women.

Emerging research on epigenetics has resulted in many novel discoveries in atherosclerosis (AS), an inflammaging-associated disease characterized by chronic inflammation primarily driven by macrophages. The bulk of evidence has demonstrated the central role of epigenetic machinery in macrophage polarization to pro- (M1-like) or anti-inflammatory (M2-like) phenotype. An increasing number of epigenetic alterations and their modifiers involved in reprogramming macrophages by regulating DNA methylation or histone modifications (e.g., methylation, acetylation, and recently lactylation) have been identified. They may act to determine or skew the direction of macrophage polarization in AS lesions, thereby representing a promising target. Here we describe the current understanding of the epigenetic machinery involving macrophage polarization, to shed light on chronic inflammation-driving onset and progression of inflammaging-associated diseases, using AS as a prototypic example, and discuss the challenge for developing effective therapies targeting the epigenetic modifiers against these diseases, particularly highlighting a potential strategy based on epigenetically-governed repolarization from M1-like to M2-like phenotype.

The Upper Ordovician Wufeng-Lower Silurian Longmaxi shale is the only yield layer of commercial deve-lopment of shale gas in China at present. However, there are significant differences in the production of individual shale gas wells in different areas of the Sichuan Basin and its periphery. This paper investigates those differences from the perspective of reservoir space. The pore development of 36 shale samples from the Lower Rhuddanian in 5 typical wells with different reservoir pressure in different tectonic areas in the Sichuan Basin was compared by applying, petromi-neralogical, structural geological and reservoir geological methods. The reservoir space in these shales is dominated by organic pores. With the increase of TOC content, the volumes of micropores (< 10 nm), mesopores (10~50 nm), macropores (>50 nm) and total pores in different structural regions show different trends, reflecting different stages of pore evolution. A preliminary organic pore development model of shale has been established. The extent of pore development in shale samples located in the overpressure area in the basin is obviously better than that in the structural transformation area of the basin margin. It is confirmed by experiments that the shale pores may be compacted under high pressure conditions, and the degree of compaction is closely related to the organic matter pore size, the rock mineral composition, the organic matter content, the domain structure conditions and the pressure coefficient. The areas affected by the weak tectonic movement and having a high pressure coefficient are favorable areas for pore development.

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing.

Data-driven soft sensors have increasingly been applied for the quality measurement of industrial polymerization processes in recent years. However, owing to the costly assay process, the limited labeled data available still pose significant obstacles to the construction of accurate models. In this study, a novel soft sensor named the selective Wasserstein generative adversarial network, with gradient penalty-based support vector regression (SWGAN-SVR), is proposed to enhance quality prediction with limited training samples. Specifically, the Wasserstein generative adversarial network with gradient penalty (WGAN-GP) is employed to capture the distribution of the available limited labeled data and to generate virtual candidates. Subsequently, an effective data-selection strategy is developed to alleviate the problem of varied-quality samples caused by the unstable training of the WGAN-GP. The selection strategy includes two parts: the centroid metric criterion and the statistical characteristic criterion. An SVR model is constructed based on the qualified augmented training data to evaluate the prediction performance. The superiority of SWGAN-SVR is demonstrated, using a numerical example and an industrial polyethylene process.

In plants, the accumulation of carotenoids can maintain the balance of the photosystem and improve crop nutritional quality. Therefore, the molecular mechanisms underlying carotenoid synthesis and accumulation should be further explored. In this study, carotenoid accumulation differed significantly among parental Brassica rapa. Genetic analysis was carried out using the golden inner leaf ‘1900264′ line and the light−yellow inner leaf ‘1900262′ line, showing that the golden inner leaf phenotype was controlled by a single dominant gene. Using bulked−segregant analysis sequencing, BraA09g007080.3C encoding the ORANGE protein was selected as a candidate gene. Sequence alignment revealed that a 4.67 kb long terminal repeat insertion in the third exon of the BrGOLDEN resulted in three alternatively spliced transcripts. The spatiotemporal expression results indicated that BrGOLDEN might regulate the expression levels of carotenoid−synthesis−related genes. After transforming BrGOLDEN into Arabidopsis thaliana, the seed−derived callus showed that BrGOLDENIns and BrGOLDENDel lines presented a yellow color and the BrGOLDENLdel line presented a transparent phenotype. In addition, using the yeast two−hybrid assay, BrGOLDENIns, BrGOLDENLdel, and Brgoldenwt exhibited strong interactions with BrPSY1, but BrGOLDENDel did not interact with BrPSY1 in the split−ubiquitin membrane system. In the secondary and 3D structure analysis, BrGOLDENDel was shown to have lost the PNFPSFIPFLPPL sequences at the 125 amino acid position, which resulted in the α−helices of BrGOLDENDel being disrupted, restricting the formation of the 3D structure and affecting the functions of the protein. These findings may provide new insights into the regulation of carotenoid synthesis in B. rapa.

BackgroundProstate cancer (PCa) is an immune-responsive disease. The current study sought to explore a robust immune-related prognostic gene signature for PCa.MethodsData were retrieved from the tumor Genome Atlas (TCGA) database and GSE46602 database for performing the least absolute shrinkage and selection operator (LASSO) cox regression model analysis. Immune related genes (IRGs) data were retrieved from ImmPort database.ResultsThe weighted gene co-expression network analysis (WGCNA) showed that nine functional modules are correlated with the biochemical recurrence of PCa, including 259 IRGs. Univariate regression analysis and survival analysis identified 35 IRGs correlated with the prognosis of PCa. LASSO Cox regression model analysis was used to construct a risk prognosis model comprising 18 IRGs. Multivariate regression analysis showed that risk score was an independent predictor of the prognosis of PCa. A nomogram comprising a combination of this model and other clinical features showed good prediction accuracy in predicting the prognosis of PCa. Further analysis showed that different risk groups harbored different gene mutations, differential transcriptome expression and different immune infiltration levels. Patients in the high-risk group exhibited more gene mutations compared with those in the low-risk group. Patients in the high-risk groups showed high-frequency mutations in TP53. Immune infiltration analysis showed that M2 macrophages were significantly enriched in the high-risk group implying that it affected prognosis of PCa patients. In addition, immunostimulatory genes were differentially expressed in the high-risk group compared with the low-risk group. BIRC5, as an immune-related gene in the prediction model, was up-regulated in 87.5% of prostate cancer tissues. Knockdown of BIRC5 can inhibit cell proliferation and migration.ConclusionIn summary, a risk prognosis model based on IGRs was developed. A nomogram comprising a combination of this model and other clinical features showed good accuracy in predicting the prognosis of PCa. This model provides a basis for personalized treatment of PCa and can help clinicians in making effective treatment decisions.

Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.

Abstract. A complex network precisely regulates the cell cycle through the G1, S, G2, and M phases and is the basis for cell division under physiological and pathological conditions. On the one hand, the transition from one phase to another as well as the progression within each phase is driven by the specific cyclin-dependent kinases (CDKs; e.g., CDK1, CDK2, CDK4, CDK6, and CDK7), together with their exclusive partner cyclins (e.g., cyclin A1, B1, D1–3, and E1). On the other hand, these phases are negatively regulated by endogenous CDK inhibitors such as p16ink4a, p18ink4c, p19ink4d, p21cip1, and p27kip1. In addition, several checkpoints control the commitment of cells to replicate DNA and undergo mitosis, thereby avoiding the passage of genomic errors to daughter cells. CDKs are often constitutively activated in cancer, which is characterized by the uncontrolled proliferation of transformed cells, due to genetic and epigenetic abnormalities in the genes involved in the cell cycle. Moreover, several oncogenes and defective tumor suppressors promote malignant changes by stimulating cell cycle entry and progression or disrupting DNA damage responses, including the cell cycle checkpoints, DNA repair mechanisms, and apoptosis. Thus, genes or proteins related to cell cycle regulation remain the main targets of interest in the treatment of various cancer types, including hematologic malignancies. In this context, advances in the understanding of the cell cycle regulatory machinery provide a basis for the development of novel therapeutic approaches. The present article summarizes the pathways as well as their genetic and epigenetic alterations that regulate the cell cycle; moreover, it discusses the various approved or potential therapeutic targets associated with the cell cycle, focusing on hematologic malignancies.

Abstract Background Earlier vascular healing after drug-eluting stent (DES) implantation may reduce the incidence of late stent thrombosis and provide theoretical evidence to shorten dual antiplatelet therapy duration in patients with high bleeding risks. The BuMA supreme stent is a newly developed DES-coated with the sirolimus by using the international patent electronic grafted eG™ technology. Previous randomized trials showed that BuMA stents had better stent-strut coverage at 3-month follow-ups, which were evaluated by optical coherence tomography (OCT). However, there have been a limited number of studies that are directly evaluating the extent of neointima formation at the first and second months after stent implantation in high-bleeding-risk patients with coronary artery disease. This clinical trial is designed to demonstrate the non-inferiority of the BuMA supreme stent compared to the XIENCE stent in early neointimal formation. Methods/design This is a prospective, multicenter, randomized trial. Forty patients will be assigned into the first-month OCT group, and another 40 patients into the second-month OCT group. The patients in each cohort will be randomized again into two groups in a 1:1 ratio, either being implanted with the BuMA Supreme stent or the Xience V/Prime/Xpedition stent. The primary endpoint is stent-strut neointimal coverage rate (%) at the first and second months, respectively. Secondary endpoints include neointimal hyperplasia area/volume, neointimal hyperplasia thickness, stent-strut malapposition rate, late lumen loss (LLL), restenosis rate, device/lesion/clinical success rate, device-oriented composite endpoints at the first and second months, stent thrombosis and other serious adverse events and bleeding events at follow-up. Discussion The results will provide the first accurate imaging evidence on neointimal formation of the BuMA Supreme stent and the Xience stent at 1–2 months post PCI. The result should inspire further exploration and adjustment of DAPT treatments. Trial registration ClinicalTrials.gov, ID: NCT02747329. Registered on 21 April 2016. Last updated 17 May 2018.