The Arabidopsis RTH plays an important role in regulation of iron (Fe) absorption and transport.

KEY MESSAGE: RTH may activate Fe assimilation related genes to promote Fe absorption, transport and accumulation in Arabidopsis. Iron (Fe) is an important nutrient element. The Fe absorption and transport in plants are well investigated over the past decade. Our previous work indicated that RTE1-HOMOLOG (RTH), the homologous gene of reversion-to-ethylene sensitivity 1 (RTE1), plays a role in ethylene signaling pathway. However, its function in Fe absorption and transport is largely unknown. In the present study, we found that RTH was expressed in absorptive tissue and conducting tissue, including root hairs, root vascular bundle, and leaf veins. Under high Fe concentration, the seedling growth of rth-1 mutant was better, while the RTH overexpression lines were retarded compared to the wild type (Col-0). When treated with EDTA-Fe3+ (400 µM), the chlorophyll content and ion leakage rate were higher and lower in rth-1 than those of Col-0, respectively. By contrast, the chlorophyll contents and ion leakage rates of RTH overexpression lines were decreased and hastened compared with Col-0, respectively. Fe measurement indicated that the Fe contents of rth-1 were lower than those of Col-0, whereas those of RTH overexpression lines were comparably higher. Gene expression analysis revealed that Fe absorption and transport genes AHA2, IRT1, FIT, FPN1, and YSL1 decreased in rth-1 but increased in RTH overexpression lines compared with Col-0. Additionally, Y2H (yeast two-hybrid) and BiFC (bimolecular fluorescence complementation) assays showed that RTH can physically interact with hemoglobin 1 (HB1) and HB2. All these findings suggest that RTH may play an important role in regulation of Fe absorption, transport, and accumulation in Arabidopsis.

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

The effect of continuous positive airway pressure on obstructive sleep apnea in children with syndromic craniosynostosis.

BACKGROUND: Obstructive sleep apnea (OSA) is common in children with syndromic craniosynostosis (SC). However, objective data on the treatment of OSA in children with SC remain inadequate. This study aimed to explore the efficacy of continuous positive airway pressure (CPAP) in the management of OSA in children with SC. METHODS: A retrospective study was performed in children with SC and OSA diagnosed by polysomnography (PSG), which was defined as an apnea hypopnea index (AHI) ≥ 1. Patients were included if they were treated with CPAP and had baseline PSG and follow-up sleep studies. Clinical and demographic data were collected from all enrolled subjects. RESULTS: A total of 45 children with SC and OSA were identified, with an average age of 6.8 ± 4.7 years. Among them, 36 cases had moderate to severe OSA (22 with severe OSA) and received CPAP therapy followed by post-treatment sleep studies. Notably, there was a significant reduction in the AHI observed after CPAP treatment (3.0 [IQR: 1.7, 4.6] versus 38.6 [IQR: 18.2, 53.3] events/h; P < 0.001). CONCLUSIONS: CPAP is effective and acceptable in treating severe OSA in children with SC.

TAF1D promotes proliferation by transcriptionally activating G2/M phase-related genes in MYCN-amplified neuroblastoma.

High-risk neuroblastoma (HR-NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5-year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR-NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR-NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box-binding protein-associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR-NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN-amplified, high-risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN-amplified NB cells compared with MYCN-non-amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN-amplified NB. RNA-seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell-cycle regulator, cell-cycle-dependent kinase 1 (CDK1), resulting in cell-cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN-amplified HR-NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR-NB patients by blocking cell-cycle progression and the proliferation of tumor cells.

BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. METHODS: The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. RESULTS: Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. CONCLUSIONS: A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

The pivotal role of MYB transcription factors in plant disease resistance.

MAIN CONCLUSION: MYB transcription factors are essential for diverse biology processes in plants. This review has focused on the potential molecular actions of MYB transcription factors in plant immunity. Plants possess a variety of molecules to defend against disease. Transcription factors (TFs) serve as gene connections in the regulatory networks controlling plant growth and defense against various stressors. As one of the largest TF families in plants, MYB TFs coordinate molecular players that modulate plant defense resistance. However, the molecular action of MYB TFs in plant disease resistance lacks a systematic analysis and summary. Here, we describe the structure and function of the MYB family in the plant immune response. Functional characterization revealed that MYB TFs often function either as positive or negative modulators towards different biotic stressors. Moreover, the MYB TF resistance mechanisms are diverse. The potential molecular actions of MYB TFs are being analyzed to uncover functions by controlling the expression of resistance genes, lignin/flavonoids/cuticular wax biosynthesis, polysaccharide signaling, hormone defense signaling, and the hypersensitivity response. MYB TFs have a variety of regulatory modes that fulfill pivotal roles in plant immunity. MYB TFs regulate the expression of multiple defense genes and are, therefore, important for increasing plant disease resistance and promoting agricultural production.

Target of rapamycin (TOR) plays a role in regulating ROS-induced chloroplast damage during cucumber (Cucumis sativus) leaf senescence.

In cucumber production, delaying leaf senescence is crucial for improving cucumber yield and quality. Target of rapamycin (TOR) is a highly conserved serine/threonine protein kinase in eukaryotes, which can integrate exogenous and endogenous signals (such as cell energy state levels) to stimulate cell growth, proliferation, and differentiation. However, no studies have yet examined the regulatory role of TOR signalling in cucumber leaf senescence. In this study, the effects of TOR signalling on dark-induced cucumber leaf senescence were investigated using the TOR activator MHY1485 and inhibitor AZD8055 combined with transient transformation techniques. The results indicate that TOR responds to dark-induced leaf senescence, and alterations in TOR activity/expression influence cucumber leaf resistance to dark-induced senescence. Specifically, in plants with elevated TOR activity/expression, we observed reduced expression of senescence-related genes, less membrane lipid damage, decreased cell apoptosis, lower levels of reactive oxygen species production, and less damage to the photosynthetic system compared to the control. In contrast, in plants with reduced TOR activity/expression, we observed higher expression of senescence-related genes, increased membrane lipid damage, enhanced cell apoptosis, elevated levels of reactive oxygen species production, and more damage to the photosynthetic system. These comprehensive results underscore the critical role of TOR in regulating dark-induced cucumber leaf senescence. These findings provide a foundation for controlling premature leaf senescence in cucumber production and offer insights for further exploration of leaf senescence mechanisms and the development of more effective control methods.

Characterization of caffeoyl shikimate esterase gene family identifies CsCSE5 as a positive regulator of Podosphaera xanthii and Corynespora cassiicola pathogen resistance in cucumber.

KEY MESSAGE: CsCSE genes might be involved in the tolerance of cucumber to pathogens. Silencing of the CsCSE5 gene resulted in attenuated resistance of cucumber to Podosphaera xanthii and Corynespora cassiicola. Caffeoyl shikimate esterase (CSE), a key enzyme in the lignin biosynthetic pathway, has recently been characterized to play a key role in defense against pathogenic infection in plants. However, a systematic analysis of the CSE gene family in cucumber (Cucumis sativus) has not yet been conducted. Here, we identified eight CsCSE genes from the cucumber genome via bioinformatic analyses, and these genes were unevenly distributed on chromosomes 1, 3, 4, and 5. Results from multiple sequence alignment indicated that the CsCSE proteins had domains required for CSE activity. Phylogenetic analysis of gene structure and protein motifs revealed the conservation and diversity of the CsCSE gene family. Collinearity analysis showed that CsCSE genes had high homology with CSE genes in wax gourd (Benincasa hispida). Cis-acting element analysis of the promoters suggested that CsCSE genes might play important roles in growth, development, and stress tolerance. Expression pattern analysis indicated that CsCSE5 might be involved in regulating the resistance of cucumber to pathogens. Functional verification data confirmed that CsCSE5 positively regulates the resistance of cucumber to powdery mildew pathogen Podosphaera xanthii and target leaf spot pathogen Corynespora cassiicola. The results of our study provide information that will aid the genetic improvement of resistant cucumber varieties.

Dual-Responsive Ratiometric Fluorescent Probe for Hypochlorite and Peroxynitrite Detection and Imaging In Vitro and In Vivo.

Hypochlorite (ClO-) and peroxynitrite (ONOO-) are two crucial highly reactive oxygen/nitrogen species, which interplay with each other, and are implicated in numerous pathophysiological processes. The simultaneous detection of ClO- and ONOO- is immensely significant in evaluating the occurrence and progress of related diseases. Herein, a dual-responsive ratiometric fluorescent probe PTZ-H for the separate and simultaneous detection of ClO- and ONOO- was designed and synthesized. In this probe, the phenothiazine-based coumarin moiety was chosen as the ClO- responsive fluorescent fragment, and the precursor of 2-(benzo[d]thiazol-2-yl)aniline was employed as the sensor for ONOO-. The PTZ-H emitted red fluorescence (640 nm) can switch to green (520 nm) and turn on blue fluorescence (450 nm) in response to ClO- and ONOO-, respectively. This allowed the specific recognition and ratiometric quantification of ClO- and ONOO- with the detection limits of 17 and 21 nM, respectively. Notably, confocal laser scanning microscopy revealed that the PTZ-H probe could target-specifically image ClO- and ONOO- in living RAW 264.7 cells, zebrafish, and tissues with distinct fluorescence signals. With the aid of this single fluorescent probe, the endogenous accumulation of ClO- and ONOO- in inflammatory RAW 264.7 cells and zebrafish can be monitored through two distinct emission channels with fast responses. Moreover, the large fluorescence signal interval, high selectivity, and good biocompatibility may enable its application in deciphering the distribution and correlation of ClO- and ONOO- engaged in biological activity.

Applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block in the supine versus lateral position during surgeries for lower limb fracture-a prospective randomized controlled trial.

BACKGROUND: Patients with lower limb fracture often have acute pain and discomfort from changes in position, and such pain affects early postoperative recovery. This study aimed to compare the applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block (LSPB) in the supine versus lateral position during lower limb fracture surgery. METHODS: We included 126 patients who underwent elective internal fixation for lower limb fracture who were divided into the S group and the L group by the random number table method and underwent LSPB guided by ultrasound combined with a nerve stimulator in the supine and lateral positions, respectively. The primary outcome was the dose of sufentanil used in surgery. The secondary outcomes were the maximum VAS (visual analogue scale) pain score at position placing for LSPB, the time of position placing, the time for nerve block,the number of puncture attempts,the haemodynamic indicators, the VAS score at 1, 12, and 24 h following surgery, postoperative satisfactory degree to analgesia and adverse events related to nerve block. RESULTS: There was no statistically significant difference in dose of sufentanil used between the two groups(P = 0.142). The maximum VAS pain score at position placing(P < 0.01), the time of position placement(P < 0.01), the time for lumbar plexus block and the time of puncture attempts were significantly lower in the S group than in the L group (P < 0.01). However, the time for sacral plexus block was higher in the S group than in the L group (P = 0.029). There was no significant difference in haemodynamic indicators,number of puncture attempts for the sacral plexus, postoperative VAS scores, postoperative satisfactory degree to analgesia or adverse events related to nerve block between the two groups (all P > 0.05). CONCLUSIONS: Our study provides a more comfortable and better accepted anaesthetic regimen for patients undergoing lower limb fracture surgery. LSPB in the supine position is simple to apply and has definite anaesthetic effects. Additionally, it has a high level of postoperative analgesia and therefore should be widely applied. TRIAL REGISTRATION: The trial was registered prior to patient enrolment at the Chinese Clinical Trail Registry (Date:11/03/2021 Number: ChiCTR2100044117 ).

Identifying Irregular Potatoes Using Hausdorff Distance and Intersection over Union.

Further processing and the added value of potatoes are limited by irregular potatoes. An ellipse-fitting-based Hausdorff distance and intersection over union (IoU) method for identifying irregular potatoes is proposed to solve the problem. First, the acquired potato image is resized, translated, segmented, and filtered to obtain the potato contour information. Secondly, a least-squares fitting method fits the extracted contour to an ellipse. Then, the similarity between the irregular potato contour and the fitted ellipse is characterized using the perimeter ratio, area ratio, Hausdorff distance, and IoU. Next, the characterization ability of the four features is analyzed, and an identification standard of irregular potatoes is established. Finally, we discuss the algorithm's shortcomings in this paper and draw the advantages of the algorithm by comparison. The experimental results showed that the characterization ability of perimeter ratio and area ratio was inferior to that of Hausdorff distance and IoU, and using Hausdorff distance and IoU as feature parameters can effectively identify irregular potatoes. Using Hausdorff distance separately as a feature parameter, the algorithm achieved excellent performance, with precision, recall, and F1 scores reaching 0.9423, 0.98, and 0.9608, respectively. Using IoU separately as a feature parameter, the algorithm achieved a higher overall recognition rate, with precision, recall, and F1 scores of 1, 0.96, and 0.9796, respectively. Compared with existing studies, the proposed algorithm identifies irregular potatoes using only one feature, avoiding the complexity of high-dimensional features and significantly reducing the computing effort. Moreover, simple threshold segmentation does not require data training and saves algorithm execution time.

Identification of NTRK3 as a potential prognostic biomarker associated with tumor mutation burden and immune infiltration in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy has played a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker for predicting tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to identify the key genes in BLCA. METHODS: Clinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups according to their calculated TMB scores. Gene Set Enrichment Analysis (GSEA) was performed to screen for significantly enriched pathways. Differentially expressed genes (DEGs) between the two groups were identified. Univariate Cox analysis and Kaplan-Meier survival analysis were applied for screening key genes. Immune infiltration was performed for TMB groups and NTRK3. RESULTS: Higher TMB scores were related with poor survival in BLCA. After filtering, 36 DEGs were identified. NTRK3 had the highest hazard ratio and significant prognostic value. Co-expressed genes of NTRK3 were mainly involved in several pathways, including DNA replication, basal transcription factors, complement and coagulation cascades, and ribosome biogenesis in eukaryotes. There was a significant correlation among TMB scores, NTRK3 expression and immune infiltration. CONCLUSIONS: Our results suggest that NTRK3 is a TMB-related prognostic biomarker, which lays the foundation for further research on the immunomodulatory effect of NTRK3 in BLCA.

Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort.

BACKGROUND: Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma, but few studies have focused on papillary renal cell carcinoma (PRCC). This study was performed to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients. METHODS: In total, 122 postoperative PRCC patients selected from 366 non-clear cell renal cell carcinoma patients were enrolled from our institution between 2012 and 2020. The optimal cutoff value of the NLR was assessed by receiver operating characteristic (ROC) curve analysis, and the Kaplan-Meier method and Cox's proportional hazards regression models were performed to analyze the association of the NLR with overall survival (OS). In addition, the potential of tumor-node-metastasis (TNM) stage, the NLR and an NLR-TNM system to predict survival were compared with ROC curves, and clinical usefulness of the predicting models were assessed by decision curve analysis. RESULTS: A threshold value of 2.39 for the NLR for OS analysis was determined by ROC curve analysis. An NLR ≥ 2.39 was associated with a more advanced TNM stage (P < 0.01) and larger tumors (P < 0.05) than a low NLR, as well as pathological subtype II (P < 0.05), and the patients with a high NLR also exhibited significantly worse overall survival outcomes (P < 0.05). The NLR was determined to be a significant independent prognostic indicator by univariable and multivariable analyses (HR = 5.56, P < 0.05). Furthermore, TNM stage and the NLR were integrated, and the area under the curve (AUC) of for the NLR-TNM system was larger than that of for the TNM system when predicting overall survival (0.84 vs 0.73, P = 0.04). Decision curve analysis also demonstrated a better clinical value for the NLR-TNM model to predict the prognosis. CONCLUSION: A high preoperative NLR was associated with poor clinical and pathologic parameters in patients with PRCC; moreover, the NLR was also an independent prognostic factor for the OS of patients with PRCC. The NLR-TNM system, which was a model that integrated the NLR with TNM staging, could improve the ability to predict overall survival.

Synthesis and biological evaluation of 4-phenoxy-phenyl isoxazoles as novel acetyl-CoA carboxylase inhibitors.

Acetyl-CoA carboxylase (ACC) is a crucial enzyme in fatty acid metabolism, which plays a major role in the occurrence and development of certain tumours. Herein, one potential ACC inhibitor (6a) was identified through high-throughput virtual screening (HTVS), and a series of 4-phenoxy-phenyl isoxazoles were synthesised for structure-activity relationship (SAR) studies. Among these compounds, 6g exhibited the most potent ACC inhibitory activity (IC50=99.8 nM), which was comparable to that of CP-640186. Moreover, the antiproliferation assay revealed that compound 6l exhibited the strongest cytotoxicity, with IC50 values of 0.22 µM (A549), 0.26 µM (HepG2), and 0.21 µM (MDA-MB-231), respectively. The preliminary mechanistic studies on 6g and 6l suggested that the compounds decreased the malonyl-CoA levels, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in MDA-MB-231 cells. Overall, these results indicated that the 4-phenoxy-phenyl isoxazoles are potential for further study in cancer therapeutics as ACC inhibitors.

[Effects of low-dose dexmedetomidine combined with hydromorphone in postoperative analgesia and on the serum IL-6 and CRP levels of prostate cancer patients].

OBJECTIVE: To explore the effects of low-dose dexmedetomidine (DM) combined with hydromorphone (HM) in postoperative analgesia and on levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) in PCa patients. METHODS: Using the random number table, we divided 102 PCa patients undergoing radical prostatectomy from January 2019 to November 2020 into a trial group (n = 51) and a control group (n = 51), the former given HM and the latter low-dose DM + HM for postoperative analgesia. We recorded the postoperative resuscitation time, extubation time and pain, perioperative cognitive function, IL-6 and CRP levels, and drug-related adverse reactions of the patients, and compared them between the two groups. RESULTS: There was no statistically significant difference in postoperative resuscitation time and extubation time between the two groups of patients (P > 0.05). The frequency of patient-controlled epidural analgesia (PCEA) compressions was lower in the trial than in the control group within 24 hours after surgery (P < 0.05). The Visual Analogue Scale (VAS) scores were higher in both of the groups at 24 hours than at 4, 12, and 48 hours after surgery (P < 0.05), at 12 hours than at 4 and 48 hours (P < 0.05) and at 4 hours than at 48 hours (P < 0.05), but lower in the trial than in the control group at 4, 12 and 24 hours postoperatively (P < 0.05). No statistically significant difference was observed in the scores of the Mini Mental State Evaluation Scale between the two groups of patients (P > 0.05). The levels of IL-6 and CRP were higher in both of the groups at 24 hours after than before and at 4, 12 and 48 hours after surgery (P < 0.05), at 48 hours after than before and at 4 and 12 hours after surgery (P < 0.05), at 12 hours after than before and at 4 hours after surgery (P <0.05), and at 4 hours after than before surgery (P < 0.05), but lower in the trial than in the control group at 4, 12, 24 and 48 hours postoperatively (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions between the two groups (P > 0.05). CONCLUSIONS: Low-dose dexmedetomidine combined with hydromorphone is a safe and effective option for postoperative analgesia in PCa patients, and it can inhibit the expression of inflammatory factors.

Association between Prediabetes and Renal Dysfunction from a Community-based Prospective Study.

Objective: Our study aimed to evaluate the association between prediabetes and renal dysfunction, and further assess which of glycemic indices of fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c) has a higher risk of renal dysfunction. Methods: This was a community-based prospective cohort study, which included 7015 participants from Beijing and Taian between May and October in 2015. The outcome was the renal dysfunction defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. Univariate and multivariate logistic regression model was performed, and calculated the odds ratio (OR) and 95% confidence interval (95%CI) of renal dysfunction. Receiver operating curve (ROC) analysis was used to predict renal dysfunction for glycemic indices. Results: 121 renal dysfunction cases were identified. We found that the adjusted ORs (95%CI) of renal dysfunction were 1.72 (1.11-2.38), 1.48 (1.09-1.93), 1.97 (1.27-2.89) and 1.35 (1.07-2.13), respectively, for those with prediabetes, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated HbA1c, compared with individuals with normal glucose tolerance. And IGT presented a higher risk of renal dysfunction than other glycemic indices. The similar results were obtained by performing the subgroup analysis. ROC analysis revealed the PPG had a higher predictive value for renal dysfunction. Conclusion: We found prediabetes was positively associated with the risk of renal dysfunction and PPG had a higher risk and predictive value of renal dysfunction than other glycemic indices of FPG and HbA1c.

[Correlation of human papillomavirus (HPV) and HPV vaccines with male reproductive health].

HPV is a very common virus worldwide spread by direct contact and involved in male reproductive health-related diseases such as infertility, condyloma acuminatum, and penile cancer. The development of HPV vaccines has contributed to the effective prevention of various subtypes of HPV and protection of males from HPV infection, especially the partners of HPV-positive females, the men who have sex with men, and those with a psychological fear of HPV infection. Therefore, HPV vaccines play an important role in the protection of males.

MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood. METHODS: Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7. RESULTS: Here we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3'-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB. CONCLUSIONS: These results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.

RRS1 gene expression involved in the progression of papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most frequent malignancies of the endocrine system, whose mechanisms of pathogenesis, progression and prognosis are still far from being clearly elucidated. Despite an increasing body of evidences highlights ribosome biogenesis regulator homolog (RRS1) as a ribosome biogenesis protein in yeast and plants, little is known about human RRS1 function. METHODS: Proliferation, cell cycle and apoptosis of PTC cells were assessed following the knockdown of RRS1 expression though MTT, colony formation assay, and flow cytometry. Then, transcriptome profiling was conducted to explore pathway changes after RRS1 silencing in PTC cells. Receiver operating characteristic curve and Youden's index were performed in twenty-four thyroid carcinoma samples to assess their potential clinical diagnostic value. RESULTS: Firstly, we found that silencing RRS1 significantly reduced cell proliferation, inhibited cell cycle, and promoted apoptosis in PTC cell line. The result also showed that knock-down of RRS1 could up-regulate genes involving apoptosis and metabolism, while, down-regulate genes relative to cell proliferation and blood vessel development. Notably, the present study confirmed the diagnostic value of RRS1 for thyroid carcinoma in both children and adults. CONCLUSIONS: In conclusion, these data afford a comprehensive view of a novel function of human RRS1 by promoting cell proliferation and could be a potential indicator for papillary thyroid carcinoma.