A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension.

BACKGROUND: Adverse environmental exposure during the prenatal period can lead to diseases in the offspring, including hypertension. Whether or not the hypertensive phenotype can be transgenerationally transmitted is not known. METHODS: Pregnant Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) on gestation days 6, 8, 10, and 12 to generate the prenatal LPS exposure model. Blood pressure was monitored by both telemetry and tail-cuff method. RNA sequencing was performed to analyze transcriptome alteration in the kidney of the third generation. Tempol and spironolactone were used to test the potential preventative and therapeutic effect of targeting reactive oxygen species and mineralocorticoid receptor signaling, respectively. Molecular biological experiments were performed to illustrate the mechanism of epigenetic and transcription regulation. RESULTS: Prenatal LPS exposure can impair the ability to excrete a salt load and induce hypertension from the first to the third generations, with the fourth and fifth generations, inducing salt-sensitive hypertension. Compared with control pups, the transcriptome in the kidney of the hypertensive third-generation prenatal LPS-exposed offspring have upregulation of the Ras-related C3 botulinum toxin substrate 1 (Rac1) gene and activation of mineralocorticoid receptor signaling. Furthermore, we found that LPS exposure during pregnancy triggered oxidative stress that upregulated KDM3B (histone lysine demethylase 3B) in the oocytes of first-generation female rats, leading to an inheritable low level of H3K9me2 (histone H3 lysine 9 dimethylation), resulting in the transgenerational upregulation of Rac1. Based on these findings, we treated the LPS-exposed pregnant rats with the reactive oxygen species scavenger, tempol, which successfully prevented hypertension in the first-generation offspring and the transgenerational inheritance of hypertension. CONCLUSIONS: These findings show that adverse prenatal exposure induces transgenerational hypertension through an epigenetic-regulated mechanism and identify potentially preventive and therapeutic strategies for hypertension.

Genome-wide identification and molecular expression profile analysis of FHY3/FAR1 gene family in walnut (Juglans sigillata L.) development.

BACKGROUND: Juglans sigillata L. (walnut) has a high economic value for nuts and wood and has been widely grown and eaten around the world. Light plays an important role in regulating the development of the walnut embryo and promoting nucleolus enlargement, which is one of the factors affecting the yield and quality of walnut. However, little is known about the effect of light on the growth and quality of walnuts. Studies have shown that far red prolonged hypocotyl 3 (FHY3) and far red damaged response (FAR1) play important roles in plant growth, light response, and resistance. Therefore, FHY3/FAR1 genes were identified in walnuts on a genome-wide basis during their growth and development to reveal the potential regulation mechanisms involved in walnut kernel growth and development. RESULTS: In the present study, a total of 61 FHY3/FAR1 gene family members in walnuts have been identified, ranging in length from 117 aa to 895 aa. These gene family members have FHY3 or FAR1 conserved domains, which are unevenly distributed on the 15 chromosomes (Chr) of the walnut (except for the Chr16). All 61 FHY3/FAR1 genes were divided into five subclasses (I, II, III, IV, and V) by phylogenetic tree analysis. The results indicated that FHY3/FAR1 genes in the same subclasses with similar structures might be involved in regulating the growth and development of walnut. The gene expression profiles were analyzed in different walnut kernel varieties (Q, T, and F). The result showed that some FHY3/FAR1 genes might be involved in the regulation of walnut kernel ripening and seed coat color formation. Seven genes (OF07056-RA, OF09665-RA, OF24282-RA, OF26012-RA, OF28029-RA, OF28030-RA, and OF08124-RA) were predicted to be associated with flavonoid biosynthetic gene regulation cis-acting elements in promoter sequences. RT-PCR was used to verify the expression levels of candidate genes during the development and color change of walnut kernels. In addition, light responsiveness and MeJA responsiveness are important promoter regulatory elements in the FHY3/FAR1 gene family, which are potentially involved in the light response, growth, and development of walnut plants. CONCLUSION: The results of this study provide a valuable reference for supplementing the genomic sequencing results of walnut, and pave the way for further research on the FHY3/FAR1 gene function of walnut.

Transcriptomics-proteomics Integration reveals alternative polyadenylation driving inflammation-related protein translation in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a complex disease involving the upregulation of many inflammation-related proteins. Alternative polyadenylation (APA), a crucial post-transcriptional regulatory mechanism, has been proven to play vital roles in many inflammatory diseases. However, it is largely unknown whether and how APA exerts function in DN. METHODS: We performed transcriptomics and proteomics analysis of glomeruli samples isolated from 50 biopsy-proven DN patients and 25 control subjects. DaPars and QAPA algorithms were adopted to identify APA events from RNA-seq data. The qRT-PCR analysis was conducted to verify 3'UTR length alteration. Short and long 3'UTRs isoforms were also overexpressed in podocytes under hyperglycemia condition for examining protein expression. RESULTS: We detected transcriptome-wide 3'UTR APA events in DN, and found that APA-mediated 3'UTR lengthening of genes (APA genes) increased their expression at protein but not mRNA level. Increased protein level of 3'UTR lengthening gene was validated in podocytes under hyperglycemia condition. Pathway enrichment analysis showed that APA genes were enriched in inflammation-related biological processes including endoplasmic reticulum stress pathways, NF-κB signaling and autophagy. Further bioinformatics analysis demonstrated that 3'UTR APA of genes probably altered the binding sites for RNA-binding proteins, thus enhancing protein translation. CONCLUSION: This study revealed for the first time that 3'UTR lengthening of APA genes contributed to the progression of DN by elevating the translation of corresponding proteins, providing new insight and a rich resource for investigating DN mechanisms.

Immunomodulatory and antiviral effects of Lycium barbarum glycopeptide on influenza a virus infection.

Influenza is caused by a respiratory virus and has a major global impact on human health. Influenza A viruses in particular are highly pathogenic to humans and have caused multiple pandemics. An important consequence of infection is viral pneumonia, and with serious complications of excessive inflammation and tissue damage. Therefore, simultaneously reducing direct damage caused by virus infection and relieving indirect damage caused by excessive inflammation would be an effective treatment strategy. Lycium barbarum glycopeptide (LbGp) is a mixture of five highly branched polysaccharide-protein conjuncts (LbGp1-5) isolated from Lycium barbarum fruit. LbGp has pro-immune activity that is 1-2 orders of magnitude stronger than that of other plant polysaccharides. However, there are few reports on the immunomodulatory and antiviral activities of LbGp. In this study, we evaluated the antiviral and immunomodulatory effects of LbGp in vivo and in vitro and investigated its therapeutic effect on H1N1-induced viral pneumonia and mechanisms of action. In vitro, cytokine secretion, NF-κB p65 nuclear translocation, and CD86 mRNA expression in LPS-stimulated RAW264.7 cells were constrained by LbGp treatment. In A549 cells, LbGp can inhibit H1N1 infection by blocking virus attachment and entry action. In vivo experiments confirmed that administration of LbGp can effectively increase the survival rate, body weight and decrease the lung index of mice infected with H1N1. Compared to the model group, pulmonary histopathologic symptoms in lung sections of mice treated with LbGp were obviously alleviated. Further investigation revealed that the mechanism of LbGp in the treatment of H1N1-induced viral pneumonia includes reducing the viral load in lung, regulating the phenotype of pulmonary macrophages, and inhibiting excessive inflammation. In conclusion, LbGp exhibits potential curative effects against H1N1-induced viral pneumonia in mice, and these effects are associated with its good immuno-regulatory and antiviral activities.

3'-Terminal 2'-O-methylation of lung cancer miR-21-5p enhances its stability and association with Argonaute 2.

Methylation of miRNAs at the 2'-hydroxyl group on the ribose at 3'-end (2'-O-methylation, 2'Ome) is critical for miRNA function in plants and Drosophila. Whether this methylation phenomenon exists for mammalian miRNA remains unknown. Through LC-MS/MS analysis, we discover that majority of miR-21-5p isolated from human non-small cell lung cancer (NSCLC) tissue possesses 3'-terminal 2'Ome. Predominant 3'-terminal 2'Ome of miR-21-5p in cancer tissue is confirmed by qRT-PCR and northern blot after oxidation/ß-elimination procedure. Cancerous and the paired non-cancerous lung tissue miRNAs display different pattern of 3'-terminal 2'Ome. We further identify HENMT1 as the methyltransferase responsible for 3'-terminal 2'Ome of mammalian miRNAs. Compared to non-methylated miR-21-5p, methylated miR-21-5p is more resistant to digestion by 3'→5' exoribonuclease polyribonucleotide nucleotidyltransferase 1 (PNPT1) and has higher affinity to Argonaute-2, which may contribute to its higher stability and stronger inhibition on programmed cell death protein 4 (PDCD4) translation, respectively. Our findings reveal HENMT1-mediated 3'-terminal 2'Ome of mammalian miRNAs and highlight its role in enhancing miRNA's stability and function.

Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia.

Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia.

Use of a digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery.

A digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery is presented. This technique integrates bone reduction and implant placement information into a dual-function surgical template and introduces a digital approach to fabricating immediate interim implant-supported fixed dental prostheses with the same occlusal relationship as the one evaluated with diagnostic removable prostheses.

Effect of neuromuscular block on surgical conditions during short-duration paediatric laparoscopic surgery involving a supraglottic airway.

BACKGROUND: Use of an LMA ProSeal™ laryngeal mask airway (P-LMA; Teleflex) with no neuromuscular block is considered a safe alternative to tracheal intubation in short-duration paediatric laparoscopic surgery. However, few studies have evaluated surgical conditions of short-duration paediatric laparoscopic surgery using this anaesthetic technique. We assessed surgical conditions for paediatric laparoscopic inguinal hernia repair using P-LMA with and without neuromuscular block. METHODS: Sixty-six patients undergoing laparoscopic inguinal hernia repair were randomised to receive a neuromuscular block (train-of-four 1-2 twitches) using rocuronium or no neuromuscular block with the P-LMA. All operations were performed by the same surgeon who determined the surgical conditions using the Leiden-surgical rating scale (L-SRS). Secondary outcomes included perioperative data, haemodynamics, and adverse events. RESULTS: Neuromuscular block improved surgical conditions compared with no neuromuscular block: mean (standard deviation) L-SRS 4.1 (0.5) vs 3.5 (0.6), respectively (P<0.0001). Mean rocuronium dose in the neuromuscular block group was 12.7 (4.4-29.7) mg or 0.7 (0.6-0.8) mg kg-1. The insufflation Ppeak was higher in the no neuromuscular block group than in the neuromuscular block group: mean (standard deviation) Ppeak 17.9 (1.8) cm H2O vs 16.2 (1.9) cm H2O, respectively (P=0.0004). Fifteen children (45.5%) in the no neuromuscular block group had adverse events during the surgery and anaesthesia vs four children (12.1%) in the neuromuscular block group (P=0.006). CONCLUSIONS: Neuromuscular block significantly improved surgical conditions and reduced the incidence of adverse events during surgery and anaesthesia when an LMA Proseal™ was used in short-duration paediatric laparoscopic surgery. CLINICAL TRIAL REGISTRATION: ChiCTR2000038529.

The effect of dexmedetomidine premedication on postoperative systemic inflammatory response in children undergoing hernia repair surgery: A randomized controlled trial.

BACKGROUND: Surgery results in systemic inflammation, which can affect the central nervous system, leading to changes in mood, emotion, and behavior. Our previous study has shown that compared to midazolam, dexmedetomidine premedication effectively decreased children's postoperative anxiety. AIM: To investigate whether dexmedetomidine infusion before hernia repair alleviates postoperative systemic inflammation in children and whether postoperative anxiety may be associated with postoperative inflammation. METHODS: This prospective double-blind randomized controlled trial was conducted in 120 children scheduled to undergo elective hernia repair. Before anesthesia induction, all children received an intravenous infusion consisted of dexmedetomidine (n = 40; 0.5 µg/g, group D), midazolam (n = 40; 0.08 mg/kg, group M), or normal saline (n = 40; group C). One-way ANOVA with least significant difference multiple comparison test was used for multigroup comparisons of postoperative plasma levels of inflammatory cytokines and m-YPAS scores. Spearman rank correlation tests were used for analyzing m-YPAS scores with postoperative plasma levels of inflammatory cytokines. RESULTS: Plasma levels of tumor necrosis factor-alpha (7.0 ± 1.6 vs. 8.1 ± 1.6, mean difference [95% CI]: 1.19 [0.26-2.11], p = .008) (pg/ml) and of interleukin-6 (1.8 ± 1.2 vs. 3.3 ± 1.6, mean difference [95% CI]: 1.49 [0.74-2.25], p < .001) (pg/ml) and neutrophils-to-lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.7, mean difference [95% CI]: 0.48 [0.17-0.78], p < .001) were significantly lower in group D than in group C. Furthermore, compared to group M, group D showed significantly lower plasma tumor necrosis factor-alpha levels (7.0 ± 1.6 vs. 7.9 ± 1.9, mean difference [95% CI]: 0.96 [0.04-1.88], p = .04) (pg/ml) and interleukin-6 levels (1.8 ± 1.2 vs. 2.9 ± 1.5, mean difference [95% CI]: 1.06 [0.31-1.81], p = .004) (pg/ml), and neutrophil-to-lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.6, mean difference [95% CI]: 0.42 [0.11-0.72], p = .004). Anxiety scores at postoperative 2 and 4 h in the three groups positively correlated with plasma levels of proinflammatory cytokines. CONCLUSION: A single preoperative intravenous dexmedetomidine dose in children undergoing same-day surgery reduces postoperative systemic inflammation.

Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients.

Background: Genetic variants of coding genes related to blood pressure regulation participate in the pathogenesis of hypertension and determines the response to specific antihypertensive drugs. G protein-coupled receptor kinase 4 (GRK4) and its variants are of great importance in pathogenesis of hypertension. However, little is known about role of GRK4 variants in determine circadian rhythm of blood pressure and response to candesartan in hypertension. The aim of this study was to analyze the correlation of GRK4 variants and circadian rhythm of blood pressure, and to explore their effect on antihypertensive efficiency of candestartan.Methods: In this study, a total of 1239 cases were eligible, completed ambulatory blood pressure monitoring (ABPm) observation and exon sequencing of G protein-coupled receptor kinase 4 (GRK4). ABPm was obtained before and after 4-week treatment of candesartan. Diurnal variation of systolic blood pressure and antihypertensive effect of candesartan were then assessed.Results: Compared to GRK4 wild type (GRK4-WT), patients with GRK4 variants were more likely to be non-dippers (odds ratio (OR) 6.672, 95% confidence interval (CI) 5.124-8.688, P < .001), with GRK4 A142V (OR 5.888, 95% CI 4.332-8.003, P < .001), A486V (OR 7.102, 95% CI 5.334-9.455, P < .001) and GRK4 R65L (OR 3.273, 95% CI 2.271-4.718, P < .001), respectively. Correlation analysis revealed that non-dippers rhythm of blood pressure were associated with GRK4 variants (r = .420, P < .001), with GRK4 A142V (r = .416, P < .001), A486V (r = .465, P < .001) and GRK4 R65L (r = .266, P < .001), respectively. When given 4-week candesartan, patients with GRK4 variants showed better antihypertensive effect as to drop in blood pressure (24 h mSBP, 21.21 ± 4.99 vs 12.34 ± 4.78 mmHg, P < .001) and morning peak (MP-SBP, 16.54 ± 4.37 vs 11.52 ± 4.14 mmHg, P < .001), as well as greater increase in trough to peak ratio (SBP-T/P, .71 ± .07 vs .58 ± .07, P < .001) and smoothness index (SBP-SI, 1.44 ± .16 vs 1.17 ± .11, P < .001) than those with GRK4 WT.Conclusion: This study indicates that hypertensive patients with GRK4 variants are more likely to be non-dippers. What's more, patients with GRK4 variants possess a significantly better antihypertensive response to candesartan than those with GRK4 WT.

Direct quantification of 3' terminal 2'-O-methylation of small RNAs by RT-qPCR.

Modification of nucleotides significantly increases the diversity of functional nucleic acids. As one of the most common modifications of RNAs, methylation of the 2'-hydroxyl-group of ribonucleotides (2'-O-methylation) has been found in various RNAs in eukaryotes. However, due to the lack of an efficient method for quantifying small RNA 3' terminal 2'-O-methylation, it is difficult to monitor the dynamic change of 3' terminal 2'-O-methylation during various biological processes. Capitalizing on the finding that 3' terminal RNA 2'-O-methylation can inhibit the activity of poly(A) polymerase, an enzyme that can add the poly(A)-tail to RNA, we develop a method by which the 2'-O-methylation level of small RNAs, such as microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), can be directly quantified based on the poly(A)-tailed RT-qPCR technique. With this method, we successfully determine the 2'-O-methylation level of miRNAs in Arabidopsis thaliana and mouse lung tissue, piRNA in human seminal plasma, and monitor the alteration of miRNA 2'-O-methylation in Drosophila Schneider 2 cells after knockdown of Drosophila methyltransferase protein Hua enhancer 1 (DmHen-1).

Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression.

As a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX-induced cell migration and capillary-like tube formation. Restored S100A4 expression rescued OSX-short hairpin RNA-suppressed cell migration and capillary-like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.

Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system.

Environmental temperature plays a role in the variation of blood pressure. Maternal cold stress could affect the physiological phenotype of the offspring, including blood pressure elevation. In the present study, we found that adult offspring of dams exposed to cold have increased systolic and diastolic blood pressure, and decreased urine volume and sodium excretion, accompanied by increased heart rate and heart rate variability, secondary to increased activity of the sympathetic nervous system. Renal denervation or adrenergic receptor blockade decreased blood pressure and increased sodium excretion. The increase in peripheral sympathetic nerve activity can be ascribed to the central nervous system because administration of clonidine, a centrally acting α2 adrenergic receptor agonist, lowered blood pressure to a greater degree in the prenatal cold-exposed than control offspring. Moreover, these prenatal cold-exposed offspring had hypothalamic paraventricular nucleus (PVN) disorder because magnetic resonance spectroscopy showed decreased N-acetylaspartate and increased choline and creatine ratios in the PVN. Additional studies found that prenatal cold exposure impaired the balance between inhibitory and excitatory neurons. This led to PVN overactivation that was related to enhanced PVN-angiotensin II type 1 (AT1) receptor expression and function. Microinjection of the AT1 receptor antagonist losartan in the PVN lowered blood pressure to a greater extent in prenatal cold-exposed that control offspring. The present study provides evidence for overactive peripheral and central sympathetic nervous systems in the pathogenesis of prenatal cold-induced hypertension. Central AT1 receptor blockade in the PVN may be a key step for treatment of this type hypertension.

Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis.

Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear. In this study we investigated the therapeutic effects of irisin in an acute MI model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for 2 weeks after MI. Cardiac function was assessed using echocardiography. We found that irisin administration significantly alleviated MI-induced cardiac dysfunction and ventricular dilation at 4 weeks post-MI. Irisin significantly reduced infarct size and fibrosis in post-MI hearts. Irisin administration significantly increased angiogenesis in the infarct border zone and decreased cardiomyocyte apoptosis, but did not influence cardiomyocyte proliferation. In human umbilical vein endothelial cells (HUVEC), irisin significantly increased the phosphorylation of ERK, and promoted the migration of HUVEC detected in wound-healing and transwell chamber migration assay. The effects of irisin were blocked by the ERK inhibitor U0126. In conclusion, irisin improves cardiac function and reduces infarct size in post-MI mouse heart. The therapeutic effect is associated with its pro-angiogenic function through activating ERK signaling pathway.

The comparison of dexmedetomidine and midazolam premedication on postoperative anxiety in children for hernia repair surgery: A randomized controlled trial.

BACKGROUND: Perioperative anxiety is common in pediatric patients undergoing surgery. AIMS: The aim of this study was to determine whether an infusion of dexmedetomidine prior to hernia repair in children provides better postoperative anxiety outcomes that a preoperative infusion of midazolam. METHODS: Ninety 6-11-year-old children, who were scheduled to undergo elective hernia repair, were enrolled for this double-blind, randomized controlled trial. Group D (n = 45) received an intravenous infusion of dexmedetomidine (0.5 µg/kg) and Group M (n = 45) received an intravenous infusion of midazolam (0.08 mg/kg) in 20 mL of normal saline for 10 minutes before the induction of anesthesia. Pre- and postoperative scores on the modified Yale Preoperative Anxiety Scale were the main outcomes. Secondary outcomes included systolic blood pressure, diastolic blood pressure, heart rate, and postoperative pain measured on a visual analogue scale and patient satisfaction using a numerical rating scale. RESULTS: Postoperative anxiety in Group D was significantly lower than preoperative anxiety (2 hours postoperatively mean difference [95% CI]: 2.83 [0.87-4.79], P = 0.036, 4 hours postoperatively mean difference [95% CI]: 3.29 [1.39-5.20], P = 0.005). Preoperative and postoperative anxiety in Group M was similar. Anxiety scores in Group D were also significantly lower than anxiety in Group M 2 hours (mean difference [95% CI]: 1.89 [0.52-3.26], P = 0.01) and 4 hours (mean difference [95% CI]: 3.32 [1.98-4.66], P < 0.001) postoperatively. Systolic blood pressure, diastolic blood pressure and heart rate were lower in Group D than in Group M after administration of sedative drugs until children left PACU (SBP mean difference [95% CI]: 13.87 [10.30-17.43], P < 0.001, DBP mean difference [95% CI]: 5.96[3.80-8.11], P < 0.001, HR mean difference [95% CI]: 10.36 [7.58-13.13], P < 0.001). Pain was also significantly lower in Group D than in Group M at 2 hours (median difference [95% CI]: 1 [0.26-1.34], P = 0.004), 4 hours (median difference [95% CI]: 1 [0.31-1.02], P = 0.003), and 1 day (median difference [95% CI]: 0 [0.22-0.76], P = 0.003) postoperatively. Patient satisfaction scores were significantly higher in Group D than in Group M 1 day (median difference [95% CI]: 0 [-0.83 to -0.24], P = 0.006) and somewhat higher 1 week (median difference [95% CI]: 0 [-0.67 to -0.04], P = 0.06) postoperatively. CONCLUSION: Compared with midazolam, a single preoperative intravenous dose of dexmedetomidine appears to provide better postoperative anxiolytic effects for children undergoing same-day surgery.

[Intracranial involvement in newly diagnosed multiple myeloma with TP53 deletion: Two case reports].

We report two rare cases of multiple myeloma (MM) with dural intracranial disease and TP53 deletion. The two patients presented with skull lytic lesion and dural involvement of myeloma. The association between intracranial involvement in MM and TP53 deletion has not been determined. The two patients received bortezomib-based intensive induction and got good response, just as that reported in literature. MM presenting with dural intracranial disease and TP53 deletion at diagnosis is associated with poor outcome. Multi-drug regime containing bortezomib followed by autologous or allogeneic stem cell transportation would improve the prognosis.

Positive and negative regulation of GlnR in validamycin A biosynthesis by binding to different loci in promoter region.

Validamycin A (VAL-A) is a C7N aminocyclitol antibiotic produced by Streptomyces hygroscopicus var. jinggangensis 5008, which has been widely used as antifungal agent against rice sheath blight disease. VAL-A biosynthesis has been proven to be affected by γ-butyrolactone and temperature. Herein, we showed that GlnR, a global regulator in nitrogen metabolism, is specifically associated with valK-valA intergenic promoter region by DNA-affinity chromatography and MS-based protein identification. Subsequent EMSA and DNase I footprinting assays revealed two GlnR binding sites in this promoter region. Targeted disruption of glnR in S. hygroscopicus 5008 led to a significant increase in the transcription of VAL-A structural genes, albeit the VAL-A production was reduced by 80 % and the sporulation of the mutant was impaired. Compared with the wild-type 5008, site-specific mutagenesis of GlnR binding site I enhanced VAL-A production by 2.5-fold, whereas the mutation of GlnR binding site II resulted in a 50 % reduction of VAL-A yield. Moreover, tandem mutation of site I in the site II mutant led to a 66 % increase of VAL-A production. The result suggested that GlnR not only serves as an inhibitor by binding site I but also as an activator by binding site II for VAL-A biosynthesis. Furthermore, overexpression of glnR in the site I mutant JG45 improved VAL-A production for 41 % compared with the control strain containing the vector. Therefore, the obtained data illustrate a novel regulatory feature of the global regulator GlnR. GlnR is firstly proved to act simultaneously as an activator and a repressor in validamycin biosynthesis by binding to different loci within a promoter region of the gene cluster.

Independent oncogenic and therapeutic significance of phosphatase PRL-3 in FLT3-ITD-negative acute myeloid leukemia.

BACKGROUND: Internal tandem duplication of FMS-like tyrosine kinase (FLT3-ITD) is well known to be involved in acute myeloid leukemia (AML) progression, but FLT3-ITD-negative AML cases account for 70% to 80% of AML, and the mechanisms underlying their pathology remain unclear. This study identifies protein tyrosine phophatase PRL-3 as a key mediator of FLT3-ITD-negative AML. METHODS: A total of 112 FLT3-ITD-negative AML patients were sampled between 2010 and 2013, and the occurrence of PRL-3 hyperexpression in FLT3-ITD-negative AML was evaluated by multivariate probit regression analysis. Overexpression or depletion of endogenous PRL-3 expression with the specific small interfering RNAs was performed to investigate the role of PRL-3 in AML progression. Xenograft models were also used to confirm the oncogenic role of PRL-3. RESULTS: Compared to healthy donors, PRL-3 is upregulated more than 3-fold in 40.2% of FLT3-ITD-negative AML patients. PRL-3 expression level is adversely correlated to the overall survival of the AML patients, and the AML relapses accompany with re-upregulation of PRL-3. Mechanistically, aberrant PRL-3 expression promoted cell cycle progression and enhanced the antiapoptotic machinery of AML cells to drug cytotoxicity through downregulation of p21 and upregulation of Cyclin D1 and CDK2 and activation of STAT5 and AKT. Depletion of endogenous PRL-3 sensitizes AML cells to therapeutic drugs, concomitant with apoptosis by upregulation of cleaved PARP (poly ADP ribose polymerase) and apoptosis-related caspases. Xenograft assays further confirmed PRL-3's oncogenic role in leukemogenesis. CONCLUSIONS: Our results demonstrated that PRL-3 is a novel independent crucial player in both FLT3-ITD-positive and FLT3-ITD-negative AML and could be a potential therapeutic target.

[Effects of Different Microbial Fertilizers on Soil Quality and Maize Yield in Coastal Saline Soil].

Microbial fertilizers have the characteristics of high efficiency and environmental protection in improving saline soils, and the application of functional microbial fertilizers is of great significance for the green abatement of saline barriers and the improvement of soil quality in coastal areas. The experiment was based on moderately saline soil in the coastal area of Hebei Province, with corn as the indicator crop, on the basis of conventional chemical fertilizer application. Different microbial fertilizer treatments, namely, T1 （conventional chemical fertilizer 750 kg·hm-2 + compound microbial agent 75 kg·hm-2）, T2 （conventional chemical fertilizer 750 kg·hm-2 + Bacillus megaterium 300 kg·hm-2）, T3 （conventional chemical fertilizer 750 kg·hm-2 + B. mucilaginosus 300 kg·hm-2）, T4 （conventional chemical fertilizer 750 kg·hm-2 + organic silicon fertilizer 600 kg·hm-2）, T5 （conventional chemical fertilizer 750 kg·hm-2 + bio-organic fertilizer 600 kg·hm-2）, T6 （conventional fertilizer 750 kg·hm-2 + active microalgae 15 kg·hm-2）, and CK （only fertilizer 750 kg·hm-2）, were used for these seven treatments, to study the effects of different microbial fertilizers on soil nutrients, salinity, bacterial community, and corn yield and economic efficiency during two critical periods （V12 stage and maturity stage） of corn. The results showed that compared with that in CK, T1 significantly increased soil total nitrogen （TN） and available phosphorus （AP） contents during the whole growth period. Over the whole reproductive period, soil organic matter （OM） at maturity increased by 10.35% over the V12 stage compared to that in CK, but there was no significant difference between treatments. Compared with that in CK, T5 and T6 significantly reduced soil total salinity and Ca2+ content during the whole growth period by an average of 14.51%-18.48% and 24.25%-25.51%. T1 significantly increased the bacterial diversity index over the whole growth period by 45.16% compared to that in CK. The dominant soil phyla were Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi, and the dominant genera were Bacillus and Geminicoccaceae. The most abundant functions of the bacterial community in the study area were chemoheterotrophy and aerobic chemoheterotrophy, with average relative abundances of 28.89% and 27.11%, and T3 and T6 significantly improved soil N cycling function. The results of redundancy analysis （RDA） indicated that Na+, SO42-, pH, and EC were important factors driving the structure of the bacterial community, and correlation heatmaps showed that Na+, SO42-, pH, and EC were significantly and positively correlated mainly with the phylum Planctomycetota, whereas soil OM and TN were significantly and positively correlated with Cyanobacteria. Compared with that in CK, T6 increased the relative abundance of Cyanobacteria and optimized the bacterial community structure during the whole growth period. Using recommended dosages of bacterial fertilizers T1 and T6 increased maize yield by 7.31%-24.83% and economic efficiency by 9.05%-23.23%, respectively. The preliminary results of soil chemical properties and yield correlation analysis revealed that EC, AP, HCO3-, and Mg2+ were the obstacle factors limiting soil productivity in coastal areas. In conclusion, the use of the compound bacterial agent （T1） and active microalgae （T6） at the recommended dosage can significantly enhance soil nutrients, reduce salinity, and improve the structural diversity of soil bacterial communities, which not only ensures the increase in maize yield and efficiency but also realizes the efficient use of microbial fertilizers and the improvement of soil quality.