Abstract Osteosarcoma, the most common pediatric bone tumor, is an aggressive heterogeneous malignancy defined by complex chromosomal aberrations. Overall survival rates remain at approximately 70%, but patients with chemoresistant or metastatic disease have extremely poor outcomes of less than 30%. A subgroup of tumors harbor amplification of chromosome 8q24.2 and increased expression of the oncogenic long noncoding RNA (lncRNA) Plasmacytoma Variant Translocation-1 (PVT-1), which is associated with an extremely poor clinical prognosis. Through in vitro assays, this study demonstrated that PVT-1 is critical for osteosarcoma tumor-initiation potential. Chromatin Hybridization by RNA Purification analysis identified Tripartite-Motif Containing Family 28 (TRIM28) as a novel PVT-1 binding partner. Mechanistically, co-immunoprecipitation studies showed the PVT-1/TRIM28 complex binds and increases SUMOylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34), which leads to enhanced ubiquitination and degradation of tumor suppressor complex 2 (TSC2), thus contributing to stem cell phenotypes. Importantly, osteosarcoma cells with increased PVT-1 have enhanced sensitivity to a SUMOylation inhibitor, TAK-981. Altogether, this study elucidated a role for PVT-1 in the enhancement of cancer stem-like behaviors, including migration and invasion, in osteosarcoma, and identified the novel PVT-1/TRIM28 axis signaling cascade as a potential therapeutic target for osteosarcoma treatment.
The ubiquitous Gram-negative bacterial pathogen Aeromonas veronii (A. veronii) can easily cause inflammatory reactions in aquatic organisms, resulting in high mortality and huge economic losses. MicroRNAs (miRNAs) participate in immune regulation and have certain conserved properties. MiRNAs are involved in the immune responses of a variety of teleost fish infected with bacteria, whereas there is no related report in silver carp (Hypophthalmichthys molitrix). Therefore, we identified the expression profiles of miRNA in silver carp stimulated by A. veronii and LPS. Among them, the quantity of differentially expressed miRNAs (DEmiRNAs) obtained in the silver carp challenge group was 73 (A. veronii) and 90 (LPS). The GO enrichment and analysis of KEGG pathways have shown that the predicted target genes are mainly associated with lipid metabolism and the immune response in silver carp. This indicates the possibility that miRNAs play a role in regulating immune-related pathways. In addition, a total of eight DEmiRNAs validated the accuracy of the sequencing result via quantitative real-time PCR (qRT-PCR). Finally, we selected the silver carp head kidney macrophage cells (HKCs) as model cells and proved that miR-30b-5p can regulate the inflammatory response in silver carp HKCs. This study lays the foundation for exploring miRNA regulation in silver carp during pathogenic bacterial infection. In addition, it provides a reference for the future development of non-coding RNA antibacterial drugs.
Background: Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. Purpose: To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. Methods: Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. Results: Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ± 1.50 months (range: 1.00–6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. Conclusion: Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.
Objective
To explore characteristics of elderly severe burn patients and to provide evidence for the development of elderly severe burn treatment strategy.
Methods
A retrospective study about elderly severe burn with patients′ age over 60 years (including 60 years) and burn area over 30% total body surface area (TBSA) admitted to Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine was conducted between 1st January 2005 and 31st December 2016, by reviewed dates, age, gender, burn extent, etiology of burn, mechanism of injury, pre-injury conditions, complications following burn, inhalation injury, length of intensive care unit (ICU) stay of survived patients and the outcomes. Data were processed with analysis of variance of repeated measurement, one-way ANOVA, t test, rank-sum test, chi-square test, Fisher exact probability test and binomial test. Correlation was analyzed between data of age, gender, burn area, full thickness burn area, etiology of burn, mechanism of injury, pre-injury conditions, complications following burn, inhalation injury, length of ICU stay of survived patients and outcomes of patients using the univariate and multivariate Cox regression analysis.
Results
Seventy-three elderly severe burn patients were enrolled in this study, the morbidity was increasing significantly with 2.7% in 2005 to 17.8% in 2016 , the difference was statistically significant(χ2=45.18, P<0.05). Male patients (65.8%) were more than female patients (34.2%), and the difference was statistically significant (P=0.01). The median age was 66 years (range 61-86 years), there was no statistically significant difference between the age of male and female(Z=-0.22, P=0.83). The average burn area was (53.9±20.9)%TBSA, median full thickness burn area was 0. There were no statistically significant differences in gender ratio, age, etiologies in patients of different severity of burn (with P values above 0.05). Critical burn patients were more likely with inhalation injury, longer length of ICU stay, higher case fatality rate (with P values below 0.05) and were easily happened at workplace. The most common etiology was flame(79.5%). The majority of injuries occurred at home(57.5%) while patients injuried at workplace accounted for 31.5%. The most common pre-injury conditions were cardiovascular diseases (43.8%), neurological diseases(9.6%), diabetes (6.8%), respiratory diseases(6.8%). The most common complications were wound infection(42.5%), multiple organ failure(11.0%), pneumonia infection(11.0%). Patients accompanying inhalation injury was 11(15.1%). Median ICU stay of survived patients was 12 days. The case fatality rate was 32.9%. Total burn area and full thickness burn area were risk factor for death of elderly severe burn patients, only full thickness burn area was independent risk factor (HR=1.024, and 95%CI 1.006-1.041, P=0.008).
Conclusions
With the development of aging society, the morbidity of elderly severe burn patients was increasing, elderly severe burn are more likely to happen at home. Burn prevention strategy to decrease the morbidity, burn extent and to improve the recovery rate is pressing issue. At the same time, building an efficient rehabilitation system to improve life quality of recovered patients is in urgent need.
Key words:
Burns; Aged; Characteristics; Analysis
Circular ribonucleic acids (circRNAs) are a type of RNA that originates through back-splicing events from linear primary transcripts. CircRNAs display high structural resistance and tissue specificity. Accurate quantification of the circRNA expression level is of vital importance to disease diagnosis. Herein, we construct a label-free fluorescent biosensor for ultrasensitive analysis of circRNAs based on the integration of target-initiated cascade signal amplification strategy with a light-up G-quadruplex. This assay involves only one assistant probe that targets the circRNA-specific back-splice junction. When circRNA is present, it hybridizes with the assistant probe to initiate the duplex-specific nuclease (DSN)-catalyzed cyclic cleavage reaction, producing abundant triggers with 3′OH termini. Then, terminal deoxynucleotidyl transferase (TdT) catalyzes the addition of dGTP and dATP at the 3′-OH termini of the resultant triggers to obtain abundant long G-rich DNA sequences that can form efficient G-quadruplex products. The addition of Thioflavin T (ThT) can light up G-quadruplex, generating an enhanced fluorescence. This assay may be performed isothermally without the involvement of any nucleic acid templates, exogenous primers, and specific labeled probes. Importantly, this biosensor can discriminate target circRNA from one-base mismatched circRNA and exhibits good performance in human serum. Moreover, it can accurately detect circRNA in cancer cells at a single-cell level and even differentiate the circRNA levels in the tissues of healthy persons and nonsmall cell lung cancer (NSCLC) patients, with promising applications in circRNA-related cancer diagnosis and therapeutics.
Abstract Introduction The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. Methods The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from 'Google Scholar'. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. Results We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16 to 0.95). Both typical (three RCTs with 965 patients, RR = 0.71; 95% CI = 0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR = 0.36; 95% CI = 0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR = 0.71; 95% CI = 0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR = 0.99; 95% CI = 0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR = 0.93; 95% CI = 0.61 to 1.43) or acetylcholinesterase inhibitors and placebo (four RCTs with 242 patients, RR = 0.95; 95% CI = 0.63 to 1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1,636 patients, pooled SMD (standard mean difference) = -0.06; 95% CI = -0.16 to 0.04). Conclusions The included studies showed great inconsistencies in definition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.
Jing medicine occupies a very prominent position in the traditional culture of the Chinese nation and has unique advantages. Through the literature review of Jing medicine, the author has a deeper understanding of Jing medicine in Guangxi. This paper mainly shows the traditional characteristic medicine culture of the Jing nationality and discusses the characteristic therapy and medication characteristics of Jing nationality medicine, which is conducive to the improvement of people’s cognition of Jing nationality medicine and the development and innovation of Jing nationality medicine.
Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.
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