N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Assessment of relationships between frailty and chronic pain: a bidirectional two-sample Mendelian randomisation study.

BACKGROUND: Previous observational studies have indicated a complex association between chronic pain and frailty. This study aimed to examine the bidirectional causal relationship between frailty and chronic pain and to quantify mediating effects of known modifiable risk factors. METHODS: A bidirectional two-sample Mendelian randomisation (MR) analysis was applied in this study. Summary genome-wide association statistics for frailty, as defined by both frailty index (FI) and Fried Frailty Score (FFS), pain at seven site-specific chronic pain (SSCP) (headache, facial, neck/shoulder, stomach/abdominal, back, hip and knee) and multisite chronic pain (MCP) were extracted from populations of European ancestry. Genetic instrumental variables strongly correlated with each exposure were selected. The inverse-variance-weighted method was the primary method used in the MR, supplemented by a range of sensitivity and validation analyses. Two-step MR analysis was undertaken to evaluate the mediating effects of several proposed confounders. RESULTS: Genetically predicted higher FI and FFS were associated with an increased risk of MCP and specific types of SSCP, including neck/shoulder pain, stomach/abdominal pain, back pain, hip pain and knee pain. In the reverse direction analysis, genetic liability to MCP was found to be associated with increased FI and FFS. These results remained consistent across sensitivity and validation assessments. Two-step MR suggested a mediating role for body mass index, smoking initiation, physical inactivity, educational attainment and depression. CONCLUSIONS: Our research provided genetic evidence that the association between frailty and chronic pain was bidirectional where the coexistence of both conditions will exacerbate each other.

Hydralazine loaded nanodroplets combined with ultrasound-targeted microbubble destruction to induce pyroptosis for tumor treatment.

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.

The MYBL2-CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages.

BACKGROUND: An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored. METHODS: A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies-namely RNA-sequencing, western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay-were used to reveal the mechanisms of MYBL2 in the OVC microenvironment. RESULTS: We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance. CONCLUSIONS: The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.

Effects of Synthetic Astaxanthin on the Growth Performance, Pigmentation, Antioxidant Capacity, and Immune Response in Black Tiger Prawn (Penaeus monodon).

Synthetic astaxanthin is an effective nutritional strategy for improving shrimp body color and promoting growth. However, the optimal amount of astaxanthin in feed also varies with the synthetic technology and purity. In the present study, five diets containing different doses of synthetic astaxanthin (0% (CON), 0.02% (AX0.02), 0.04% (AX0.04), 0.08% (AX0.08), and 0.16% (AX0.16)) were administered to Penaeus monodon (initial body weight: 0.3 ± 0.03 g) for 8 weeks. With an increase in astaxanthin content in feed, weight gain and specific growth rate increased initially and subsequently decreased, with the highest value appearing at AX0.08. Dietary astaxanthin supplementation obviously improved the carapace and muscle color by enhancing astaxanthin pigmentation. Meanwhile, the fatty acid profile was altered by dietary astaxanthin, as evidenced by a decline in palmitic acid proportion, along with an increase in n-3 polyunsaturated fatty acids (n-3 PUFA) contents in muscle. In addition, dietary astaxanthin supplementation regulated prawn's antioxidant capacity. In the hemolymph, the activities of glutamic pyruvic transaminase (GPT) showed a significantly decrease trend with linear effect. The activities of glutamic oxaloacetic transaminase (GOT) and the contents of malondialdehyde (MDA) were first downregulated and then upregulated with significantly quadratic pattern. In the hepatopancreas, the activities of superoxide dismutase (SOD) and the contents of MDA were significantly downregulated with the increase of dietary astaxanthin levels. Reduced glutathione (GSH) contents and catalase (CAT) activities were also significantly decreased in group AX0.08. Correspondingly, astaxanthin decreased GSH and MDA contents under transportation stress. Moreover, the mRNA expression of immune genes (traf6, relish, and myd88) were inhibited by dietary astaxanthin supplementation. Based on the results of polynomial contrasts analysis and Duncan's test, dietary synthetic astaxanthin is a suitable feed additive to improve the growth, body color, antioxidant capacity, and nonspecific immunity of P. monodon. According to the second-order polynomial regression analysis based on the weight gain, the optimal supplementation level of dietary astaxanthin was 90 mg kg-1 in P. monodon.

The Chinese lexicon of deaf readers: A database of character decisions and a comparison between deaf and hearing readers.

We present a psycholinguistic study investigating lexical effects on simplified Chinese character recognition by deaf readers. Prior research suggests that deaf readers exhibit efficient orthographic processing and decreased reliance on speech-based phonology in word recognition compared to hearing readers. In this large-scale character decision study (25 participants, each evaluating 2500 real characters and 2500 pseudo-characters), we analyzed various factors influencing character recognition accuracy and speed in deaf readers. Deaf participants demonstrated greater accuracy and faster recognition when characters were more frequent, were acquired earlier, had more strokes, displayed higher orthographic complexity, were more imageable in reference, or were less concrete in reference. Comparison with a previous study of hearing readers revealed that the facilitative effect of frequency on character decision accuracy was stronger for deaf readers than hearing readers. The effect of orthographic-phonological regularity differed significantly for the two groups, indicating that deaf readers rely more on orthographic structure and less on phonological information during character recognition. Notably, increased stroke counts (i.e., higher orthographic complexity) hindered hearing readers but facilitated recognition processes in deaf readers, suggesting that deaf readers excel at recognizing characters based on orthographic structure. The database generated from this large-scale character decision study offers a valuable resource for further research and practical applications in deaf education and literacy.

NiCo Alloy Nanoparticles on a N/C Dual-Doped Matrix as a Cathode Catalyst for Improved Microbial Fuel Cell Performance.

The cathode material properties of the microbial fuel cell (MFC) have a quite important effect on their power generation capacity. Excellent oxygen reduction reaction (ORR) performance is the key to obtaining the remarkable capability of MFC. In this study, a series of catalysts are successfully prepared by a simple step-by-step hydrothermal, in situ growth, solution polymerization, and pyrolysis procedure. Here, the NiCo nanoparticles loading on nitrogen/carbon dual-doped matrix annealing at 800 °C (NiCo@DNC-800) under Ar shows good ORR activity with a maximum power density of 2325.60 ± 41.96 mW m-2 in the case of the 2 mg cm-2 minimal catalyst loading, and which is about 2.16 times more than that achieved by 20% Pt/C (1074.21 ± 39.36 mW m-2 ). The unique N/C duel-doped matrix provides more graphitic-N and pyridinic-N that can reduce the resistance of electron diffusion and transport, together with the synergistic catalysis of NiCo active sites improving the oxygen reduction reaction performance of MFC greatly. In addition, the NiCo@DNC-800 cathode catalyst demonstrates that composite materials have great application potential in water pollution treatment and new green energy strategies.

A CLE-BAM-CIK signalling module controls root protophloem differentiation in Arabidopsis.

Exogenous application of CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE) peptides suppresses protophloem differentiation and leads to the consumption of the proximal root meristem. However, the exact CLE peptides and the corresponding receptor complex regulating protophloem differentiation have not yet been clarified. Through expression pattern and phylogenetic analyses, CLE25/26/45 were identified as candidate peptides. Further genetic analyses, physiological assays and specific protophloem marker observations indicated that CLE25/26/45, BARELY ANY MERISTEM1/3 (BAM1/3) and CLV3 INSENSITIVE KINASEs (CIKs) are involved in regulating protophloem differentiation. The cle25 26 45 and cik2 3 4 5 6 mutation can greatly rescue the root defects of brevis radix (brx) and octopus (ops) mutants. The protophloem differentiation and proximal root meristem consumption of clv1 bam1 3 and cik2 3 4 5 6 were insensitive to CLE25/26/45 treatments. cle25 26 45, clv1 bam1 3 and cik2 3 4 5 6 displayed similar premature protophloem. In addition, CLE25/26/45 induced the interactions between BAMs and CIKs in vivo. Furthermore, CLE25/26/45 enhanced the phosphorylation levels of CIKs, which were greatly impaired in clv1 bam1 3 mutant. Our work clarifies that the CLE25/26/45-BAM1/3-CIK2/3/4/5/6 signalling module genetically acts downstream of BRX and OPS to suppress protophloem differentiation.

Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.

Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.

Comparison of Two Noninvasive Ventilation Strategies (NHFOV Versus NIPPV) as Initial Postextubation Respiratory Support in High-Risk Infants After Congenital Heart Surgery.

OBJECTIVE: This study aimed to compare the effects of nasal high-frequency oscillatory ventilation (NHFOV) and noninvasive positive-pressure ventilation (NIPPV) as the initial postextubation therapies on preventing extubation failure (EF) in high-risk infants younger than three months after congenital heart surgery (CHS). DESIGN: This was a single-center, randomized, unblinded clinical trial. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: Between January 2020 and January 2021, a total of 150 infants underwent CHS in the authors' hospital. INTERVENTIONS: Infants younger than three months with a high risk for extubation failure who were ready for extubation were randomized to either an NHFOV therapy group or an NIPPV therapy group, and received the corresponding noninvasive mechanical ventilation to prevent EF. MEASUREMENTS: Primary outcomes were reintubation, long-term noninvasive ventilation (NIV) support (more than 72 hours), and the time in NIV therapy. The secondary outcomes were adverse events, including mild-moderate hypercapnia, severe hypercapnia, severe hypoxemia, treatment intolerance, signs of discomfort, unbearable dyspnea, inability to clear secretions, emesis, and aspiration. MAIN RESULTS: Of 92 infants, 45 received NHFOV therapy, and 47 received NIPPV therapy after extubation. There were no significant differences between the NHFOV and the NIPPV therapy groups in the incidences of reintubation, long-term NIV support, and total time under NIV therapy. No significant difference was found of the severe hypercapnia between the two groups, but NHFOV treatment significantly decreased the rate of mild-moderate hypercapnia (p < 0.05). Other outcomes were similar in the two groups. CONCLUSIONS: Among infants younger than three months after CHS who had undergone extubation, NIPPV therapy and NHFOV therapy were the equivalent NIV strategies for preventing extubation failure, and NHFOV therapy was more effective in avoiding mild-moderate hypercapnia.

Impact of High-Frequency Oscillatory Ventilation Combined With Volume Guarantee on Lung Inflammatory Response in Infants With Acute Respiratory Distress Syndrome After Congenital Heart Surgery: A Randomized Controlled Trial.

OBJECTIVES: Congenital heart disease (CHD) after cardiopulmonary bypass can cause systemic inflammation, and its degree is closely related to the incidence of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine the effectiveness of high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) in reducing systemic inflammation in infants with ARDS after cardiopulmonary bypass for congenital heart surgery. DESIGN: A randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: A total of 58 infants with ARDS after congenital heart surgery were eligible and were randomized to the HFOV (n = 29) or the HFOV-VG (n = 29) between January 2020 and January 2021. INTERVENTIONS: Tracheal aspirate samples for the measurement of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were obtained on days one, two, and three of HFOV or HFOV-VG ventilation. MEASUREMENTS AND MAIN RESULTS: The authors found a significantly increasing trend in the HFOV group mean values of IL-6, IL-8, and TNF-α (p < 0.05 on days two and three v day one), and IL-6, IL-8, and TNF-α levels were significantly higher on day three in the HFOV group versus the HFOV+VG group (p < 0.05). In addition, the incidences of hypocapnia and hypercapnia in infants supported with HFOV-VG were significantly lower (p < 0.05). Furthermore, the postoperative mechanical ventilation duration in the HFOV-VG group also was shorter than that in the HFOV group (p < 0.05). CONCLUSION: Compared with HFOV alone, HFOV-VG reduced proinflammatory systemic reactions after congenital cardiac surgery, decreased the incidences of hypercapnia and hypocapnia, and shortened the postoperative mechanical ventilation duration.

Effect of postoperative administration of inhaled nitric oxide combined with high-frequency oscillatory ventilation in infants with acute hypoxemic respiratory failure and pulmonary hypertension after congenital heart surgery: A retrospective cohort study.

OBJECTIVE: To evaluate the effect of inhaled nitric oxide (iNO) combined with high-frequency oscillatory ventilation (HFOV) in the treatment of infants with acute hypoxemic respiratory failure (AHRF) and pulmonary hypertension (PH) after congenital heart surgery. METHODS: A retrospective study was conducted on 63 infants with AHRF and PH after congenital heart surgery in our cardiac intensive care unit (CICU) from January 2020 to March 2021. A total of 24 infants in the A group were treated with HFOV combined with iNO, and 39 infants in the B group were treated with HFOV. Relevant clinical data were collected. RESULTS: Comparing the two groups, the improvement of the oxygenation index, PaO2 and PaO2 /FiO2 was more obvious for patients in the A group than for those in the B group after intervention (p < .05). Reexamination on the third day after the initiation of HFOV treatment indicated that the systolic pulmonary artery pressure in the A group was significantly lower than that in the B group (p < .05). In addition, the duration of mechanical ventilation and the length of CICU stay in the A group were shorter than those in the B group (p < .05). However, complications between the two groups were not statistically significant. No important adverse effects arose. CONCLUSIONS: For infants with AHRF and PH after congenital heart surgery, iNO combined with HFOV is superior to HFOV alone to improve oxygenation, decrease pulmonary pressure, and shorten the duration of mechanical ventilation and the length of CICU stay, with no adverse effects.

Midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.

OBJECTIVES: To investigate the safety and feasibility of midazolam for conscious sedation in transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography. METHODS: A retrospective analysis was performed on 55 patients who underwent transcatheter device closure of atrial septal defects from October, 2019 to May, 2020. All patients received intravenous midazolam and local anesthesia with lidocaine to maintain sedation. A group of previous patients with unpublished data who underwent the same procedure with general anesthesia was set as the control group. The relevant clinical parameters, the Ramsay sedation scores, the numerical rating scale, and the post-operative satisfaction questionnaire were recorded and analyzed. RESULTS: In the midazolam group, the success rate of atrial septal defect closure was 98.2%. Hemodynamic stability was observed during the procedure. None of the patients needed additional endotracheal intubation for general anesthesia. Compared with the control group, the midazolam group had no statistically significant differences in the Ramsay sedation score and numerical rating scale scores. Patients in the midazolam group experienced more post-operative satisfaction than those in the control group. CONCLUSIONS: Conscious sedation using midazolam is a safe and effective anesthetic technique for transcatheter device closure of atrial septal defects guided solely by transthoracic echocardiography.

WeChat-assisted health education and preoperative care improve the mental state of parents of children with ventricular septal defect.

Many studies have shown that parents of children with congenital heart disease have more stress, anxiety and depression. This study was aimed to explore the effect of implementing WeChat-assisted health education and preoperative care on parents of children with the restrictive ventricular septal defect to improve the psychological state. A prospective randomized controlled study was conducted in a provincial hospital in China. Participants were randomly divided into an intervention group and a control group to explore the psychological state of parents of children with the restricted ventricular septal defect. Before surgery, the state-trait anxiety inventory scale score (STAI) of the WeChat group were 26.8 ± 8.2 and 27.3 ± 7.0, which were significantly higher than those of the leaflet group (37.6 ± 12.9 and 39.3 ± 11.7). Compared with the STAI score at the first visit, the WeChat group preoperative score was significantly lower (P < 0.05). The rate of loss to follow-up in the WeChat group (0%) was significantly lower than that of the leaflet group (14.3%). The complication of the leaflet group was significantly higher than that of the WeChat group. Health education and preoperative care for parents of children with restrictive ventricular septal defect through WeChat can effectively improve the parents' mental state and reduce the incidence of complications and the rate of loss to follow-up.

Objective ages of acquisition for 3300+ simplified Chinese characters.

We report the construction of two age-of-acquisition (AoA) norms for 3300+ characters in simplified Chinese, which make up about 99% of the texts used in daily life. We determined a character's AoA according to the time in which the character is formally learned in two sets of leading textbooks of Chinese in compulsory education, published respectively on the basis of the 2001 and 2011 national curriculum. Apart from having a significantly larger coverage of characters than previous norms, the current norms also outperformed them in explaining accuracy and reaction times in four large-scale databases for character decision, character naming, or character handwriting, even after controlling for the effects of frequency, number of meanings, and number of strokes. The explanatory advantage of the current norms suggests that, compared to earlier norms, the current norms capture more up-to-date character AoAs; these findings also highlight the diachronic nature of some lexical variables such as AoA and frequency. The developed objective AoA norms can be used for subsequent research on Chinese character recognition or production.

Tendon-derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor-ß crosstalk-mediated mechanism.

Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-ß (TGF-ß) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-ß/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-ß receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-ß signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-ß signaling decreased tECM-mediated expression of integrin α1, α2, and ß1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-ß signaling crosstalk. Understanding how integrins interact with signaling by TGF-ß and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair.

WeChat-assisted pre-operative health education improves the quality of life of parents of children with ventricular septal defects: A prospective randomised controlled study.

AIM: This study aimed to explore the effect of implementing pre-operative WeChat-assisted health education for parents of children with restrictive ventricular septal defects to improve their quality of life. METHODS: A prospective randomised controlled study was conducted in a provincial hospital in China. Participants were randomly divided into the intervention group (WeChat group, n = 35) and the control group (leaflet group, n = 35). The quality of life of parents of children with restricted ventricular septal defects was studied. RESULTS: Compared with the leaflet group, the WeChat group had a significantly lower score for the pre-operative Self-Rating Anxiety Scale (SAS) (P < 0.05). The pre-operative SAS score in the WeChat group was significantly lower than that at the first visit (P < 0.05). However, the SAS score in the leaflet group was similar at the time of preoperation and the first visit (P > 0.05). The pre-operative scores of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale in the physiological, psychological, social, and environmental fields and the total life quality score in the WeChat group were significantly higher than those of the leaflet group (P < 0.05). CONCLUSION: Implementing pre-operative WeChat-assisted health education for parents of children with restrictive ventricular septal defects can effectively relieve their anxiety and improve their quality of life.

Evaluation of analgesic and sedative effects of remifentanil-based fast-track anesthesia in children undergoing transthoracic device closure of ventricular septal defects.

BACKGROUND: This study aimed to evaluate the analgesic and sedative effects of remifentanil-based fast-track cardiac anesthesia in children undergoing transthoracic device closure of ventricular septal defects (VSDs). METHODS: A retrospective analysis was conducted on 62 children who underwent transthoracic device closure of VSDs from May 2019 to August 2019. The patients were divided into two groups based on the anesthesia methods: group F was given remifentanil-based fast-track cardiac anesthesia, and Group C was given conventional anesthesia. Patient-related clinical data, postoperative analgesia scores, and sedation scores were collected and analyzed. RESULTS: There was no significant difference in intraoperative hemodynamic changes, bispectral index values, postoperative analgesia scores, sedation scores, or the incidence of adverse events between the two groups. Compared with Group C, the duration of mechanical ventilation and the length of intensive care unit (ICU) and hospital stay in group F were significantly lower. CONCLUSION: Remifentanil-based fast-track anesthesia can be safely applied in children undergoing transthoracic device closure of VSDs, with acceptable postoperative analgesia and sedation effects and shorter mechanical ventilation times and ICU and hospital stays compared with conventional anesthesia.

Impact of Music Therapy on Preoperative Anxiety and Degree of Cooperation With Anesthesia Induction in Children With Simple Congenital Heart Disease.

PURPOSE: To evaluate the impact of music therapy (MT) on preoperative anxiety and degree of cooperation with anesthesia induction in children with simple congenital heart disease (CHD). DESIGN: A randomized controlled clinical study. METHODS: Ninety children were randomly assigned to the MT and control groups. The MT groups underwent a preoperative 30-minute session of MT, whereas the control group did not listen to any music and had the same amount of quiet time. The modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) was used to evaluate the patients' preoperative anxiety on entering the anesthesia waiting area (T1), 10 minutes after entering the waiting area (T2), and during the initiation of anesthesia induction (T3); the degree of cooperation with anesthesia induction was assessed using the Induction Compliance Checklist. The mean arterial blood pressure (MAP) and heart rate (HR) at T1, T2, T3, and T4 (the time of successful anesthesia) were also recorded. FINDINGS: One child was excluded from the MT group, and one was excluded from the control group. No difference was found in the mYPAS-SF score, MAP, or HR between the two groups at T1. The mYPAS-SF scores of the MT group were significantly lower than those of the control group at T2 and T3. At T2, T3, and T4, the MAP and HR of the MT group were lower than those of the control group. A statistically significant difference was found in the Induction Compliance Checklist score between the two groups. CONCLUSIONS: MT can reduce preoperative anxiety and improve the degree of cooperation with anesthesia induction.

Ubiquitination of IGF2BP3 by E3 ligase MKRN2 regulates the proliferation and migration of human neuroblastoma SHSY5Y cells.

Neuroblastoma (NB) is a paediatric tumour that shows great biomolecule and clinical heterogeneity, and patients with NB often develop various neurological complications. Currently, the disease is mainly treated by surgery and still lacks specific therapeutic drugs; therefore, targets are urgently needed. Makorin ring finger protein 2 (MKRN2) is an E3 ligase whose effects on neuroblastoma have not been illustrated. shRNAs for MKRN2 have been designed, and MKRN2-knockdown human neuroblastoma SHSY5Y cells were established. MKRN2 knockdown promotes the proliferation and migration of SHSY5Y cells. Because MKRN2 is an E3 ligase, we performed a series of experiments, and Insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) was identified as a new substrate for MKRN2. IGF2BP3 is an RNA-binding protein that regulates the stability of many mRNAs, including CD44 and PDPN, and our study demonstrated that MKRN2 regulates the expression of CD44 and PDPN in an IGF2BP3-dependent manner. These results suggest that MKRN2 might be a potential therapeutic target for neuroblastoma.