Barriers and facilitators to guideline for the management of pediatric off-label use of drugs in China: a qualitative descriptive study.

BACKGROUND: Despite being a global public health concern, there is a research gap in analyzing implementation strategies for managing off-label drug use in children. This study aims to understand professional health managers' perspectives on implementing the Guideline in hospitals and determine the Guideline's implementation facilitators and barriers. METHODS: Pediatric directors, pharmacy directors, and medical department directors from secondary and tertiary hospitals across the country were recruited for online interviews. The interviews were performed between June 27 and August 25, 2022. The Consolidated Framework for Implementation Research (CFIR) was adopted for data collection, data analysis, and findings interpretation to implement interventions across healthcare settings. RESULTS: Individual interviews were conducted with 28 healthcare professionals from all over the Chinese mainland. Key stakeholders in implementing the Guideline for the Management of Pediatric Off-Label Use of Drugs in China (2021) were interviewed to identify 57 influencing factors, including 27 facilitators, 29 barriers, and one neutral factor, based on the CFIR framework. The study revealed the complexity of the factors influencing managing children's off-label medication use. A lack of policy incentives was the key obstacle in external settings. The communication barrier between pharmacists and physicians was the most critical internal barrier. CONCLUSION: To our knowledge, this study significantly reduces the implementation gap in managing children's off-label drug use. We provided a reference for the standardized management of children's off-label use of drugs.

SLITRK6 promotes the progression of lung adenocarcinoma by regulating PI3K/AKT/mTOR signaling and Warburg effect.

To investigate the role of SLITRK6 in lung adenocarcinoma (LUAD) and the underlying mechanism in it, clinical tissues and tissue microarray of LUAD were used to detect the expression of SLITRK6. In vitro cell viability assay and colony formation assay in LUAD cells were conducted to investigate SLITRK6 related biological functions. In vivo subcutaneous model was used to determine the role of SLITRK6 in LUAD growth. It was found that the expression of SLITRK6 was significantly upregulated in LUAD tissues compared with that in para-cancerous tissues. Knockdown of SLITRK6 suppressed the proliferation and colony formation of LUAD cells in vitro. Meanwhile, the growth of LUAD cells was also inhibited by SLITRK6 knockdown in vivo. Furthermore, we found that SLITRK6 knockdown could suppress the glycolysis of LUAD cells by regulating the phosphorylation of AKT and mTOR. All results suggest that SLITRK6 promotes LUAD cell proliferation and colony formation by regulating PI3K/AKT/mTOR signaling and Warburg effect. SLITRK6 may serve as a potential therapeutic target for LUAD in future.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

Metabolism of an insecticide fipronil by soil fungus Cunninghamella elegans ATCC36112.

In this study, the metabolic pathway of the phenylpyrazole insecticide fipronil in Cunninghamella elegans (C. elegans) was investigated. Approximately 92% of fipronil was removed within 5 days, and seven metabolites were accumulated simultaneously. The structures of the metabolites were completely or tentatively identified by GC-MS and 1H, 13C NMR. To determine the oxidative enzymes involved in metabolism, piperonyl butoxide (PB) and methimazole (MZ) were used, and the kinetic responses of fipronil and its metabolites were determined. PB strongly inhibited fipronil metabolism, while MZ weakly inhibited its metabolism. The results suggest that cytochrome P450 (CYP) and flavin-dependent monooxygenase (FMO) may participate in fipronil metabolism. Integrated metabolic pathways can be inferred from the control and inhibitor experiments. Several novel products from the fungal transformation of fipronil were identified, and similarities between C. elegans transformation and mammalian metabolism of fipronil were compared. Therefore, these results will help to gain insight into the fungal degradation of fipronil and potential applications in fipronil bioremediation. At present, microbial degradation of fipronil is the most promising approach and maintains environmental sustainability. In addition, the ability of C. elegans to mimic mammalian metabolism will assist in illustrating the metabolic fate of fipronil in mammalian hepatocytes and assess its toxicity and potential adverse effects.

Microwave ablation versus surgical resection for subcapsular hepatocellular carcinoma: a propensity score-matched study of long-term therapeutic outcomes.

OBJECTIVES: The therapeutic efficacy of microwave ablation (MWA) for subcapsular hepatocellular carcinoma (HCC) has not been well characterized. We aimed to compare the long-term outcomes of MWA and surgical resection (SR) in patients with subcapsular HCC. METHODS: This retrospective study comprised 321 patients with subcapsular HCC meeting the Milan criteria who received MWA (n = 99) or SR (n = 222). Local tumor progression (LTP), overall survival (OS), and disease-free survival (DFS) were analyzed using propensity score matching (PSM) to compare the therapeutic efficacy. RESULTS: In the total cohort, there were no significant differences in 5-year LTP rates (14.0% vs. 8.9%, p = 0.12), OS rates (70.7% vs. 73.2%, p = 0.63), and DFS rates (38.3% vs. 41.2%, p = 0.22) between the MWA and SR groups. After PSM, the cumulative LTP rates at 1, 3, and 5 years were 9.7%, 14.0%, and 16.4% in the MWA group (n = 84) and 7.2%, 8.6%, and 10.6% in the SR group (n = 84), respectively, with no significant difference (p = 0.31). Neither corresponding OS rates (96.4%, 84.8%, and 73.0% vs. 95.2%, 85.5%, and 72.1%, p = 0.89) nor DFS rates (76.0%, 52.6%, and 38.1% vs. 76.2%, 44.7%, and 32.3%, p = 0.43) were significantly different between the MWA and SR groups. Whereas MWA obtained fewer complications for both cohorts (both p < 0.05). CONCLUSION: MWA showed comparable long-term therapeutic outcomes to SR, and it might be an alternative curative option for subcapsular HCC within the Milan criteria. KEY POINTS: • Microwave ablation showed comparable local tumor progression, overall survival, and disease-free survival to surgical resection for subcapsular hepatocellular carcinoma meeting the Milan criteria. • Microwave ablation obtained fewer complications and shorter postoperative hospital stay.

Facilitating combined biopsy and percutaneous microwave ablation of pulmonary ground-glass opacities using lipiodol localisation.

OBJECTIVES: Whether preoperative localisation is necessary and valuable for the microwave ablation (MWA) of small pulmonary lesions with ground-glass opacity (GGO) remains unclear. This study aimed to explore the role of the Chiba needle and lipiodol localisation techniques in facilitating MWA and biopsy. METHODS: This retrospective before-after study included patients with GGOs who underwent conventional MWA and biopsy treatment in our hospital between January 2018 and December 2019 (group A) or who underwent the Chiba needle and lipiodol localisation treatment before MWA and biopsy between January 2020 and December 2020 (group B). The characteristics of each patient and GGO lesion were collected and analysed to evaluate the safety and effectiveness of the localisation technique. RESULTS: A total of 122 patients with 152 GGOs and 131 patients with 156 GGOs underwent MWA and biopsy in groups A and B, respectively. The primary technique efficacy rate of MWA differed significantly between the two groups (A vs. B: 94.1% vs. 99.4%; p = 0.009). The positive biopsy rate in the two groups was determined by the difference (A vs. B: 93.4% vs. 98.1%; p = 0.042). The incidence of complications did not increase in group B. CONCLUSIONS: Compared with the unmarked group, the Chiba needle and lipiodol localisation technique improved the positive rate of biopsy and the initial effective rate of MWA, without significantly increasing the complication rate. KEY POINTS: • The localisation of the Chiba needle and lipiodol could improve the positive biopsy rate and the initial effective rate of MWA. • The localisation of the Chiba needle and lipiodol does not affect the subsequent MWA and biopsy and does not increase the incidence of pneumothorax and haemorrhage.

Microwave ablation versus laparoscopic resection for hepatocellular carcinoma in patients with clinically significant portal hypertension: a propensity score-matched study of postoperative liver decompensation.

OBJECTIVES: The study of postoperative liver decompensation after microwave ablation (MWA) for hepatocellular carcinoma (HCC) in patients with clinically significant portal hypertension (CSPH) is still lacking. The purpose of the present study was to compare the postoperative liver decompensation after MWA and laparoscopic resection (LR) for HCC in patients with CSPH. METHODS: The present retrospective study enrolled 222 HCC patients with CSPH who underwent MWA (n = 67) or LR (n = 155). Postoperative liver decompensation, complications, postoperative hospital stays, and overall survival were analyzed. Factors associated with postoperative liver decompensation were identified. RESULTS: After propensity score matching, the postoperative liver decompensation rate was significantly lower in the MWA group than that in the LR group (15.5% versus 32.8%, p = 0.030). The multivariable regression analysis identified that type of treatment (MWA vs. LR, odds ratio [OR] 0.44; 95% confidence interval [CI], 0.21-0.91; p = 0.026) and Child-Pugh B (OR, 2.86; 95% CI, 1.24-6.61; p = 0.014) were independent predictors for postoperative liver decompensation. The rate of complications for patients in the MWA group was significantly lower than that in the LR group (p < 0.001). And MWA showed shorter postoperative hospital stays than LR (3 days vs. 6 days, p < 0.001). Overall survival rate between the two groups was not significantly different (p = 0.163). CONCLUSION: Compared with laparoscopic resection, microwave ablation has a lower rate of postoperative liver decompensation and might be a better option for HCC patients with CSPH. CLINICAL RELEVANCE STATEMENT: Microwave ablation exhibited a lower incidence of postoperative liver decompensation in comparison to laparoscopic resection, thereby conferring greater advantages to hepatocellular carcinoma patients with clinically significant portal hypertension. KEY POINTS: •Postoperative liver decompensation rate after microwave ablation was lower than that of laparoscopic resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. •Microwave ablation showed shorter postoperative hospital stays than laparoscopic resection. •Microwave ablation had fewer complications than laparoscopic resection.

The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K2, in healthy subjects.

Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid-liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.

Exosomal miR-133a-3p promotes the growth and metastasis of lung cancer cells following incomplete microwave ablation.

PURPOSE: Exosomal miRNAs play key roles in various biological processes such as cell proliferation, angiogenesis, migration and invasion. We explored whether exosomal miRNAs can promote local recurrence (LR) of lung tumors following incomplete microwave ablation (MWA) therapy. METHODS: Exosomal miRNA profiles before and after incomplete MWA in lung cancer (LC) patients with LR (n = 3) were sequenced and compared. The differentially expressed miRNAs of interest were validated in clinical samples (n = 10) and MWA-treated cells using RT-qPCR analysis. Target genes of the miRNAs were predicted and validated. The biological functions of miRNAs in proliferation, angiogenesis and metastasis of A549 cells were evaluated in vitro and in vivo. RESULTS: A total of 270 miRNAs (243 upregulated and 27 downregulated) were differentially expressed after incomplete MWA in patients with local recurrence. Upregulation of miR-133a-3p after MWA was validated in the cells and clinical samples. Cell functional experiments suggested that miR-133a-3p overexpression derived from serum exosomes increased cell viability, migration and invasion ability, tube formation activity and proliferation of A549 cells. Sirtuin 1 (SIRT1) was identified as a target gene for miR-133a-3p. Moreover, miR-133a-3p delivered by exosomes significantly promoted tumor growth, paralleled by reduced SIRT1 expression in a subcutaneous tumorigenesis animal model and increased the number of lung nodules by tail vein metastasis in vivo. CONCLUSION: Exosomal miR-133a-3p overexpression promoted tumor growth and metastasis following MWA and could be a promising biomarker for LC recurrence after incomplete MWA.

Metabolic pathway of tebuconazole by soil fungus Cunninghamella elegans ATCC36112.

Tebuconazole is the most widely used fungicide in agriculture. Due to its long half-life, tebuconazole residues can be found in the environment media such as in soil and water bodies. Here, the metabolic pathway of tebuconazole was studied in Cunninghamella elegans (C. elegans). Approximately 98% of tebuconazole was degraded within 7 days, accompanied by the accumulation of five metabolites. The structures of the metabolites were completely or tentatively identified by gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). To identify representative oxidative enzymes that may be involved in the metabolic process, treatment with piperonyl butoxide (PB) and methimazole (MZ) was performed. PB had a strong inhibitory effect on the metabolic reactions, while MZ had a weak inhibitory effect. The results suggest that cytochrome P450 (CYP) and flavin-dependent monooxygenase are involved in the metabolism of tebuconazole. Based on the results, we propose a metabolic pathway for the fungal metabolism of tebuconazole. Data are of interest to gain insight into the toxicological effects of tebuconazole and for tebuconazole bioremediation.

Biodegradation and metabolic pathway of quinalphos by Cunninghamella elegans ATCC36112.

Quinalphos is a long-term, wide-spectrum organophosphate insecticide with residual problems in the natural environment. Cunninghamella elegans (C. elegans) is a member of Mucoromycotina. Since the degradation products of its exogenous compounds are similar to those of mammals, it is often used to simulate the metabolism pathways of mammals. In this study, the detailed metabolic pathways of quinalphos were investigated with C. elegans. Quinalphos was degraded by 92% in 7 days, while ten metabolites were produced. The metabolites were analyzed and identified by GC-MS. To determine the responsible enzymes in quinalphos metabolism, piperonyl butoxide (PB) and methimazole included in the culture flasks, and the kinetic responses of quinalphos and its metabolites by C. elegans were measured. Results indirectly demonstrated that cytochrome P450 monooxygenases were involved in the metabolism of quinalphos, but that methimazole inhibited the metabolism less efficiently. Comprehensive metabolic pathways can be deduced from the detailed analysis of metabolite profiles in control and inhibitor assays.

Genomic insight into transmission mechanisms of carbapenem-producing Citrobacter spp. isolates between the WWTP and connecting rivers.

Carbapenem-resistant Enterobacteriaceae (CRE) poses major health risks worldwide. Most studies have focused on carbapenem resistance in Klebsiella pneumoniae and Escherichia coli; however, the occurrence and transmission of carbapenem-resistant Citrobacter spp. (CRCS) are poorly understood. In this study, we investigated the occurrence and potential transmission patterns of CRCS in different functional areas of an urban wastewater treatment plant (WWTP) and connecting rivers during one-year monitoring in Shandong Province, China. In total, 14 CRCS were detected in 376 environmental samples, including those from the WWTP inlet (n = 7), WWTP anaerobic tank (n = 2), and rivers (n = 5). Citrobacter braakii (n = 6) was the dominant subtype among 14 CRCS isolates, followed by Citrobacter freundii (n = 5), Citrobacter sedlakii (n = 2), and Citrobacter werkmanii (n = 1). All CRCS were resistant to imipenem, meropenem, ampicillin, amoxicillin/clavulanic acid, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, and ciprofloxacin. Plasmid analysis showed that the blaKPC-2 gene was located on IncN and IncFII (Yp) plasmids, whereas the blaNDM gene was located on IncX3 and IncN2 plasmids. Clonal transmission of CRCS harboring carbapenem genes occurred between the WWTP and connecting rivers on a temporal or spatial scale. High genomic relatedness of NDM-5-producing C. sedlakii was identified between river water and WWTP aerosol, suggesting a potential exposure risk of CRCS for workers and surrounding residents near the WWTP. Furthermore, NDM-5-producing C. sedlakii isolated from rivers was related to C. sedlakii isolated from soil and well water in different regions of China, indicating that NDM-5-producing C. sedlakii may be widespread in China. These findings indicate that rare healthcare-associated pathogens such as CRCS can contribute to widespread carbapenem production in the environment; thus, CRCS should be continuously monitored.

Association of serum uric acid with risk of stroke in US adults: A cross-sectional study from NHANES 1999-2020.

BACKGROUND AND AIMS: The validity of high uric acid levels as an independent cause of stroke remains controversial, and the association between its low concentration and stroke is unclear. This study determines how different serum uric acid (SUA) levels are associated with stroke risk. METHODS: This cross-sectional study used continuous National Health and Nutrition Examination Survey data in the United States during 1999-2020. The SUA levels of 6.0, 6.8, and 9.0 mg/dL were all considered as cut-off points. Restricted cubic spline interpolation and logistic regression models were used to evaluate the different associations. Subgroup analyses and sensitivity analyses were conducted to evaluate the influence of multiple factors on the outcomes. RESULTS: The study included 23,413 participants aged ≥ 20 years. A J-shaped curve existed between SUA and stroke risk, and the risk of stroke was positively correlated with SUA levels in the overall population. Subgroup analysis of all adults in the SUA 6.8-9.0 mg/dL group showed that stroke risk for non-Hispanic white, obese, ex-smoker, and heavy drinking groups was increased, but for the other Hispanic group was reduced. In the SUA < 6.0 mg/dL group, stroke risk for ex-smoker, heavy drinkers, and no chronic kidney disease groups was increased. CONCLUSION: Our findings indicate a J-shaped relationship between SUA levels and stroke risk. Low and high SUA levels increased stroke risk for different populations, except in the other Hispanic population. Early SUA management is highly significant for stroke prevention in high-risk populations.

Comprehensive Transcriptomic and Metabolic Profiling of Agrobacterium-tumefaciens-Infected Immature Wheat Embryos.

The transformation efficiency (TE) was improved by a series of special chemical and physical methods using immature embryos from the cultivar Fielder, with the PureWheat technique. To analyze the reaction of immature embryos infected, which seemed to provide the necessary by Agrobacterium tumefaciens in PureWheat, a combination of scanning electron microscopy (SEM), complete transcriptome analysis, and metabolome analysis was conducted to understand the progress. The results of the SEM analysis revealed that Agrobacterium tumefaciens were deposited under the damaged cortex of immature embryos as a result of pretreatment and contacted the receptor cells to improve the TE. Transcriptome analysis indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, starch and sucrose metabolism, plant-pathogen interaction, plant hormone signal transduction, and the MAPK (Mitogen-activated protein kinase) signaling pathway. By analyzing the correlation between differentially expressed genes and metabolites, the expression of many genes and the accumulation of metabolites were changed in glucose metabolism and the TCA cycle (Citrate cycle), as well as the amino acid metabolism; this suggests that the infection of wheat embryos with Agrobacterium is an energy-demanding process. The shikimate pathway may act as a hub between glucose metabolism and phenylpropanoid metabolism during Agrobacterium infection. The downregulation of the F5H gene and upregulation of the CCR gene led to the accumulation of lignin precursors through phenylpropanoid metabolism. In addition, several metabolic pathways and oxidases were found to be involved in the infection treatment, including melatonin biosynthesis, benzoxazinoid biosynthesis, betaine biosynthesis, superoxide dismutase, and peroxidase, suggesting that wheat embryos may be under the stress of Agrobacterium and, thus, undergo an oxidative stress response. These findings explore the physiological and molecular changes of immature embryos during the co-culture stage of the PureWheat technique and provide insights for Agrobacterium-mediated transgenic wheat experiments.

Tracking spatio-temporal distribution and transmission of antibiotic resistance in aquatic environments by using ESBL-producing Escherichia coli as an indicator.

Wastewater treatment plants (WWTPs) play an important role in the production, and transmission of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) as a convergence for human, animal, and environmental wastewater. The aim of this study was to investigate the spatio-temporal variation and influencing factors of ARB in different functional areas of the urban WWTP and the connecting rivers for 1-year monitoring using extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec) as an indicator bacteria, and to study the transmission patterns of ARB in the aquatic environment. The results showed that ESBL-Ec isolates were identified from the WWTP (n = 219), including influent (n = 53), anaerobiotic tank (n = 40), aerobiotic tank (n = 36), activated sludge tank (n = 31), sludge thickner tank (n = 30), effluent (n = 16), and mudcake storage area (n = 13). The dehydration process can significantly remove the ESBL-Ec isolates; however, ESBL-Ec was still detected in samples collected from the effluent of the WWTP (37.0%). The detection rate of ESBL-Ec was significantly different across seasons (P < 0.05), and ambient temperature was negatively correlated with the detection rate of ESBL-Ec (P < 0.05). Furthermore, a high prevalence of ESBL-Ec isolates (29/187, 15.5%) was detected in samples collected from the river system. These findings emphasize that the high majority of ESBL-Ec in aquatic environments is alarming because it poses a significant threat to public health. Clonal transmission of ESBL-Ec isolates between the WWTP and rivers based on the spatio-temporal scale was observed by pulsed-field gel electrophoresis analysis, ST38 and ST69 ESBL-Ec clone were selected as prioritized isolates for antibiotic resistance monitoring in the aquatic environment. Further phylogenetic analysis showed human-associated (feces, blood) E. coli was the main source contributing to the presence of antibiotic resistance in aquatic environments. Longitudinal and targeted monitoring of ESBL-Ec in WWTPs and the development of effective wastewater disinfection strategies before effluent discharge from WWTPs are urgently required, to prevent and control the spread of antibiotic resistance in the environment.

The association between sleep and empathy in young preschoolers: A population study.

Sleep is vital for children's early socio-emotional development, particularly empathy. This study aimed to explore the associations between sleep and empathy in young preschoolers. A sample of 23,259 preschoolers (4.3 ± 0.3 years) at the entry year of preschool was recruited as part of the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) study. Caregivers reported on child sleep, affective empathy, and cognitive empathy through the Children's Sleep Habits Questionnaire and the Griffith Empathy Measure. Ordinary least-square regression and quantile regression were performed for the associations between sleep and empathy. Sex differences were also investigated. Night sleep duration was negatively associated with affective empathy (ß = -0.35, p < 0.001), and positively associated with cognitive empathy (ß = 0.41, p < 0.001). Longer nap duration was associated with higher affective empathy (ß = 0.28, p < 0.001). Sleep disturbances were positively associated with affective empathy (ß = 0.04, p < 0.001) and negatively associated with cognitive empathy (ß = -0.09, p < 0.001). These associations were generally stronger in children at higher empathy quantiles and also those at the 10th cognitive empathy quantile. The associations between sleep and affective empathy were mainly contributed by girls, and were more common in boys in terms of cognitive empathy, particularly at the 10th and the 30th quantiles. In conclusion, longer night sleep duration and fewer sleep disturbances are associated with a more mature empathy pattern in young preschoolers. The associations are more prominent in children at the higher end of the empathy spectrum, and vary by sex. These findings highlight the importance to promote sleep health in young children for optimal socio-emotional development.

Microwave ablation versus radiofrequency ablation for subcapsular hepatocellular carcinoma: a propensity score-matched study.

OBJECTIVES: Thermal ablation is now accepted as one of the curative treatments for patients with early-stage hepatocellular carcinoma (HCC), but the efficacy of this treatment for subcapsular HCC is not well characterized. Therefore, we aimed to compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) for patients with subcapsular HCC. METHODS: In total, 195 patients with subcapsular HCC who met the Milan criteria and underwent MWA or RFA were included. Local tumor progression (LTP), overall survival (OS), recurrence beyond the Milan criteria (RBM), and complications of these patients were compared. RESULTS: After propensity score matching, the 1-, 3-, and 5-year cumulative LTP rates were 6.7%, 9.6%, and 11.4% in the MWA group, and 13.4%, 24.6%, and 29.1% in the RFA group, respectively (p = 0.006). The cumulative rates of RBM were lower in patients treated with MWA than in those treated with RFA (4.4% versus 12% at 1 year; 14.5% versus 23.0% at 3 years; and 37.4% versus 53.9% at 5 years; p = 0.03). The OS rates at 1, 3, and 5 years were 97.1%, 85.9%, and 73.4% in the MWA group, and 95.6%, 80.4%, and 61.4% in the RFA group, respectively (p = 0.36). The rate of major complications showed no significant difference between the MWA group and the RFA group (17.4% vs. 11.6%, p = 0.33). CONCLUSION: Compared to RFA, MWA showed better tumor control for subcapsular HCC within the Milan criteria. There was no difference in the incidence of major complications between the two groups. KEY POINTS: •Compared to radiofrequency ablation, microwave ablation showed better local tumor control for patients with subcapsular hepatocellular carcinoma. •Microwave ablation showed similar major complication rates for patients with subcapsular hepatocellular carcinoma. •Microwave ablation may be preferred for patients with subcapsular hepatocellular carcinoma when they need to receive thermal ablation.

Microwave ablation treatment for medically inoperable stage I non-small cell lung cancers: long-term results.

OBJECTIVES: In the present study, we aim to show the results of microwave ablation (MWA) for medically inoperable stage I non-small cell lung cancers (NSCLCs) with long-term follow-up. METHODS: From Feb 2011 to Mar 2016, patients with histologically proven clinical stage I NSCLC were treated with CT-guided MWA and retrospectively analyzed. The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and complications. RESULTS: A total of 105 patients with 105 lesions underwent MWA. The mean age was 70.7 years (range: 40-86 years), and the mean diameter of all lesions was 2.40 cm (range: 0.9-4.0 cm). Adenocarcinoma was the most common histological type (77, 73.3%), followed by squamous cell carcinomas (21, 20%) and undefined NSCLC (7, 6.7%). With a median follow-up of 54.8 months, the median DFS was 36.0 months, and 1-, 3-, and 5-year DFS rates were 89.5%, 49.4%, and 42.7%, respectively. The median CSS and OS were 89.8 and 64.2 months, respectively. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years, while the CSS rates were 99%, 78.9%, and 60.9%, respectively. Patients with stage IB lesions had significant shorter DFS (22.3 months vs. undefined, HR: 11.5, 95%CI: 5.85-22.40) and OS (37.3 vs. 89.8 months, HR: 8.64, 95% CI: 4.49-16.60) than IA disease. CONCLUSION: MWA is a safe, effective, and potentially curative therapy for medically inoperable stage I NSCLC patients. KEY POINTS: • In this multicenter retrospective study which included 105 patients, we found the median overall survival (OS) was 64.2 months. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years. • Procedures were technically successful and well tolerated in all patients. Most MWA complications were mild or moderate.

Off-label use of drugs in pediatrics: a scoping review.

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166).    Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: • There exist a large number of studies on off-label drug use in children. What is New: • This is the first scoping review of studies on off-label drug use in children. • Off-label use of antipsychotic agents is widely reported.

Perceptions of exercise and exercise instruction in patients with type 2 diabetes mellitus and sarcopenia : a qualitative study.

BACKGROUND: Exercise plays a major role in helping patients with type 2 diabetes mellitus and sarcopenia to increase muscle mass and muscle strength. However, little is known about perceptions of exercise and exercise instruction in these patients. This study aimed to explore the perceptions of exercise and exercise instruction from the patient's perspective. METHODS: In a descriptive qualitative study, semi-structured face-to-face in-depth interviews were conducted with 16 patients with type 2 diabetes mellitus and sarcopenia at a tertiary hospital. The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines were followed to ensure rigor in the study. The interviews were analysed using a thematic analysis method. RESULTS: Four themes and 13 sub-themes were identified in this study. The four themes were knowledge-attitudes-practices surrounding exercise, motivators and barriers regarding exercise, and attitudes towards professional exercise instruction. CONCLUSION: This study provides a detailed understanding of the knowledge-attitudes-practices, motivators and barriers regarding exercise among patients with type 2 diabetes mellitus and sarcopenia, as well as attitudes related to exercise instruction. The current findings can guide healthcare professionals, patients' families, and policymakers to motivate patients to be physically active through policy initiatives and other types of incentives and programmes, such as providing more health education and holistic support, increasing family and friends' companionship and care, and providing suitable exercise conditions.