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Xiao, F, Yang, Y, Xiao, L, Xia, Z, Wang, L, Yang, K, and Wang, S. Reduction of T cells and hsa-miR150-5p in female canoeing athletes: Preliminary evidence between exercise training and immune. J Strength Cond Res 36(11): e106-e113, 2022-This article aims to reveal the alteration of immune profile in teenage canoeing athletes, by which applies a clue for regulation of exercise on human immune. Thirty-one teenagers of female canoeing athletes and age-matched subjects participated in this research. Peripheral leukocytes' microRNAs (miRNAs) were analyzed using Agilent human microRNA 2.0 and gene software. The miRNA candidates were quantified by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The percentages of various lymphocytes were tested using flow cytometry. There were 6 miRNAs (hsa-miR150-5p, 31-5p, 3659, 4419a, 650, and 8485) lower in canoeing athletes, and the reduction of miR-150 was identified by RT-qPCR ( p = 0.021). Canoeing athletes had lower percent of CD3 + T cells than the subjects with no exercise training had ( p0.001), but the ratio of CD4 + to CD8 + and the percent of CD4 + T cells and CD8 + T cells showed no significant difference between these 2 groups. T cells and hsa-miR150-5p are sensitive to the long-time heavy exercise training, and the exercise for winning competition regulates the immune system by inhibiting T cells and hsa-miR150-5p.

This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB).We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) statuses of 154 patients by interphase fluorescence in situ hybridization of BM cells. The clinical characteristics of patients with the three markers and their associations with prognosis were analysed.MYCN amplification and LOH at 1p36 and 11q23 were identified in 16.2%, 33.1% and 30.5% of patients, respectively. There were strong associations between MYCN amplification and 1p36 LOH as well as 11q23 LOH. Both MYCN amplification and 1p36 LOH were strongly associated with high levels of lactate dehydrogenase (LDH) and neuron-specific enolase, more than 3 metastatic organs, and more events. 11q23 LOH occurred mainly in patients older than 18 months, and those who had high LDH levels. In univariate analysis, patients with MYCN amplification had poorer prognosis than those without. Patients with 1p36 LOH had a 3-year event-free survival (EFS) and overall survival lower than those without. 11q23 LOH was associated with poorer EFS only for patients without MYCN amplification. In a multivariate model, MYCN amplification was independently associated with decreased EFS in all cohorts. 11q23 LOH was an independent prognostic factor for patients without MYCN amplification, whereas 1p36 LOH was not an independent marker regardless of MYCN amplification. Compared with all cohorts, patients with both MYCN amplification and 1p36 LOH had the worst outcome and clinical features.Patients with both MYCN amplification and 1p36LOH had the worst survival rate, indicating an ultra high-risk group. Our results may be applied in clinical practice for accurate risk stratification in future studies.

Background Z score utility is emphasized in classifying coronary artery lesions in Kawasaki disease patients. The present study is the largest such multicenter Chinese pediatric study about coronary artery diameter reference values and Z score regression equation to date. It is useful in Chinese pediatric echocardiography. Methods A multicenter cohort was assembled, which consisted of 852 healthy children between 1 month and 17 years of age, ten children were excluded because their ultrasound images were not clear, or lost in following up. Diameters of the right coronary artery, left coronary artery, and left anterior descending coronary artery were assessed using echocardiography. Data were body surface area (BSA)-corrected using BSA calculated via either the Stevenson BSA formula or the Haycock BSA formula. Coronary artery diameter reference values and Z score regression equations were established for use in the Chinese pediatric population. Results No difference was observed between coronary artery diameter data corrected using BSAste or BSAhay. Of the five assessed regression models, the exponential model exhibited the best fit and was therefore selected as the basis for derivation of the SZ method. When comparing Z scores, those produced by the SZ method conformed to the standard normal distribution, while those produced by the D method did not. In addition, there was a statistically significant difference between Z scores produced by the SZ and D methods (P Conclusions Coronary artery diameter reference values for echocardiography were successfully established for use in the Chinese pediatric population, and a Z score regression equation more suitable for clinical use in this population was successfully developed.

Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5–10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation, fortunately, did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.

To explore the incidence and risk factors of readmission of elderly patients with hip fracture after hip hemiarthroplasty.A retrospective analysis of 237 elderly hip fracture patients who underwent hip hemiarthroplasty from February 2015 to October 2020 were performed. According to the readmission status of the patients at 3 months postoperatively, the patients were divided into readmission group (39 cases)and non-readmission group(198 cases). In readmission group, there were 7 males and 32 females with an average age of(84.59±4.34) years old, respectively, there were 34 males and 164 females with average age of (84.65±4.17) years old in non-readmission group. The general information, surgical status, hip Harris score and complications of patients in two groups were included in univariate analysis, and multivariate Logistic regression was used to analyze independent risk factors of patients' readmission.The proportion of complications(cerebral infarction and coronary heart disease) in readmission group was significantly higher than that of non-readmission group (The complications of the elderly patients who were readmission after hip hemiarthroplasty for hip fractures were significantly higher than those who were non-readmission. Cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis are risk factors that lead to patient readmission. Corresponding intervention measures can be taken clinically based on these risk factors to reduce the incidence of patient readmissions.

Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in the treatment of non‑small cell lung cancer (NSCLC). However, erlotinib resistance leads to high mortality in patients with NSCLC, while the activation of STAT3 is closely related to erlotinib resistance. Studies have shown that the main components of Huanglian Jiedu Decoction (HJD) have antitumor effects. Therefore, the anticancer effect of HJD combined with erlotinib on NSCLC cells was investigated. The NSCLC HCC827, HCC827ER, and H1975 cell lines as well as xenograft nude mice were selected as models to study the effects of HJD. The proapoptotic effects of HJD were examined by CCK‑8 and apoptosis assays. ELISA, immunostaining, and western blot analysis were also performed. HJD considerably enhanced the anticancer effect of erlotinib in both EGFR‑TKI‑resistant and ‑sensitive NSCLC cells. HJD promoted erlotinib‑induced apoptosis and caspase 3 activity. The co‑treatment also inhibited the expression of Bcl‑XL, Bcl‑2, and p‑STAT3. In addition, siSTAT3 had similar functions with HJD. In particular, the apoptotic rates of erlotinib‑stimulated HCC827, HCC827ER, and H1975 cells were enhanced by transfecting siSTAT3. Furthermore, overexpression of STAT3 significantly inhibited HJD‑mediated erlotinib sensitization. The combined use of HJD with erlotinib significantly reduced tumor growth in erlotinib‑resistant HCC827ER and H1975 xenografts, induced caspase 3, and inhibited Ki67, STAT3, and Bcl‑2 expression. HJD significantly alleviated erlotinib resistance by regulating the STAT3/Bcl‑2 signaling pathway, which is a promising method to overcome the EGFR‑TKI resistance of NSCLC.

Objectives Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. Methods We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. Results First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. Conclusion Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.

Low expression levels of CREB‑binding protein (CREBBP) have been demonstrated to be associated with high minimal residual disease at the end of induction therapy and adverse long‑term outcomes in pediatric patients with acute lymphoblastic leukemia (ALL). However, the effect of low CREBBP expression on the prognosis of ALL has not yet been investigated. In the present study, CREBBP was downregulated and overexpressed in ALL cell lines (Jurkat and Reh). Sensitivity to chemotherapy and cell proliferation activity was determined via a Cell Counting Kit‑8 assay. Cell cycle analysis was performed using flow cytometry. Immunofluorescence confocal microscopy and co‑immunoprecipitation (Co‑IP) assays were performed to determine the interaction between CREBBP and E2F transcription factor 3a (E2F3a). The binding of CREBBP to downstream gene caspase 8 associated protein 2 (CASP8AP2) promoters was assessed using a chromatin immunoprecipitation assay, and mRNA expression levels were detected via reverse transcription‑quantitative PCR. Western blot analysis was performed to detect protein expression of CREBBP, E2F3a and CASP8AP2. Downregulation of CREBBP increased the IC50 value of daunorubicin; however, no significant affects were observed on the IC50 values of vincristine and L‑asparaginase. Furthermore, downregulation of CREBBP notably inhibited leukemia cell proliferation, accumulated cells in the G0/G1 phase and decreased cell proportions in the S and G2/M phases. Co‑IP analysis demonstrated that CREBBP interacted with E2F3a, a transcription factor involved in G1/S transition. Immunofluorescence confocal microscopy indicated co‑localization of CREBBP and E2F3a at the cell nucleus. Furthermore, E2F3a protein expression decreased in CREBBP RNA interference treated Jurkat and Reh cells. CASP8AP2, a target gene of E2F3a, was also identified to be a downstream gene of CREBBP. In addition, decreased IC50 value and cell proportions in the G0/G1 phase, accelerated cell proliferation and upregulated E2F3a and CASP8AP2 expression were exhibited in CREBBP overexpressed cells. Taken together, the results of the present study suggested that CREBBP downregulation affects proliferation and cell cycle progression in leukemia cells, potentially via the interaction and regulation of E2F3a, resulting in chemotherapy resistance. Thus, targeting CREBBP may be a therapeutic strategy for treating pediatric patients with ALL.

Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public. Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins. Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation. Conclusions The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.

This study was designed to review published literature to determine the efficacy and safety of intranasal dexmedetomidine versus oral chloral hydrate (CH) for sedation in pediatric patients based on qualified studies. We searched the PubMed, Cochrane, and Embase databases for qualified studies published before March 2021. For each study, we analyzed the relative risk or weighted mean difference combined with a 95% CI. Fourteen studies including 3749 pediatric patients were included in this meta-analysis. Compared with oral CH, intranasal dexmedetomidine significantly increased the success rate of sedation and decreased the duration and latency of sedation, time of recovery from sedation, and total sedation time. Compared with oral CH, intranasal dexmedetomidine significantly decreased the incidence of adverse events, including vomiting, but increased the incidence of bradycardia. In conclusion, intranasal dexmedetomidine provides better sedation than oral CH for pediatric patients with good safety; however, the incidence of bradycardia is increased.

Background The objective of this study was to explore the stigma and related influencing factors in individuals with chronic insomnia disorder (CID). Methods A total of 70 CID patients and 70 healthy controls (CON) were enrolled in the study. All subjects completed the assessments of sleep, emotion, and cognition. Their stigma and life quality were measured using the Chronic Stigma Scale and the 36-Item Short-Form Health Survey (SF-36). Results The ratio of individuals with stigma was significantly different between CID and CON groups (C2 = 35.6, p p p p p p p Conclusion Patients with CID have an increased risk of stigma. Moreover, illness duration and Mental Health may be primary factors related to stigma.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60–69, 70–79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years ( p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

The purpose of the present study was to assess whether optic nerve sheath diameter (ONSD) measured by ultrasound could predict brain injury in sepsis associated encephalopathy (SAE).A total of 48 male New Zealand White rabbits were used to establish sepsis model. The levels of neuro-specific enolase (NSE), S100B, myeloperoxidase (MPO), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immuno sorbent assay and ONSD were measured before modeling, 6 h, 12 h and 24 h after modeling. Sixteen rabbits were sacrificed for hematoxylin-eosin (HE) staining of brain tissue and the brain water content at above time points. Rabbits demonstrated brain injury by HE staining were included in the SAE group, the others were enrolled in the control group. The correlation between ONSD and MPO, NSE and S100B in the SAE group were analyzed. Receiver operator characteristic curves were generated to analyze the area under the curve (AUC), specificity and sensitivity of ONSD values for SAE.Twenty-nine of 48 rabbits had brain injury, while 19 cases were enrolled in the control group. The level of MPO, NSE, S100B, TNF-α at 6 h, 12 h and 24 h in SAE group were all higher than those of the control group with statistical significance. The ONSD in SAE group increased with time and significantly wider than those in the control group. Correlation analysis revealed that ONSD was positively correlated with MPO, NSE and S100B in the SAE group. The AUCs for the ONSD value in diagnosing SAE at 6 h, 12 h and 24 h were 0.864, 0.957, 0.877, respectively.Alterations in ONSD strongly correlated with MPO, NSE and S100B among SAE rabbits. Monitoring of ONSD exhibited a high predictive value for SAE.

Background To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants. Methods A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation. Results Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO2 is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p, NAVA ventilation, a new ventilation mode, can maximize human–machine coordination while ensuring that the ventilator supports the appropriate ventilation level for patients, reducing complications related to mechanical ventilation, protecting organ functions, improving respiratory mechanics and hemodynamics.

Objective This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI). Methods A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting. Results CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression. Conclusions CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

The activity of influenza A at the end of 2019 was higher than previous two years in children younger than 6 years old in Wuhan, China. The 2019–2020 winter peak of seasonal influenza preceded the COVID‐19 outbreak, with a higher and earlier peak than those of the 2017–2018 and 2018–2019 seasons. We speculate this could be due to the earlier CNY holiday season in 2019–2020 than in previous two years. We compared these results with those of two previous studies to further discuss the possible interference between influenza and COVID‐19 in young children.

Background To improve cure rates for neuroblastoma (NB), it is important and necessary to evaluate therapy response. Our investigation focuses on using plasma cell free DNA (cfDNA) as a biomarker to determine tumor burden and minimal residual disease (MRD) of NB patients during chemotherapy. Methods Total 58 NB patients were recruited from July 2016 to December 2017. Therapy regime and risk classification were based on COG standard and BCH‐NB‐2007 protocol. RECIST study was used to judge response to therapy at the end of fourth cycle of chemotherapy (CC4) and maintenance stage (MS) respectively. Serial quantifications of cfDNA, NSE, and LDH were examined at four stages, including newly diagnosed, second and CC4, and maintenance. Results During early chemotherapy, 65.5% of NB kids responded well. Consistently, cfDNA, NSE, and LDH levels were down‐regulated in NB patients with partial remission (PR) compared to those with stable disease (SD). In both training and predicting sets, the levels of cfDNA were significantly comparable between PR and SD only at CC4 stage. To predict the insufficient response to early chemotherapy, the optimal AUC value of cfDNA was 0.732 and 0.747 in training and predicting sets respectively, with a sensitivity of 63.2% and 80% specificity at 11.59 ng/ml and a sensitivity of 68.4% and 90% specificity at 10.35 ng/ml. At MS, responded NB patients were slightly increased up to 70%. This evaluation was confirmed by further decrease in cfDNA and NSE levels during intermediate chemotherapy in comparison with early stage. Conclusion The dynamic change of cfDNA was considered as a surrogate biomarker to evaluate tumor burden and MRD of NB during early and intermediate therapy periods.

BACKGROUND: The COVID-19 pandemic has become a new challenge to the medical system in various countries. The patients with ST-segment elevated myocardial infarction (STEMI) were also affected. METHODS: We used a random-effects mode to analyze the differences of the baseline characteristics and therapeutic features between STEMI patients admitted before and after the start of the COVID-19 pandemic. RESULTS: Thirty eight studies involving 79,753 patients were included in this analysis. The number of hospitalized STEMI patients decreased by 26% after the start of the COVID-19 pandemic. There were no differences in age, sex, prevalence of diabetes, hypertension, dyslipidemia or percutaneous coronary intervention rate between the STEMI patients before and after the start of the COVID-19 pandemic. However, the STEMI patients admitted after the start of the COVID-19 pandemic had a significantly increased time from symptom onset to first medical contact (standard mean difference: 0.51, 95% confidence interval: 0.24-0.78, p < .001) and an increased in-hospital mortality (odds ratio: 1.70, 95% confidence interval:1.14-2.56, p < .001); The in-hospital mortality of the STEMI patients with COVID-19 was 24% (95% confidence interval: 0.15-0.33); The in-hospital mortality of the STEMI patients with COVID-19 was significantly higher than that of the STEMI patients without COVID-19 at the initial stage of the COVID-19 pandemic (odds ratio: 7.28, 95% confidence interval: 2.75-19.28, p < .001). CONCLUSION: The number of admitted STEMI patients was reduced while the in-hospital mortality and the time from symptom onset to first medical contact were increased during the COVID-19 pandemic.

Background Neuroblastoma (NB) is the most common extracranial solid tumor in children. It is known for high heterogeneity and concealed onset. In recent years, the mechanism of its occurrence and development has been gradually revealed. The purpose of this study is to summarize the clinical characteristics of children with NB and abnormal chromosome 10, and to investigate the relationship between the number and structure of chromosome 10 abnormalities and NB prognosis. Methods Chromosome G-banding was used at the time of diagnosis to evaluate the genetics of chromosomes in patients with NB and track their clinical characteristics and prognosis. All participants were diagnosed with NB in the Medical Oncology Department of the Beijing Children’s Hospital from May 2015 to December 2018 and were followed up with for at least 1 year. Results Of all 150 patients with bone marrow metastases, 42 were clearly diagnosed with chromosomal abnormalities. Thirteen patients showed abnormalities in chromosome 10, and chromosome 10 was the most commonly missing chromosome. These 13 patients had higher LDH and lower OS and EFS than children with chromosomal abnormalities who did not have an abnormality in chromosome 10. Eight patients had both MYCN amplification and 1p36 deletion. Two patients had optic nerve damage and no vision, and one patient had left supraorbital metastases 5 months after treatment. Conclusions The results indicated that chromosome 10 might be a new prognostic marker for NB. MYCN amplification and 1p36 deletion may be related to chromosome 10 abnormalities in NB. Additionally, NB patients with abnormal chromosome 10 were prone to orbital metastases.

Crosstalk between cancer cells and macrophages plays a crucial role in the development of cancer. In this study, our data showed that M1 macrophages attenuate, while M2 macrophages and tumor-associated macrophages enhance the EGFR-TKIs resistance in non-small cell lung cancer (NSCLC) cell line H1975. Next, long non-coding RNA SOX2 overlapping transcript (SOX2-OT) is highly expressed in NSCLC cells-derived exosomes. NSCLC cells-derived exosomes promote macrophages M2 polarization and inhibit M1 polarization through transferring SOX2-OT to macrophages. Subsequently, our results indicated that NSCLC cells-induced M2-polarized macrophages enhance the EGFR-TKIs resistance in H1975 cells. Furthermore, our data revealed that NSCLC cells-derived exosomes inhibit the expression of miR-627-3p, while promote Smads expression in THP-1 cells. SOX2-OT acts as miR-627-3p sponge to facilitate Smad2, Smad3 and Smad4 expression. Finally, our results indicated that NSCLC cells promote macrophages M2 polarization and suppress M1 polarization through targeting miR-627-3p/Smads signaling pathway by transferring exosomes to THP-1 cells. In conclusion, our data revealed that NSCLC cells promote macrophages M2 polarization through transferring exosomal SOX2-OT, thus to enhance its own EGFR-TKIs resistance. Mechanismly, NSCLC cells-derived exosomal SOX2-OT promotes macrophages M2 polarization via promoting Smads by sponging miR-627-3p. Our data provide a novel therapeutic target for EGFR-TKIs resistance in NSCLC.

Epithelial-mesenchymal transformation(EMT) exists in embryonic development and is closely related to cell migration and invasion. The increased EMT level in tumors showed that E-cadherin was replaced by N-cadherin, and the expression of interstitial markers such as α-SMA and vimentin was up-regulated. It has been reported that lupeol can reduce the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9) and N-cadherin to inhibit the metastasis of osteoma cells. However lupeol has been less studied in liver cancer. Therefore, this paper investigated the effect of lupanol on invasion and metastasis of human hepatoma cell line HepG2 and SK-HEP-1 and its possible mechanism. MTT assay and Annexin V/PI double staining were used to investigate the effect of lupeol on activity and apoptosis of HepG2 cells and SK-HEP-1 cells. Moreover, the effect of lupeol on the invasion of HepG2 cells and SK-HEP-1 cells were evaluated by Transwell assay. The expressions of E-cadherin, N-cadherin, α-SMA, vimentin and MMP-9 were measured by Western blot. The model of subcutaneous transplantation of nude mice and the lung metastasis model of H22 hepatocellular carcinoma cells were established to evaluate the efficacy of lupeol in vivo on tumor growth and lung metastasis by HE staining combined with immunohistochemical assay. The results showed that lupeol inhibited the activity and invasion of HepG2 cells and SK-HEP-1 cells in a dose-dependent manner and induced apoptosis. Western blot showed that the expression of E-cadherin, a landmark protein for EMT, was induced by lupeol, and the expressions of N-cadherin, α-SMA, vimentin and MMP-9 were decreased. In vivo experiments showed that lupeol inhibited tumor growth in mice bearing xenograft. In addition, immunohistochemical experiments confirmed that lupeol could up-regulate the expression of E-cadherin in tumor tissues of nude mice, reduce the expression of N-cadherin, and inhibit the metastasis of liver cancer H22 cells in the lungs of mice. The above results indicated that the mechanism of lupeol inhibiting the invasion and metastasis of HCC cells may be related to the regulation of EMT process.

OBJECTIVE: To study the changes in metabolic markers and clinical outcome after treatment with different drug regimens in children with bipolar affective disorder. METHODS: A retrospective analysis was performed on the medical data of 220 children with bipolar affective disorder who attended the hospital from January 2017 to January 2020. According to the treatment method, 112 children treated with atypical antipsychotic drugs alone were enrolled as the control group, and 108 children treated with atypical antipsychotic drugs combined with mood stabilizer were enrolled as the study group. The two groups were compared in terms of baseline data, changes in related metabolic markers[fasting insulin (FIN), glycosylated hemoglobin (HbAlc), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after treatment, incidence rate of metabolic syndrome, and clinical outcome. RESULTS: There were no significant differences in the baseline data including age, sex, and course of disease between the two groups (P > 0.05). The study group had a significantly higher overall response than the control group (92.6% vs 82.1%, P < 0.05). Before treatment, there were no significant differences in the levels of FIN and HbAlc between the two groups (P > 0.05). After treatment, the control group had a significant increase in the level of FIN and a significantly higher level of FIN than the study group (P < 0.05). The study group showed no significant change in the level of FIN after treatment (P > 0.05). There was no significant difference in the level of HbAlc between the two groups before and after treatment (P > 0.05). Before treatment, there were no significant differences in the levels of TC, TG, HDL-C, and LDL-C between the two groups (P > 0.05), and after treatment, the control group had significant increases in TC and TG and significantly higher levels of TC and TG than the study group (P < 0.05). The study group showed no significant changes in TC and TG after treatment (P > 0.05). There were no significant differences in the levels of HDL-C and LDL-C between the two groups before and after treatment (P > 0.05). The study group had a significantly lower incidence rate of metabolic syndrome than the control group (2.8% vs 9.8%, P < 0.05). CONCLUSIONS: Atypical antipsychotic drugs combined with mood stabilizer in the treatment of bipolar disorder in children have little effect on the level of metabolic markers, and the curative effect is significant.

Invasive pulmonary aspergillosis (IPA) is a serious infectious disease with high mortality. However, the rapid diagnosis of IPA remains difficult since the microbiological evidence is difficult to obtain or time-consuming. Thus, we attempted to rapidly diagnose two pediatric cases with respiratory failure due to IPA via bronchoalveolar lavage fluid with Calcofluor White fluorescence staining, which has rarely been used before.

Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50‑year‑old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient's parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32.

In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future.

Background The delayed diagnosis of neuroblastoma (NB) is common in China, which results in the prognosis of NB in China lagging behind that in developed countries. Methods A referral flowchart for suspected NB was implemented in nononcology clinics at Beijing Children's Hospital (BCH). Patients with symptoms of suspected NB were referred from nononcology clinics in BCH to oncology clinics and confirmed NB cases were regarded as referral group. The control group comprised patients initially diagnosed with NB who came directly to oncology clinics in BCH from other regions nationwide. The age at NB diagnosis was compared as primary outcome, and the 5-year overall survival (OS) and event-free survival (EFS) were compared via the Kaplan-Meier method and log-rank tests. Results In total, 3337 children with suspected NB were screened consecutively from 687 070 pediatric patients. Through examination of urine vanillylmandelic acid and homovanillic acid, or B-ultrasound, 102 of 3337 patients were referred to oncologists for comprehensive evaluations. Eventually, 29 referred patients were diagnosed as NB and the hospital-based diagnosis rate of NB was 4.2 per 100 000 visits. The median age at diagnosis in the referral group was 21.0 months, which was 9 months earlier than that of the control group (30.0 months, P = .026). The 5-year OS rate was 72.4% in the referral group, which was higher than that of the control group (66.7%) but without statistical significance (P = .664). Conclusion Delayed NB detection could be avoided by training pediatricians in nononcology clinics to detect suspected NB and refer these patients to oncologists.

Background Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children. Case presentation A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency. Conclusions A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.

Ultrasonography offers a unique advantage in the clinical diagnosis of intussusception. We aimed to evaluate the diagnostic accuracy of ultrasonography in pediatric intussusception. The PubMed, Embase, Web of Science, Cochrane Library databases, and African Journals Online database were searched for studies pertaining to ultrasonographic diagnosis of intussusception in children. Finally, 14 studies (combined n = 2367) were found eligible for inclusion. Pooled sensitivity and specificity were 0.94 (95% confidence interval: 0.91-0.96) and 0.96 (95% confidence interval: 0.93-0.98), respectively. In conclusion, ultrasonography has high sensitivity and specificity in the diagnosis of intussusception.

To investigate the expression of miR-146a and miR-211 in peripheral blood mononuclear cells (PBMNC) of children with acute T-lymphoblastic leukemia (T-ALL) and their clinical significance.One hundred and thirty newly diagnosed children with T-ALL from Hainan Third People's Hospital (T-ALL group) and 50 healthy persons (control group) were selected. The newly diagnosed T-ALL patients before treatment were taken as initial group, the patients reachived complete remission after induction therapy for 33 days were taken as remission group (n=98), the patients not reachived complete remission after induction therapy fore 33 days were taken as rafractory group (n=32). The expression levels of miR-146a and miR-221 in PBMNC were detected by real-time fluorescence quantitative PCR. ROC curve analysis was used to evaluate the diagnostic value of miR-146a and miR-221 for T-ALL, Pearson correlation analysis was used to estimate the correlation of miR-146a and miR-221 expression with white blood cell count in children with T-ALL.The expression levels of miR-146a and miR-221 of PBMNC in T-ALL group were significantly higher than those in control group (5.83±1.54 vs 0.96±0.17) (7.13±2.60 vs 1.64±0.51) (P＜0.01). The expression levels of miR-146a and miR-221 in refractory group were significantly higher than those in remission group and initial group (8.74±2.35 vs 1.70±0.63 and 5.83±1.54) (11.316±4.83 vs 2.62±0.85 and 7.13±2.60) (P＜0.01). The expression levels of miR-146a and miR-221 correlated with white blood cell count, risk typing and MRD (P＜0.05). ROC curve analysis showed that the best cutoff values of miR-146a and miR-221 for diagnosing childhood T-ALL were 3.90 and 5.28, resoectively. While the AUC (95% CI) of the T-ALL jointy diagnosed by miR-146a and miR-221 was 0.835 (0.764-0.892), and it's sensitivity and specificity were 85.0% and 77.2%, respectively. The correlation analysis showed that the expression levels of miR-146a and miR-221 in PBMNC of children with T-ALL positively correlated with the white blood cell count (r=0.705, r=0.653, P＜0.01), and that of miR-146a positively correlated with miR-221 (r=0.784, P＜0.01).The expression of miR-146a and miR-221 is up-regulated in children with T-ALL and closely relates with the prognosis of children with T-ALL. The combined detection of miR-146a and miR-221 is certain value for diagnosis of T-ALL.miR-146a和miR-221在儿童急性T淋巴细胞白血病中的表达及其临床意义.探讨急性T淋巴细胞白血病（T-ALL）患儿外周血单个核细胞（PBMNC）中miR-146a和miR-221表达水平及临床意义.选取海南省第三人民医院收治的初诊T-ALL患儿130例（T-ALL组）和体检健康者50例（对照组）。T-ALL患儿以治疗前作为初发组，诱导治疗d 33达完全缓解者作为缓解组（n=98），未完全缓解者作为难治组（n=32）。采用实时荧光定量PCR方法检测各组PBMNC的miR-146a及miR-221表达水平。ROC曲线分析miR-146a及miR-221对T-ALL的诊断价值，Pearson相关分析评价T-ALL患儿miR-146a及miR-221表达与白细胞计数的相关性.T-ALL组PBMNC的miR-146a及miR-221表达水平均明显高于对照组（5.83±1.54 vs 0.96±0.17）（7.13±2.60 vs 1.64±0.51）（P＜0.01）。难治组PBMNC的miR-146a及miR-221表达水平均明显高于缓解组和初发组（8.74±2.35 vs 1.70±0.63, 5.83±1.54）（11.316±4.83 vs 2.62±0.85, 7.13±2.60）（P＜0.01）。miR-146a及miR-221表达水平与白细胞计数、危险度分型和MRD相关（P＜0.05）。ROC曲线分析显示，miR-146a及miR-221诊断T-ALL的最佳截值分别为3.90和5.28，2项联合诊断T-ALL的AUC（95%CI）为0.835（0.764-0.892），其敏感度和特异度分别为85.0%和77.2%。相关分析显示，T-ALL患儿PBMNC的miR-146a及miR-221表达水平与白细胞计数均呈正相关（r=0.705，r=0.653，P＜0.01），miR-146a与miR-221呈正相关（r=0.784，P＜0.01）.miR-146a及miR-221在T-ALL患儿中表达上调，且与T-ALL患儿预后密切相关，2项联合检测对T-ALL诊断具有一定价值.

The goal of valgus knee brace treatment is to reduce medial knee joint loading during walking, often indicated by external knee adduction moment (KAM) measures. However, existing healthy-subjects studies have been equivocal in demonstrating KAM reduction with valgus knee bracing.What are the immediate effects of valgus bracing at different tension levels on KAM during walking at a controlled speed and does body height modify the brace-KAM associations?Data from 32 knee-healthy participants were analysed in this randomized crossover trial. Participants performed walking trials at controlled speed (1.3 ± 0.065 m/s) both with and without an Ossür Unloader One® brace. During the bracing condition, valgus tension was incrementally increased, from zero tension to normal tension and to maximum tolerable tension.Valgus bracing minimally increased knee flexion at heel-strike (P0.001) in a dose-dependent manner and minimally reduced gait velocity (∼0.015m/s) across all tension levels. Valgus bracing, overall, did not significantly reduce the various KAM measures. However, brace use at maximal tension was associated with a 0.04Nm/kg (9.2 %) increase in first peak KAM amongst participants with a body height of 1.75 m and a 0.03Nm/kg (7.6 %) decrease in first peak KAM amongst participants with a body height of 1.55 m.Valgus bracing did not reduce the various KAM measures during walking; however, body height may play a moderating role. Given knee brace sizes vary more in circumference than length, this result may be due to the ratio between effective moment arm length relative to limb length. A deeper understanding of the potential neuro-biomechanical effects of valgus knee bracing and how these effects are potentially modified by body height may be critical to the design of effective knee braces.

Background Previous studies have reported good test-retest reliability for peak knee adduction moment (KAM) during walking. However, reliability of other KAM measurements has not been established. Research question What is the test-retest reliability of peak KAM, KAM impulse, and KAM loading rate measurements during walking in knee-healthy individuals? Methods Data from 32 knee-healthy participants were analysed in this test-retest reliability study. Various KAM measurements were reported for two sessions with kinematic and kinetic data obtained from a motion capture system synchronised with force plates, with a median of 1 week between sessions. Results For all KAM measures, intra-class correlation coefficients were above 0.90 and their lower bound 95 % confidence limits exceeded 0.81. However, absolute measurement variability differed across measures, with normalized SEM (8 %–15 %), normalized MDC95 (20 %–40 %), intra-session MAD (10 %–18 %), and inter-session MAD (12 %–22 %) varying over a 2-fold range. Overall and first peak KAM, KAM impulse over 50 % stance, and KAM loading rate (15 frame window) showed ≤10 % and ≤15 % intra- and inter-session MAD, respectively. Significance This study provided previously undefined test-retest reliability estimates for various KAM measures during walking. Researchers and clinicians should not assume that the various aspects of the KAM curve share similar reliability.

Objectives This study aims to investigate potential herb–drug interactions (HDI) of Epimedium koreanum Nakai. Methods Human liver microsomes (HLMs) were used to determine the enzyme kinetics of the major human cytochrome P450s (CYPs). Inducible potential of E. koreanum on CYP1A2, 2B6, 2C19 and 3A4 activities of human primary hepatocytes was also examined. Key findings Ethanol extract of E. koreanum showed direct inhibitory potency for CYP1A2 (IC50 = 121.8 μg/ml, Ki = 110.7 ± 36.8 μg/ml) and CYP2B6 (IC50 = 59.5 μg/ml, Ki = 18.1 ± 2.9 μg/ml). For CYP2C9, 2C19, 2D6, 2E1 and 3A4, only negligible effect was observed. Time-dependent (irreversible) inhibition by E. koreanum was observed for CYP1A2 (KI = 32.9 ± 18.4 μg/ml, kinact = 0.031 ± 0.006 min−1). However, ethanol extract of E. koreanum (1.5–150 μg/ml) did not change the activity or mRNA expressions for CYP3A4, 1A2, 2C19 and 2B6. Conclusions The ethanol extract of E. koreanum is not likely to cause HDI via inducing the major human CYPs. But the potential for interactions between E. koreanum extract and substrates of CYP1A2 or 2B6 cannot be overlooked.

Aims and objectives To identify self-acceptance and associated socio-demographic and disease factors among Chinese women with breast cancer. Background Although it is recognised that breast cancer can affect a woman's feelings of self-acceptance, there are few studies concerning the level of self-acceptance among women with breast cancer and factors associated with self-acceptance in this population. Design Cross-sectional research design. Methods Data were collected using the convenience sampling method. A total of 308 women with breast cancer were investigated using the Self-Acceptance Questionnaire. Results The mean score on the Self-Acceptance Questionnaire was 39·79 ± 5·14, indicating that the women in this study had low levels of self-acceptance. Multiple regression analysis indicated that self-acceptance was positively associated with the time since diagnosis, household income and the presence of medical insurance/government-funded medical treatment, while Tumour, Lymph Node, Metastasis stage was negatively associated with self-acceptance. With respect to work status, retired patients had the highest levels of self-acceptance, those who had returned to work had moderate levels of self-acceptance and those who had not yet returned to work had the lowest levels of self-acceptance. Conclusions This study demonstrates that the level of self-acceptance among women with breast cancer in China is low, and suggests that there is room to improve. Several factors are significantly associated with the self-acceptance of women with breast cancer. Relevance to clinical practice Medical staff should realise that the level of self-acceptance among women with breast cancer in China is low and has room to improve. It is important to conduct appropriate interventions to improve self-acceptance among these women, based on an understanding of the factors associated with self-acceptance.

Background: Ginkgolides are widely used in cardio-protective therapy; however, poor bioavailability currently limits their application. Objective: The purpose of this study was to demonstrate whether solid dispersions prepared with Low- Molecular-Weight Chitosan (LMWC) could improve the protective effect of ginkgolides on Myocardial Injury (MI). Methods: Ginkgolide Solid Dispersions (GKSD) were prepared with LMWC. Their properties were then characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In vivo pharmacokinetic studies were performed in rats, and the protective effect of GKSD on MI was investigated by western blotting and immunohistochemical analyses. Results: Drug dissolution testing showed that GDSD were released at a significantly higher rate than ginkgolides, dissolved by alternative methods, suggesting that LMWC facilitates the release of ginkgolides. Differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy all showed that GKSD was amorphous. In-vivo testing revealed larger AUC0-t, higher Cmax, and shorter Tmax for GKSD compared to that in original ginkgolides. Myocardial injury was induced in rats with isoproterenol to test the protective effect of GKSD. GKSD alleviated MI and reduced myocardial fibrosis, as observed by Hematoxylin and Eosin staining. Compared with the crude drug group, the secretion of malonyl dialdehyde and nitric oxide and expression of NOX-2 and NOX-4 were lower. The activities of the cardiac marker enzymes SOD, CAT, GPX, GPX-1, and GSH were higher in GKSD-administered rats, indicating a beneficial effect of GKSD in eliminating free radicals during myocardial injury. Additionally, western blotting and immunohistochemical analysis showed that GKSD markedly reduced the expression of signaling proteins RHOA, ROCK1, ROCK2, and RAC1. Conclusion: Solid dispersions prepared with low molecular weight chitosan improved the oral bioavailability of ginkgolide and enhanced its protective effect on myocardial injury.

Accurate diagnosis of splenic diseases is important for timely and accurate treatment. The objective of this study was to compare the accuracy of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in detecting splenic lesions. A systematic literature search was undertaken, and 8 studies met the inclusion criteria. The sensitivity and specificity of the consolidated results of CEUS were 0.95 (95% confidence interval [CI], 0.92-0.97) and 0.97 (95% CI, 0.90-0.99), respectively (I2 = 27.4%; area under the curve [AUC] from a summary receiver operating characteristic curve = 0.97). The sensitivity and specificity of the consolidated results of conventional US were 0.70 (95% CI, 0.56-0.80) and 0.96 (95% CI, 0.76-0.99; I2 = 83.4%; AUC = 0.84). In this systematic review and meta-analysis, the sensitivity and specificity of CEUS were higher than those of conventional US in diagnosing splenic lesions. Contrast-enhanced US is a promising method for accurately diagnosing splenic lesions.

Objective To reveal the effects and related mechanism of cisatracurium on colorectal cancer (CRC) development. Methods HCT116 and SW480 cells were treated with various concentrations of cisatracurium or transforming growth factor-β (TGF-β). Chemokine C-X-C-Motif Receptor 4 (CXCR4) was overexpressed and let-7a-5p was silenced in cells by transfection with pcDNA3.1-CXCR4 or let-7a-5p inhibitor. Cell Counting Kit-8 (CCK-8) assay measured cell viability, and transwell and wound healing assays evaluated cell invasion and migration, respectively. The expression levels of let-7a-5p and CXCR4 were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was conducted to test the levels of CXCR4, TGF-β/SMAD2/3 signalling and metastasis-related proteins. A tumour xenograft assay was performed to assess tumour growth. Results Cisatracurium treatment suppressed the viability and metastasis of HCT116 and SW480 cells in a concentration-dependent manner, whereas activating TGF-β/SMAD2/3 signalling significantly reversed these effects. Cisatracurium treatment markedly reduced CXCR4 expression by inhibiting TGF-β/SMAD2/3 signalling. Besides, let-7a-5p was identified as a target of CXCR4 and could be upregulated by cisatracurium. Both CXCR4 overexpression and let-7a-5p knockdown alleviated the biological roles of cisatracurium in CRC cells. Moreover, a tumour xenograft assay further confirmed that cisatracurium inhibited tumour growth and metastasis by increasing let-7a-5p expression. Conclusion Cisatracurium suppressed the viability, metastasis and tumour growth of CRC by regulating the CXCR4/let-7a-5p axis via inhibiting TGF-β/SMAD2/3 signalling. These findings provide a theoretical basis for the role of cisatracurium in the prognosis of CRC patients.

Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal intervention including combined both aerobic and resistance exercise training and 5% leucine supplementation has the potential to maintain skeletal muscle protein synthesis and attenuate losses in muscular strength during the aging process.

Hao Wu,1–3 Qingxiang Zhong,1,2 Rongling Zhong,4 Houcai Huang,4 Zhi Xia,4 Zhongcheng Ke,1,5 Zhenhai Zhang,1 Jie Song,1,2 Xiaobin Jia1–3 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 2Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu, 3College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 4Laboratory Animal Center, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu, 5College of Chemistry and Chemical Engineering, Huangshan University, Huangshan, Anhui, People’s Republic of China Abstract: Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-D-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7µM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7µM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial–mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment. Keywords: oleanolic acid, Pluronic P105, vitamin E-TPGS, polymer–drug conjugate, NSCLC

The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS–Icariside II–phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.

// Xianli Gong 1 , Wei Wei 1 , Lan Chen 1 , Zhi Xia 1 , Chengbo Yu 2 1 Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, China 2 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China Correspondence to: Chengbo Yu, email: yuchengbo1974@126.com Keywords: hepatitis B virus, hepatocellular carcinoma, lncRNA, expression profile Received: March 05, 2016 Accepted: May 09, 2016 Published: June 7, 2016 ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common kinds of malignancies and is closely correlated with hepatitis B virus (HBV) infection. Recent evidence has proved that long non-coding RNAs (lncRNAs) are implicated in development and progression of cancer. However, the contributions of lncRNAs to HBV-related HCC remain largely unknown. Here, we comprehensively investigated lncRNA expression profiles in HBV-related HCC by annotating and analyzing microarray datasets. By analyzing 42 HCC tissue samples with different etiology (HBV-related, alcohol-related, and primary HCC) and 15 normal liver tissues, we identified 182 lncRNAs that were specifically differentially expressed in HBV-related HCC, namely HBV-related HCC specific lncRNAs(HH-lncRNAs). Using an online function annotation tool, we found these HH-lncRNAs were associated many oncogenes and immunity related biological processes. 6 candidate HH-lncRNAs were selected and further validated by quantitative real-time PCR analysis in a cohort of HCC tissue samples. Function of a candidate HH-lncRNAs, BAIAP2-AS1, was further predicted by co-expression network and gene set enrichment analysis. These findings provide insights into HH-lncRNAs and offer resource for further search of biomarkers and therapeutic targets of HBV-related HCC.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC -mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC -signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal ( CBX4 and CBX8 . In our combined cohort, we identified frequent inactivating mutations in AJUBA , ZNF750 , and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1 , in addition to known mutations. Functional analyses suggest roles for several genes ( CBX4 , CBX8 , AJUBA , and ZNF750 ) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.

Introduction Child emotional or behavioral problems and insufficient social development has been a heavy burden on family and society. However, currently large-scale studies on emotional and behavioral problems as well as social competence among school children in China are still lacking. This cross-sectional study analyzed the current status and risk factors of behavioral problems and social competences in Beijing students. Method A total of 9,295 students, with ages ranging from 6 to 16 years old, were enrolled in the study. The Child Behavior Checklist (CBCL) was used to screen emotional and behavioral problems, social competences of students. We then assessed significant predictors factors associated with children behavioral problems and social competences. Results The total detection rate of behavioral problems of this cohort was 16.7%. All kinds of social competence scores of boys were lower than girls (P

Background Autosomal recessive Myotonia congenita (Becker’s disease) is caused by mutations in the CLCN1 gene. The condition is characterized by muscle stiffness during sustained muscle contraction and variable degree of muscle weakness that tends to improve with repeated contractions. Case presentation A 21-year-old man presented with transient muscle stiffness since the last 10 years. He had difficulty in initiating movement and experienced muscle weakness after rest, which typically improved after repeated contraction (warm-up phenomenon). There was no significant family history. Medical examination showed generalized muscle hypertrophy. Serum creatine kinase level was 2-fold higher than the normal value. Electromyogram showed myotonic discharges. DNA sequence analysis identified a novel splice mutation (c.1401 + 1G > A) and a known mutation (c.1657A > T,p.Ile553Phe). He rapidly responded to treatment with mexiletine 100 mg three times a day for 6 months. Conclusions This case report of autosomal recessive Myotonia congenita caused by a novel compound heterozygous mutation expands the genotypic spectrum of CLCN1 gene.

Background: The pro-inflammatory cytokine, interleukin-6 (IL-6), stimulates the metastasis of several neoplasms. An association of its serum level and the single nucleotide polymorphism (SNP) rs1800795 with neuroblastoma (NB) has been reported in American and Italian cohorts. This study was to clarify whether the same association exists in Chinese children. Methods: A total of 130 NB patients, with 77 boys (59%), 53 girls (41%), mean age 41 ± 5 months, were assigned to two groups: high risk (HR) versus intermediate-low risk (non-HR), and 50 healthy children were randomly selected as the age- and gender-matched controls. Peripheral blood samples were analyzed to determine serum IL-6 level using enzyme linked immunosorbent assay and rs1800795 SNPs phenotype using polymerase chain reaction and gene sequencing. Results: There were 87 NB patients in the HR group and 43 NB patients in the non-HR group. A comparison of allele and genotype frequencies of the rs1800795 polymorphism between patients and controls found no association with NB risk (P > 0.05). The frequency of GG+GC genotype was higher in HR-NB patients than in non-HR-NB patients (64.4% vs. 48.8%, P = 0.02), and serum IL-6 level was much higher in HR-NB patients with GG+GC genotype than in HR-NB patients with CC genotype (4.36 ± 1.1 pg/ml vs. 1.83 ± 0.5 pg/ml; P = 0.02), but not in Non-HR-NB patients. Conclusions: The polymorphism rs1800795 is associated with serum IL-6 level and level of NB risk. GG genotype might indicate that the tumor is highly malignant (prone to metastasis) and associated with poor prognosis. Key words: Children; Interleukin-6; Neuroblastoma; Single Nucleotide Polymorphism

ARS2 protein is important to early development and cell proliferation, in which ARS2-CASP8AP2 interaction is implicated. However, the predictive significance of ARS2 in childhood acute lymphoblastic leukemia (ALL) is unknown. Here we evaluate the predictive values of ARS2 expression and combined ARS2 and CASP8AP2 expression in relapse. We showed that ARS2 expression in ALL bone marrow samples at initial diagnosis was markedly lower than that in complete remission (CR). Likewise, the levels of ARS2 expression in the patients suffering from relapse were significantly lower than that of patients in continuous CR. Furthermore, low expression of ARS2 was closely correlated to poor treatment response including poor prednisone response and high minimal residual disease (MRD), and the patients with high MRD (≥10(-4)) and low ARS2 were more subject to relapse. The multivariate analyses for relapse free survival and event free survival revealed that ARS2 expression remained an independent prognostic factor after adjusting other risk factors. In addition, combined assessment of ARS2 and CASP8AP2 expression was more accurate to predict relapse, based on which an algorithm composed of ARS2 and CASP8AP2 expression, prednisone response and MRD (day 78) was proposed. Together, ARS2 and CASP8AP2 expressions can precisely predict high-risk of relapse and ALL prognosis.

The positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.