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The integration of traditional music culture into music education in higher education institutions is crucial for enhancing students’ musical literacy and cultural refinement and fostering cultural self-confidence. This paper addresses the integration of music teaching with traditional music culture, employing a coupled coordination degree model based on the CRITIC method to quantitatively assess this integration at a specific music college. Key influencing factors were identified across seven dimensions and were used as condition variables in a fuzzy-set Qualitative Comparative Analysis (fsQCA). The analysis indicates that the current level of integration at the institution is critically low, categorized as “endangered dysfunction,” with an average coupling coordination degree of 0.478. The fsQCA identified four distinct pathways, accounting for approximately 82.6% of the variance in integration levels. To enhance the integration of music teaching and traditional music culture effectively, institutions should focus on several strategic dimensions: curriculum development, instructional materials, interactive teaching methods, technology integration, faculty development, the incorporation of traditional music cultural practices, and the promotion of scholarly research in traditional music culture. This multifaceted approach promises to significantly advance the integration process, benefiting both educational outcomes and cultural preservation.

OBJECTIVE: To elucidate the regulatory effect of microRNA-34b on the occurrence of pediatric acute myeloid leukemia and the underlying mechanism. PATIENTS AND METHODS: The expression of microRNA-34b in the bone marrow of 72 children with newly diagnosed acute myeloid leukemia (AML) was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between microRNA-34b expression and pathological characteristics was analyzed. Kaplan-Meier curve was introduced for evaluating the prognostic value of microRNA-34b in pediatric AML. The regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of leukemia cells were accessed by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Bioinformatics prediction and dual-luciferase reporter gene assay were conducted to evaluate the binding between microRNA- 34b and lactate dehydrogenase A (LDHA). LDHA expression after overexpression of microRNA-34b was determined by qRT-PCR and Western blot. Rescue experiments were conducted to verify whether microRNA-34b could regulate proliferative and apoptotic behaviors of leukemia cells by suppressing LDHA expression. RESULTS: MicroRNA-34b was markedly downregulated in AML children. Low expression of microRNA-34b was correlated to FAB typing, cytogenetic abnormality, and day 7 response to the treatment of pediatric AML. By collecting the follow-up data, it was found that low expression of microRNA- 34b was correlated to the poor prognosis of AML. Overexpression of microRNA-34b inhibited proliferative ability and cell cycle progression, but accelerated apoptosis of AML cells. Dual-luciferase reporter gene assay verified that microRNA-34b could bind to LDHA, thereafter inhibiting LDHA expression. Overexpression of LDHA reversed the regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of AML cells. CONCLUSIONS: We found that microRNA-34b is lowly expressed in pediatric AML patients, and low expression of microRNA-34b may serve as an indicator of malignant progression and poor prognosis of pediatric AML. MicroRNA-34b may affect the proliferation and apoptosis of leukemia cells by regulating the expression of LDHA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the role of miR-410 in regulating the proliferation and apoptosis of pediatric acute lymphoblastic leukemia (ALL) cells and to explore the possible underlying mechanism. PATIENTS AND METHODS: The expression level of miR-410 in ALL cases and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Luciferase reporter gene assay was performed to evaluate the interaction between miR-410 and FKBP5. MTT and colony formation assay were used to determine the effect of miR-410 on the proliferation and colony formation ability of ALL cells. The effect of miR-410 on cell apoptosis was measured by Annexin V-fluorescein isothiocyanate 1 (FITC) and propidium iodide (PI). Western blot was used to analyze the effect of miR-410 on the protein expression levels of phosphorylated Akt (p-Akt) and cleaved caspase-3. RESULTS: In our investigation, miR-410 was significantly up-regulated in ALL cases and cells. We searched three public databases to predict the potential target of miR-410, and found that FKBP5 was a direct target of miR- 410. Meanwhile, Luciferase reporter gene assay confirmed our hypothesis. The overexpression of miR-410 accelerated the proliferation and colony formation ability of ALL cells, whereas remarkably decreased cell apoptosis rate. Western blotting showed that miR-410 inhibited the activation of Akt signaling pathway. However, FKBP5 could reverse the effects of miR-410. CONCLUSIONS: MiR-410 regulated the proliferation, colony formation and apoptosis of ALL cells through targeting FKBP5 and Akt signal pathway, indicating that miR-410 might be a potential therapeutic target for the treatment of ALL. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mounting evidence suggests that long noncoding RNAs (lncRNAs) function in multiple cancers. This study aimed to determine the expression, clinical significance, and possible biological function of a novel lncRNA LINC00265 in acute myeloid leukemia (AML). PATIENTS AND METHODS: The expression levels of LINC00265 were systematically evaluated in TCGA datasets. RT-PCR was performed to examine the expression level of LINC00265 in bone marrow and serum obtained from AML patients and healthy controls. The clinical data were interpreted by x2 test, Kaplan-Meier analyses, univariate analysis, and multivariate analysis. The functional role of LINC00265 was verified using cell experiments. Western blotting was used to examine the modulatory effect of LINC00265 on AKT/PI3K pathway in AML. RESULTS: LINC00265 was significantly highly expressed in the bone marrow and serum of AML patients. High serum LINC00265 was significantly associated with FAB classification and cytogenetics. ROC analyses showed that serum LINC00265 levels were reliable in distinguishing patients with AML from normal controls. Clinical assay indicated that AML patients with higher serum LINC00265 expression suffered poorer overall survival. Functionally, overexpression of LINC00265 suppressed the capability of proliferation, migration and invasion in AML cell lines. By using Western blot, we further illustrated that LINC00265 activated PI3K/AKT signaling in AML cell lines. CONCLUSIONS: Our findings not only demonstrated that LINC00265 contributes to AML proliferation, migration and invasion via modulation of PI3K/AKT signaling, but also suggested the potential value of LINC00265 as a clinical prognostic and a diagnostic marker for AML. [ABSTRACT FROM AUTHOR]

We have previously described sintered Na0.5Bi0.5TiO3-Bi12TiO20 composites as flexoelectric-type polar ceramics because they have a net macroscopic flexoelectric polarization. Here, we report on the universal existence of the macroscopic flexoelectric polarization in the (Na0.5Bi0.5)1-xSrxTiO3-Bi12TiO20 system, in which enhanced piezoelectricity is observed. By combining Raman spectroscopy and x-ray photoelectron spectroscopy techniques, we have identified the local flexoelectric polarization as distorted BiO5 polyhedra and TiO6 octahedra in the SrTiO3-Bi12TiO20 ceramic. The macroscopic polarization may be due to the partial alignment of these distorted units located within the grain boundary amorphous phases. Bi12TiO20 could have an important role in these flexoelectric-type polar ceramics. [ABSTRACT FROM AUTHOR]

The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0-2 years (18.09%, 1054/5,828) and lowest among adults aged 45-64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time., (© 2024. The Author(s).)

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Brucellosis is among the key zoonotic infectious diseases in China, and The Ningxia Hui Autonomous Region represents a major endemic area, and it is one of the main causes of poverty in the region due to illness. In Ningxia, there is substantial research on Brucella melitensis, studies on the molecular epidemiology of Brucella abortus are notably scarce. Consequently, this study aims to undertake pathogenic isolation and molecular epidemiological research on Brucella abortus isolated from the environment in Ningxia, providing insights and evidence to advance the prevention and control measures for brucellosis in the region. Building on traditional pathogenic detection methods, this research employs whole-genome sequencing(WGS) techniques and bioinformatics software to conduct a phylogenetic comparison of Ningxia strains and strains of Brucella abortus from various geographical origins. The results indicate that four Brucella abortus strains are classified as biovar 3 and MLST type ST2. It is shown that the local strains were closer phylogenetic relationships with strains from Asian and European countries. The presence of Brucella abortus in certain environmental sectors of Ningxia indicates a risk of transmission from the environment to animals and subsequently to humans. In conclusion, the Brucella abortus exists in some farming environments in Ningxia, and exists for a long time. Therefore, it is necessary to strengthen the monitoring of the disinfection effect of the farming environment to provide a basis for the forward movement of the gate of brucellosis prevention and control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Stomolophus meleagris envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive because of the complicated venom components. The biological activity and molecular regulation mechanism of Troxerutin (TRX) was firstly examined as a potential treatment for jellyfish dermatitis., Methods: We examined the inhibit effects of the TRX on tentacle extract (TE) obtained from S. meleagris in vivo and in vitro using the mice paw swelling models and corresponding assays for Enzyme-Linked Immunosorbent Assay (ELISA) Analysis, cell counting kit-8 assay, flow cytometry, respectively. The mechanism of TRX on HaCaT cells probed the altered activity of relevant signaling pathways by RNA sequencing and verified by RT-qPCR, Western blot to further confirm protective effects of TRX against the inflammation and oxidative damage caused by TE., Results: TE significantly induced the mice paw skin toxicity and accumulation of inflammatory cytokines and reactive oxygen species in vivo and vitro. Moreover, a robust increase in the phosphorylation of mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways was observed. While, the acute cutaneous inflammation and oxidative stress induced by TE were significantly ameliorated by TRX treatment. Notablly, TRX suppressed the phosphorylation of MAPK and NF-κB by initiating the nuclear factor erythroid 2-related factor 2 signaling pathway, which result in decreasing inflammatory cytokine release., Conclusion: TRX inhibits the major signaling pathway responsible for inducing inflammatory and oxidative damage of jellyfish dermatitis, offering a novel therapy in clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang, Kuai, Li, Wang, Xiao and Wu.)

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC)., Methods: A total of 155 patients with CHB-related HCC who received ICI-based therapy (in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were evaluated. Patients were divided into two groups: MASLD concurrent with CHB [MASLD-CHB] ( n = 38), and CHB ( n = 117)., Results: The median progression-free survival (PFS, 6.9 months vs. 9.3 months; P = 0.001), progressive disease (57.89% vs. 37.61%; P = 0.028), and disease control rate (42.11% vs. 62.39%; P = 0. 028) in the MASLD-CHB group were significantly worse than the CHB group. The median overall survival was not attained. The percentage of CD4+PD1+ (17. 56% vs. 8.89%; P < 0.001) and CD8+PD1+ T cells (10.50% vs. 7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB group. Concurrent MASLD [hazard ratio (HR) = 1.921; 95% CI, 1.138-3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment (HR = 2.412; 95% CI, 1.360-4.279; P = 0.003) were independent risk factors for PFS in all patients., Conclusions: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Background: Since 2019, the incidence of anthrax in the Ningxia Hui Autonomous Region has increased significantly compared with previous years, so in this situation the anthrax in the Ningxia region not only had a detrimental impact on public health, but also inflicted significant economic repercussions. Therefore, we conducted a molecular epidemiological study of 20 strains from 2019-2023 isolates. This study investigated the origin of Bacillus anthracis and its genetic diversity., Methods: We conducted canonical single-nucleotide polymorphisms (CanSNPs) typing and whole genome sequencing based on the extracted nucleic acid of Bacillus anthracis . Based on the whole genome drafts, we studied the genomic characteristics of 20 isolates. Meanwhile, we performed phylogenetic studies based on genome-wide core single-nucleotide polymorphisms (SNPs) using MEGA's Maximum Likelihood (ML) method and core-genome-based multilocus sequence typing (cgMLST) of the core genomes of these strains using BioNumerics' minimum spanning tree (MST) model., Results: The 20 isolates were categorized into sub-lineages A.Br.001/002, and comparative genomic analyses of these strains with other isolates from other parts of the world showed that the strains from Ningxia were correlated with isolates from Europe, Indonesia, Georgia (USA), and Beijing (China). For the 20 isolates in Ningxia, the genetic relationship of the isolates isolated from the same year or region was relatively close., Conclusion: The A.Br.001/002 subgroup was the dominant endemic strain in Ningxia. The genetic relationship and phylogenesis between isolates from Ningxia and strains from Europe and Indonesia suggest that anthrax spread around the globe through ancient trade routes.

Objective: To construct a diagnostic model for fatty liver using body composition analysis and further evaluate the diagnostic effect of the model on fatty liver. Methods: 726 cases with chronic liver disease who visited Tianjin Second People's Hospital from April 2019 to June 2022 and had body composition analysis tests were retrospectively enrolled and were divided into a fatty liver group (551 cases with fatty liver) and a control group (175 cases without fatty liver) according to the measured values of abdominal ultrasound and controlled attenuation parameter. An independent sample t-test and a non-parametric rank sum test were used for statistical processing. Logistic regression was used to construct a diagnostic model. Hosmer-Lemeshow was used to validate the fit of model. Receiver operating characteristic curve was used to confirm the diagnostic efficiency of the model. In addition, 341 cases of chronic liver disease who visited Tianjin Second People's Hospital were included to further verify the application effect of the model between July 2022 and February 2023. Results: Compared with the control group, the differences in various indicators of body composition analysis in the fatty liver group were statistically significant ( P < 0.05). Basal metabolic rate (X1), visceral fat area (X2), and body fat (X3) were eventually included in the diagnostic model for BCA-FL (body composition analysis-fatty liver)= -7.771+0.002X1-0.035X2+0.456X3 with the Hosmer-Lemeshow test (P=0.059). The measured area under the receiver operating characteristic curve, the sensitivity, and the specificity were 0.888, 0.889, and 0.726, respectively, when the diagnostic threshold value was 0.615 with the Youden index and the receiver operating characteristic curve. In the validated model group, the area under the receiver operating characteristic curve, Youden index, sensitivity, and specificity were 0.875, 0.624, 0.799, and 0.825, respectively. Conclusion: The diagnostic model BCA-FL for fatty liver constructed using human body composition analysis has good diagnostic efficacy and is suitable for screening fatty liver in different basic liver disease populations.

G3P (Matthijnssens et al., 2008b [9]) is a rare combination of human rotavirus VP7/VP4 genotypes with a complex evolutionary pattern but limited related studies. Detailed genomic characterisation and genetic evolutionary analyses of G3P (Matthijnssens et al., 2008b [9]) rotaviruses have helped to enhance our understanding of rotavirus diversity. For the first time, we detected two human G3P (Matthijnssens et al., 2008b [9]) Rotavirus A (RVA) strains, RVA/Human-tc/CHN/2020999/2020/G3P (Matthijnssens et al., 2008b [9]) and RVA/Human-wt/CHN/23582009/2023/G3P (Matthijnssens et al., 2008b [9]), in diarrhoea patients from the Ningxia region of China, and carried out a whole-genome analysis of these strains. 2,020,999 and 23,582,009 have identical gene constellations: G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3, and this genotypic constellation was reported first time in China. They are closely related in 11 genome segments. The genotypes of these two strains are different from the human RVA strains L621 and E2451, which are only G3P (Matthijnssens et al., 2008b [9]) strains reported so far in China, but are identical to those of the Thai feline strain Meesuk and the Korean human strain CAU12-2-51.Phylogenetic analysis showed that the VP6, VP1-VP3, and NSP2 genes of the two strains in this study clustered with human/bovine and feline/bovine rotavirus strains to form a sublineage distinct from the common DS-1-like G2 human rotavirus. In contrast, the VP7, VP4, NSP1, and NSP3-NSP5 gene segments were closely associated with human/feline rotavirus and feline rotavirus strains. These findings suggest that the evolutionary origin of the G3P (Matthijnssens et al., 2008b [9]) human rotavirus found in Ningxia, China, is consistent with the Meesuk and CAU12-2-51 strains， may have arisen through reassortment between uncommon human/bovine， feline/bovine rotavirus strains and human/feline， feline rotaviruses. However, VP1-VP2 gene segments did not have the same lineage as strains Meesuk and CAU12-2-51, suggesting that these genes might be derived from additional reassortment event., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

While the GII.4 norovirus was the predominant genotype, non-GII.4 genotype was increasingly focused since the non-GII.4 genotype caused regional epidemics. In this study, the detection rate was16.51% (183/1108) in Ningxia from January to December 2020. Among identified genotypes, GII.4[P31] and GII.4[P16] were the dominant genotypes (n = 20 and 18, respectively) while GII.6[P7] was the main type (n = 6) in non-GII.4 strains which was mainly detected in from May to July. The whole genome sequences of the norovirus diarrhea samples identified as GII.6 [P7] with Ct ≤ 30 collected in 2020 were determined. In this study, the complete genome sequences of norovirus strains PL20-044 and QTX20-071 were identified and analyzed phylogenetically. Phylogenetic analysis of the ORF1and ORF2 regions showed that these strains evolved from the GII·P7-GII.6 strains detected in recent years from different country. The results showed that PL20-044 had intra-type recombination with GII·P7-GII.6c and GII·P7-GII.6a, while QTX20-071 had intre-type recombination within GII·P7-GII.6a. The evolutionary rates of the RdRp gene region of the GII·P7 genotype and the VP1 gene region of the GII.6 genotype were 2.91 × 10 -3 (95%HPDs2.32-3.51 × 10 -3 ) and 2.61 × 10 -3 (95%HPDs2.14-3.11 × 10 -3 ) substitutions/site/year, respectively. Comparative analysis of the amino acid mutation sites in VP1 with the GII·P7-GII.6a strains before 1997, the later detected strains have changed in aa131 and aa354. Moreover, PL20-044 strains showed special mutations at aa316 and aa395. These results help to understand the norovirus genotype circulating in the human population in Ningxia, and discover the evolutionary characteristics of the GII·P7-GII.6 strain., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organization that can inappropriately influence our work, there is no professional or other personal interest of any nature or king in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023. Published by Elsevier B.V.)

Background: Group A rotaviruses (RVA) are the primary pathogens of acute gastroenteritis. Currently, two live attenuated RVA vaccines, LLR and RotaTeq, have been introduced into mainland China but are not included in the national immunization program. Because of the unknown genetic evolution of group A rotavirus in an all-age population in Ningxia, China, we monitored the epidemiological characteristics and circulating genotypes of RVA as a reference for developing vaccine strategies., Methods: We conducted seven years of consecutive surveillance of RVA based on stool samples from patients with acute gastroenteritis in sentinel hospitals in Ningxia, China, from 2015 to 2021. Reverse transcription quantitative polymerase chain reaction(RT-qPCR) was used to detect RVA in stool samples. Genotyping and phylogenetic analysis of VP7, VP4 and NSP4 genes were performed by reverse transcription-polymerase chain reaction(RT-PCR) and nucleotide sequence determination., Results: RVA was detected in 16.58% (1436/8662) of 8662 stool samples. The positive rates were 7.17% (201/2805) and 21.09% (1235/5857) in adults and children, respectively. The most affected age group was infants and children aged 12-23 months, with a positive rate of 29.53% (p < 0.05). A significant winter/spring seasonality was observed. 23.29% positive rate in 2020 was the highest in 7 years (p < 0.05). The region with the highest positive rate in the adult group was Yinchuan, and the children's group was Guyuan. A total of 9 genotype combinations were found to be distributed in Ningxia. The dominant genotype combinations in this region gradually changed from G9P[8]-E1, G3P[8]-E1, G1P[8]-E1 to G9P[8]-E1, G9P[8]-E2, and G3P[8]-E2 during these seven years. Rare strains (e.g., G9P[4]-E1, G3P[9]-E3 and G1P[8]-E2) were occasionally detected during the study., Conclusions: During the study period, changes in the significant RVA circulating genotype combinations and the emergence of reassortment strains were observed, particularly the emergence and prevalence of G9P[8]-E2, G3P[8]-E2 reassortants in the region. These results indicate the importance of continuous monitoring of the molecular evolution and recombination characteristics of RVA, and should not be limited to G/P genotyping but should consider multi-gene fragment co-analysis and whole genome sequencing., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorganic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log 10 IU/ml and from 3.59±0.81 to 3.32±0.55 log 10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log 10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log 10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

BACKGROUND The aim of this study was to investigate the clinical features and prognostic factors of childhood acute megakaryoblastic leukemia (AMKL). MATERIAL AND METHODS The data of 27 cases of childhood AMKL admitted from November 2009 to July 2018 were retrospectively analyzed. The survival analysis and prognostic factors were analyzed by Kaplan-Meier method. RESULTS The median follow-up time was 26.4 months in 27 cases, and the complete response rate was 92.31% after 2 chemotherapy courses. Eight patients underwent bone marrow transplantation after 3-6 courses. Five patients died after transplantation, 4 of whom died due to recurrence after transplantation. Of the 27 patients, 10 developed recurrence (37.04%), and 8/10 had recurrence within 1 year. The 3-year overall survival rate and disease-free survival rates were (47±12)% and (36±14)%, respectively. Of the 27 AMKL cases, the 3 with Down syndrome (DS-AMKL) all survived after treatment, and the 3-year overall survival rate was 100%. However, of the other 24 AMKL patients without Down syndrome (non-DS-AMKL), 6 died and 6 abandoned treatment, and the 3-year overall survival rate was only 50%. Univariate analysis showed that 3-year overall survival rate was not correlated to gender, age, number of newly diagnosed white blood cells, karyotype, remission after 2 courses of treatment, and transplant after 3 courses of treatment of childhood AMKL cases. Nevertheless, recurrence and remission after 2 courses of treatment were significantly correlated with 3-year overall survival rate. CONCLUSIONS Children with non-DS-AMKL have a high degree of malignancy and are prone to early recurrence with a poor prognosis, whereas the prognosis of DS-AMKL is relatively good. Recurrence after treatment and remission after 2 courses of treatment are important factors influencing the prognosis of childhood AMKL. Recurrence after transplantation is the leading cause of death in transplantation patients.

Background: Programmed cell death receptor 1 (PD-1) and T cell immunoglobulin mucin-3 (Tim-3) are considered as important immunosuppressive molecules and play an important role in tumor immune escape and cancer progression. However, it remains unclear whether PD-1 and Tim-3 are coexpressed in stage I-III colorectal cancer (CRC) and how they impact on the prognosis of the disease., Materials and Methods: A total of two cohorts with 451 patients who underwent surgery for stage I-III CRC treatment were enrolled in the study. Among which, 378 cases were from The Cancer Genome Atlas (TCGA) database and 73 cases were from the Fourth Hospital of Hebei Medical University (FHHMU) cohort. The mRNA expressions of PD-1 and Tim-3 in tumor tissue in stage I-III CRC were obtained from TCGA database. Immunohistochemistry was used to assess the expressions of PD-1 and Tim-3 in tumor tissue in stage I-III CRC in the FHHMU cohort. Interactive relationships between PD-1 and Tim-3 were retrieved through the online STRING database, which was used to study the interactions between proteins. DAVID, consisting of comprehensive biological function annotation information, was applied for the GO and KEGG pathway enrichment analysis of the interactive genes., Results: In the FHHMU cohort, the high expressions of PD-1 and Tim-3 were, respectively, found in 42.47% and 84.93% of stage I-III CRC tissue. PD-1 was significantly associated with age, primary site, and lymphatic metastasis. Tim-3 was closely related to the primary site. Correlation analysis showed that PD-1 and Tim-3 were positively correlated ( r = 0.5682, P < 0.001). In TCGA cohort, PD-1 and Tim-3 were associated with the prognosis of CRC patients in terms of 5-year survival ( P < 0.05). In the FHHMU cohort, the 5-year survival of patients with high levels of PD-1 and Tim-3 was 54.84% and 65.85%, respectively. Among which, the high expression of PD-1 was associated with poor prognosis (5-year OS: 54.84% vs. 88.10%, P = 0.003). The 5-year survival rate of CRC patients with coexpression of PD-1 and Tim-3 was 45.00%, which was significantly worse than non-coexpression (72.73%, 85.71%, and 90.48% separately). The functional network of PD-1 and Tim-3 primarily participates in the regulation of immune cell activation and proliferation, immune cell receptor complex, cell adhesion molecules, and T cell receptor signaling pathway., Conclusion: In summary, upregulation of PD-1 and Tim-3 in stage I-III CRC tumor tissue could be associated with the poor prognosis of patients. Those patients with coexpression of PD-1 and Tim-3 may have a significantly worse prognosis., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Wentao Kuai et al.)

Mesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into numerous cell types, including well-known inherent osteoblasts, adipocytes, and chondrocytes, and other cell types, such as hepatocytes, cardiomyocytes and nerve cells. They have become a favorite source of cell-based therapy. Therefore, knowing the mechanism that determines the cell fate of MSCs is important not only for deep understanding of the MSC function but also for the manipulation of MSCs for clinical application. Recently, studies have demonstrated that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), the two best studied noncoding RNAs, show key roles in cell fate determination of MSCs by functioning as vital regulators of their target gene expression or signaling transduction. Here, we summarize the characteristics of miRNAs and lncRNAs, and review the recent advances proving their profound involvement in determining the cell fate of MSCs to inherent osteoblast, adipocyte, and chondrocyte cells, and to several key cell types including hepatocytes, cardiomyocytes and nerve cells. This will provide researchers with a deep understanding of the role of miRNAs and lncRNAs in MSCs and provide guidance for future research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Long non-coding RNAs (lncRNAs) function as critical regulator in human cancers. However, the biological regulatory mechanisms of lncRNAs in Ewing's sarcoma are still elusive. This study tries to investigate the clinical significance and pathological role of lncRNA SOX2 overlapping transcript (SOX2OT) in Ewing's sarcoma progression. SOX2OT was identified to be up-regulated in Ewing's sarcoma tissue and cells. In vitro, SOX2OT knockdown suppressed Ewing's sarcoma cells proliferation and invasion, and triggered apoptosis. In vivo xenograft assays, SOX2OT knockdown significantly inhibited Ewing's sarcoma growth. With the help of bioinformatics analysis and luciferase assay, SOX2OT was validated to harbor miR-363, acting as miRNA sponge or competing endogenous RNA (ceRNA). Furthermore, FOXP4 was validated to be the target protein of miR-363. Western blot and RT-PCR confirmed that SOX2OT was positively correlated with FOXP4 protein via sponging miR-363, forming a negative cascade regulation. In conclusion, our study realizes that SOX2OT acted as oncogene in the tumorigenesis of Ewing's sarcoma, suggesting the SOX2OT/miR-363/FOXP4 pathway in Ewing's sarcoma., Competing Interests: None.

Therapeutic antibodies targeting PD-1 have made major breakthroughs in cancer treatment. However, the majority of colorectal cancer (CRC) cases are microsatellite stable (MSS) and do not respond to anti-PD-1-based immunotherapy. Combination therapy will be an ideal strategy to overcome this limitation. Gegen Qinlian decoction (GQD), a classical traditional Chinese medicine (TCM) formula, has been clinically proven to be effective in the treatment of ulcerative colitis (UC) and type 2 diabetes mellitus. Here, a systemic pharmacological study revealed that GQD acts through multiple targets and pathways in the human body. Combination therapy with GQD and anti-mouse PD-1 potently inhibited the growth of CT26 tumours in a xenograft model. Gut microbiota analysis revealed that combination therapy with GQD and anti-mouse PD-1 significantly enriched for s&#95;&#95;Bacteroides&#95;acidifaciens and s&#95;&#95;uncultured&#95;organism&#95;g&#95;&#95;norank&#95;f&#95;&#95;Bacteroidales&#95;S24-7&#95;group. Based on metabolomic analyses, profoundly altered metabolites were identified in the combination therapy group. Two metabolic signalling pathways, namely, glycerophospholipid metabolism and sphingolipid metabolism, were explored. In particular, we found that combination therapy with GQD and anti-mouse PD-1 significantly increased the proportion of CD8+ T cells in peripheral blood and tumour tissues. Direct treatment with GQD and anti-mouse PD-1 increased the expression of IFN-γ, which is a critical factor in antitumour immunotherapy. In addition, combination therapy with GQD and anti-mouse PD-1 downregulated PD-1 and increased IL-2 levels, suggesting that the combination therapy could effectively restore T-cell functions by suppressing inhibitory checkpoints. The application of the Chinese medicinal formula GQD with PD-1 blockade-based immunotherapy can be a novel therapeutic strategy for CRC patients with MSS tumours.

Background: Fatigue is a common, distressing, and persistent symptom for patients with malignant tumor including colorectal cancer (CRC). Although studies of cancer-related fatigue (CRF) have sprung out in recent years, the pathophysiological mechanisms that induce CRF remain unclear, and effective therapeutic interventions have yet to be established., Methods: To investigate the effect of the traditional Chinese medicine YangZheng XiaoJi (YZXJ) on CRF, we constructed orthotopic colon cancer mice, randomly divided into YZXJ group and control (NS) group. Physical or mental fatigue was respectively assessed by swimming exhaustion time or suspension tail resting time. At the end of the experiment, serum was collected to measure the expression level of inflammatory factors by ELISA and feces to microbiota changes by 16s rDNA, and hepatic glycogen content was detected via the anthrone method., Result: The nutritional status of the YZXJ group was better than that of the control group, and there was no statistical difference in tumor weight. The swimming exhaustion times of YZXJ group and control group were (162.80 ± 14.67) s and (117.60 ± 13.42, P < 0.05) s, respectively; the suspension tail resting time of YZXJ group was shorter than that of the control group (49.85 ± 4.56) s and (68.83 ± 7.26) s, P < 0.05)). Serum levels of IL-1 β and IL-6 in YZXJ group were significantly lower than the control group ( P < 0.05). Liver glycogen in YZXJ group was (5.18 ± 3.11) mg/g liver tissue, which was significantly higher than that in control group (2.95 ± 2.06) mg/g liver tissue ( P < 0.05). At phylum level, increased abundance of Bacteroidetes, Verrucomicrobia, Actinobacteria, and Cyanobacteria and decreased Proteobacteria in YZXJ group emerged as the top differences between the two groups, and the Firmicutes/Bacteroidetes ratio was decreased in YZXJ group compared to the control group. At genus level, the abundance of Parabacteroides , unidentified Saprospiraceae, and Elizabethkingia which all belong to phylum Bacteroidetes were increased, while Arcobacter, Marinobacter, Alkanindiges, Sulfuricurvum, Haliangium , and Thiobacillus in phylum Proteobacteria were decreased after YZXJ intervention. YZXJ can also increase Pirellula , Microbacterium, and Alpinimonas and decrease Rubrobacter and Iamia ., Conclusion: YZXJ may reduce the physical and mental fatigue caused by colorectal cancer by inhibiting inflammatory reaction, promoting hepatic glycogen synthesis, and changing the composition of intestinal microbiota.

Objective: The aim of this study was to investigate the role of miR-410 in regulating the proliferation and apoptosis of pediatric acute lymphoblastic leukemia (ALL) cells and to explore the possible underlying mechanism., Patients and Methods: The expression level of miR-410 in ALL cases and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Luciferase reporter gene assay was performed to evaluate the interaction between miR-410 and FKBP5. MTT and colony formation assay were used to determine the effect of miR-410 on the proliferation and colony formation ability of ALL cells. The effect of miR-410 on cell apoptosis was measured by Annexin V-fluorescein isothiocyanate 1 (FITC) and propidium iodide (PI). Western blot was used to analyze the effect of miR-410 on the protein expression levels of phosphorylated Akt (p-Akt) and cleaved caspase-3., Results: In our investigation, miR-410 was significantly up-regulated in ALL cases and cells. We searched three public databases to predict the potential target of miR-410, and found that FKBP5 was a direct target of miR-410. Meanwhile, Luciferase reporter gene assay confirmed our hypothesis. The overexpression of miR-410 accelerated the proliferation and colony formation ability of ALL cells, whereas remarkably decreased cell apoptosis rate. Western blotting showed that miR-410 inhibited the activation of Akt signaling pathway. However, FKBP5 could reverse the effects of miR-410., Conclusions: MiR-410 regulated the proliferation, colony formation and apoptosis of ALL cells through targeting FKBP5 and Akt signal pathway, indicating that miR-410 might be a potential therapeutic target for the treatment of ALL.

References: ATCC. www.lgcstandards-atcc.org/Products/All/CRL-1441.aspx?geo&#95;country=it Memorial Sloan Kettering Cancer Cancer. https://www.mskcc.org/research-advantage/support/technology/tangiblematerial/sk-nep-1-human-ewing-sarcoma-cell-line.

Drop on Demand inkjet printing is an attractive method for device fabrication. However, the reliability of the key printing steps is still challenging. This explains why versatile functional inks are needed. Epoxy based ink described in this study could solve this critical issue because it can be printed with low drawbacks (satellites droplets, long-lived filaments, etc.). Moreover, a wide concentration range of solute allows the fabrication of films from thin to high aspect ratio. Optimizing experimental parameters (temperature, overlap) and ink composition (single or cosolvent) is useful to tune the film profile. As a result, many shapes can be obtained such as donuts or hemispherical caps for a droplet and smooth or wavy shape for a thin film. This study demonstrates that epoxy based versatile ink can be used in numerous fields of applications (organic electronics, optics, sensors, MEMS, etc.). To prove this assertion, organic field effect transistors and light emitting films have been fabricated.

Objectives: As a member of miR-29 family, miR-29a can act as either oncogene or tumor suppressor. However, its expression patterns in acute myeloid leukemia (AML) are controversial according to previous studies. Thus, the aim of this study was to determine the expression and clinical significance of miR-29a in pediatric AML., Methods: Expression levels of miR-29a in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. The prognostic values of miR-29a in pediatric AML were also analyzed., Results: Compared with normal controls, we demonstrated a significantly decreased expression of miR-29a in the bone marrow of pediatric AML patients (P<0.001). The expression levels of miR-29a were significantly lower in French-American-British classification subtype M7 than in other subtypes (P<0.001) and differed significantly across cytogenetic risk groups (P=0.002) with high miR-29a expression among those with favorable karyotypes. Moreover, low miR-29a expression was significantly associated with shorter relapse-free (P<0.001) and overall (P=0.008) survival in pediatric AML patients. Cox proportional hazards multivariate analysis of the univariate predictors identified cytogenetic risk and miR-29a expression as independent prognostic factors for relapse-free survival and overall survival. More interestingly, the prognostic value of miR-29a expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics., Conclusion: Our data indicate for the first time that the down-regulation of miR-29a was associated with advanced clinical features and poor prognosis of pediatric AML patients, suggesting that miR-29a down-regulation may be used as an unfavorable prognostic marker in pediatric AML., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Objective: MicroRNA-100 (miR-100), a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML), but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML., Methods: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed., Results: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001) was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French-American-British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively). Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients., Conclusion: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.