The trend of unintentional injury-related mortality among children aged under-five years in China, 2010-2020: a retrospective analysis from a national surveillance system.

BACKGROUND: In this study, we estimated the trend of unintentional injury mortality among children aged under-five years in China during 2010-2020. METHODS: Data were obtained from China's Under 5 Child Mortality Surveillance System (U5CMSS). The total unintentional injury mortality and all specific-causes unintentional injury mortality was calculated, annual numbers of deaths and live births were adjusted by a 3-year moving average under-reporting rate. The Poisson regression model and the Cochran-Mantel-Haenszel method were used to calculate the average annual decline rate (AADR) and the adjusted relative risk (aRR) of the unintentional injury mortality. RESULTS: In 2010-2020, a total of 7,925 unintentional injury-related deaths were reported in U5CMSS, accounting for 18.7% of all reported deaths. The overall proportion of unintentional injury-related deaths to total under-five children deaths has increased from 15.2% to 2010 to 23.8% in 2020 (χ2 = 227.0, p < 0.001), the unintentional injury mortality significantly decreased from 249.3 deaths per 100,000 live births in 2010 to 178.8 deaths per 100,000 live births in 2020, with an AADR 3.7% (95%CI 3.1-4.4). The unintentional injury mortality rate decreased from 2010 to 2020 in both urban (from 68.1 to 59.7 per 100,000 live births) and rural (from 323.1 to 230.0 per 100,000 live births) areas (urban: χ2 = 3.1, p < 0.08; rural: χ2 = 113.5, p < 0.001). The annual rates of decline in rural areas and urban areas were 4.2% (95%CI 3.4-4.9) and 1.5% (95%CI 0.1-3.3), respectively. The leading causes of unintentional injury mortality were suffocation (2,611, 32.9%), drowning (2,398, 30.3%), and traffic injury (1,428, 12.8%) in 2010-2020. The cause-specific of unintentional injury mortality rates decreased with varying AADRs in 2010-2020, except for traffic injury. The composition of unintentional injury-related deaths also varied by age group. Suffocation was the leading cause in infants, drowning and traffic injury were the leading causes in children aged 1-4 years. Suffocation and poisoning has high incidence in October to March and drowning has high in June to August. CONCLUSION: The unintentional injury mortality rate of children aged under-five years decreased significantly from 2010 to 2020 in China, but great inequity exists in unintentional injury mortality in urban and rural areas. Unintentional injuries are still an important public health problem affecting the health of Chinese children. Effective strategies should be strengthened to reduce unintentional injury in children and these policies and programmes should be targeted to more specific populations, such as rural areas and males.

Molecular phylogeny and morphology reveal four new species of Thelephora (Thelephorales, Basidiomycota) from subtropical China, closely related to T. ganbajun.

The genus of Thelephora is a group of cosmopolitan ectomycorrhizal fungi with basidiocarps of morphological diversity that has an extremely scarce species reported from the forest ecosystem in China. In this study, phylogenetic analyses of Thelephora species from subtropical China were carried out based on multiple loci including the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), and the small subunit of mitochondrial rRNA gene (mtSSU). Maximum likelihood and Bayesian analyses were used to construct the phylogenetic tree. The phylogenetic positions of four new species, Th. aquila, Th. glaucoflora, Th. nebula, and Th. pseudoganbajun, were revealed based on morphological and molecular evidence. Molecular analyses demonstrated that the four new species were closely related to Th. ganbajun and formed a clade with robust support in the phylogenetic tree. Regarding morphology, they share some common morphological characteristics, including flabelliform to imbricate pilei, generative hyphae more or less covered by crystals, and subglobose to irregularly lobed basidiospores (5-8 × 4-7 µm) with tuberculate ornamentation. These new species are described and illustrated and are compared to similar morphological or phylogenetically related species. A key to the new and allied species from China is provided.

Mitochondrial fragmentation is crucial for c-Myc-driven hepatoblastoma-like liver tumors.

Hepatoblastoma is the most common liver cancer in children, and the aggressive subtype often has a poor prognosis and lacks effective targeted therapy. Although aggressive hepatoblastoma (HB) is often accompanied by abnormally high expression of the transcription factor c-Myc, the underlying mechanism remains unclear. In this study, we found that mitochondrial fragmentation was enhanced by c-Myc overexpression in human aggressive HB tissues and was associated with poor prognosis. Then, a mouse model resembling human HB was established via hydrodynamic injection of c-Myc plasmids. We observed that liver-specific knockout of the mitochondrial fusion molecule MFN1 or overexpression of mitochondrial fission molecule DRP1 promoted the occurrence of c-Myc-driven liver cancer. In contrast, when MFN1 was overexpressed in the liver, tumor formation was delayed. In vitro experiments showed that c-Myc transcriptionally upregulated the expression of DRP1 and decreased MFN1 expression through upregulation of miR-373-3p. Moreover, enhanced mitochondrial fragmentation significantly promoted aerobic glycolysis and the proliferation of HB cells by significantly increasing reactive oxygen species (ROS) production and activating the RAC-alpha serine/threonine-protein kinase (AKT)/mammalian target of rapamycin (mTOR) and nuclear factor κB (NF-κB) pathways. Taken together, our results indicate that c-Myc-mediated mitochondrial fragmentation promotes the malignant transformation and progression of HB by activating ROS-mediated multi-oncogenic signaling.

Mitochondrial transcription factor A plays opposite roles in the initiation and progression of colitis-associated cancer.

BACKGROUND: Mitochondria are key regulators in cell proliferation and apoptosis. Alterations in mitochondrial function are closely associated with inflammation and tumorigenesis. This study aimed to investigate whether mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA transcription and replication, is involved in the initiation and progression of colitis-associated cancer (CAC). METHODS: TFAM expression was examined in tissue samples of inflammatory bowel diseases (IBD) and CAC by immunohistochemistry. Intestinal epithelial cell (IEC)-specific TFAM-knockout mice (TFAM△IEC ) and colorectal cancer (CRC) cells with TFAM knockdown or overexpression were used to evaluate the role of TFAM in colitis and the initiation and progression of CAC. The underlying mechanisms of TFAM were also explored by analyzing mitochondrial respiration function and biogenesis. RESULTS: The expression of TFAM was downregulated in active IBD and negatively associated with the disease activity. The downregulation of TFAM in IECs was induced by interleukin-6 in a signal transducer and activator of transcription 3 (STAT3)/miR-23b-dependent manner. In addition, TFAM knockout impaired IEC turnover to promote dextran sulfate sodium (DSS)-induced colitis in mice. Of note, TFAM knockout increased the susceptibility of mice to azoxymethane/DSS-induced CAC and TFAM overexpression protected mice from intestinal inflammation and colitis-associated tumorigenesis. By contrast, TFAM expression was upregulated in CAC tissues and contributed to cell growth. Furthermore, it was demonstrated that ß-catenin induced the upregulation of TFAM through c-Myc in CRC cells. Mechanistically, TFAM promoted the proliferation of both IECs and CRC cells by increasing mitochondrial biogenesis and activity. CONCLUSIONS: TFAM plays a dual role in the initiation and progression of CAC, providing a novel understanding of CAC pathogenesis.

[Therapeutic effect of Actovegin on acute oral mucositis caused by radiotherapy].

PURPOSE： To explore the clinical effect of Actovegin in the treatment of acute oral mucositis in patients with radiotherapy. METHODS： One hundred and thirteen patients with acute oral mucositis caused by radiotherapy for nasopharyngeal carcinoma admitted to the Department of Oncology, the Fifth People's Hospital of Qinghai Province from July 2015 to September 2017 were randomly divided into the experimental group (57 cases) and control group (56 cases). Patients in the experimental group were treated with Aiweizhi, while patients in the control group were treated with new rehabilitation. The changes of VAS score, oral mucositis grade, serum CRP, IL-6, TGF-ß1 and TNF-α were compared between the 2 groups. The data were analyzed with SPSS 16.0 software package. RESULTS: Before treatment, there was no significant difference in VAS score between the 2 groups (P>0.05). After 1 week and 2 weeks of treatment, the VAS scores of the two groups were significantly lower than those before treatment (P<0.05). The VAS score of the experimental group was significantly lower than that of the control group (P<0.05). After 2 weeks of treatment, oral mucositis grade of the experimental group was significantly lower than that of the control group (P<0.05). There was no significant difference in serum CRP, IL-6, TGF-ß1, and TNF-α level between the 2 groups before treatment (P>0.05). After 2 weeks of treatment, the level of serum CRP, IL-6, TGF-ß1, and TNF-α in both groups was significantly lower than that before treatment (P<0.05). The serum level of CRP, IL-6, TGF-ß1 and TNF-α in the experimental group was significantly lower than that in the control group (P<0.05). CONCLUSIONS: Actovegin has a clear clinical effect on acute oral mucositis in patients with radiotherapy, which can significantly alleviate the pain of patients and reduce the level of serum inflammatory factors.

P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12.

PURPOSE: Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme. METHODS: In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154. RESULTS: We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12. CONCLUSION: Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.

Genetic variants in NPAS2 gene and clinical outcomes of resectable non-small-cell lung cancer.

Background: A series of studies have demonstrated that NPAS2 plays a critical role in the development and progression of several cancers. However, the association between genetic variants in the NPAS2 gene and the clinical outcome of patients with non-small-cell lung cancer (NSCLC) has not been investigated. Methods: Six functional SNPs in NPAS2 were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 484 Chinese NSCLC patients undergoing surgery. Multivariate Cox proportional hazards model were used for the prognosis analysis. Results: We found that SNP rs2305158 exhibited a significant association with overall survival of NSCLC patients in the dominant model (hazard ratio [HR]: 0.68; 95% CI: 0.49-0.95; p = 0.02). Lymph node metastasis was significantly associated with increased death risk (HR: 1.73; 95% CI: 1.24-2.40; p = 0.001) in patients with the homozygous wildtype (WW) genotype of rs2305158. However, no significant association was observed between them in patients carrying a heterozygous variant (WV) or homozygous variant (VV) genotype of rs2305158. Finally, in the joint and interaction analysis, the patients carrying homozygous wildtype (WW) genotype and lymph node metastasis from N1 to N3 conferred a significant increased effect on death (HR: 2.29; 95% CI: 1.40-3.76; p = 0.001). Conclusions: Our results suggest that NPAS2 polymorphisms may serve as an independent prognostic marker for NSCLC patients.

Acupotomy for knee osteoarthritis: A systematic review protocol.

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Acupotomy has been widely used to treat KOA. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA. METHODS: Relevant studies will be searched from the databases of PubMed, EMBASE, Cochrane Library, China Knowledge Resource Integrated Database, Weipu Database for Chinese Technical Periodicals, SinoMed, and Wanfang Database from their inception to June 10, 2019. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RESULTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019132082.