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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. With the emergence of disease-modifying therapies, the prognosis of SMA has significantly improved, drawing increased attention to the importance of home rehabilitation and nursing management. Long-term, standardized home rehabilitation and nursing can delay the progression of SMA, enhance the psychological well-being, and improve the quality of life of both patients and caregivers. This article provides an overview of the goals of home rehabilitation, basic functional training methods, respiratory management, and nutritional management for SMA patients, as well as psychological health issues, emphasizing the significance of obtaining appropriate home rehabilitation and support during the care process.

Current understanding of children's head shape and its impact on health: a cross-sectional study among pediatric medical staff in China.

Background: Head shape problems are common in infancy and early childhood, and thus their early identification and management can benefit the health of children. This study aimed to investigate pediatric healthcare professionals' existing knowledge of children's head shape abnormalities and their associated effects in China, providing guidelines for future clinical interventions, training, and interdisciplinary collaboration. Methods: We conducted a survey among pediatric medical staff, encompassing various age groups, genders, hospitals, and professional levels. The electronic questionnaire queried respondents' basic information, knowledge pertaining to head shape issues, diagnosis and treatment approaches, and the clinical development status of head shape problems. All surveys and data collection were conducted anonymously. Results: A total of 214 valid questionnaires were collected. Differences in the level of understanding among medical staff regarding head shape issues were observed. Medical staff in tertiary care facilities showed the highest proficiency in diagnosing and treating positional plagiocephaly and cranial asymmetry (P<0.05), while those in primary care facilities exhibited the lowest competency in diagnosing head shape abnormalities (P<0.05). Most medical staff had a partial understanding of specific aspects of head shape issues, such as identifying high-risk individuals (n=144, 67.29%), making diagnoses (n=176, 82.24%), and understanding the consequences (n=151, 70.56%), with no significant differences across medical facilities of various levels. Additionally, 99.07% (n=212) of the medical staff believed that head shape measurements should be included as a routine component of pediatric physical examinations, and 75.23% (n=161) incorporate head shape assessment as part of their routine physical examination. Furthermore, 91.12% (n=195) of the medical staff received consultations on children's head shape issues, with a higher prevalence in secondary and tertiary care facilities. Finally, 93.97% (n=201) of the participants expressed the need for further education and knowledge on pediatric head shape, with no significant differences across medical facilities of various levels. Conclusions: There is a limited understanding among medical personnel in China regarding children's head shape issues. Therefore, it is imperative to enhance training and educational initiatives for medical staff in China, with the goal of enhancing their awareness and knowledge regarding children's head shape problems.

Histone H3K36me3 mediates the genomic instability of Benzo[a]pyrene in human bronchial epithelial cells.

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair. H3K36 mutation at both H3.1 and H3.3 exhibited the most significant impacts. In addition, we found that the expression of SET domain containing 2 (SETD2), the unique methyltransferase catalyzed H3K36me3, was downregulated by BaP dose-dependently in vitro and in vivo. Knockdown of SETD2 aggravated DNA damage of BaP exposure, which was consistent with the effects of H3K36 mutation. With the aid of chromatin immunoprecipitation (ChIP) -seq and RNA-seq, we found that H3K36me3 was responsible for transcriptional regulation of genes involved in pathways related to cell survival, lung cancer, metabolism and inflammation. The enhanced enrichment of H3K36me3 in genes (CYP1A1, ALDH1A3, ACOXL, WNT5A, WNT7A, RUNX2, IL1R2) was positively correlated with their expression levels, while the reduction of H3K36me3 distribution in genes (PPARGC1A, PDE4D, GAS1, RNF19A, KSR1) were in accordance with the downregulation of gene expression. Taken together, our findings emphasize the critical roles and mechanisms of histone lysine methylation in mediating cellular homeostasis during BaP exposure.

The transcription activity of OTX2 on p16 expression is significantly blocked by methylation of CpG shore in non-promoter of lung cancer cell lines.

Background: The aberrant expression of the classical tumor suppressor gene p16 is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how p16 expression and function are affected are largely unknown. Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of p16. The effects of methylation editing were detected by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS), transwell migration and wound healing tests. Chromatin immnoprecipitation-quantitative polymerase chain reaction (CHIP-qPCR) was performed to explore the impact of Cgi shore methylation on the binding abilities of transcription factors (TFs) including YY1, SP1, ZNF148 and OTX2 to p16 gene. A rescue experiment was performed to verify the regulatory effect of OTX2 on p16. The negative relationship between p16 expression and the methylation level of Cgi shore in non-promoter region was further verified with datasets from The Cancer Genome Atlas (TCGA) program and lung adenocarcinoma (LUAD) patients' samples. Results: The suppressive effect of p16 Cgi shore methylation on its expression was demonstrated in both HEK293 and A549 cells using CRISPR/dCas9-mediated specific site methylation editing. Methylation of the Cgi shore in the p16 non-promoter region significantly decreased its expression and promoted cell growth and migration. The ability of OTX2 bound to p16 was significantly reduced by 19.35% after methylation modification. Over-expression of OTX2 in A549 cells partly reversed the inhibitory effect of methylation on p16 expression by 19.04%. The verification results with TCGA and LUAD patients' samples supported that the p16 Cgi shore is a key methylation regulatory region. Conclusions: Our findings suggested that methylation of the Cgi shore in the p16 non-promoter region can hamper the transcriptional activity of OTX2, leading to a reduction in the expression of p16, which might contribute to the development of lung cancer.

Mucin2 regulated by Ho1/p38/IL-10 axis plays a protective role in polystyrene nanoplastics-mediated intestinal toxicity.

Micro/nano-plastics (MPs/NPs) are a newly discovered environmental pollutant that can be ingested by humans through food and drinking water. In this study we evaluated the impact of MPs/NPs on the intestinal barrier and its mechanism. Doses of MPs/NPs were used to treat Caco-2/HT29-MTX in-vitro model and in-vivo model. In in-vitro model, 20 nm polystyrene nanoplastics (PS-NPs) had higher cytotoxicity than larger particles (200 nm and 2000 nm), and led to the increase of the permeability along with the decreased expression of tight junction proteins. Intriguingly, 20 nm PS-NPs elevated the expression of MUC2 simultaneously. Further studies revealed that PS-NPs increased the expression of HO1 through ROS generation, and then activated p38 to elevate IL-10 secretion in Caco-2 cell. The IL-10 secreted by Caco-2 cell promoted the expression of MUC2 in HT29-MTX cell through STAT1/3. Elevated MUC2 expression alleviates the cytotoxicity of PS-NPs. Besides, increased intestinal permeability and up-regulation of MUC2 through Ho1/p38/IL-10 pathway was also observed in 20 nm PS-NPs treated mouse model. In conclusion, PS-NPs can induce the intestinal toxicity and result in the increased adaptive expression of MUC2 to resist this adverse effect. People with inadequate mucin expression need to pay more attention to the toxicity of PS-NPs. This study provided a valuable insight for clarifying the mechanism and potential risk of intestinal toxicity induced by nanoplastics.

Health risk assessment of cadmium exposure by integration of an in silico physiologically based toxicokinetic model and in vitro tests.

Cadmium (Cd) is a common environmental pollutant that can damage multiple organs, including the kidney. To prevent renal effects, international authorities have set health-based guidance values of Cd from epidemiological studies. To explore the health risk of Cd exposure and whether human equivalent doses (HEDs) derived from in vitro tests match the current guidance values, we integrated renal tubular epithelial cell-based assays with a physiologically based toxicokinetic model combined with the Monte Carlo method. For females, the HEDs (µg/kg/week) derived from KE2 (DNA damage), KE3 (cell cycle arrest), and KE4 (apoptosis) were 0.20 (2.5th-97.5th percentiles: 0.09-0.48), 0.52 (0.24-1.26), and 2.73 (1.27-6.57), respectively; for males the respective HEDs were 0.23 (0.10-0.49), 0.60 (0.27-1.30), and 3.11 (1.39-6.78). Among them, HEDKE4 (female) was close to the tolerable weekly intake (2.5 µg/kg/week) set by the European Food Safety Authority. The margin of exposure (MOE) derived from HEDKE4 (female) indicated that risks of renal toxicity for populations living in cadmium-contaminated regions should be of concern. This study provided a new approach methodology (NAM) for environmental chemical risk assessment using in silico and in vitro methods.

Bioinformatics analysis of key genes and potential mechanism in cadmium-induced breast cancer progression.

Cadmium (Cd) may be associated with breast cancer progression, but the detailed molecular mechanism has not been fully elucidated. In this study, one public dataset (GSE136595) was used to identify differentially expressed genes (DEGs) in Cd-treated MCF-7 breast cancer cells. We determined a total of 2077 DEGs, and Ingenuity Pathway Analysis (IPA) software showed that 246 of them were related to tumor progression. Pathway analysis of these DEGs indicated that the HIF1α signaling and the epithelial-mesenchymal transition (EMT) pathway regulated by growth factors might be activated. Moreover, twist family bHLH transcription factor 1 (TWIST1), lysine demethylase 3A (KDM3A), Kruppel-like factor 4 (KLF4), nuclear protein 1 (NUPR1), neurogenin 3 (NEUROG3), and HNF1 homeobox B (HNF1B) might be the key transcription factors. And the result of protein-protein interaction (PPI) analysis showed that the hub genes in these 246 DEGs were tumor protein p53 (TP53), polo-like kinase 1 (PLK1), sirtuin 1 (SIRT1), protein tyrosine phosphatase non-receptor type 11 (PTPN11), caspase 8 (CASP8), cyclin-dependent kinase 6 (CDK6), calmodulin 3 (CALM3), KRAS proto-oncogene (KRAS), extra spindle pole bodies like 1 (ESPL1), and marker of proliferation Ki-67 (MKI67). Further analysis indicated that TWIST1, NUPR1, KRAS, and PTPN11 were related to the prognostic of breast cancer based on the Cancer Genome Atlas (TCGA) and they were validated to be upregulated in the Cd-treated MCF-7 cells. Our results suggested that the HIF1α signaling and the EMT pathway regulated by growth factors might be participant in the Cd-induced breast cancer progression and TWIST1, NUPR1, KRAS, and PTPN11 might be potential key genes.

Aberrant expression of SNHG12 contributes to N, N-dimethylformamide-induced hepatic apoptosis both in short-term and long-term DMF exposure.

N, N-Dimethylformamide (DMF) can cause liver damage in occupationally exposed workers, but the molecular mechanism of DMF-induced liver damage has not been fully elucidated. Researches have proved that lncRNA plays a major function in chemical-induced liver toxicity and can be used as a biomarker and therapeutic target for liver injury. In order to verify that lncRNA also participates in DMF-induced liver damage, we treated HL-7702 cells with 75 or 150 mM DMF, and obtained lncRNA expression profiles through high-throughput sequencing. Among the differentially expressed lncRNAs, lncRNA SNHG12 was proved to be significantly downregulated in DMF-treated HL-7702 cells and participate in DMF-mediated apoptosis, even under long-term low-dose DMF exposure (5-10 mM, 8 weeks). In addition, according to bioinformatics analysis, miR-218-5p is expected to be a potential target of SNHG12, which was verified by the dual luciferase reporter assay in HEK293FT cells. MiR-218-5p mimic can induce apoptosis in HL-7702 cells. Among the predicted targets of miR-218-5p, protein kinase C epsilon (PRKCE) was reported to be involved in apoptosis, and was indeed downregulated by miR-218-5p mimic in our study. Further experiments showed that changes of the expression of SNHG12 can affect the expression of PRKCE. In the epidemiological study of occupational population, we also found that SNHG12 was downregulated in the serum exosomes of workers exposed to DMF. These results indicated that SNHG12 can mediate DMF-induced apoptosis of HL-7702 cells through miR-218-5p/PRKCE pathway.

Hsa_circ_0005915 promotes N,N-dimethylformamide-induced oxidative stress in HL-7702 cells through NRF2/ARE axis.

N,N-dimethylformamide (DMF) is an organic compound widely used in industrial production processes as a solvent with a low evaporation rate. Excessive exposure to DMF may lead to liver damage. Oxidative stress has been reported as one of the main causes of DMF-induced hepatotoxicity. Several doses of DMF (0, 1, 5, and 10 mM) were used to treat HL-7702 cells for a relatively long period to simulate the actual exposure pattern in occupational settings, and oxidative stress was induced. Previous studies illustrated that circular RNA (circRNA) plays a vital role in sustaining hepatocyte physiological function. To explore whether aberrant circRNA expression is involved in DMF-induced excessive ROS generation and hepatotoxicity, high-throughput transcriptional sequencing was performed to identify the altered circRNA expression profiles in HL-7702 liver cells after treatment with 0, 75, or 150 mM DMF for 48 h. We found that levels of induced oxidative stress were similar to those in the long-term exposure model. Among the altered circRNAs, one circRNA (hsa_circ_0005915) was significantly upregulated after DMF exposure, and it affected DMF-mediated oxidative stress in HL-7702 cells. Further experiments revealed that hsa_circ_0005915 downregulated the expression of nuclear factor erythoid-2-related factor 2 (NRF2) at the post-transcriptional level via promoting the ubiquitination and degradation of NRF2, which led to the increase of ROS accumulation. Further investigation demonstrated that the expression levels of NRF2-regulated antioxidative genes-heme oxygenase 1 (HO1) and NAD(P)H quinone dehydrogenase 1 (NQO1)-indeed declined after the overexpression of hsa_circ_0005915. In vivo study also indicated that DMF exposure can upregulate the expression of mmu_circ_0007941 (homologous circRNA of hsa_circ_0005915) and downregulated Nrf2 and Ho1 proteins. In summary, our results revealed that hsa_circ_0005915 plays an important role in promoting DMF-induced oxidative stress by inhibiting the transcriptional activity of the NRF2/ARE axis, which provides a potential molecular mechanism of DMF-mediated hepatotoxicity.

Primary angiosarcoma of the small intestine with metastasis to the liver: a case report and review of the literature.

Angiosarcoma is a rare disease with a poor prognosis; significantly, patients with intestinal angiosarcomas who survive over 1 year after diagnosis are extraordinarily rare. This article describes the case of a 33-year-old gentleman who presented with abdominal pain of 4 months duration, which had increased in severity 2 weeks prior to presentation. After a complicated diagnostic and therapeutic process, the diagnosis of primary angiosarcoma of the small intestine with metastasis to the liver was made by pathological and immunohistochemical examinations. We reviewed previous cases of angiosarcoma described in the English literature to determine their risk factors, diagnosis and treatment, and we found that angiosarcoma is extremely rare, especially in the small intestine. To the best of our knowledge, this may be the youngest case of primary angiosarcoma of the small intestine with metastasis to the liver reported in the English literature.