A medical image segmentation method for rectal tumors based on multi-scale feature retention and multiple attention mechanisms.

BACKGROUND: With the continuous development of deep learning algorithms in the field of medical images, models for medical image processing based on convolutional neural networks have made great progress. Since medical images of rectal tumors are characterized by specific morphological features and complex edges that differ from natural images, achieving good segmentation results often requires a higher level of enrichment through the utilization of semantic features. PURPOSE: The efficiency of feature extraction and utilization has been improved to some extent through enhanced hardware arithmetic and deeper networks in most models. However, problems still exist with detail loss and difficulty in feature extraction, arising from the extraction of high-level semantic features in deep networks. METHODS: In this work, a novel medical image segmentation model has been proposed for Magnetic Resonance Imaging (MRI) image segmentation of rectal tumors. The model constructs a backbone architecture based on the idea of jump-connected feature fusion and solves the problems of detail feature loss and low segmentation accuracy using three novel modules: Multi-scale Feature Retention (MFR), Multi-branch Cross-channel Attention (MCA), and Coordinate Attention (CA). RESULTS: Compared with existing methods, our proposed model is able to segment the tumor region more effectively, achieving 97.4% and 94.9% in Dice and mIoU metrics, respectively, exhibiting excellent segmentation performance and computational speed. CONCLUSIONS: Our proposed model has improved the accuracy of both lesion region and tumor edge segmentation. In particular, the determination of the lesion region can help doctors identify the tumor location in clinical diagnosis, and the accurate segmentation of the tumor edge can assist doctors in judging the necessity and feasibility of surgery.

Overexpression of Bruton Tyrosine Kinase Inhibits the Proliferation, Migration, and Invasion of Non-Small Cell Lung Cancer Cells.

Lung cancer is one of the most lethal malignant tumors in the world. Non-small cell lung cancer (NSCLC) is the most common pathological subtype. However, the molecular mechanism of NSCLC progress is still unclear. We extracted the expression data of the Bruton's tyrosine kinase (BTK) gene in NSCLC tissues from the TCGA database. The results of paired t-test showed that the BTK gene was significantly underexpressed in NSCLC tissues. To further verify the above results, we detected the expression of the BTK gene in NSCLC cell lines A549, H1299, and H1650 at the RNA and protein levels by real-time fluorescent quantitative polymerase chain reaction and Western Blot analysis, respectively. The results showed that BTK was low expressed in NSCLC tissues and cells. More importantly, the expression of the BTK gene is also significantly related to the patient's age, gender, tumor range (T), lymph node invasion (N), tumor stage, and prognosis, and its expression level gradually decreases with the progress of the disease. It is speculated that BTK may be an independent prognostic factor of NSCLC. Our experimental results are consistent with the above clinical correlation analysis results. Overexpression of BTK can significantly inhibit the proliferation, migration, and invasion of NSCLC cells and can block the G0/G1 tumor cell cycle, indicating that overexpression of BTK can inhibit the growth, migration, and invasion of NSCLC cells.

LINC01117 inhibits invasion and migration of lung adenocarcinoma through influencing EMT process.

BACKGROUND: Studying the mechanism of action of LncRNAs in lung adenocarcinoma (LUAD) is of great importance for an in-depth understanding of the molecular mechanism of lung adeno carcinogenesis and development. OBJECTIVE: The aim is to identify a long non-coding RNA LINC01117 that is specifically and highly expressed in LUAD cells and to investigate its biological functions and molecular mechanisms in LUAD cells, providing a new potential target for targeting LUAD therapy. METHODS: This study used publicly available data downloaded from The Cancer Genome Atlas (TCGA) database. Construction of siRNA and overexpression plasmid-packed lentiviral constructs were used to knock down and increase the expression of LINC01117 in LUAD cells. The effect of LINC01117 on LUAD cell migration and invasion was verified by scratch assays and Transwell assays. Western blot assays were performed to verify the effect of knocking down LINC01117 expression on key proteins of the EMT process. The effect of overexpression and knockdown LINC01117 expression on key proteins of the EMT process and the nuclear and cytoplasmic distribution of YAP1, a key effector molecule of the Hippo pathway, was verified by Western blot assays. RESULTS: LINC01117 expression was upregulated in LUAD tissues and cell lines. Clinical correlation and prognostic analyses showed that LINC01117 was associated with poorer clinical features (staging and N classification) and poorer prognosis and could be analyzed as an independent prognostic factor. Cell migration and invasion were significantly inhibited in the knockdown group compared to the control group; in contrast, cell migration and invasion were promoted in the overexpression group. Overexpression of LINC01117 resulted in down-regulation of E-cadherin expression and increased expression levels of N-cadherin, vimentin, ZEB1, snail and slug; in contrast, knockdown of LINC01117 appeared to have the opposite effect. Furthermore, knockdown of LINC01117 increased the enrichment of YAP1 protein in the cytoplasm and reduced its level in the nucleus; overexpression of LINC01117 produced the opposite intracellular distribution results. CONCLUSIONS: LINC01117 was highly expressed in LUAD, and knockdown of LINC01117 significantly inhibited the migration and invasion of LUAD cells, while overexpression of LINC01117 significantly promoted the migration and invasion of LUAD cells, and affected the EMT process, and was able to alter the distribution of YAP1 in the nucleus and cytoplasm. This suggests that LINC01117 may regulate the activity of the Hippo pathway by altering the nuclear and cytoplasmic distribution of YAP1, which in turn induces the EMT process in lung adenocarcinoma cells and thus exerts a pro-cancer effect. It suggests that LINC01117 may play a key role in the occurrence and development of LUAD.

Development of a novel embryonic germline gene-related prognostic model of lung adenocarcinoma.

BACKGROUND: Emerging evidence implicates the correlation of embryonic germline genes with the tumor progress and patient's outcome. However, the prognostic value of these genes in lung adenocarcinoma (LUAD) has not been fully studied. Here we systematically evaluated this issue, and constructed a novel signature and a nomogram associated with embryonic germline genes for predicting the outcomes of lung adenocarcinoma. METHODS: The LUAD cohorts retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used as training set and testing set, respectively. The embryonic germline genes were downloaded from the website https://venn.lodder.dev. Then, the differentially expressed embryonic germline genes (DEGGs) between the tumor and normal samples were identified by limma package. The functional enrichment and pathway analyses were also performed by clusterProfiler package. The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. Survival and Receiver Operating Characteristic (ROC) analyses were performed to validate the model using training set and four testing GEO datasets. Finally, a prognostic nomogram based on the signature genes was constructed using multivariate regression method. RESULTS: Among the identified 269 DEGGs, 249 were up-regulated and 20 were down-regulated. GO and KEGG analyses revealed that these DEGGs were mainly enriched in the process of cell proliferation and DNA damage repair. Then, 103 DEGGs with prognostic value were identified by univariate Cox regression and further filtered by LASSO method. The resulting sixteen DEGGs were included in step multivariate Cox regression and an eleven embryonic germline gene related signature (EGRS) was constructed. The model could robustly stratify the LUAD patients into high-risk and low-risk groups in both training and testing sets, and low-risk patients had much better outcomes. The multi-ROC analysis also showed that the EGRS model had the best predictive efficacy compared with other common clinicopathological factors. The EGRS model also showed robust predictive ability in four independent external datasets, and the area under curve (AUC) was 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094). More importantly, the expression level of some genes in EGRS has a significant correlation with the progression of LUAD clinicopathology, suggesting these genes might play an important role in the progression of LUAD. Finally, based on EGRS genes, we built and calibrated a nomogram for conveniently evaluating patients' outcomes.

[Study on prevalence of occupational musculoskeletal disorders and their risk factors among workers in three industries in Zhongshan, China].

OBJECTIVE: To determine the prevalence of occupational musculoskeletal disorders (OMSD) and its risk factors among workers in three manufacturing industries in Zhongshan, China by cross-sectional epidemiological investigation. METHODS: A total of 2 035 workers from the industries of metals (1001 persons), electrical appliances (455 persons), and furniture (579 persons), including 1 402 males and 633 females, were selected; the mean age was 32.9 ± 8.2 years, and the mean length of service was 6.4 ± 5.6 years. A revised Northern Europe Standardized Questionnaire was used for cross-sectional epidemiological investigation of OMSD. RESULTS: The results showed that OMSD in these workers was primarily located in the neck, waist, and shoulder, with annual prevalence rates of 23.1%, 20.1%, and 15.8%, respectively. The overall prevalence of OMSD was 43.1% in metal industry, 44.0% in electrical appliance industry, and 26.6% in furniture industry. OMSD prevalence showed significant differences between different industries (χ(2) = 54.2, P < 0.01). The prevalence of OMSD in the shoulder and back increased with working years (P < 0.05). Logistic regression analysis showed that the risk factors for OMSD were working age >10 years, safety behavior such as "bending down when lifting heavy things from the ground", and different types of industries. CONCLUSION: OMSD is mainly manifested by neck pain, waist pain, and shoulder pain among front-line manufacturing workers in Zhongshan, and working age, poor labor posture, and different types of industries were risk factors for waist pain.

[Preparation of cyclosporine A loaded mPEG-PLGA copolymer micelles and study its pharmacokinetics in rats].

To prepare cyclosporine A (CyA) loaded block copolymer micelles and observe its release behaviors in vitro and pharmacokinetics in rats, methoxylpoly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (mPEG-PLGA) was synthesized by ring-opening copolymerization of lactide and glycolide in the presence of methoxylpoly (ethylene glycol) (mPEG) as initiator. The structure of the mPEG-PLGA copolymer was confirmed with 1H NMR and FT-IR. The cyclosporine A loaded micelles (CyA-PM) were prepared by solvent evaporation method and their morphology was observed by the transmission electron microscope (TEM). The mean size and size distribution were determined by dynamic light scattering (DLS). The release behaviors in vitro and pharmacokinetics in rats were investigated by HPLC method using cyclosporine A injection commercial agent, sandimmune, as the reference. The obtained CyA-PM showed spherical shape with the core-shell structure, the mean particle sizes are in the range of 136.1-141.9 nm. The drug loading amount and entrapment efficiency were increased and the particle size became smaller with decreasing the ratio of acetone to water. With the increasing of the amount of cyclosporine A fed the drug loading increased, entrapment efficiency decreased and the particle size had no change. CyA-PM showed significant sustained release behave in vitro compared with sandimmune and only 9.7% of encapsulated cyclosporine A was released after 12 hours, the release characteristics was well fitted with Higuchi equation (r = 0.999). The Pharmacokinetics study at equal administration dosage (5 mg x kg(-1)) in rats showed the half-life (t1/2) of CyA-PM extended and the area under concentration-time curve (AUC) increased compared to sandimmune. The results also showed that cyclosporine A concentration-time data were all in accord with two compartment model. Cyclosporine A loaded mPEG-PLGA micelles showed obviously solubility enhancement, sustained release and overcome the side effect and toxicity of sandimmune resulted from solubiling agent-polyoxyethylene castor oil (Cremophor EL) and might be developed as a novel dosage form of cyclosporine A.