Cause Of Death In Patients Research Articles

A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.

Metastasis of breast cancer is the main cause of death for patients with breast cancer. The interaction between metadherin (MTDH) and staphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting breast cancer development. However, the binding details between MTDH and SND1 remain unclear. In this study, we employed all-atom molecular dynamics simulations (MDs) and conducted binding energy calculations to investigate the binding details and the impact of key residue mutations on binding. The mutations in key residues have not significantly affected the overall stability of the structure and the fluctuation of residues near the binding site; they have exerted a substantial impact on the binding of SND1 and MTDH peptide. The electrostatic interactions and van der Waals interactions play an important role in the binding of SND1 and the MTDH peptide. The mutations in the key residues have a significant impact on electrostatic and van der Waals interactions, resulting in weakened binding. The energy contributions of key residues mainly come from the electrostatic energy and van der Waals interactions of the side chain. In addition, the key residues form an intricate and stable network of hydrogen bonds and salt-bridge interactions with the MTDH peptide. The mutations in key residues have directly disrupt the interactions formed between SND1 and MTDH peptide, consequently leading to changes in the binding mode of the MTDH peptide. These analyses unveil the detailed atomic-level interaction mechanism between SND1 and the MTDH peptide, providing a molecular foundation for the development of antibreast cancer drugs.

Cholesterol synthesis is essential for the growth of liver metastasis-prone colorectal cancer cells.

Metastasis to the liver is a leading cause of death in patients with colorectal cancer. To investigate the characteristics of cancer cells prone to metastasis, we utilized an isogenic model of BALB/c and colon tumor 26 (C26) cells carrying an active KRAS mutation. Liver metastatic (LM) 1 cells were isolated from mice following intrasplenic transplantation of C26 cells. Subsequent injections of LM1 cells generated LM2 cells, and after four cycles, LM4 cells were obtained. Invitro, using a perfusable capillary network system, we found comparable extravasation frequencies between C26 and LM4 cells. Both cell lines showed similar growth rates invitro. However, C26 cells showed higher glucose consumption, whereas LM4 cells incorporated more fluorescent fatty acids (FAs). Biochemical analysis revealed that LM4 cells had higher cholesterol levels than C26 cells. A correlation was observed between fluorescent FAs and cholesterol levels detected using filipin III. LM4 cells utilized FAs as a source for cholesterol synthesis through acetyl-CoA metabolism. In cellular analysis, cholesterol accumulated in punctate regions, and upregulation of NLRP3 and STING proteins, but not mTOR, was observed in LM4 cells. Treatment with a cholesterol synthesis inhibitor (statin) induced LM4 cell death invitro and suppressed LM4 cell growth in the livers of nude mice. These findings indicate that colorectal cancer cells prone to liver metastasis show cholesterol-dependent growth and that statin therapy could help treat liver metastasis in immunocompromised patients.

Effect of fruits granola (Frugra®) consumption on blood pressure reduction and intestinal microbiome in patients undergoing hemodialysis

Cardiovascular diseases (CVDs) are a major cause of death in patients undergoing hemodialysis (HD). Blood pressure (BP) and uremic toxins are well-known risk factors for CVDs, which are influenced by diet. Dietary fiber supplementation in patients undergoing HD may reduce the risk of CVDs by improving lipid profiles and inflammatory status and lowering the levels of the uremic toxin indoxyl sulfate (IS). In this study, we investigated the relationship between the intestinal microbiota and risk factors for CVDs, such as BP and serum IS, in patients undergoing HD who consumed fruits granola (FGR). The study participants were selected from patients undergoing HD at the Izu Nagaoka Daiichi Clinic and consumed FGR for 2 months. Body composition and blood samples were tested at months 0, 1, 2 and fecal samples were collected at months 0 and 2 for intestinal microbiota analysis. FGR consumption decreased systolic and diastolic BP, estimated salt intake, and serum IS levels and improved the stool characteristics according to the Bristol Stool Form Scale (N = 24). Gut microbiota analysis showed an increase in the alpha diversity and abundance of Blautia and Neglecta. The abundance of lactic acid- and ethanol-producing bacteria also significantly increased, whereas the abundance of indole-producing bacteria significantly decreased. FGR consumption could be a useful tool for salt reduction, fiber supplementation, and improvement of the intestinal environment, thus contributing to improvement of BP and the reduction of other risk factors for CVDs in patients undergoing HD.

Predictive factors for intrathoracic anastomotic leakage and postoperative mortality after esophageal cancer resection

BackgroundEsophageal cancer is currently one of the high-risk malignant tumors worldwide, posing a serious threat to human health. This study aimed to analyse the causes of postoperative mortality and intrathoracic anastomotic leakage(IAL) after esophagectomy.MethodsA retrospective analysis was conducted on 172 patients with esophageal cancer resection and focused on the preoperative and postoperative indicators. Cox regression analysis was performed to identify factors affected IAL and evaluated the potential factors on postoperative mortality. The Kaplan-Meier curve was applied to evaluate the effect of leakage on postoperative mortality after propensity score matching.ResultsUnivariable and multivariable Cox regression analysis showed that infection and high BMI were significant risk factors for IAL, patients with BMI over 24 kg/m2 in IAL group was two times higher than that of the group without IAL (95% CI = 1.01–6.38; P = 0.048). When patients were infected, the hazard ratios(HRs) of anastomotic leakage was twice that of patients without infection (95% CI = 1.22–4.70; P = 0.011). On the other hand, IAL was a significant cause of postoperative mortality, the 40-day postoperative mortality rate in the leakage group was significantly higher than the non leakage group (28.95% in leakage group vs. 7.46% in non leakage group, P<0.01). After propensity score matching, IAL still significantly affected postoperative mortality. The total length of hospital stay of the leakage group was inevitably longer than that of the non leakage group (22.19 ± 10.79 vs. 15.27 ± 8.59).ConclusionIAL was a significant cause of death in patients underwent esophageal cancer resection. Patients with high BMI over 24 kg/m2 and infection may be more prone to developing IAL after esophagectomy. IAL inevitably prolonged the length of hospital stay and increased postoperative mortality.

Using machine learning methods to investigate the impact of age on the causes of death in patients with early intrahepatic cholangiocarcinoma who underwent surgery.

The impact of age on the causes of death (CODs) in patients with early-stage intrahepatic cholangiocarcinoma (ICC) who had undergone surgery was analyzed in this study. A total of 1555 patients (885 in the older group and 670 in the younger group) were included in this study. Before and after applying inverse probability of treatment weighting (IPTW), the different CODs in the 2 groups were further investigated. Additionally, 7 different machine learning models were used as predictive tools to identify key variables, aiming to evaluate the therapeutic outcome in early ICC patients undergoing surgery. Before (5.92 vs. 4.08years, P < 0.001) and after (6.00 vs. 4.08years, P < 0.001) IPTW, the younger group consistently showed longer overall survival (OS) compared with the older group. Before IPTW, there were no significant differences in cholangiocarcinoma-related deaths (CRDs, P = 0.7) and secondary malignant neoplasms (SMNs, P = 0.78) between the 2 groups. However, the younger group had a lower cumulative incidence of cardiovascular disease (CVD, P = 0.006) and other causes (P < 0.001) compared with the older group. After IPTW, there were no differences between the 2 groups in CRDs (P = 0.2), SMNs (P = 0.7), and CVD (P = 0.1). However, the younger group had a lower cumulative incidence of other CODs compared with the older group (P < 0.001). The random forest (RF) model showed the highest C-index of 0.703. Time-dependent variable importance bar plots showed that age was the most important factor affecting the 2-, 4-, and 6-year survival, followed by stage and size. Our study confirmed that younger patients have longer OS compared with older patients. Further analysis of the CODs indicated that older patients are more likely to die from CVDs. The RF model demonstrated the best predictive performance and identified age as the most important factor affecting OS in early ICC patients undergoing surgery.

Study Reveals a New Approach to Treating Tripple Negative Breast Cancer

riple-negative breast cancer (TNBC) makes up about 15% of all breast cancer cases worldwide. It's particularly hard to treat because it lacks the three common receptors that most therapies target. As a result, most TNBC patients undergo high doses of non-targeted chemotherapy, which often leads to severe side effects such as hair loss, nausea, and pain. The spread of TNBC cells to other organs, such as the brain or lungs, is the main cause of death in patients.

Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Vitamin D status and intermediate vascular and bone outcomes in chronic kidney disease: a secondary post hoc analysis of IMPROVE-CKD.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and has been associated with abnormalities of mineral metabolism and vascular calcification. Vitamin D influences parathyroid hormone values and calcium and phosphate metabolism, and may play a role in vascular function and bone health. We aimed to test our hypothesis that vitamin D deficiency is associated with arterial stiffness, aortic calcification and lower bone mineral density (BMD) in patients with CKD. A cross-sectional analysis was performed using baseline data from the IMpact of Phosphate Reduction On Vascular Endpoints in CKD (IMPROVE-CKD) study cohort. Clinical and laboratory parameters were compared between those with and without vitamin D deficiency, defined as 25-hydroxyvitamin D (25(OH)D) <50 nmol/L. Univariable and multivariable linear regression analyses were performed to assess associations between serum 25(OH)D levels and pulse wave velocity (PWV), augmentation index (AIx), abdominal aortic calcification (measured by the Agatston score) and lumbar spine BMD. Baseline 25(OHD) values were available in 208 out of 278 IMPROVE-CKD study participants, with a mean value of 70.1 ± 30.7 nmol/L. Of these, 57 (27%) patients had vitamin D deficiency. Those with 25(OH)D deficiency were more likely to have diabetes (56% vs 38%), cardiovascular disease (54% vs 36%) and lower serum calcium (2.29 ± 0.13 vs 2.34 ± 0.13 mmol/L). On univariable and multivariable regression analyses, baseline 25(OH)D values were not associated with PWV, the AIx, Agatston score or BMD. Baseline 25(OH)D levels were not associated with intermediate markers of vascular function and BMD in patients with CKD stages 3b and 4.

Understanding Causes of Death in Patients With Acute Respiratory Distress Syndrome: A Narrative Review.

To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.

Interstitial Lung Disease as an Emerging Contributor to Mortality in Patients With Inflammatory Bowel Disease: A Population-Based Epidemiological Study.

We aim to investigate the contribution of interstitial lung disease (ILD) to mortality in patients with inflammatory bowel disease (IBD). We performed a comprehensive retrospective, population-based epidemiological study across the United States from 2001 to 2020, using the Wide-ranging Online Data for Epidemiologic Research database. Mortality data were classified according to the International Classification of Diseases, Tenth Revision , with the codes J84 for ILD, K50 for Crohn's disease, and K51 for ulcerative colitis. To discern patterns, age-adjusted mortality rates (AMR) were computed, stratified by sex, geographic census region, and racial/ethnic demographics. From 2001 to 2020, there were 57,967 reported deaths among patients with IBD with an AMR per million significantly rising from 10.989 in 2001-2005 to 11.443 in 2016-2020 ( P < 0.0001). ILD was a contributor to death in 1.19% (692/57,967) of these cases, with AMR rising from 0.092 to 0.143 per million ( P = 0.010). The percentage of ILD-related deaths in the IBD population increased from 1.02% to 1.30% over 2 decades. ILD was a more common cause of death in patients with Crohn's disease than with ulcerative colitis (54.6% vs 45.4%), with a significant increase for both conditions from 2001 to 2020 ( P < 0.05). An upward trend in ILD-related mortality was observed in both sexes ( P < 0.05) and within the White population ( P = 0.010). The observed increase in mortality rates due to ILD among patients with IBD is concerning and highlights a critical need for systematic ILD screening protocols within the IBD patient population to facilitate early detection and management.

Gene Signature for Predicting Metastasis in Prostate Cancer Using Primary Tumor Expression Profiles.

Metastasis is the leading cause of death in patients diagnosed with prostate cancer (PCa), underscoring the need for reliable prediction tools to forecast the risk of metastasis at an early stage. Here, we utilize the gene expression profiles of 1,000 unique primary tumors from patients with localized PCa to develop a gene signature capable of predicting metastasis. Our signature, termed Meta-Score, comprises forty-five genes that can accurately distinguish primary tumor with high propensity for metastasis across different patient cohorts. Notably, Meta-Score maintained its robust predictive performance in an internal validation cohort of comprising primary tumor samples from 239 patients. In addition to its robust predictive performance, Meta-Score demonstrates a significant association with survival, independent of Gleason score in two independent patient cohorts, underscoring its prognostic utility. Taken together, Meta-Score is a robust risk-stratification tool that can be leveraged to identify patients at high-risk of metastasis and unfavorable survival using their primary tumor gene expression profiles.

Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy, with metastasis being the leading cause of death in patients. Unfortunately, therapeutic options for metastatic OSCC remain limited. Peptidylarginine deiminases (PADI) are implicated in various tumorigenesis and metastasis processes across multiple cancers. However, the role of PADI2, a type of PADI, in OSCC is not well understood. This study aimed to explore the impact of PADI2 on epithelial-mesenchymal transition (EMT), angiogenesis, and OSCC metastasis. The effect of PADI2 on EMT was evaluated using cell lines by Western blot analysis with shRNA targeting PADI2. In addition, the selective PADI2 inhibitor AFM32a was used to assess the effect of PADI2 on cancer metastasis and angiogenesis in animal models. Our findings indicated that PADI2 expression correlated with EMT changes, and PADI2 knockdown reversed these changes, reducing cell proliferation, cell migration, and invasion. PADI2 inhibition also diminished tube formation in HUVECs and decreased secretion of angiogenesis-related chemokines CCL3, CCL5 and CCL20. In a mouse model, AFM32a markedly reduced lung metastasis and production of CCL3 and CCL5. Our in vitro and in vivo studies suggested inhibiting PADI2 could prevent OSCC metastasis by impeding EMT and angiogenesis via AKT/mTOR signaling pathway. These results highlight PADI2 as a potential therapeutic target for combating OSCC metastasis.

A nomogram to predict cancer-specific mortality in adult patients with malignant meningioma: a competing risk analysis

BackgroundComprehensive investigations of the prognosis factors and treatment strategies with adjustment of competing causes of death for patients with malignant meningioma (MM) is still lacking.Patient and methodThe surveillance, Epidemiology, and End Results (SEER) database were used to include adult patients with this rare disease between 2004 and 2018. The probability of MM-caused mortality (MMCM) and non-MM-caused mortality (non-MMCM) were presented by cumulative incidence function curves. Then, the association between variates with non-MMCM was evaluated by the cox proportional hazard model, and the prognostic factors of MMCM were identified by Fine-Gray competing risk regression model. Furthermore, a nomogram was developed to predict the 1-year, 2-year, and 5-year MMCM and the performance was tested by a time-dependent area under the receiver operating characteristic (ROC) curve and calibration.Result577 patients were included, with a median age of 62 (18–100) years old and a median overall survival time of 36 (0–176) months. The percentage of non-MMCM was 15.4% (n = 89) in the entire population and 21.7% (n = 54) in elderly patients. The multivariable Cox proportional hazard regression model revealed that older age and other tumor(s) before or after MM had an independently significant association with higher non-MMCM. After adjustment of competing causes of death, the multivariable Fine-gray regression model identified age group ≥ 65 year, tumor size > 5.3 cm, recurrent MM, and histologic type 9530/3 (Meningioma, malignant) had an independently significant association with higher MMCM. Compared with gross total (GTR) of tumor, subtotal resection of tumor (HR 1.66, 95%CI 1.08–2.56, P = 0.02), partial resection of lobe (HR 2.26, 95%CI 1.32–3.87, P = 0.003), and gross total resection of lobe (HR 1.69, 95%CI 1.12–2.51, P = 0.01) had an independently significant association with higher MMCM.ConclusionThe competing risk nomogram including age group, tumor size, initial status, histologic type, and extent of resection is discriminative and clinically useful. This study emphasized the importance of the GTR of tumor in the treatment of MM patients, which had a significantly lower incidence of MMCM compared with biopsy, STR of tumor, partial resection of lobe, and GTR of lobe.

Integrin-β1 aggravates paraquat-induced pulmonary fibrosis by activation of FAK/ ERK1/2 pathway depending on fibrotic ECM

BackgroundIrreversible pulmonary fibrosis induced by paraquat is the most prevalent cause of death in patients with paraquat poisoning. Pulmonary fibrosis is characterized by abnormal deposition of extracellular matrix (ECM). Currently, the role of fibrotic ECM microenvironment in paraquat-induced pulmonary fibrosis has not been established. MethodsRat pulmonary fibrosis model was induced by paraquat, ATN-161 (an integrin-β1 antagonist) was given to investigate their effect on Rat survival and pulmonary fibrosis. Lungs were decellularized to generate normal and fibrotic acellular ECM scaffolds using Triton and SDS. Fibroblasts were cocultured with ECM scaffolds to established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts. Then we explored the effect of fibrotic ECM microenvironment systematically promoting on integrin-β1/FAK/ERK1/2 pathway and established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts. ResultsAntagonism of integrin-β1 could alleviate paraquat-induced pulmonary fibrosis and ameliorate survival status of rats. Compared to normal ECM, fibrotic extracellular microenvironment promoted the differentiation of fibroblasts to myofibroblasts. Antagonism of integrin-β1 could also ameliorate the promotion of fibrotic extracellular microenvironment on differentiation of fibroblasts to myofibroblasts. Fibrotic ECM microenvironment promotes fibroblasts transforming into myofibroblasts through integrin-β1/FAK/ERK1/2 signaling pathway. Moreover, this phenomenon holds independent on exogenous integrin-β1. ConclusionsActivation of integrin-β1/FAK/ERK1/2 pathway aggravates paraquat-induced pulmonary fibrosis depend on fibrotic ECM and integrin-β1 may be a prospective therapeutic target for paraquat-induced pulmonary fibrosis in the future.

Treatment of interstitial lung disease in systemic sclerosis: guidelines and new clinical trial results.

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The American College of Rheumatology (ACR), in conjunction with the American College of Chest Physicians (CHEST), recently published clinical practice guidelines for the treatment of adults with systemic autoimmune rheumatic disease-associated ILD, including SSc-ILD. Herein, we summarize evidence from randomized trials evaluating the safety and efficacy of pharmacologic therapies for the treatment of SSc-ILD. In this review, we present findings from recent randomized controlled trials in SSc-ILD. The pharmacologic therapies discussed include immunosuppressive medications (mycophenolate, cyclophosphamide, rituximab, and tocilizumab) and antifibrotic medications (nintedanib and pirfenidone). Randomized trials provide an evidence base for the SSc-ILD treatment recommendations put forth in the ACR/CHEST Guidelines for the treatment of ILD in people with systemic autoimmune rheumatic diseases. These guidelines will help inform clinical practice and highlight areas in which further research is needed.

Prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus: a retrospective study

BackgroundSystemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection.MethodsWe retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival.ResultsThere were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p < 0.01), respiratory failure, intensive care unit admission, non-invasive ventilation, and hospital-acquired pneumonia (p < 0.05). The non-survival group showed a higher neutrophil percentage, lactate dehydrogenase, D-dimer (p < 0.001), urea, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (p < 0.05). It also had lower minimal albumin, hemoglobin (p < 0.001), immunoglobulin G, complement 3, peripheral lymphocyte count, platelet, NK cell count, and CD4+ T-cell count (p < 0.05). Multivariate analysis indicated that hyperglycemia or diabetes mellitus (HR = 4.25, p < 0.01, 95% CI: 1.51–11.97), thrombocytopenia (HR = 4.22, p < 0.01, 95% CI: 1.63–10.91) and lower complement 3 (C3) (HR = 4.06, p < 0.01, 95% CI: 1.60-10.33) were independent risk factors for the survival of SLE-PJP patients.ConclusionsThe mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors.

Overexpression of microRNA-611 inhibits TGF-β-induced epithelial-mesenchymal transition and migration in lung cancer cells through MAPKAP1

Metastasis is a major cause of death in patients with lung cancer (LC). microRNA-611 (miR-611), a miRNA, has been little studied in cancer. Here, we aimed to further elucidate the roles of miR-611 in epithelial-mesenchymal transition (EMT) and migration induced by transforming growth factor-β (TGF-β) in LC cells and the possible underlying mechanisms. miR-611 and MAPKAP1 expression was first identified in LC tissues from metastatic and nonmetastatic patients, and their expression was associated with overall survival. Gain- and loss-of-function experiments were performed to verify the impacts of miR-611 and MAPKAP1 on pAKT expression, EMT, and migration in LC cells treated with TGF-β. The interaction between miR-611 and MAPKAP1 was also determined with a luciferase reporter assay. In our study, miR-611 was expressed at low levels, and MAPKAP1 was highly expressed in LC tissues, which was associated with metastasis and short overall survival. Functionally, miR-611 inhibition or MAPKAP1 overexpression accelerated EMT and migration and upregulated pAKT in TGF-β-treated A549 and H1299 cells; miR-611 overexpression or MAPKAP1 silencing exerted the opposite effects as miR-611 inhibition or MAPKAP1 overexpression. Mechanistically, miR-611 could target and downregulate MAPKAP1. MAPKAP1 expression was also negatively correlated with miR-611 expression in LC tissues. In addition, miR-611 overexpression reduced the EMT and migration of TGF-β-treated A549 and H1299 cells by targeting MAPKAP1. In conclusion, miR-611 overexpression attenuated EMT and migration by targeting MAPKAP1 in TGF-β-induced LC cells, indicating that miR-611 is a biological target for LC treatment.

RGS10 deficiency facilitates distant metastasis by inducing epithelial–mesenchymal transition in breast cancer

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial–mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and MIR539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer.

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial-mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and MIR539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

A Novel Rational Medicine Use System Based on Domain Knowledge Graph

Medication errors, which could often be detected in advance, are a significant cause of patient deaths each year, highlighting the critical importance of medication safety. The rapid advancement of data analysis technologies has made intelligent medication assistance applications possible, and these applications rely heavily on medical knowledge graphs. However, current knowledge graph construction techniques are predominantly focused on general domains, leaving a gap in specialized fields, particularly in the medical domain for medication assistance. The specialized nature of medical knowledge and the distinct distribution of vocabulary between general and biomedical texts pose challenges. Applying general natural language processing techniques directly to the medical domain often results in lower accuracy due to the inadequate utilization of contextual semantics and entity information. To address these issues and enhance knowledge graph production, this paper proposes an optimized model for named entity recognition and relationship extraction in the Chinese medical domain. Key innovations include utilizing Medical Bidirectional Encoder Representations from Transformers (MCBERT) for character-level embeddings pre-trained on Chinese biomedical corpora, employing Bi-directional Gated Recurrent Unit (BiGRU) networks for extracting enriched contextual features, integrating a Conditional Random Field (CRF) layer for optimal label sequence output, using the Piecewise Convolutional Neural Network (PCNN) to capture comprehensive semantic information and fusing it with entity features for better classification accuracy, and implementing a microservices architecture for the medication assistance review system. These enhancements significantly improve the accuracy of entity relationship classification in Chinese medical texts. The model achieved good performance in recognizing most entity types, with an accuracy of 88.3%, a recall rate of 85.8%, and an F1 score of 87.0%. In the relationship extraction stage, the accuracy reached 85.7%, the recall rate 82.5%, and the F1 score 84.0%.