Design and practice of blended teaching of internal medicine nursing based on O-AMAS effective teaching model.

BACKGROUND: Self-directed learning (SDL) ability is the basis for cultivating nursing students' ability to find and solve problems, lifelong learning, and providing high-quality nursing talents for healthcare. The O-AMAS (Objective, Activation, Multi-learning, Assessment, Summary) model adheres to the teaching philosophy of student-centered, result-oriented, combines the advantages of online and offline teaching, enriching teaching resources and learning channels, diversifying teaching and evaluation methods, and emphasizing integrating and applying knowledge conducive to improving students' SDL ability and achieving teaching objectives. This study explored the course design, practical, and application effects under the O-AMAS effective teaching model in internal medicine nursing to provide a basis and reference for combining effective teaching models with blended teaching in future nursing courses. METHODS: This study is a self-controlled before-after trial. The participants were 76 nursing undergraduates from Hunan Normal University. This study utilizes the O-AMAS effective teaching model to design internal medicine nursing courses and implement blended online and offline teaching. Main links: The overall course design and application are student-centered, after clarifying macro and micro multi-dimensional learning objectives, with online and offline blended teaching environments activated students' learning behavior and diversified teachers' teaching activities, then based on instant and dynamic provide effective feedback; finally, students take the initiate to make a brief and potent summary under the teacher guidance. After the course, a unified assessment of the learning effect of nursing students was conducted, including the evaluation of the SDL ability of nursing students, a final comprehensive evaluation grade, and a teaching satisfaction survey. RESULTS: The nursing students' SDL ability scores are higher than before teaching, and the results were statistically significant (P < 0.05). The final average comprehensive evaluation grade of nursing students was 78.38 ± 7.12. More than 96% of the students are satisfied with this course. CONCLUSION: Applying for internal medicine nursing blended teaching integrated with the O-AMAS effective teaching model is conducive to improving nursing students' SDL ability, academic grades, and teaching satisfaction.

Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators.

BACKGROUND: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. METHODS: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (ß2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. RESULTS: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and ß2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). CONCLUSIONS: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function.

Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators

Background: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. Methods: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (β2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. Results: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and β2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). Conclusions: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function (AU)

A Rare Case of Abnormal Hemoglobin Variant Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu-Pro]: A First Report in the Chinese Population.

A 6-month-old female infant presented with unexplained hemolytic anemia, showing no abnormalities by capillary electrophoresis and genetic testing for α- and ß-thalassemia mutations that are commonly seen in the Chinese population. A rare Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu- Pro] variant was identified by next-generation sequencing (NGS) and verified by Sanger sequencing. Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu- Pro] is not easily detectable because it is extremely unstable, and the correct diagnosis is usually made via DNA sequencing. This is the first report of this variant in the Chinese population.

CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).

[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.

Carbon storage capacity of Castanopsis hystrix plantations at different stand-ages in South China.

The establishment of forest plantations is an excellent silvicultural alternative to improve atmospheric carbon (C) sequestration for climate change mitigation. In recent years, the importance of forest growth and C dynamics at different stand ages have drawn huge attention for investigation. To evaluate the impacts of different stand ages on the C storage capacity of Castanopsis hystrix plantations ecosystems, we measured biomass and C content in trees, understory, litter, and soil components from field measurements at different stand ages, i.e., 6-, 10-, 15-, 25-, and 34-year-old stands. Results showed that the C stocks in trees, understory vegetation, litter, soil and the whole ecosystem increased steadily with stand age. C. hystrix C storage capacity in the 6-, 10-, 15-, 25-, and 34-year-old stands were 29.17, 56.18, 85.60, 132.19 and 157.79 Mg ha-1, respectively, while the total ecosystem C storage capacity was 68.11, 106.11, 136.13, 187.34 and 226.14 Mg ha-1, respectively. Meanwhile, the C sequestration rate in the 6-10, 10-15, 15-25 and 25-35-year-old stands were 675.28, 588.35, 465.97 and 284.39 g m2 year-1, respectively. Similarly, total biomass of trees, understory, and litter increased with stand age. Our study indicated that C. hystrix plantations are still developing in the area, since live biomass and soil C continue to accumulate despite reduced C sequestration rates. The information provided here highlight the C stock and C sequestration rates of C. hystrix at different stand ages, providing baseline information on the C dynamics of young and older stand of C. hystrix in this region; Hence, such knowledge could be useful for designing more realistic policies to mitigate climate change, such as programs to maintain continuous forest growth.

Clinical effects of combined treatment of traditional Chinese medicine and western medicine for viral hepatitis B cirrhosis and the effects on serum miR-122, miR-200a.

The aim is to explore the clinical effects of combined treatment of Traditional Chinese Medicine (TCM) and western medicine in viral hepatitis B cirrhosis and the effects on microRNA (miR)-122 and miR-200a. 116 patients with chronic hepatitis B cirrhosis were admitted to our hospital. Real-time fluorescent quantitative PCR (qPCR) was employed to reveal the level of serum miR-122 and miR-200a in the three groups. The clinical effects of the two groups were compared, including alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL) and alpha fetoprotein (AFP) indexes, coagulation function indexes, liver elasticity value and the main therapeutic effects. After treatment, the ALT, AST, TBIL and AFP indexes significantly decreased in both groups, which were much lower in the western medicine (WM) + TCM Group. The levels of albumin (ALB) all increased, and the increase was more significant in the WM + TCM Group. The prothrombin time (PT) was down-regulated while the prothrombin activity (PTA) was up-regulated in both groups. Both groups showed a decrease in liver elasticity after treatment, which was more obvious in the WM + TCM Group. The incidence of primary peritonitis, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding and electrolyte disturbance in the WM + TCM Group was significantly lower than those in the WM Group. The combination of Chinese and western medicine in the treatment of cirrhosis can reduce the occurrence of complications, improve the clinical symptoms and improve the clinical effects effectively, which is worthy of further study and clinical popularization. Viral hepatitis B, Liver cirrhosis, Combination of TCM and Western medicine, miR-122, miR-200a.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Predictive role of red blood cell distribution width to platelet ratio combined mean platelet volume in patients with microscopic polyangiitis.

BACKGROUND: We aimed to investigate the role of red blood cell distribution width (RDW)-to-platelet ratio (RPR) and mean platelet volume (MPV) in evaluating the disease activity of microscopic polyangiitis (MPA). MATERIALS AND METHODS: A total of 73 newly diagnosed MPA patients and 57 healthy controls were enrolled in this study. The hematologic and biochemical indexes of two groups were assessed. The RPR was calculated as the ratio of RDW and platelet counts, and Birmingham Vasculitis Activity Score (BVAS) was used to evaluate the disease activity. RESULTS: Compared with the healthy controls, RPR and RDW were significantly increased, and MPV was significantly decreased in MPA patients. In the MPA group, RPR was positively correlated with BVAS (p = 0.032), but negatively correlated with lymphocyte, hemoglobin, and complement 3 (all p < 0.05). MPV was negatively correlated with white blood cell (p = 0.045). Patients with BVAS > 15 had significantly higher RPR than patients with BVAS ≤ 15 (p = 0.011). A cut-off level of 0.066 for RPR had 47.9% sensitivity and 90.4% specificity in predicting MPA, and the combination of RPR and MPV had 75.3% sensitivity and 78.9% specificity in differentiating MPA patients from healthy controls. CONCLUSION: The study suggests that RPR may be a potential marker of diagnosis and disease activity in newly diagnosed MPA patients. Additionally, a higher predictive value in monitoring and evaluation of MPA was found when RPR and MPV were combined.

Association between loneliness and its components and cognitive function among older Chinese adults living in nursing homes: A mediation of depressive symptoms, anxiety symptoms, and sleep disturbances.

OBJECTIVE: This study aimed to investigate the associations between loneliness and its components and cognitive function among older Chinese adults living in nursing homes and to test whether depressive symptoms, anxiety symptoms, and sleep disturbances mediate these associations. METHODS: The sample comprised 228 Chinese individuals aged ≥ 65 years living in nursing homes who were free of dementia and psychiatric or serious somatic diseases. Loneliness was evaluated using the UCLA Loneliness Scale. Global cognitive function was assessed using the Beijing version of the Montreal Cognitive Assessment. Multivariable linear regression analyses were performed to examine the associations between loneliness and its components and global cognitive function. A mediation analysis was used to test the potential mediating effects of depressive symptoms, anxiety symptoms, and sleep disturbances. RESULTS: The mean (SD) age of the participants was 80.8 (6.3) years, and 58.3% were women. Compared with the lowest quartile of loneliness degree, the multivariable-adjusted beta coefficient (95% confidence interval [95% CI]) for the highest quartile was -1.32 (-2.61 to -0.02) (P for trend = 0.03). Loneliness components, personal feelings of isolation and the lack of relational connectedness but not the lack of collective connectedness, were also inversely associated with cognitive function. Significant indirect effects on cognitive function were observed for loneliness and its two components (personal feelings of isolation and the lack of relational connectedness) in mediating pathways via depressive symptoms, anxiety symptoms, and sleep disturbances (all p < 0.05). CONCLUSIONS: A higher degree of loneliness and its two components, personal feelings of isolation and the lack of relational connectedness, are associated with worse cognitive function among Chinese residents in nursing homes. Depressive symptoms, anxiety symptoms, and sleep disturbances may at least partially mediate these associations.

PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via the TLR4/MyD88/NF-κB Signaling Pathway.

PAUF, a tumor-promoting protein secreted by cancer cells, exerts paracrine effects on immune cells through TLR4 receptors expressed on immune cell surfaces. This study aimed to investigate if PAUF elicits autocrine effects on pancreatic cancer (PC) cells through TLR4, a receptor that is overexpressed on PC cells. In this study, TLR4 expression was detected in PC cells only, but not normal pancreatic cells. The migration of TLR4 high-expressing PC cells (i.e., BxPC-3) was reduced by a selective TLR4 inhibitor, in a dose-dependent manner. Using TLR4 overexpressed and knockout PC cell lines, we observed direct PAUF-TLR4 binding on the PC cell surfaces, and that PAUF-induced cancer migration may be mediated exclusively through the TLR4 receptor. Further experiments showed that PAUF signaling was passed down through the TLR4/MyD88 pathway without the involvement of the TLR4/TRIF pathway. TLR4 knockout also downregulated PC membrane PD-L1 expression, which was not influenced by PAUF. To the best of our knowledge, TLR4 is the first receptor identified on cancer cells that mediates PAUF's migration-promoting effect. The results of this study enhanced our understanding of the mechanism of PAUF-induced tumor-promoting effects and suggests that TLR4 expression on cancer cells may be an important biomarker for anti-PAUF treatment.

The Role of the Monocyte-to-Lymphocyte Ratio in Acute Ischemic Stroke Patients with Acute Kidney Injury.

Objective: The objective of the study was to determine if acute kidney injury (AKI) in patients with acute ischemic stroke was associated with the monocyte-to-lymphocyte ratio (MLR) assessed upon admission to the neurology intensive care unit (NICU) (AIS). We also looked into the MLR's function in predicting hospital mortality in AIS patients. Methods: This retrospective analysis included 595 adult patients with AIS who were hospitalized to the NICU of the First Affiliated Hospital of South China between January 2017 and December 2019. Clinical signs and imaging studies were used to diagnose AIS. KDIGO criteria were used to define AKI. The ratio of monocytes to lymphocytes was used to compute MLR, the ratio of neutrophils to lymphocytes was used to calculate NLR, and the ratio of platelets to lymphocytes was used to calculate PLR. Result: 361 males and 234 women between the ages of 66.27 ± 12.05 years took part in the study. The individuals' MLR was 0.4729 ± 0.3461 and their neutrophil-to-lymphocyte ratio (NLR) was 8.18 ± 5.45. There were notable disparities in MLR and NLR between the AKI and non-AKI groups (p < 0.001). The link between MLR and AKI development risk was enhanced after adjustment, with respective cutoff values of 0.4581 and 9.26. For the MLR-based prediction of AKI incidence, the areas under the receiver-operating characteristic curves (AUCs) were 0.711 (95% CI: 0.663-0.758). And NLR-based prediction of AKI incidence the AUCs was (95% CI: 0.742-0826). Additionally, MLR was associated with a higher rate of in-hospital mortality (2.825, 95% confidence interval: 1.058, 7.545), whereas NLR was associated with a risk of in-hospital mortality of 1.085. (95 percent CI: 1.022, 1.151). An AUC of 0.745 (95% CI: 0.601-0.889, p = 0.026) was obtained for in-hospital mortality based on the MLR, whereas an AUC of 0.724 (95% CI: 0.531-0.916, p = 0.042) was obtained for in-hospital mortality based on the NLR. Conclusion: MLR and neutrophil-to-lymphocyte ratio (NLR) were associated with a higher risk of AKI and in-hospital death in AIS patients.

The Monocyte-to-Lymphocyte Ratio Predicts Acute Kidney Injury After Acute Hemorrhagic Stroke.

Objectives: Acute kidney injury (AKI) is a serious complication of acute hemorrhagic stroke (AHS). Early detection and early treatment are crucial for patients with AKI. We conducted a study to analyze the role of the monocyte-to-lymphocyte ratio (MLR) in predicting the development of AKI after AHS. Methods: This retrospective observational study enrolled all subjects with AHS who attended the neurosurgical intensive care unit (NSICU) at the First Affiliated University of South China between 2018 and 2021. Patient demographics, laboratory data, treatment details, and clinical outcomes were recorded. Results: Of the 771 enrolled patients, 180 (23.3%) patients developed AKI. Compared to patients without AKI, those with AKI had a higher MLR and the neutrophil-lymphocyte ratio (NLR) at admission (P < 0.001). The MLR and the NLR at admission were associated with an increased AKI risk, with odds ratios (ORs) of 8.27 (95% CI: 4.23, 16.17, p < 0.001) and 1.17 (95% CI: 1.12, 1.22, p < 0.001), respectively. The receiver operating characteristic curve (ROC) analysis was conducted to analyze the ability of the MLR and NLR to predict AKI, and the areas under the curve (AUCs) of the MLR and the NLR were 0.73 (95% CI: 0.69, 0.77, p < 0.001) and 0.67 (95% CI: 0.62, 0.72, p < 0.001), with optimal cutoff values of 0.5556 and 11.65, respectively. The MLR and the NLR at admission were associated with an increased in-hospital mortality risk, with ORs of 3.13 (95% CI: 1.08, 9.04) and 1.07 (95% CI: 1.00, 1.14), respectively. The AUCs of the MLR and the NLR for predicting in-hospital mortality were 0.62 (95% CI: 0.54, 0.71, p = 0.004) and 0.52 (95% CI: 0.43, 0.62, p = 0.568), respectively. The optimal cutoff value for the MLR was 0.7059, with a sensitivity of 51% and a specificity of 73.3%. Conclusions: MLR and NLR measurements in patients with AHS at admission could be valuable tools for identifying patients at high risk of early AKI. The MLR was positively associated with in-hospital mortality and the NLR showed a weak ability for the prediction of in-hospital mortality.

Monocyte-to-lymphocyte ratio: a potential novel predictor for acute kidney injury in the intensive care unit.

Monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) are considered as surrogate inflammatory indexes. Previous studies indicated that NLR was associated with the development of septic acute kidney injury (AKI). The objective of the present study was to explore the value of MLR and NLR in the occurrence of AKI in intensive care unit (ICU) patients. The clinical details of adult patients (n = 1500) who were admitted to the ICU from January 2016 to December 2019 were retrospectively examined. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. The development of AKI was the main outcome, and the secondary outcome was in-hospital mortality. Overall, 615 (41%) patients were diagnosed with AKI. Both MLR and NLR were positively correlated with AKI incidence (p < 0.001). Multivariate logistic regression analysis suggested that the risk value of MLR for the occurrence of AKI was nearly three-fold higher than NLR (OR = 3.904, 95% CI: 1.623‒9.391 vs. OR = 1.161, 95% CI: 1.135‒1.187, p < 0.001). The areas under the receiver operating characteristic curve (AUC) for MLR and NLR in the prediction of AKI incidence were 0.899 (95% CI: 0.881‒0.917) and 0.780 (95% CI: 0.755‒0.804) (all p < 0.001), with cutoff values of 0.693 and 12.4. However, the AUC of MLR and NLR in the prediction of in-hospital mortality was 0.583 (95% CI: 0.546‒0.620, p < 0.001) and 0.564 (95% CI: 0.528‒0.601, p = 0.001). MLR, an inexpensive and widely available parameter, is a reliable biomarker in predicting the occurrence of AKI in ICU patients.

PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer.

Pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in tumor growth, metastasis, and immune evasion in the pancreatic tumor microenvironment, and recent studies suggest an association between PAUF expression and poor prognosis in ovarian cancer patients. The current study aimed 1) to characterize the potential tumor-promoting role of PAUF in ovarian cancer, using in vitro and in vivo models, including a PAUF-knockout OVCAR-5 cell line, and 2) to explore the potential therapeutic effects of an anti-PAUF antibody for ovarian cancer. Recombinant PAUF significantly increased tumor metastatic capacity (migration, invasion, and adhesion) in all the ovarian cancer cell lines tested, except for the OVCAR-5 cell line which expresses PAUF at a much higher level than the other cells. PAUF-knockout in the OVCAR-5 cell line led to apparently delayed tumor growth in vitro and in vivo. Furthermore, the administration of an anti-PAUF antibody exhibited notable sensitizing and synchronizing effects on docetaxel in mice bearing the OVCAR-5 xenograft tumors. Taken together, this study shows that the expression level of PAUF is an independent factor determining malignant behaviors of ovarian cancer and, for the first time, it suggests that PAUF may be a promising therapeutic target for high PAUF-expressing ovarian cancer.

Non-Invasive Prediction of Survival Time of Midline Glioma Patients Using Machine Learning on Multiparametric MRI Radiomics Features.

Objectives: To explore the feasibility of predicting overall survival (OS) of patients with midline glioma using multi-parameter magnetic resonance imaging (MRI) features. Methods: Data of 84 patients with midline gliomas were retrospectively collected, including 40 patients with OS > 12 months (28 cases were adults, 14 cases were H3 K27M-mutation) and 44 patients with OS < 12 months (29 cases were adults, 31 cases were H3 K27M-mutation). Features were extracted from the largest slice of tumors, which were manually segmented on T2-weighted (T2w), T2 fluid-attenuated inversion recovery (T2 FLAIR), and contrast-enhanced T1-weighted (T1c) images. Data were randomly divided into training (70%) and test cohorts (30%) and normalized and standardized using Z-scores. Feature dimensionality reduction was performed using the variance method and maximum relevance and minimum redundancy (mRMR) algorithm. We used the logistic regression algorithm to construct three models for T2w, T2 FLAIR, and T1c images as well as one combined model. The test cohort was used to evaluate the models, and receiver operating characteristic (ROC) curves, areas under the curve (AUCs), sensitivity, specificity, and accuracy were calculated. The nomogram of the combined model was built and evaluated using a calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical application value of the four models. Results: A total of 1,316 features were extracted from T2w, T2 FLAIR, and T1c images, respectively. And then the best non-redundant features were selected from the extracted features using the variance method and mRMR. Finally, five features were extracted each from T2w, T2 FLAIR, and T1c images, and 12 features were extracted for the combined model. Four models were established using the optimal features. In the test cohort, the combined model performed the best out of all models. The AUCs of the T2w, T2 FLAIR, T1c, and combined models were 0.73, 0.78, 0.74, and 0.87, respectively, and accuracies were 0.72, 0.76, 0.72, and 0.84, respectively. The ROC curves and DCA showed that the combined model had the highest efficiency and most favorable clinical benefits. Conclusion: The combined radiomics model based on multi-parameter MRI features provided a reliable non-invasive method for the prognostic prediction of midline gliomas.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4. / MiR-133b通过抑制SOX4è°ƒèŠ‚è†€èƒ±ç™Œç»†èƒžçš„å¢žæ®–ã€å ‹éš†å½¢æˆå’Œä¾µè¢­èƒ½åŠ›.

OBJECTIVES: Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells. METHODS: The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay. RESULTS: Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells. CONCLUSIONS: The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

The clinical relevance of epithelial-mesenchymal transition and its correlations with tumorigenic immune infiltrates in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a cancer with extremely high mortality. Epithelial-mesenchymal transition (EMT) may play an important role in the occurrence, invasion and prognosis of HCC; however, its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC. We first proposed a quantitative metric of EMT activity, the EMT score. After applying this metric to 20 datasets from the Integrative Molecular Database of Hepatocellular Carcinoma, the Cancer Genome Atlas, and the Gene Expression Omnibus, we explored the ability of the EMT score to stratify across sample types. We then applied the EMT score for survival analysis and to differentiate patients with/without vascular invasion to test its prognostic value. We also collected and calculated data on the abundance of immune cells and immune cell markers in HCC and investigated their correlations with EMT scores. Finally, we synthesized and analyzed 20 datasets and constructed an EMT-gene-immune linkage network. The results showed higher EMT scores in HCC samples than in cirrhotic and normal livers. The cases with higher EMT scores also showed poorer performance in terms of prognostic factors such as vascular invasion and overall survival time. Our research demonstrated a broad correlation between EMT and the tumor immune microenvironment, and we uncovered multiple potential linkers associated with both EMT and immunity. Studying EMT has clinical relevance and high diagnostic and prognostic value for HCC.

MicroRNA miR-124-3p suppresses proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma via ARRDC1 (arrestin domain containing 1).

Hepatocellular carcinoma (HCC) is responsible for high morbidity and mortality worldwide. Increasing evidence suggests that microRNAs intensively participate in HCC development and progression. In the current study, we aimed to explore the impact of miR-124-3p in the proliferation and epithelial-mesenchymal transition (EMT) of HCC. The RT-qPCR assay was employed to determine miR-124-3p expression in human HCC specimens and cell lines. Luciferase assay was used to validate the miR-124-3p target gene. Western Blot and RT-qPCR were performed to study the effects of miR-124-3p modulation on ARRDC1 (Arrestin Domain Containing 1) mRNA and protein expressions. MTT assay, wound healing assay, EdU assay, and Transwell assay were utilized to verify the impact of miR-144-3p modulation on HCC proliferation and EMT via ARRDC1. We found that MiR-124-3p expression downregulates in HCC. Overexpression of miR-124-3p reduced the HCC cell proliferation and EMT. Meanwhile, we determined that the expression of ARRDC1 is increased in HCC, and miR-124-3p directly binds the 3'UTR of ARRDC1 and inhibits its expression at mRNA and protein level, suggesting that miR-124-3p was capable of negatively modulating ARRDC1. Besides, cotransfection of ARRDC1-overexpression plasmid and miR-124-3p mimics increased the cell proliferation and EMT as compared to miR-124-3p mimics. Our study concluded that miR-124-3p directly binds the 3'UTR of ARRDC1 and exerts anti-tumorous effects by inhibiting the HCC proliferation and EMT. Therefore, miR-124-3p/ARRDC1 axis may serve as a novel therapeutic target to inhibit HCC growth and metastasis.

Hypothermia therapy for the treatment of acute myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: In patients with acute myocardial infarction (AMI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We performed a protocol for systematic review and meta-analysis to investigate the effect of systemic therapeutic hypothermia in patients with AMI receiving PCI. METHODS: This study will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database. The search terms were hypothermia, cooling, myocardial infarction, myocardial ischemia and acute coronary syndrome. Quality assessment of the included studies was evaluated using the Cochrane risk of bias assessment tool. Statistical analyses were performed using RevMan 5.4 software. RESULTS: The findings of this study will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide evidence to determine whether hypothermia therapy is an effective and safe intervention for patients with AMI receiving PCI.Registration number: 10.17605/OSF.IO/9XJSB.