Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

Introduction: This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. Methods: We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. Results: The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Conclusion: Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Kinetic nitrogen isotope effects of 18 amino acids degradation during burning processes.

Understanding the nitrogen isotopic variations of individual amino acids (AAs) is essential for utilizing the nitrogen isotope values of individual amino acids (δ15N-AA) as source indicators to identify proteinaceous matter originating from biomass combustion processes. However, the nitrogen isotope effects (ε) associated with the degradation of individual amino acids during combustion processes have not been previously explored. In this study, we measured the nitrogen isotope values of residual free amino acids -following a series of controlled combustion experiments at temperatures of 160-240 °C and durations of 2 min to 8 h, as described in Part 1. δ15N values of proline, aspartate, alanine, valine, glycine, leucine, and isoleucine are more positive than their initial δ15N values after prolonged combustion. Variations in δ15N values of the most AAs conform to the Rayleigh fractionation during combustion and their nitrogen isotope effects (ε) are greatly impacted by their respective combustion degradation pathways. This is the first time the ε values associated with the degradation pathways of AAs during combustion have been characterized. Only the ε values associated with Pathway 1 (dehydration to form dipeptide) and 2 (simultaneous deamination and decarboxylation) are found to be significant and temperature-dependent, ranging from + 2.9 to 6.4‰ and + 0.9‰ to + 3.8‰, respectively. Conversely, ε values associated with other pathways are minor. This improves the current understanding on the degradation mechanisms of protein nitrogen during biomass burning.

Radiofrequency ablation versus microwave ablation for hepatocellular carcinoma with cirrhosis: a propensity score analysis.

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used percutaneous ablation techniques for the treatment of liver cancer. The aim of our study was to identify the ablation method that had a better long-term prognosis for patients with cirrhotic hepatocellular carcinoma (HCC). Methods: This retrospective study consisted of HCC patients with cirrhosis who underwent RFA and MWA between January 2014 to December 2021 at Beijing You'an Hospital. Patients were divided into two groups according to the therapeutic approaches: the RFA group and the MWA group. The prognosis was compared before and after 1:1 propensity score matching (PSM). Results: A total of 800 HCC patients with cirrhosis who received interventional treatment from January 2014 to December 2021 were prospectively enrolled. After PSM, there were 268 patients in each of the RFA and MWA groups. The statistically significant differences in recurrence-free survival (RFS) and overall survival (OS) between RFA and MWA groups can be observed, both before and after PSM. Besides, 1-, 3-year RFS, and 5-year OS rates were higher in those the RFA group than in the MWA group. Age, tumor size, gamma glutamyl transferase (GGT), and hepatitis B surface antigen (HBsAg) were independent risk factors for RFS. Child-Pugh, lymphocyte (Lym), GGT, and treatment modality were independent risk factors for OS. Conclusions: For patients with HCC associated with cirrhosis, RFA can provide a better prognosis than MWA, with lower recurrence and mortality rate.

A Novel Nomogram to Predict Prognosis in Elderly Early-Stage Hepatocellular Carcinoma Patients After Ablation Therapy.

Purpose: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Early diagnosis is crucial for improving prognosis. Elderly HCC patients often have underlying liver diseases such as chronic hepatitis and cirrhosis, leading to impaired liver function and suboptimal liver reserve. Radiofrequency ablation (RFA) has rapidly become one of the most important methods for treating early-stage hepatocellular carcinoma (EHCC) due to its advantages, including minimal trauma, short operation time, less intraoperative bleeding, quick postoperative recovery, cost-effectiveness, and few postoperative-complications. However, the prognostic model for early recurrence after local ablation in elderly EHCC patients has not been widely evaluated. We have developed a prognostic model for the recurrence of local RFA in elderly EHCC patients. This is expected to provide a new early warning system for preventing early recurrence in elderly EHCC patients, prolonging patient's life, and improving overall quality of life. Methods: In this study, we included 661 EHCC patients who underwent local ablation, dividing them into a Primary cohort and a Validation cohort in a 7:3 ratio. We characterized the cohorts and utilized the primary cohort to develop a prognostic nomogram model for recurrence after local ablation in elderly EHCC patients. Additionally, the validation cohort was used to assess the potential of the nomogram as a non-invasive biomarker for post-ablation recurrence in EHCC. Results: The user-friendly nomogram incorporates common clinical variables including gender, BCLC stage, tumor number, tumor size, red blood cell (RBC), gamma-glutamyl transferase (GGT), and prothrombin time activity (PTA). The nomogram constructed using the identified seven variables exhibits robust discriminatory capabilities, favorable predictive performance, and noteworthy clinical utility. Conclusion: We developed a user-friendly nomogram based on the BCLC stage classification, which may provide prognostic assessments for elderly EHCC patients at 1, 3, and 5 years post-RFA.

Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis.

Introduction: This study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram. Methods: Data from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You'an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves. Results: The nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell's concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703-0.785) and 0.724 (95% CI: 0.644-0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram's reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram's efficacy in distinguishing varying recurrence risks. Conclusion: This study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.

GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation.

BACKGROUND: Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC. METHODS: This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility. CONCLUSION: This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

Machine Learning-Based Nomogram for Predicting Overall Survival in Elderly Patients with Cirrhotic Hepatocellular Carcinoma Undergoing Ablation Therapy.

Purpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS). Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell's concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes. Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification. Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.

Inhibition of keloid fibroblast proliferation by artesunate is mediated by targeting the IRE1α/XBP1 signaling pathway and decreasing TGF-ß1.

BACKGROUND: Keloid is a benign hyperplastic dermatosis with high recurrence rate and complex pathogenesis. There is no universally effective treatment yet. New therapies and elucidation of pathogenesis are urgently required. AIMS: To explore the function of IRE1α/XBP1 in keloid fibroblasts and to investigate the potential mechanism of artesunate in inhibiting keloid hyperplasia. METHODS: Human keloid fibroblasts (KFs) were cultured, and the expressions of XBP1 and TGF-ß1 were detected by immunohistochemistry. The expression of IRE1 was interfered with through cell transfection and the effects of IRE1 interference on cell proliferation and the cell cycle were assessed using MTS, colony formation assays, and flow cytometry. Detection of the expressions of XBP1 and TGF-ß1 by qRT-PCR and Western blot. Then artesunate was applied to a subset of the cells, and its effects on cell viability and the expression of related proteins using the same methods. RESULTS: The IRE1α/XBP1 pathway was activated in KFs. Knocking out the gene IRE1α can inhibit the expression of TGF-ß1, in addition, the cell viability and cell cycle progression of KFs were also significantly affected. After artesunate treatment, there was a remarkable reduction in cell proliferation. Meanwhile, the cell cycle of KFs treated with artesunate was blocked in G1 phase.After upregulating the expression of IRE1α and treating KFs with artesunate, both cell cycle and proliferation showed inhibitory effects, and related proteins also exhibited suppressed expression. CONCLUSIONS: The IRE1α/XBP1 pathway is activated in keloid, and inhibiting the expression of this pathway can affect the cell proliferation activity. In addition, artesunate also has a significant effect on fibroblast proliferation, and the IRE1α/XBP1 pathway may participate in this process. These findings suggest that IRE1α/XBP1 signal pathway may be a potential target for scar treatment, and artesunate could also be a powerful candidate for keloid treatment.

Development and Validation of a Nomogram to Predict the Recurrence of HCC Patients Undergoing CECT After Ablation.

Purpose: We first aimed to compare the prognostic difference between the application of Contrast-enhanced computed tomography (CECT) and Non-enhanced computed tomography (NECT) in hepatocellular carcinoma(HCC) patients with early-stage immediately after ablation. We secondly propose to explore the risk factors for recurrence in patients undergoing CECT, and then develop a nomogram. Patients and Methods: Clinical data were collected from 711 patients who received TACE combined with ablation from January 1, 2015, to December 31, 2022, at Beijing Youan Hospital. According to the imaging methods applied after ablation, patients were categorized into the CECT group and the NECT group and then were compared by Kaplan-Meier (KM) curves. Lasso regression is used to screen risk factors for recurrence and the nomogram was plotted. Finally, discrimination, calibration plot, and decision curve analysis (DCA) were used to measure the performance of the nomogram. Results: The KM curve indicates that recurrence-free survival (RFS) was longer in the CECT group than in the NECT group (HR =0.759, 95% CI 0.606-0.951, P=0.016). Six variables were selected to construct the nomogram. 1-, 3-, and 5-year area under the curves (AUCs) (0.867, 0.731, 0.773 and 0.896, 0.784, 0.773) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the two groups in the training and validation cohorts (P<0.001). Conclusion: We demonstrated that HCC patients who underwent CECT evaluation after ablation had a better prognosis, making this evaluation method highly recommended for guiding clinical management.

Incidence and risk factors for hypotension after carotid artery stenting: Systematic review and meta-analysis.

OBJECTIVE: Hypotension is recognized as a common complication after carotid artery stenting, but its incidence and the risk factors associated with it are uncertain. Therefore, we performed a systematic review and meta-analysis to investigate and identify risk factors for hypotension after surgery. METHODS: We retrieved risk factors from eight databases for case-control and cross-sectional studies of hypotension after carotid artery stenting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on 28 November 2022. Data were analyzed by using R4.2.1 and Review Manager 5.3. RESULTS: A total of 2843 samples were searched, and 17 publications were included in the analysis. The meta-analysis results showed that the incidence of hypotension after surgery was 28.6% (95% confidence interval [CI] (0.225, 0.347)). Age ⩾ 65 years (odds ratio [OR] = 4.55, 95% CI (2.50, 8.29), P < 0.00001), stenosis site (bulb) (OR = 4.41, 95% CI (2.50, 7.79), P < 0.00001), severe stenosis (OR = 3.56, 95% CI (1.62, 7.85), P = 0.002), stenosis proximity (⩽ 10 mm) to bifurcation (OR = 2.69, 95% CI (1.74, 4.15), P < 0.00001), calcified plaques (OR = 4.64, 95% CI (1.93, 11.14), P = 0.0006), post-balloon dilation (OR = 5.95, 95% CI (2.31, 15.31), P = 0.0002), bilateral carotid stenting (OR = 30.51, 95% CI (2.33, 399.89), P = 0.009), and intravenous fluid intake/mL on the first postoperative day (mean difference = 444.99, 95% CI (141.40, 748.59), P = 0.004) were risk factors for hypotension after surgery. CONCLUSIONS: A high incidence of hypotension was observed after carotid artery stenting. Age, stenosis site, severe stenosis, stenosis proximity to bifurcation, calcified plaques, post-balloon dilation, type of surgery, and intravenous fluid intake were identified as risk factors.

Copper-binding proteins genes set predicting the overall survival and immune infiltration in hepatocellular carcinoma by bioinformatic analysis.

Abnormal Copper (Cu) accumulation shared a close association with hepatocellular carcinoma (HCC), but the regulatory role of Copper-binding proteins in HCC remains largely unknown. The aim of study was to identify the potential regulatory role of Cu-binding proteins, including copper homeostasis maintainer and the downstream effectors of Cu, in the progression of HCC. We conducted a comprehensive bioinformatic analysis of Cu-binding proteins in HCC using data from TCGA and ICGC database. Univariate cox regression analysis was conducted, and four prognostic Cu-binding proteins was identified to be differentially expressed between the normal liver tissues and HCC tissues. In addition, the Cu-binding proteins-based predictive signature (CuPscore) model was generated using the least absolute shrinkage and selection operator (LASSO) cox regression model. Here, we identified the crucial prognostic value of CuPscore in HCC. The pathological stage and CuPscore were independent risk factors for the prognosis of HCC patients. Pathological stage and CuPscore-based nomogram model exhibited great performance in predicting the prognosis of HCC patients. We also observed that the CuPscore shared a close association with several immunomodulatory molecules and the proportion of several tumor infiltrating immune cells, suggesting a potential value of CuPscore in predicting the response to immunotherapy in HCC. Our results demonstrated the prognostic value of Cu-binding proteins and its correlation with immune microenvironment in HCC, providing a therapeutic basis for the precision medicine strategy through targeting Cu-binding proteins in HCC.

[Effects of P on the Uptake and Transport of Cd and As in Wheat Seedlings].

The aim of this study was to explore the effect of P on the physiological mechanism of Cd and As uptake and transport of wheat seedlings. Taking Bainong 207 as the test material, we investigated the effects of exogenous P supply and P deficiency treatment on the growth, root morphology, photosynthetic parameters, antioxidant system, ion content, and rhizome transfer coefficient of wheat seedlings under Cd and As stress using hydroponic experiments. The results showed that compared with that in the P deficiency treatment, the supply of exogenous P significantly increased the chlorophyll content of wheat seedlings under As stress, promoted the growth and development of roots, and increased biomass, whereas there were no significant effects on the growth of wheat seedlings under Cd stress. The contents of P and Cd in the root system under the condition of Cd stress were significantly increased by the supply of exogenous P, and the contents of P and Cd in the aboveground part were reduced. At the same time, the P and As content in the shoot and the transfer coefficient of As from the root to the shoot under As stress were significantly improved. Therefore, the effects of P on the poisoning of wheat Cd and As in this study showed obvious differences. Under As stress, exogenous P supply mainly promoted the growth of wheat seedlings by improving the transport of As from the root to the shoot and the CAT activity in the root system, reducing the poisoning of As in wheat. Under Cd stress, P and Cd showed a certain synergistic effect, and the toxic effect of Cd on wheat was aggravated to a certain extent after the supply of P.

Selenium uptake, translocation, subcellular distribution and speciation in winter wheat in response to phosphorus application combined with three types of selenium fertilizer.

BACKGROUND: Selenium (Se) deficiency causes a series of health disorders in humans, and Se concentrations in the edible parts of crops can be improved by altering exogenous Se species. However, the uptake, transport, subcellular distribution and metabolism of selenite, selenate and SeMet (selenomethionine) under the influence of phosphorus (P) has not been well characterized. RESULTS: The results showed that increasing the P application rate enhanced photosynthesis and then increased the dry matter weight of shoots with selenite and SeMet treatment, and an appropriate amount of P combined with selenite treatment increased the dry matter weight of roots by enhancing root growth. With selenite treatment, increasing the P application rate significantly decreased the concentration and accumulation of Se in roots and shoots. P1 decreased the Se migration coefficient, which could be attributed to the inhibited distribution of Se in the root cell wall, but increased distribution of Se in the root soluble fraction, as well as the promoted proportion of SeMet and MeSeCys (Se-methyl-selenocysteine) in roots. With selenate treatment, P0.1 and P1 significantly increased the Se concentration and distribution in shoots and the Se migration coefficient, which could be attributed to the enhanced proportion of Se (IV) in roots but decreased proportion of SeMet in roots. With SeMet treatment, increasing the P application rate significantly decreased the Se concentration in shoots and roots but increased the proportion of SeCys2 (selenocystine) in roots. CONCLUSION: Compared with selenate or SeMet treatment, treatment with an appropriate amount of P combined with selenite could promote plant growth, reduce Se uptake, alter Se subcellular distribution and speciation, and affect Se bioavailability in wheat.

Correlation between nuclear expression of heat shock protein 90 in dermis and glucocorticoid resistance in bullous dermatosis.

BACKGROUND: bullous dermatosis is a group of skin diseases that occur on the skin and mucous membrane, with blister and bulla as basic damage, mainly including pemphigus and bullous pemphigoid. Glucocorticoid (GC) is still the preferred drug for its treatment, but some patients respond poorly to GC and even develop glucocorticoid resistance (GCR). However, at present about the disease the understanding of the mechanisms for GCR is limited. OBJECTIVE: This study attempted to investigate the molecular mechanism of GCR in bullous dermatosis with heat shock proteins 90 (HSP90) and glucocorticoid receptor (GR) as molecular targets. METHODS: In this study, flow cytometry was used to measure and analyze the expression of HSP90 and GR in the lesions of patients with glucocorticoid-resistant bullosa dermatosis. Immunohistochemistry and immunofluorescence were used to observe the expression distribution and cell localization of HSP90 and GR. RESULTS: The expression of HSP90 in skin lesions of GCR group was significantly higher than that of glucocorticoid-sensitive (GCS) group, while the expression level of GR was lower than that of GCS group. In the epidermis, the expression and distribution of HSP90 were not different between the GCR group and the GCS group. And in the dermis, HSP90 and GR were more likely to be expressed in the nucleus in the GCR group. CONCLUSION: The overexpression and nuclear distribution of HSP90 may be related to the occurrence of GCR in patients with bullous dermatosis. And this correlation is more likely to occur in the dermis than in the epidermis.

Relationship of family function and pre-hospital delay among Chinese patients with recurrent ischaemic stroke and the mediation effect of stigma.

AIMS: Pre-hospital delay refers to the time span from the onset of symptoms to arrival at a hospital ≥ 3 h and is the main limitation of stroke reperfusion therapies. Family factors and stroke-related stigma may influence pre-hospital delay. However, few studies have confirmed the influence of stigma on pre-hospital delay or explored the relationships between family function, stigma, and pre-hospital delay among patients with recurrent stroke. This study aimed to explore the relationship between family function and pre-hospital delay among patients with recurrent stroke and examine the mediation role of stigma in this relationship. METHODS AND RESULTS: A cross-sectional study was performed at the neurology departments of two hospitals in Guangzhou, China between July 2021 and April 2022. A total of 115 patients with recurrent stroke completed questionnaires and were included in the analysis. Data were collected using the Short Form Family Assessment Device, the Stroke Stigma Scale, and the Stroke Knowledge Questionnaire. Spearman's correlation and a structural equation model were used for data analysis. Family function directly influenced pre-hospital delay [ß=0.27, P = 0.033, 95%CI = (0.02-0.51)] and indirectly influenced pre-hospital delay [ß=0.17, P = 0.038, 95%CI = (0.02-0.34)] through stigma. Moreover, stigma partially mediated the effect of family function on pre-hospital delay. CONCLUSION: Family function and stigma directly and indirectly influenced pre-hospital delay among patients with recurrent stroke. Future health education and interventions need to focus on strengthening and improving emotional support from family members to improve family function and reduce stigma, thereby reducing pre-hospital delay among patients with recurrent stroke.

CXCL11 negatively regulated by MED19 favours antitumour immune infiltration in breast cancer.

BACKGROUND: Through microarray results, we found that the C-X-C motif chemokine ligand 11 (CXCL11) was negatively regulated by mediator complex subunit 19 (MED19), a protumour factor. However, the biological role and potential mechanism of CXCL11 need to be explored in breast cancer (BRCA). METHODS: The BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) dataset. Our microarray data and the BRCA dataset of TCGA were analysed and visualized using the R software package. The mRNA and protein levels were measured by qRT-PCR and western blotting. RESULTS: Inhibition of MED19 in MDA-MB-231 cells caused CXCL11 upregulation. The relative positive regulation of cytokine pathways was enriched after MED19 knockdown. High CXCL11 was determined to be positively correlated with immune response activation, increased antitumour immune cell infiltration, immune checkpoint molecule expression, and enhanced sensitivity to immunotherapy and chemotherapy. Collectively, CXCL11 promoted antitumour immunity and was regulated by MED19 in BRCA. Clarifying the prognostic value and underlying mechanism of CXCL11 in BRCA could provide a theoretical basis to find new diagnostic and therapeutic targets.

LINC00536 Promotes Breast Cancer Progression by Regulating ROCK1 via Sponging of miR-214-5p.

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play a significant role in regulating gene expression and participating in the progression of various malignancies. In our study, by analyzing data from The Cancer Genome Atlas (TCGA), LINC00536 was found to be highly expressed in breast cancer (BC) tissues, but its function and clinical significance in BC are still unknown. Therefore, we aimed to explore the role and molecular mechanism of LINC00536 in BC. We collected human BC tissue specimens and validated that LINC00536 was overexpressed in BC tissues. Increased LINC00536 expression was associated with advanced TNM stage, larger tumor diameter, lymph node metastasis and poor prognosis in patients with BC. Univariate and multivariate Cox regression analyses showed that high LINC00536 expression was an independent prognostic risk factor for overall survival in BC patients. Furthermore, quantitative reverse transcription PCR (qRT-PCR) showed that LINC00536 was upregulated in BC cell lines. Then, we confirmed that LINC00536 silencing-inhibited BC cell proliferation, migration, and invasion and led to cell cycle arrest in vitro. Animal experiments showed that knockdown of LINC00536 expression suppressed tumorigenesis in vivo. Mechanistically, LINC00536 serves as a ceRNA for miR-214-5p, increasing the expression of ROCK1, which acts as a tumor promoter in BC. Rescue assays revealed that miR-214-5p inhibition or ROCK1 overexpression could neutralize the suppressive effects of LINC00536 knockdown on cell proliferation, migration and invasion. Our data indicated that LINC00536 accelerates BC progression by regulating the miR-214-5p/ROCK1 pathway, which might provide a new perspective to investigate the development process of BC.

Interim efficacy and safety of PD-1 inhibitors in preventing recurrence of hepatocellular carcinoma after interventional therapy.

Introduction: Locoregional interventional therapy including transcatheter arterial chemoembolization (TACE) and ablation are the current standard of treatment for early-to-mid-stage hepatocellular carcinoma (HCC). However, questions remain unanswered regarding the management of recurrence after locoregional treatment. PD-1 inhibitors can block inhibitory signals of T-cell activation and proliferation to reduce the recurrence. We conducted a single-arm phase 2 trial to evaluate the efficacy and safety of PD-1 inhibitors following locoregional interventional therapy in HCC patients with high recurrence risk guided by our novel scoring system. Methods: Patients enrolled initially treated by TACE combined with ablation, then willingly joined the experimental group. One month later, they received the anti-PD-1 adjuvant therapy (intravenous injection of 200 mg), which was repeated every 3 weeks for a total of 4 or 8 cycles. Within this same period, other patients were screened into the control group to match the experimental group by 1:1 based on the propensity score matching method (PSM). The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS) recurrence modality, safety, and quality of life. Result: At the time of data cutoff, the median RFS of the control group was 7.0 months while the experimental group had not reached it. Moreover, the 1-year RFS rate was 73.3% in the experimental group and 46.7% in the control group, showing a significant difference (P =0.02). The rate of local tumor progression in the experimental group was clearly lower than that in the control group (P = 0.027). Benefits associated with anti-PD-1 adjuvant therapy were observed in patients with multiple tumors and tumor size ≤2cm. Univariate and multivariate analyses demonstrated that anti-PD-1 adjuvant therapy was an independent favorable prognostic factor for RFS in HCC patients. The most frequent AE observed in this study was RCCEP, and other AEs included diarrhea, hepatotoxicity, rash, pruritus, and fatigue. The incidence of GRADE ≥3 AE and withdrawal in this study was low with no deaths recorded. Conclusions: Interim analysis from the study suggest the addition of anti-PD-1 adjuvant therapy after TACE combined with ablation could significantly prolong RFS with controllable safety for early-to-mid-stage HCC patients with high recurrence risk.

The Effects of Electroacupuncture as an Adjunct Therapy on Poststroke Aphasia: A Systematic Review and Meta-Analysis.

Background: To systematically collate, appraise, and synthesize evidence of electroacupuncture (EA) as an adjunct therapy for poststroke aphasia (PSA) from randomized controlled trials (RCTs) through a systematic review and meta-analysis. Methods: An electronic search was conducted in eight databases to identify RCTs evaluating EA adjuvant therapy versus speech and language therapy (SLT). Methodological quality of the included trails was assessed by the Cochrane risk of bias. The software Review Manager 5.4 was used for data analysis. Results: Nineteen RCTs enrolling a total of 1263 subjects were identified. The use of EA combined with speech and language therapy (SLT) showed significant improvements in effective rate (RR 1.31, 95% CI [1.21, 1.41]), oral expression score (SMD 1.34, 95% CI [1.13, 1.56]), comprehension score (SMD 1.95, 95% CI [0.88, 3.03]), repetition score (SMD 1.84, 95% CI [0.75, 2.93]), naming score (SMD 1.97, 95% CI [0.81, 3.13]), and reading score (SMD 1.55, 95% CI [1.07, 2.04]) compared to the use of SLT alone. Conclusions: The pooled data indicate that EA combined with SLT for the treatment of PSA may improve clinical effectiveness, compared with SLT alone. Future high quality RCTs with large samples are still needed to confirm and expand our findings.

YOLO-SASE: An Improved YOLO Algorithm for the Small Targets Detection in Complex Backgrounds.

To improve the detection ability of infrared small targets in complex backgrounds, an improved detection algorithm YOLO-SASE is proposed in this paper. The algorithm is based on the YOLO detection framework and SRGAN network, taking super-resolution reconstructed images as input, combined with the SASE module, SPP module, and multi-level receptive field structure while adjusting the number of detection output layers through exploring feature weight to improve feature utilization efficiency. Compared with the original model, the accuracy and recall rate of the algorithm proposed in this paper were improved by 2% and 3%, respectively, in the experiment, and the stability of the results was significantly improved in the training process.