Prognosis Mortality Research Articles

Comparison of laparoscopic and open pancreaticoduodenectomy for distal cholangiocarcinoma and impact factors on textbook outcome.

Distal cholangiocarcinoma (dCCA) is an aggressive malignancy with poor prognosis. This study aimed to compare the short-term and long-term outcomes and "textbook outcome (TO)" between laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for dCCA after the learning curve of surgeons. Clinical and follow-up data were included for dCCA patients treated with LPD or OPD at our center between January 2017 and December 2022. The propensity score matching (PSM) method was used to minimize bias between groups. Univariate and multivariate logistic regression analyses were used to determine independent prognostic factors for TO. A total of 430 patients were enrolled in the study, 224 in the LPD group and 206 in the OPD group. After PSM, 184 patients were included in each group. There were no significant differences in operative duration, lymph nodes harvest, intraoperative transfusion, vascular resection, R0 resection, severe complications, readmission rate, 30-day mortality, TO, and long-term prognosis between the two groups before and after PSM (all P > 0.05). Compared with OPD, LPD had less estimated blood loss (160 vs. 250mL, P < 0.001) and shorter postoperative length of stay (13 vs. 16 days, P < 0.001). Multivariate analysis showed that texture of pancreas [hard vs. soft, Odds Ratio (OR) 2.016; 95% confidence interval (CI) 1.276-3.184; P = 0.003] and operation duration (> 360 min vs. ≤ 360 min, OR 0.595, 95% CI 0.375-0.944, P = 0.027) were independent prognostic factors for TO. After learning curve, LPD is safe and feasible for the treatment of dCCA, with the advantages of less intraoperative blood loss and faster postoperative recovery.

Carbon quantum dots amplify beneficial effects of EGCG against neural injuries by NLRP3 inflammasome after intracerebral hemorrhage.

Neuroinflammation plays an indispensable role in neural damages after ICH, responsible for the induced high mortality and poor prognosis. NLRP3 inflammasome, which is known mediated by ROS, has been widely documented to aggravate brain injuries. Therefore, suppressing neural injuries by ROS/NLRP3 pathway may be beneficial in treating ICH. As the major catechin found in green tea, epigallocatechin-3-gallate (EGCG) shows excellent anti-oxidative and anti-inflammatory effects. In this study, EGCG-carbon quantum dots (EGCG-CQDs) were successfully fabricated based on EGCG by hydrothermal synthesis method. EGCG-CQDs exhibited an excellent aqueous solubility, and emerged more abundant phenolic oxygens as well as oxygen-rich functional groups. Importantly, EGCG-CQDs showed superior free radical scavenging activity by DPPH and ABTS assays in vitro than EGCG. In vivo, a significant antioxidative activity was presented by EGCG-CQDs rather than EGCG. Furthermore, the upregulated NLRP3 and the induced inflammatory cascades (NF-κB, Caspase-1 and GSDMD) in ICH were attenuated by EGCG-CQDs. Inflammatory factor productions were also decreased by EGCG-CQDs, such as IL-1β, IL-18, IL-6 and TNF-α. Finally, the disturbed neural viability, disordered cytomorphology, and neurological deficits were significantly improved by EGCG-CQDs rather than EGCG. Therefore, CQDs might be an effective form to amplify the efficacy and bioavailability of EGCG, exerting considerable effects on treating ICH by suppressing ROS/NLRP3.

Surgical stabilisation of rib fractures in non-ventilated patients: a retrospective propensity-matched analysis using the data from the trauma registry of the German Trauma Society (TraumaRegister DGUⓇ)

PurposeSevere thorax trauma including multiple rib fractures and flail chest deformity are leading causes of death in trauma patients. Increasing evidence supports the use of surgical stabilisation of rib fractures (SSRF) in these patients. However, there is currently a paucity of evidence for its use in non-ventilator-dependent patients.MethodsA retrospective propensity-matched analysis of the data of the TraumaRegister DGU® for non-ventilator-dependent patients with severe rib injury (abbreviated injury score ≥ 3) was performed. Subgroup analyses with respect to injury severity score, American society of anaesthesiologists physical status classification and age were performed. Furthermore, the effect of time to surgery was analysed.RegistrationTR-DGU project ID 2023-007; ClinicalTrials.gov protocol ID: NCT06464289.ResultsSSRF led to reduced mortality compared to conservative treatment (1.6% vs. 4.8%; p = 0.002) and in comparison to the mortality prognosis of the revised injury severity classification II (RISC II) of 5.2%. Interestingly, SSRF was associated with increased length of hospital and intensive care unit stay, higher rates of organ failure and secondary intubation. The patients with organ failure received SSRF later than those without organ failure.ConclusionHere we report on the largest currently published dataset of non-intubated patients receiving SSRF, which showed reduced mortality in the SSRF cohort. The data indicates that SSRF is a viable treatment option for non-intubated patients. The observed late surgical time points, which may be due to cross over after failed conservative treatment, might be the cause for the observed increased rate of organ failure.

Air pollution and coronary atherosclerosis.

The recently introduced concept of 'exposome' emphasizes the impact of non-traditional threats onto cardiovascular health. Among these, air pollutants - particularly fine particulate matter < 2.5 μm (PM2.5) - have emerged as significant environmental risk factors for cardiovascular disease and mortality. PM2.5 exposure has been shown to induce endothelial dysfunction, chronic low-grade inflammation, and cardiometabolic impairment, contributing to the development and destabilization of atherosclerotic plaques. Both short- and long-term exposure to air pollution considerably increase the incidence of ischemic heart disease (IHD)-related events, with clinical evidence linking pollution to higher mortality and adverse prognosis, especially in vulnerable populations. In this review, we explore the mechanistic pathways through which air pollutants exacerbate atherosclerotic cardiovascular disease (ASCVD) and discuss their clinical impact.Furthermore, special attention will be directed to the outcomes and prognosis of patients with pollution-aggravated coronary atherosclerosis, as well as the potential role of targeted public health interventions.

Survival machine learning methods for mortality prediction after heart transplantation in the contemporary era.

Although prediction models for heart transplantation outcomes have been developed previously, a comprehensive benchmarking of survival machine learning methods for mortality prognosis in the most contemporary era of heart transplants following the 2018 donor heart allocation policy change is warranted. This study assessed seven statistical and machine learning algorithms-Lasso, Ridge, Elastic Net, Cox Gradient Boost, Extreme Gradient Boost Linear, Extreme Gradient Boost Tree, and Random Survival Forests in a post-policy cohort of 7,160 adult heart-only transplant recipients in the Scientific Registry of Transplant Recipients (SRTR) database who received their first transplant on or after October 18, 2018. A cross-validation framework was designed in mlr. Model performance was also compared in a seasonally-matched pre-policy cohort. In the post-policy cohort, Random Survival Forests and Cox Gradient Boost had the highest performances with C-indices of 0.628 and 0.627. The relative importance of some predictive variables differed between the pre-policy and post-policy cohorts, such as the absence of ECMO in the post-policy cohort. Survival machine learning models provide reasonable prediction of 1-year posttransplant mortality outcomes and continual updating of prediction models is warranted in the contemporary era.

Elevated Platelet-to-Lymphocyte Ratio as a Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Individuals.

The platelet-to-lymphocyte ratio (PLR) has been proposed as a promising inflammatory biomarker, with potential implications for cardiovascular prognosis. However, its association with mortality outcomes in hypertensive individuals is not fully elucidated. This investigation sought to clarify the linkage between PLR and both overall and cardiovascular mortality in hypertensive individuals. Data from 15483 hypertensive adults in the NHANES (2005-2018) were analyzed. Mortality data, including all-cause and cardiovascular deaths, were sourced from the National Death Index (NDI) up to December 31, 2019. The linkage between PLR and mortality risk was depicted using restricted cubic spline (RCS) models. Cox proportional hazards regression models assessed the independent association of PLR with mortality risk, with adjustments incrementally applied: Model 1 without adjustments; Model 2 adjusted for age and sex; Model 3 adjusted further for age, gender, race, marital status, diabetes, alcohol intake, smoking status, body mass index (BMI), history of cardiovascular disease (CVD), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), and creatinine (CR). Over a median follow-up of 79 months, there were 2820 all-cause deaths and 758 cardiovascular deaths. The multivariate Cox analysis showed that those in the highest PLR quartile had significantly elevated risks of all-cause mortality (Model 1: HR = 1.28, 95% CI 1.16-1.42, p<0.001; Model 2: HR = 1.14, 95% CI 1.03-1.26, p = 0.014; Model 3: HR = 1.16, 95% CI 1.05-1.29, p = 0.004)and cardiovascular mortality (Model 1: HR = 1.59, 95% CI 1.30-1.94, p<0.001; Model 2: HR = 1.38, 95% CI 1.13-1.68, p = 0.001; Model 3: HR = 1.47, 95% CI 1.20-1.80, p<0.001). The study reveals a U-shaped relationship between PLR and all-cause mortality, alongside a linear association with cardiovascular mortality. A PLR threshold of 118.83 has been identified as indicative of an adverse prognosis for all-cause mortality. Elevated PLR independently predicts heightened risks of both all-cause and cardiovascular mortality among hypertensive patients.

Prognosis and predictive factors of all-cause mortality in elderly patients with AF in Tunisia

Prognosis and predictive factors of all-cause mortality in elderly patients with AF in Tunisia

Meld-Lactate As A Predictor Of In-Hospital Mortality In Patients With Variceal Gastrointestinal Bleeding.

Variceal upper gastrointestinal bleeding is a common cause of decompensation in patients with liver cirrhosis. While mortality data, which are from 10 to 15%, are available, there are no validated scales to predict in-hospital mortality in this patient population. To determine whether the MELD-Lactate (MELD-LA) level is associated with in-hospital mortality in patients with chronic liver disease who are admitted for variceal bleeding. A prospective, observational, and analytical study was conducted that included 120 patients. The MELD-LA cut-off point was obtained, and in-hospital mortality was obtained using conventional prognostic scales that had the highest sensitivity and specificity for comparison purposes. Additionally, a survival analysis was performed using the MELD-LA cut-off point obtained. In our cohort, 6 (5.0%) patients died during hospitalization. Patients who died had a mean MELD-LA value of 20.0 (±4.97) as opposed to those who did not die, 13.62 (±3.29), (p<0.001). The MELD-LA cut-off point of > 14.0, with a sensitivity of 100%, a specificity of 71.0%, a positive predictive value of 15.4%, a negative predictive value of 100.0%, and an AUC (area under the curve) of 0.886, was most well correlated with higher in-hospital mortality. Survival was 71.1% in patients with MELD-LA levels > 14.0 versus 100.0% in those with lower levels (p=0.001) during hospitalization. The measurement of MELD-LA at admission seems to be a good complementary marker for the evaluation and prognosis of in-hospital mortality in patients with liver cirrhosis, and variceal upper gastrointestinal bleeding.

Fluorescent Polymer Nanocomposites as Novel Drug-Loading and Targeted Delivery Nanocarriers for Glioma Therapy by Modulating ERBB4.

Gliomas are the most common type of tumor in the human central nervous system, characterized by high aggressiveness, elevated mortality, and poor prognosis. Therefore, developing new therapeutic strategies is crucial for improving glioma treatment. Temozolomide (TMZ) is widely used in glioma therapy due to its excellent ability to penetrate the blood-brain barrier. In this study, we synthesized HA-PEG@ICG using hyaluronic acid (HA) and polyethylene glycol (PEG), modified with the fluorescent compound indocyanine green (ICG), and thoroughly characterized the product's structure. Subsequently, compound 1 and TMZ were co-loaded onto this carrier to construct a synergistic drug delivery system (HA-PEG@ICG@1@TMZ). Additionally, we evaluated the inhibitory effects and mechanisms of HA-PEG@ICG@1@TMZ on glioma cell proliferation. Our study lays the foundation for further exploration of TMZ-based therapies for glioma treatment.

Exploring the prognostic impact of triglyceride-glucose index in critically ill patients with first-ever stroke: insights from traditional methods and machine learning-based mortality prediction

BackgroundThe incidence and mortality of first-ever strokes have risen sharply, especially in the intensive care unit (ICU). Emerging surrogate for insulin resistance, triglyceride-glucose index (TyG), has been linked to stroke prognosis. We aims to explore the relationships between TyG with ICU all-cause mortality and other prognosis, and to develop machine learning (ML) models in predicting ICU all-cause mortality in the first-ever strokes.MethodsWe included first-ever stroke patients from the eICU Collaborative Research Database in 2014–2015 as the primary analysis cohort (then divided into training and internal validation cohorts) and from local hospital’s ICUs as the external validation cohort. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to evaluate the association between TyG and ICU/hospital all-cause mortality. Linear regression and correlation analyses were performed to examine the relationships between TyG with length of ICU/hospital stay and Glasgow Coma Score.ResultsThe primary analysis cohort included 3173 first-ever strokes (median age 68.0 [55.0–68.0] years; 63.0% male), while the external validation cohort included 201 first-ever strokes (median age 71.0 [63.0–77.0] years; 62.3% male). Multivariate Cox proportional hazards models revealed that the high TyG group (TyG ≥ 9.265) was associated with higher ICU (HR 1.92, 95% CI 1.38–2.66) and hospital (HR 1.69, 95% CI 1.32–2.16) all-cause mortality, compared with low TyG group (TyG < 9.265). TyG was also correlated with ICU length of stay (r = 0.077), hospital length of stay (r = 0.042), and Glasgow Coma Score (r = -0.132). TyG and other six features were used to construct ML models. The random forest model performed best in internal validation with AUC (0.900) and G-mean (0.443), and in external validation with AUC (0.776) and G-mean (0.399).ConclusionTyG (optimal cut-off: 9.265) was identified as an independent risk factor for ICU and hospital all-cause mortality in first-ever strokes. The ML model incorporating TyG demonstrated strong predictive performance. This emphasises the importance of insulin resistance (with TyG as a surrogate measure) in the prognostic assessment and early risk stratification of first-time stroke patients.

Role of continuous renal replacement therapy in management of the preliver transplant patient.

Highlight the importance of acute kidney injury (AKI) among liver transplant candidates, its importance of survival and the vital role of continuous renal replacement therapy (CRRT) as a supportive therapy. Kidney dysfunction is common in the preliver transplant patient. Early recognition, broad diagnostic work up, and therapeutic interventions are vital in minimizing morbidity and mortality in this critically ill group of patients. Liver dysfunction can impact kidney function in multiple ways, leading to worsening of clinical illness. High mortality and poor prognosis in those with AKI without CRRT and Liver Transplant are highlighted. Etiology of AKI may not be as important as is the potential for liver transplant (LT) listing in offering CRRT. Non eligibility for a LT does not by default imply non eligibility for CRRT. Multidisciplinary approach should be adopted among those with a need for CRRT in the setting of end-stage liver disease. Goals of care conversations are key, in evaluating the role of CRRT in this group of individuals as they have a very high risk of mortality.

Peripheral and Organ Perfusion's Role in Prognosis of Disease Severity and Mortality in Severe COVID-19 Patients: Prospective Cohort Study.

Severe COVID-19 is associated with a generalized inflammatory response leading to peripheral and organ perfusion disorders. Objectives: This study aimed to evaluate the usefulness of peripheral and organ perfusion assessments in the prediction of prognosis and mortality in patients with severe COVID-19. Patients and Methods: In the first 48 h of hospitalization, peripheral perfusion (saturation, Finger Infrared Thermography-FIT; Capillary Refill Time-CRT), and the color Doppler renal cortex perfusion (RCP) were estimated in a group of 102 severe COVID-19 patients. Results: In total, 40 patients experienced deterioration and required intensification of oxygen treatment, and 24 finally died. In comparison with a stable course of the disease, patients with deterioration had initially higher WBC, CRP, AST, LDH, and CRT, but a lower oxygenation ratio and RCP. Deceased patients were older, had higher CRP, LDH, and CRT, but lower hemoglobin, oxygenation ratio, and RCP compared to survivors. In the multivariable regression analysis from perfusion parameters, only RCP and CRT were independently linked with deterioration (OR 0.002, p < 0.001; OR 1.825, p = 0.003, respectively) and death (OR 0.001, p = 0.004; OR 1.910, p = 0.003, respectively). Conclusions: Initial assessment of peripheral and organ perfusion can be helpful in identifying hospitalized severe COVID-19 patients with a higher risk of deterioration and death. Capillary Refill Time and Renal Cortical Perfusion were prognostic markers of deterioration or death. On the other hand, Finger Infrared Thermography and saturation were not statistically significant in predicting patient outcome. An RCP cut-off value below 0.127 and 0.112 [cm/s] and a Capillary Refill Time longer than 3.25 and 4.25 [s] indicate the risk of deterioration or death, respectively.

AKR1C3 mediates gastric cancer cell invasion and metastasis via the AKT and JNK/p-NF-κB signaling pathways

Gastric cancer (GC) is globally recognized as the fifth most common cancer and the third leading cause of cancer-related mortality. Early metastasis in GC significantly contributes to its high mortality and unfavorable prognosis. However, the underlying mechanisms of this phenomenon remain largely unexplored. Among the various factors involved, AKR1C3 has emerged as a crucial component in the pathways of tumorigenesis and metastasis across multiple cancer types. Yet, the precise significance of AKR1C3 in GC patients’ prognosis and its role in GC progression remain elusive. This study illuminated the significant downregulation of AKR1C3 in GC tissues, linking it to an aggressive phenotype and poor prognosis. Interestingly, while AKR1C3 overexpression did not affect the proliferation of GC cells, it significantly inhibited their ability to invade and metastasize. The underlying mechanism appears to involve AKR1C3’s inhibition of the p-JNK pathway, which leads to reduced phosphorylation of IKKα/β and IKBα, lowering p-NF-κB levels and hindering its movement into the nucleus, thereby stifling the epithelial-mesenchymal transition (EMT) process in GC cells. These insights reveal AKR1C3’s tumor-suppressive effects in GC and suggest its potential as a diagnostic and prognostic biomarker, offering new avenues for targeted therapies in gastric cancer management.

TRAIP enhances progression of tongue squamous cell carcinoma through EMT and Wnt/β-catenin signaling by interacting with DDX39A

BackgroundTongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors with high mortality and poor prognosis. Its incidence rate is increasing gradually. Tumor necrosis factor receptor-associated factor interacting protein (TRAIP), as a factor related to several tumors, reveals that its gene expression is different between normal tissue and primary tumor of head and neck squamous cell carcinoma using bioinformatics analysis.MethodIn our study, TCGA database, immunohistochemistry, proliferation assay, colony formation, wound healing assay, Transwell, cell cycle analysis and tumor xenografts model were used to determine the expression and functions of TRAIP in TSCC.ResultWe found that TRAIP may promote the proliferation, migration and invasion of TSCC. Furthermore, the results of bioinformatics analysis, mass spectrometry and co-immunoprecipitation suggested that DDX39A may be a TRAIP interacting protein. DDX39A has been proven to be an oncogene in several tumors, which may have an important effect on cell proliferation and metastasis in multiple tumors. In addition, the high expression of DDX39A implies the poor prognosis of patients. Our study demonstrated that TRAIP probably interact with DDX39A to regulate cell progression through epithelial-mesenchymal transition and Wnt/β-catenin pathway. In addition, we show that the necessary domain of DDX39A for the interaction between DDX39A and TRAIP region.ConclusionThese results indicate that TRAIP is important in occurrence and development of TSCC and is expected to become the new promising therapeutic target.

Hypoalbuminemia is Associated with Higher 90-Day Mortality and Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma and Liver Cirrhosis Receiving Radiotherapy-Based Therapy.

Liver cirrhosis (LC) is common among patients with esophageal squamous cell carcinoma (ESCC) due to shared etiologic factor, alcohol. For non-metastatic ESCC (nmESCC) patients with cirrhosis, surgery is often contraindicated or associated with high morbidity, therefore radiotherapy-based therapy was commonly applied. This study aims to investigate prognosticators for overall survival (OS) in nmESCC and cirrhotic patients receiving radiotherapy-based therapy. Furthermore, we will also evaluate the predictors for the 90-day mortality rate to reduce avoidable treatment-related toxic effects, and prevent medical waste. Between January 2001 and December 2021, we retrospectively reviewed medical records of 1298 ESCC patients. Total 78 patients with nmESCC and liver cirrhosis identified based on abdominal ultrasonography, computerized tomography, or liver biopsy were enrolled. Clinicopathologic parameters were collected and correlated with OS and 90-day mortality. Univariate analysis revealed that Child-Pugh classification B/C (P<0.001, versus A), radiotherapy alone (P=0.03, versus chemoradiotherapy), prothrombin time (PT) prolonged≧2seconds (P=0.024), albumin≦3.5g/dl (P<0.001), controlled/refractory ascites (P=0.01, versus none of ascites), and total bilirubin≧1.5mg/dl (P=0.004) were significantly associated with inferior OS. In multivariate analyses, albumin≦3.5g/dl (P=0.001, odds ratio (OR): 2.500) and total bilirubin≧1.5mg/dl (P=0.019, OR: 2.012) were independent adverse prognosticators. The 90-day mortality in these 78 patients receiving radiotherapy-based therapy was 10.3% (n=8), including ESCC progression in 4 patients, liver failure in 1 patient, and others in 3. Clinical 8th AmericanJoint Committee on Cancer (AJCC) stage IVA (P=0.02), clinical T classification T3/4 (P=0.049), PT prolonged≧4seconds (P=0.009), and albumin≦3.5g/dl (P=0.027) were significantly correlated with higher 90-day mortality. Logistic model showed albumin≦3.5g/dl (P=0.015, OR: 16.129) and clinical 8th AJCC stage IVA (P=0.012, OR: 17.544) were independently correlated with higher 90-day mortality. Hypoalbuminemia is associated with higher 90-day mortality and poor prognosis in nmESCC and liver cirrhosis patients receiving radiotherapy-based therapy.

Research progress on the early warning effectiveness of early warning score in patients with in-hospital cardiac arrest

In-hospital cardiac arrest (IHCA) is a critical medical issue threatening the survival and prognosis of hospitalized patients, characterized by high incidence, high mortality and poor prognosis. Early warning and intervention for IHCA are urgently needed. The early warning score (EWS) is developed as a point-of-care warning tool for early identification and intervention of hospitalized patients with deteriorating condition. In recent years, EWS has become one of the important methods for early warning of IHCA, especially EWS based on machine learning (ML) has shown great potential. This review mainly focuses on the traditional EWS and ML-based EWS, discusses the research status of EWS worldwide, and focuses on the research progress of EWS in early warning of IHCA.

National trends in surgical treatment and clinical outcomes among patients with aneurysmal subarachnoid hemorrhage in the Republic of Korea.

In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07-1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89-0.98, P=0.0050). According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer and is characterized by aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintaining the cellular energy balance, and its inactivation is associated with malignant breast cancer. Here, we identified the pharmacological mechanism of the 1,4-naphthoquinone derivative ZSW-4B. MTT, colony formation, and nude mouse xenograft tumour models demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells both in vitro and in vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomic analysis revealed activation of the AMPK signalling pathway by ZSW-4B. Additionally, the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines was demonstrated to reverse the antitumour effects elicited by ZSW-4B both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cellular apoptosis through the activation of AMPK.

Therapeutic hypothermia success for hypoxic-ischaemic encephalopathy in Latin America: Eight-year experience in EpicLatino Neonatal Network.

A study reported that therapeutic hypothermia (TH) did not reduce the combined prognosis of mortality and disability at 18 months, in low- and middle-income countries for patients with hypoxic ischaemic encephalopathy (HIE) who received TH, suggesting its no implementation in these regions. We described characteristics, mortality, and neurological response before and after the use of TH in newborns with HIE within the EpicLatino Neonatal Network (ENN) and described the population of infants with HIE treated and not treated with TH. Data were collected from 2015 to 2022 for patients with HIE. Mortality rates and Sarnat scores were compared before and after TH. The Wilcoxon Signed-Rank Test was used for comparisons. In this observational study 518 neonates of our total population of 26 970, had HIE (1.92%) of whom 150 underwent TH. Ten out of 21 neonatal intensive care units (NICUs) provided TH. The Wilcoxon Signed Rank Test for 138 cases with complete data showed a significant difference. The findings support the benefits of TH in HIE within this cohort. TH should not be withheld solely due to the economic status of the country. A strict patient selection and TH protocol are essential.

Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2–3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC.MethodsIn this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo.ResultsTwelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967–0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033–6.605, P < 0.001; multivariate Cox regression analysis: HR = 2.801%, 95% CI = 1.553–5.049, P < 0.001). Additionally, in vitro and in vivo experiments demonstrated that SLC22A1 inhibits HCC tumor development, suggesting it may be a potential therapeutic target for HCC.ConclusionsThese findings indicate a considerable value of specific FA metabolism-related genes in the diagnostic and prognostic evaluation of HCC, which provide novel insights into the disease’s management, as well as has potential implications for personalized treatment strategies. However, further investigation of the effects of these model genes on HCC is required.