Prognosis Of Patients Research Articles

Current aspects of diabetic polyneuropathy in children

Diabetes mellitus (DM) is a serious medical and social problem of our time due to its high prevalence, lethality, early onset of disability and increasing morbidity. In children and adolescents, type 1 diabetes (DM1), characterized by absolute insulin deficiency due to autoimmune or idiopathic lesions of pancreatic β-cells, is registered more often. Every year, the total number of patients with DM1 under 18 years of age in the Russian Federation increases by several tens of thousands of people. DM is accompanied by various complications and one of the most frequent is diabetic polyneuropathy (DP), which occurs in half of children with DM1 more than 3 years. The progressive course of DP leads to the development of serious consequences affecting the quality of life and prognosis of patients. At the same time, at present, many aspects of this complication are insufficiently studied or have contradictory data, which justifies the expediency of systematization of materials on the pathogenesis of DP, effective methods of diagnostics and treatment of the disease in childhood.The aim of the work was to analyze modern scientific publications devoted to the study of DP in children, based on the search of literature sources in PubMed, CyberLeninka and RINC databases. A total of 58 bibliographic publications were reviewed, including contemporary resources from the period 2019–2023.

Study on the clinical characteristics, treatment, and outcome influencing factors of severe pneumonia complicated with ARDS.

To investigate the clinical characteristics, treatment methods, and factors influencing the prognosis of patients with severe pneumonia complicated by Acute Respiratory Distress Syndrome (ARDS), aiming to provide references for clinical decision-making and improve patient outcomes. A retrospective analysis was conducted on 118 patients with severe pneumonia complicated by ARDS treated at our hospital from June 2018 to December 2022. Based on treatment outcomes, patients were divided into a death group (n = 75) and a survival group (n = 43). General data and clinical laboratory indicators, including blood urea nitrogen, serum creatinine, C-reactive protein, procalcitonin, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide, were collected and compared between the 2 groups to identify independent factors affecting prognosis. Among the 118 patients, the mortality rate was 63.56%. Patients in the death group had a significantly higher average age (57.15 ± 13.38 years) and a higher proportion of severe ARDS (66.67%) compared to the survival group (40.02 ± 11.41 years, 30.23%, P < .001). The death group had significantly lower white blood cell counts (8.10 ± 1.64 × 109/L), oxygenation index (19.82 ± 2.29), and duration of mechanical ventilation (7.79 ± 2.11 days) compared to the Survival group (8.92 ± 1.22 × 109/L, 13.42 ± 1.82, 12.23 ± 3.05 days, P < .05). Conversely, the death group had significantly higher levels of blood urea nitrogen (6.87 ± 1.80 mmol/L), C-reactive protein (130.55 ± 50.28 mg/L), procalcitonin (5.50 ± 2.11 ng/mL), arterial partial pressure of carbon dioxide (41.12 ± 5.56 mm Hg), and a higher proportion of viral infections (48.00%) compared to the survival group (5.90 ± 1.72 mmol/L, 101.77 ± 55.56 mg/L, 3.98 ± 1.15 ng/mL, 35.59 ± 6.22 mm Hg, 27.91%, P < .05). Logistic regression analysis revealed that age (odds ratios [OR] = 1.990, 95% confidence interval [CI]: 1.306-3.033, P < .001), oxygenation index (OR = 1.426, 95% CI: 1.123-1.649, P < .001), and duration of mechanical ventilation (OR = 0.694, 95% CI: 0.557-0.864, P < .001) were independent factors influencing patient prognosis. This indicates that an increase in age and a decrease in oxygenation index are associated with a significantly higher risk of mortality, while shorter mechanical ventilation duration is related to poorer prognosis. Advanced age, lower oxygenation index, and shorter duration of mechanical ventilation are unfavorable prognostic factors in patients with severe pneumonia complicated by ARDS. These findings aid clinicians in identifying high-risk patients, optimizing treatment plans, and improving patient prognosis.

FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis.

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in murine macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cell lines, which promotes cancer cell migration in vitro and metastasis in vivo. Notably, a deficiency of FABP4 in murine macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.

Unveiling Tim-3 immune checkpoint expression in hepatocellular carcinoma through abdominal contrast-enhanced CT habitat radiomics

IntroductionImmune checkpoint inhibitors (ICIs) are important systemic therapeutic agents for hepatocellular carcinoma (HCC), among which T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) is considered an emerging target for ICI therapy. This study aims to evaluate the prognostic value of Tim-3 expression and develop a predictive model for Tim-3 infiltration in HCC.MethodsWe collected data from 424 HCC patients in The Cancer Genome Atlas (TCGA) and data from 102 pathologically confirmed HCC patients from our center for prognostic analysis. Multivariate Cox regression analyses were performed on both datasets to determine the prognostic significance of Tim-3 expression. In radiomics analysis, we used the K-means algorithm to cluster regions of interest in arterial phase enhancement and venous phase enhancement images from patients at our center. Radiomic features were extracted from three subregions as well as the entire tumor using pyradiomics. Five machine learning methods were employed to construct Habitat models based on habitat features and Rad models based on traditional radiomic features. The predictive performance of the models was compared using ROC curves, DCA curves, and calibration curves.ResultsMultivariate Cox analyses from both our center and the TCGA database indicated that high Tim-3 expression is an independent risk factor for poor prognosis in HCC patients. Higher levels of Tim-3 expression were significantly associated with worse prognosis. Among the ten models evaluated, the Habitat model constructed using the LightGBM algorithm showed the best performance in predicting Tim-3 expression status (training set vs. test set AUC 0.866 vs. 0.824).DiscussionThis study confirmed the importance of Tim-3 as a prognostic marker in HCC. The habitat radiomics model we developed effectively predicted intratumoral Tim-3 infiltration, providing valuable insights for the evaluation of ICI therapy in HCC patients.

FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in murine macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cell lines, which promotes cancer cell migration in vitro and metastasis in vivo. Notably, a deficiency of FABP4 in murine macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer.

Hypernatremia is associated with mortality in severe elderly sepsis patients.

To explore the relationship between hypernatremia and 28-day mortality in elderly sepsis patients. A total of 179 elderly patients (age ≥65 years) with elevated serum sodium admitted to the Department of Critical Care Medicine of Nanjing Hospital affiliated with Nanjing Medical University from September 2021 to September 2022 were included in this retrospective observational study. The clinical data of all patients were collected, and the patients were divided into septic group and nonseptic groups according to the Sepsis 3.0 definition. The clinical features, acute physiological and chronic health II score (APACHE II score), mechanical ventilation time, serum sodium value and duration of serum sodium elevation were compared between the two groups. ROC curves were drawn to evaluate the predictive value of each index on the prognosis of sepsis patients, and Kaplan‒Meier survival analysis was carried out on patients with different serum sodium peaks. (1) The changes in serum sodium within 48 hours after admission in the sepsis group were small and statistically significant compared with those in the nonsepsis group (P = 0.039); however, the serum sodium elevation duration was longer (P = 0.018). (2) Compared with nonseptic patients, the 7-day mortality of septic patients was higher (15.8 vs. 7.7, P<0.001). The 28-day mortality of septic patients was higher than that of nonseptic patients, but there was no significant difference between the two groups (P = 0.086). (3) The serum sodium level in the sepsis group was higher than that in the nonsepsis group on the 1st, 3rd, 5th and 7th days (P<0.001). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (4) The ROC curve analysis showed that the peak value of serum sodium had predictive value for the prognosis severity of elderly patients with sepsis. The area under the curve (AUC) was 0.753, the 95% confidence interval (95% CI) was 0.639~0.867, and the best cut-off value was 154.9 mmol/L. (5) According to the best cut-off value of the serum sodium peak, the septic patients were divided into two groups: the peak value of serum sodium was ≥154.9 mmol/L (group A), and the peak value of serum sodium was <154.9 mmol/L (group B). Among them, the case fatality rate was higher at 7 days and 28 days when the peak value of serum sodium was ≥154.9 mmol/L (group A) (22.0% vs. 8.6%); the χ2 value was 35.379, P<0.05; 75.6% vs. 37.1%, χ2 = 14.21, P = 0.003). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (6) Kaplan‒Meier survival analysis showed that the median survival time of patients with a serum sodium peak ≥154.9 mmol/L (group A) was significantly shorter than that of patients with a serum sodium peak < 154.9 mmol/L (group B) (16.7±1.4 d vs. 24.8±1.2 d, P <0.05). The serum sodium increase in elderly sepsis patients lasts for a long time, and the serum sodium fluctuation is relatively small. The serum sodium peak value has predictive value for 28-day mortality.

Thyroid hormones and prognosis in adults with status epilepticus: a retrospective study

ObjectivesThyroid hormone levels have been indicated to be associated with the functional outcome in critical illness. However, the studies on thyroid hormones and status epilepticus (SE) are rare. This study aimed to evaluate the predictive value of serum thyroid hormone levels on admission for unfavorable outcome in adult patients with SE.MethodsWe investigated and validated the predictive value of serum thyroid hormone levels on admission for the prognosis of adult SE patients. We extracted the clinical information and outcomes of patients. Modified Rankin scale (mRS) scores were applied to assess the patients’ functional outcome, and mortality at 30 days after SE onset was identified. Serum levels of thyroid hormones including free thyroxin (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) were detected on admission.ResultsWe first analyzed the discovery cohort of 87 patients with SE. We found that 35.6% (31/87) of the patients had a poor outcome at discharge, and 18.4% (16/87) of the patients died during hospital stay and at 30-day follow up. The serum FT3 levels in the non-survivors group were significantly lower than those in the survivors group. Low T3 syndrome occurred in 29.9% (26/87) of SE cases and patients with low T3 syndrome were more likely to have unfavorable outcomes. Furthermore, we observed similar results in the external cohort, which validated our findings.ConclusionsSerum FT3 levels measured on admission are independently associated with 30-day mortality in SE patients. Additionally, low T3 syndrome may be a promising candidate for predicting SE prognosis.

Serum calcium-magnesium ratio at admission predicts adverse outcomes in patients with acute coronary syndrome.

Evidence from observational studies suggests that increased calcium exposure may elevate the risk of adverse events in patients with coronary artery disease, while magnesium may exert a protective effect on disease risk. However, there have been limited investigations into the relationship between these minerals and acute coronary syndrome (ACS). Therefore, this study aimed to explore the association between the Serum calcium-magnesium ratio (Ca/Mg ratio) in patients with acute coronary syndrome and their clinical outcomes. This retrospective analysis reviewed the clinical data of 1,775 patients with ACS who underwent coronary angiography and/or percutaneous coronary intervention (PCI) at the Fujian Heart Center between May 2017 and December 2022. The patients were categorized into four groups based on their Ca/Mg ratio at admission (Group 1, ≤2.373, n = 443; Group 2, 2.374-2.517, n = 442; Group 3, 2.518-2.675, n = 446; Group 4, ≥2.676, n = 444). Single-factor analysis and multivariate logistic regression were employed to analyze the clinical characteristics and postoperative clinical outcomes of patients in different groups. The primary outcome included major adverse cardiovascular and cerebrovascular events (MACCEs), while the secondary outcomes included contrast-induced nephropathy (CIN)、all-cause rehospitalization raten and hematorrhea. Univariate analysis showed that the patients had a mean age of 64.50±10.79 years, with 370 female patients (20.8%). Additionally, 1,158 patients had hypertension (65.2%), and 710 patients had diabetes (40.5%). Univariate analysis showed an inverse relationship between the serum calcium-to-magnesium ratio and all-cause in-hospital mortality, with patients in the lowest quartile having the highest mortality rate. Multivariate analysis showed that the Ca/Mg ratio at admission was independently associated with MACCEs. Among them, this ratio was inversely associated with all-cause mortality [adjusted odds ratio (aOR) 0.07; 95% CI 0.01-0.63; P<0.05] and positively associated with new-onset atrial fibrillation (aOR 1.86; 95% CI 1.08-3.21; P<0.05). Additionally, the Ca/Mg ratio was positively correlated with an increased risk of postoperative major bleeding (aOR 6.58; 95% CI 1.43-30.29; P<0.05). In this large retrospective study, serum calcium and magnesium levels at admission were significantly associated with adverse outcomes in patients with ACS. The Ca/Mg ratio was identified as a reliable predictor of poor prognosis in ACS patients.

Nanoparticles and their application in the diagnosis of hepatocellular carcinoma

Abstract Most patients are at advanced stages when they are diagnosed with hepatocellular carcinoma, leading to poor prognosis and a low 5-year survival rate. Serological markers, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and liver biopsy are the common clinical diagnostic techniques for liver cancer. Effective interventions in the early stage will be beneficial to improve the prognosis of liver cancer patients and reduce the global burden. Therefore, it is urgent to develop new diagnostic methods to improve the diagnosis and management of liver cancer. Nanotechnology has become a new frontier subject in medical detection along with the application of nanomaterials in the manufacture of drug carriers, diagnostic tools, and therapeutic devices. Many studies have shown that nanoparticles (NPs) can be applied to the clinical diagnosis of liver cancer in combination with existing technologies, providing a new method for the early diagnosis of liver cancer. In this review, we elaborate on the theoretical basis and characteristics of NPs in the diagnosis of liver cancer, and the research progress and prospects of NPs in the diagnosis of liver cancer are summarized.

The Mechanism of TRIM21 Inhibiting the Invasion and Migration of ccRCC by Stabilizing ASS1.

Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive invasion and metastasis, presenting significant clinical challenges. Gaining insights into the molecular mechanisms underlying its progression is crucial for the development of effective therapeutic strategies. Addressing a critical knowledge gap in understanding ccRCC tumorigenesis, this study aims to elucidate the expression patterns of TRIM21 in ccRCC, unravel its impact on ccRCC patient prognosis, and investigate the regulatory role of TRIM21 in ASS1 expression and urea cycle dysregulation within the context of ccRCC. The results demonstrate that TRIM21 is downregulated in ccRCC, and low expression of TRIM21 predicts an unfavorable prognosis for ccRCC patients. Furthermore, the upregulation of TRIM21 can inhibit the migration and invasion of ccRCC cells by regulating the ubiquitination modification of ASS1. This not only expands the functional role of TRIM21 in ccRCC tumorigenesis but also demonstrates its ability to reverse urea cycle dysregulation through stabilizing ASS1 expression. Specifically, abnormal downregulation of TRIM21 in ccRCC reduces K63 ubiquitination modification of ASS1, leading to decreased stability of the ASS1 protein, aggravated urea cycle dysregulation, and facilitated migration and invasion of ccRCC cells. Additionally, reduction in ASS1 reverses the depressed migration and invasion caused by overexpression of TRIM21 in ccRCC cells. In summary, our findings contribute to a deeper understanding of the functional role played by TRIM21 in ccRCC progression, pinpoint a unique and novel regulatory mechanism involving ectopic downregulation-mediated ASS1 ubiquitination modification and urea cycle dysfunction during ccRCC progression, and provide fresh insights for further investigation into the pathogenesis and metabolic reprogramming associated with ccRCC.

First-line benmelstobart plus anlotinib and chemotherapy in advanced or metastatic/recurrent esophageal squamous cell carcinoma: a multi-center phase 2 study

Although first-line immunochemotherapy has improved prognosis for patients with advanced esophageal squamous cell carcinoma (ESCC), more effective strategies still require further investigation. This multi-center, phase II study (ClinicalTrials.gov NCT05013697) assessed the feasibility of benmelstobart (a novel PD-L1 inhibitor) plus anlotinib (multitargeted TKI) and chemotherapy in advanced or metastatic/recurrent ESCC. Eligible patients received 4–6 cycles (21-day) of benmelstobart (1200 mg), anlotinib (10 mg) plus paclitaxel (135 mg/m2)/cisplatin (60–75 mg/m2), then maintained with benmelstobart and anlotinib. Primary endpoint was progression-free survival (PFS) assessed according to RECIST v1.1. Secondary endpoints were tumor response, overall survival (OS), and safety assessed by adverse events (AEs). From September 2021 to November 2023, 50 patients were enrolled and received study treatment. With median follow-up of 23.7 months as of April 1, 2024, median PFS was 14.9 months (95% CI, 11.4-not estimable [NE]) and the 1-year PFS was 58.5% (95% CI, 41.9%–71.9%). Among 50 patients, confirmed objective response rate was 72.0% and disease control rate was 84.0%. Median duration of response of 36 responders was 16.2 months (95% CI, 10.2-NE). At the cutoff date, 31 patients remained alive; median OS was not reached (95% CI, 13.2 months-NE) with 1-year OS of 74.8% (95% CI, 59.8%–84.8%). Forty-six (92.0%) patients reported treatment-related AEs, with 37 (74.0%) were grade ≥3. Overall, benmelstobart plus anlotinib and chemotherapy showed promising efficacy and acceptable toxicity in advanced or metastatic/recurrent ESCC.

CAF Specific Expression of Podoplanin May Be Dispensable for the Malignancy of Malignant Melanoma.

Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) were shown to be an active and pivotal cell population, supporting many protumorigenic mechanisms. Podoplanin (PDPN)-positive CAFs are of special interest since their abundance correlated with a worse prognosis for patients of different cancer entities, including malignant melanoma. In this study, we applied a loss-of-function approach in an in vivo mouse melanoma model to evaluate the contribution of CAF-specific PDPN expression to melanoma formation and progression. Surprisingly, despite its prominent expression in CAFs deletion of PDPN in this cell type did neither affect the onset, nor growth of MM tumors. These data imply that PDPN expression in CAFs represents a biomarker for poor prognosis but does not serve as a useful target for stroma-directed therapy of malignant melanoma.

Early Adequate Nutrition in ICU is Associated with Survival Gain : Retrospective Cohort Study in Patient with Traumatic Brain Injury.

Patients with traumatic brain injury (TBI) commonly exhibit a poor mental health status and can easily develop aspiration pneumonia. Thus, early proper nutrition through oral or tube feeding is difficult to achieve, leading to malnutrition. However, evidence regarding early nutritional support in the intensive care unit (ICU) is lacking. We aimed to assess the effect of early nutrition in patients with TBI admitted to the ICU. Data of adult patients with TBI admitted to the trauma ICU of a regional trauma center in Korea between 2022 and 2023 were retrospectively analyzed. Those with ICU stay <7 days, younger than 18 years, and with underlying diseases that could alter baseline metabolism, were excluded. Nutritional support on day 4 of ICU admission was measured. The patients were classified into mortality and survival groups, and risk factors for mortality were evaluated. Subgroup analyses were performed based on TBI severity. Overall, 864 patients were diagnosed with acute TBI, of whom 227 were included in this study. The mortality rate in the study population was 15% (n=34). Those in the survival group were younger, had longer hospital stays, had a higher initial Glasglow Coma Scale (GCS) score, and had a higher intake of calorie supplements than those in the mortality group. In a subgroup analysis of patients with non-severe TBI (GCS>8), total calorie intake (751.4 vs 434.2 kcal, p=0.029), total protein intake (37.5 vs. 22.1 g, p=0.045), and ratio of supplied to target calories (0.49 vs 0.30, p=0.047) were higher in the survival group than in the mortality group. Logistic regression analysis revealed that calorie intake (B=-0.002, p=0.040) and initial hemoglobin level (B=-0.394, p=0.005) were risk factors for mortality in patients with non-severe TBI. More calories were supplied to the survival group than the mortality group among patients with TBI. Additionally, logistic regression analysis showed that increased calorie supply was associated with reduced mortality in patients with non-severe TBI. The mortality group had low protein intake; however, this did not emerge as a risk factor for mortality. Early sufficient nutritional support improves the prognosis of patients with TBI.

Understanding Hemodynamic Incoherence: Mechanisms, Phenotypes, and Implications for Treatment.

The reversal of microcirculation dysfunction is crucial for assessing the success of shock resuscitation and significantly influences patient prognosis. However hemodynamic incoherence is observed when microcirculatory dysfunction persists despite the restoration of macrocirculatory function post-resuscitation. Recent advancements in technology have enabled bedside assessment of microcirculation in shock patients, allowing for direct visualization of microcirculatory morphology and quantitative evaluation of its functional status. This article reviews the pathophysiological mechanisms that lead to hemodynamic incoherence. It also introduces the current understanding and classification framework for the different phenotypes of hemodynamic incoherence. Existing evidence indicates that the diverse mechanisms leading to microcirculatory disorders result in varied manifestations among patients experiencing hemodynamic incoherence, highlighting the heterogeneity of this population. Some classification frameworks have been proposed to enhance our understanding of these phenotypes. By integrating pathophysiological mechanisms, clinical symptoms, indicators of macrocirculation, microcirculation, tissue metabolism, and biomarkers, we can summarize certain clinical features of phenotypes in hemodynamic incoherence to form a conceptual framework. Additionally, strategies for creating targeted treatments based on different phenotypes require further validation.

Prognostic Implications of Initial Radiological Findings of Pulmonary Fibrosis in Patients with Acute SARS-CoV-2 Infection: A Prospective Multicentric Study

Pulmonary fibrosis detected during the acute phase of SARS-CoV-2 infection may significantly influence patient prognosis. This study aimed to evaluate the prognostic value of initial high-resolution computed tomography (HRCT) findings of pulmonary fibrosis in hospitalized COVID-19 patients and to examine how these findings relate to disease severity and clinical outcomes, with a particular focus on the development and validation of predictive scoring systems. In this multicentric prospective cohort study from January 2023 to January 2024, 120 adult patients with confirmed SARS-CoV-2 infection requiring hospitalization were enrolled from two Romanian university hospitals. Patients were categorized based on the presence (n = 60) or absence (n = 60) of pulmonary fibrosis signs on admission HRCT scans, identified by reticular opacities, traction bronchiectasis, honeycombing, and architectural distortion. Biochemical analyses, severity scores (SOFA, APACHE II, NEWS 2), and novel compound scores combining clinical and radiological data were assessed. Patients with HRCT evidence of pulmonary fibrosis had significantly higher severity scores and worse clinical outcomes. The HRCT score alone was a strong predictor of severe COVID-19 (area under the ROC curve [AUC] = 0.885), with a best cutoff value of 9.72, yielding 85.7% sensitivity and 79.8% specificity. Compound Score 1, integrating SOFA, APACHE II, and HRCT scores, demonstrated excellent predictive performance with an AUC of 0.947, sensitivity of 92.5%, and specificity of 88.9%. Compound Score 2, combining systemic inflammation markers (SIRI, SII) and NEWS 2, also showed a strong predictive capability (AUC = 0.913), with 89.2% sensitivity and 85.7% specificity at the optimal cutoff. Regression analysis revealed that Compound Score 1 had the highest hazard ratio for severe COVID-19 outcomes (HR = 4.89; 95% CI: 3.40–7.05), indicating its superior prognostic value over individual markers and traditional severity scores. Initial HRCT findings of pulmonary fibrosis are significantly associated with increased disease severity in hospitalized COVID-19 patients. The HRCT score is a valuable prognostic tool, and, when combined with clinical severity scores into Compound Score 1, it enhances the prediction of severe COVID-19 outcomes with high sensitivity and specificity. These compound scores facilitate the early identification of high-risk patients, guiding clinical decision-making and optimizing patient management to improve outcomes.

Construction of a novel mitochondrial oxidative stress-related genes prognostic system and molecular subtype characterization for breast cancer

PurposeBreast cancer (BRCA) is the most common malignant tumor among women, characterized by high incidence rates and mortality rates. Oxidative stress and immunity, particularly in relation to mitochondria, have emerged as pivotal factors in breast carcinogenesis. Nonetheless, limited research has explored the specific contribution of mitochondrial oxidative stress to the prognosis of BRCA.MethodIn this study, we conducted univariate and multivariate Cox regression analyses to pinpoint independent prognostic genes associated with mitochondrial oxidative stress (MOSRGs) and their correlation with BRCA clinical outcomes. Subsequently, we developed a robust and accurate MOS scoring system for BRCA patients based on these identified independent prognostic MOSRGs.ResultOur findings were further substantiated by immune infiltration and somatic mutation analyses, providing additional evidence that the MOS scoring system holds predictive value for clinical outcomes in patients and correlates directly with three subtypes of BRCA. In vitro experiments in the MCF7 cell and breast tissue further verified the mRNA and protein expression level of independent prognostic genes, validating the consistency of the MOS prognostic signatures in BRCA.ConclusionThis research has unveiled a novel prognostic scoring system, providing valuable insights for improving patient prognosis assessment and developing individualized treatment strategies in BRCA patients.

Cross-sectional study on the diagnostic significance of plasma exosomal miRNAs in HBV-related hepatocellular carcinoma

PurposeHepatocellular carcinoma (HCC) associated with Hepatitis B Virus (HBV) is one of the most severe malignancies in East Asia, where early diagnosis is crucial for improving patient prognosis. So we aim to identify effective early diagnostic model for HCC.Design and methodsWe enrolled 108 early-stage HCC patients and 102 non-HCC individuals underlying HBV infection, collecting plasma exosomal miRNAs (exo-miRNAs) from all participants. These patients were randomly assigned to sequencing, screening, training, and validation group. After preliminary screening of candidate exo-miRNAs by next-generation high-throughput sequencing, qPCR data from the screening group were utilized in conjunction with the random forest machine learning algorithm to identify candidate exo-miRNAs with diagnostic potential. Subsequently, logistic regression diagnostic model was constructed using the relative expression levels of candidate exo-miRNAs, alpha-fetoprotein (AFP) levels and clinical parameters of gender and the presence of cirrhosis from the training group. The diagnostic accuracy of diagnostic model was subsequently validated in the validation group.ResultsFirstly, we identified miR-212-5p, miR-1248, and miR-1250-5p as candidate exo-miRNAs with potential diagnostic value. The exo-miRNAs panel, which consisted of miR-212-5p, miR-1248, miR-1250-5p, along with clinical parameters of gender and cirrhosis, achieved an AUC of 0.8634 (95% CI: 0.8027–0.9241), demonstrating diagnostic performance non-inferior to AFP in the independent dataset. Subsequently, by combining exo-miRNAs, AFP level and clinical parameter of gender, we enhanced the diagnostic panel, miRAGe, which exhibited an AUC of 0.9499 (95% CI: 0.9192–0.9806), sensitivity of 0.8900, and specificity of 0.9468.ConclusionOur study indicates that the miRAGe panel has low rate of both missed diagnosis and misdiagnosis rates, potentially serving as a useful diagnostic tool for HBV-related HCC in early stage, which may subsequently contribute to improve the prognosis.

The Demographic and Clinical Characteristics, Prognostic Factors, and Survival Outcomes of Head and Neck Carcinosarcoma: A SEER Database Analysis

Background: Head and neck carcinosarcoma (HNCS) is a rare and highly aggressive malignancy with limited research, resulting in an incomplete understanding of disease progression and a lack of reliable prognostic tools. This study aimed to retrospectively analyze the clinical characteristics and outcomes of HNCS patients using data from the Surveillance, Epidemiology, and End Results (SEER) database and to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Patients diagnosed with HNCS from 1975 to 2020 were identified in the SEER database. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic indicators, with the optimal model selected using the minimal Akaike Information Criterion (AIC). The identified prognostic factors were incorporated into nomograms to predict OS and CSS. Model performance was assessed using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Survival curves were generated using Kaplan–Meier analysis and compared via the log-rank test. Results: A total of 152 HNCS patients were included, with 108 assigned to the training cohort and 44 to the validation cohort in a 7:3 ratio. Prognostic factors including age, primary tumor site, marital status, radiotherapy, chemotherapy, tumor size, pathological grade, and tumor stage were incorporated into the nomogram models. The models demonstrated strong predictive performance, with C-index values for OS and CSS of 0.757 and 0.779 in the training group, and 0.777 and 0.776 in the validation group, respectively. AUC values for predicting 3-, 5-, and 10-year OS were 0.662, 0.713, and 0.761, and for CSS the values were 0.726, 0.703, and 0.693. Kaplan–Meier analysis indicated significantly improved survival for patients with lower risk scores. The 3-, 5-, and 10-year OS rates for the entire cohort were 54.1%, 45.6%, and 35.1%, respectively, and the CSS rates were 62.9%, 57.5%, and 52.2%, respectively. Conclusions: This study provides validated nomograms for predicting OS and CSS in HNCS patients, offering a reliable tool to support clinical decision-making for this challenging malignancy. These nomograms enhance the ability to predict patient prognosis and personalize treatment strategies.

CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis.

Cleavage stimulation factor subunit 2 (CSTF2) is a fundamental factor in the regulation of 3'-end cleavage and alternative polyadenylation of pre-mRNAs. Previous work has identified a tumor-promoting role of CSTF2, suggesting that it may represent a potential therapeutic target. Here, we aimed to elucidate the mechanistic function of CSTF2 in hepatocellular carcinoma (HCC). CSTF2 upregulation was frequent in HCC, and elevated levels of CSTF2 correlated with poor patient prognosis. While CSTF2 inhibition did not suppress HCC growth under non-stress conditions, it supported tolerance and survival of HCC cells under hypoxic conditions. Mechanistically, CSTF2 increased PGK1 protein production to enhance glycolysis, thereby sustaining the energy supply under hypoxic conditions. CSTF2 shortened the 3' untranslated region (3' UTR) of phosphoglycerate kinase 1 (PGK1) pre-mRNA by binding near the proximal polyadenylation site (pPAS). This shortening led to a loss of N6-methyladenosine (m6A) modification sites that are bound by YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) and increase degradation of PGK1 mRNA. Concurrently, hypoxia increased m6A modification of PGK1 mRNA near the pPAS that was recognized by the YTH N6-methyladenosine RNA-binding protein C1 (YTHDC1), which recruited CSTF2 to enhance the shortening of the PGK1 3'-UTR. A small molecule screen identified masitinib as an inhibitor of CSTF2. Masitinib counteracted PGK1 upregulation by CSTF2 and suppressed the growth of HCC xenograft and patient-derived organoid models. In conclusion, this study revealed a function of CSTF2 in supporting HCC survival under hypoxia conditions through m6A modification evasion and metabolic reprogramming, indicating inhibiting CSTF2 may overcome hypoxia tolerance in HCC.

H2 protects H9c2 cells from hypoxia/reoxygenation injury by inhibiting the Wnt/CX3CR1 signaling pathway.

Myocardial ischemia-reperfusion injury is a severe cardiovascular disease, and its treatment and prevention are crucial for improving patient prognosis and reducing the economic burden. This study aimed to explore the impact of hydrogen (H2) on hypoxia/reoxygenation (H/R) injury in H9c2 cells (derived from rat embryonic heart tissue) induced by hydrogen peroxide (H2O2) and to elucidate its underlying mechanism. An H/R injury model was established in H9c2 cells via exposure to 15 μM H2O2 for 3 hours, followed by incubation in a 5% CO2 atmosphere at 37°C for 24 hours. Then, the cells were treated with H2 (50%) for 6, 12 or 24 hours. The results demonstrated that H9c2 cells exposed to H2O2 and subjected to H/R injury presented a marked decrease in the cell survival rate, accompanied by severe morphological alterations, such as curling and wrinkling, and elevated lactate dehydrogenase levels. Notably, H2 mitigated H/R injury induced by H2O2 in a time-dependent manner, improving the morphological damage observed in H9c2 cells and decreasing lactate dehydrogenase levels. Compared with the model group, treatment with H2 increased the activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, while concurrently reducing the level of malondialdehyde, an indicator of cellular damage. Furthermore, H2 treatment downregulated the expression of inflammatory cytokines and inflammatory-related factors, specifically interleukin-6, high-mobility group box 1, tumor necrosis factor-alpha, and Toll-like receptor 4, in H9c2 cells post-H/R injury. Furthermore, H2 treatment resulted in a marked decrease in the expression levels of proteins associated with the Wnt/C-X3-C-motif receptor 1 signaling pathway, such as β-catenin, glycogen synthase kinase-3 beta, adenomatous polyposis coli, and Wnt and C-X3-C-motif receptor 1. This observation suggests a potential mechanism for its protective effects against H/R injury. Therefore, H2 exerts a protective effect against H/R injury in H9c2 cells induced by H2O2, potentially by inhibiting the activated Wnt/C-X3-C-motif receptor 1 signaling pathway. This inhibition, in turn, prevents the generation of oxidative stress, inflammatory cytokines, and inflammation-associated factors.