International Journal of Clinical Practice最新文献

Objective

This study investigates the causal relationship between cathepsins and myocardial infarction (MI) through bidirectional Mendelian randomization (MR) analysis and examines cathepsin G (CTSG) in relation to various cancers using pan-cancer analysis.

Methods

We used data from the FinnGen database (28,546 MI cases and 378,019 controls) and 3301 participants from the INTERVAL study. The inverse variance weighted (IVW) method assessed the causal effect between exposure and outcome. MR-Egger regression, weighted median, simple mode, and weighted mode analyses were used for validation. Pan-cancer data were obtained from the UCSC database to explore CTSG expression across 39 tumor types.

Results

Among nine cathepsins, only elevated CTSG was linked to a higher likelihood of MI (IVW p = 0.0062, OR = 1.0576, 95% CI = 1.0160–1.1009). No significant causal effect was found between MI and CTSG levels. Pan-cancer analysis revealed CTSG downregulation in 16 tumor types, with significant expression differences in lung and colon cancers. High CTSG expression correlated with poor prognosis in stomach and bladder cancers, while low expression was linked to worse prognosis in sarcoma and other tumors. CTSG expression varied across tumor stages in multiple cancers.

Conclusion

Elevated CTSG is a potential risk factor for MI. Our findings suggest CTSG as a novel biomarker for MI prognosis and highlight its potential role in cancer prognosis and stage differentiation.

Background and Objective

Cancer-related fatigue (CRF) is recognized as one of the most common side effects of cancer and its treatment and can affect the quality of life of individuals. Studies have shown that there is an inseparable link between CRF and inflammation. Selenium, known as an antioxidant and anti-inflammatory agent, reduces the production of inflammatory markers as well as the accumulation of free oxygen radicals. Therefore, a decrease in selenium levels leads to increased inflammation and, consequently, greater fatigue. This study aimed to determine the level of selenium and its relationship with CRF.

Methodology

A total of 70 patients who met the entry criteria for the study were examined after the level of fatigue was determined through the Multidimensional Fatigue Inventory (MFI) questionnaire, and the selenium content in the serum was measured by atomic absorption spectrophotometry.

Findings

In this study, 70 cancer patients who underwent chemotherapy, including 32 men and 38 women, were examined. The total fatigue score measured through the MFI questionnaire was 57.82 ± 10.42, and the level of selenium in the blood of the patients was 77.75 ± 19.24 μg/L.

Conclusion

The results of this study demonstrated that there was a significant negative correlation between selenium levels and CRF (p <  0.001, r = −0.524), indicating that with decreasing selenium levels, the amount of CRF increased. These results vary depending on the type of cancer.

Introduction

The occurrence of hypokalemia during the management of diabetic ketoacidosis (DKA) remains high, even with the availability of comprehensive potassium replacement guidelines for its treatment. This study aims to assess the predictive value of pH-adjusted potassium (pHK) as a biomarker for the development of hypokalemia in patients treated for DKA.

Methods

We conducted a retrospective analysis of 126 hospitalized patients diagnosed with DKA. Patients were categorized based on their lowest serum potassium levels during treatment into two groups: DKA hypokalemia group and normal serum potassium group. Demographic and clinical parameters, including glycated hemoglobin (HbA1c), admission blood glucose, admission serum potassium, pHK, arterial blood pH(pH), bicarbonate(HCO3⁻), hospital stay, and hospitalization costs, were compared between groups. Influencing factors of DKA hypokalemia were analyzed to identify predictors of its occurrence during treatment.

Results

The DKA hypokalemia group exhibited significantly lower arterial blood pH, HCO3⁻, and pHK levels compared with the normal serum potassium group (p < 0.01). Conversely, HbA1c, hospital stay, and hospitalization costs were higher in the hypokalemia group (p < 0.01 or p < 0.05). The incidence of hypokalemia was markedly higher in patients with low admission pHK compared with those with normal or high pHK (p < 0.01). Binary logistic regression identified HCO3⁻ and pHK as independent risk factors for DKA hypokalemia (β = −0.13, −0.83, p < 0.01). The receiver operating characteristic (ROC) curve analysis indicated that both HCO3⁻ and pHK had an area under the curve of 0.74 for predicting the development of hypokalemia during DKA treatment (p < 0.01).

Conclusion

pHK level is a predictive marker for the risk of hypokalemia and correlates with the severity of acidosis.

Background

Lactylation, a novel post-translational modification of proteins, has been shown to promote tumor growth and inhibit the antitumor response of the tumor microenvironment (TME) in various ways. However, the complex mechanism of this modification in gastric cancer, particularly nonhistone lactylation and its interplay with tumor metabolism and immune escape, remains enigmatic.

Methods

Using single-cell RNA sequencing data and the AddModuleScore algorithm, we screened for lactylation-related genes at the single-cell level. We then integrated 10 machine learning algorithms and 101 combinations of these to construct a lactylation-related gene signature (LRS) model. The results were validated in the GEO dataset. Ultimately, we identified genes with prognostic predictive value, forming three gene feature profiles. We further analyzed the associations between lactylation-related gene risk scores and clinical features, mutation profiles, biological functions, immune cell infiltration, and immunotherapy response. For the core genes, we explored in-depth biological mechanisms through bioinformatics analysis and in vitro experiments.

Results

We identified 119 lactylation-related genes at the single-cell level. Utilizing a computational framework with 101 combinations of machine learning algorithms, we successfully constructed a risk prediction model that includes three lactylation-associated genes. This model showed excellent performance in prognosis prediction and clinical translation. The study also found significant differences in clinical features, biological functions, immune cell infiltration, immune checkpoint expression, and immunotherapy response among patients in different risk groups.

Conclusions

The LRS model demonstrates significant potential for improving the management of gastric cancer patients and enhancing treatment outcomes, particularly in the areas of immunotherapy and immune escape. This discovery highlights the clinical importance of overall lactic acidification in gastric cancer and provides a foundation for mechanistic studies and targeted therapeutic strategies.

Background

The global cancer survivor population is growing rapidly. Heavy metals like lead (Pb), cadmium (Cd), and mercury (Hg) can affect cancer progression and mortality, but systematic studies on their impact are limited.

Method

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) (2005–2018) on 2,369 cancer survivors. Serum levels of Pb, Cd, and Hg were measured using mass spectrometry. We used Kaplan–Meier (KM) curves and Cox regression models to study the effects of these metals on mortality.

Results

Higher serum levels of Pb and Cd were associated with increased all-cause, cancer-specific, and noncancer mortalities, as shown by KM curves. Cox regression showed that cancer survivors with higher levels of Pb and Cd had significantly higher risks of all-cause (hazard ratios [HRs]: 2.37 and 3.17), cancer-specific (HRs: 2.45 and 3.37), and noncancer mortalities (HRs: 2.73 and 3.80). Combined high levels of Pb and Cd were linked to the highest risks of all-cause and noncancer mortalities compared with low exposure levels. Hg exposure was not significantly linked to mortality outcomes. Survivors with high levels of both Pb and Cd had greater risks of all-cause, cancer-specific, and noncancer mortalities than those exposed to just one metal.

Conclusion

Cancer survivors with higher serum levels of Pb and Cd face increased mortality risks. The lack of a significant association between Hg exposure and mortality is notable. The synergistic effect of Pb and Cd on mortality risk highlights the importance of considering multiple heavy metal exposures when assessing health risks in this population.

Introduction

Vagal modulation is achieved directly by transcutaneous auricular vagus nerve stimulation, whereas breathing exercises stimulate arterial baroreceptors. In this study, we aimed to compare these two methods, which have similar effects.

Methods

88 healthy participants aged 18–35 were randomly divided into breathing exercises (Group BE) and vagus stimulation (Group VNS). Thoracic expansion exercise was performed in the BE group. In the VNS group, biphasic electrical stimulation was applied to both ears with a pulse width of 300 ms, a frequency of 10 Hz, and 20 min. Pulmonary function tests were measured on the first and last days. Heart rate, systolic and diastolic blood pressure, RMSSD, PNN50, LF/HF, LF Power, and HF Power values were measured before and after each of the 10 sessions for both groups.

Results

Heart rate decreased significantly in both groups, with significant superiority in the BE group compared to that in the VNS group. In both groups, blood pressure values decreased significantly. RMSSD, PNN50, and HF values increased significantly in the VNS group, while LF and LF/HF values decreased significantly in the BE group. In pulmonary function test results, the FEV1 value increased significantly in both groups. A significant increase in the FVC value was observed in both groups, but the BE group was superior. The two groups had no significant superiority in the FEV1/FVC value.

Conclusion

As a result, auricular vagus stimulation seems superior to breathing exercises in increasing the parasympathetic system activity, reducing sympathetic activity, and partially increasing respiratory functions.

Clinical Trial Registration

NCT06531954

Introduction

The Quality of Life Scale for Patients with Aplastic Anemia (QLS-AA), a self-reporting tool, assesses the quality of life among patients with aplastic anemia (AA). This study aimed to compare the QLS-AA with the commonly used 36-item Short Form Health Survey (SF-36) questionnaire.

Methods

In this cross-sectional study, we administered the SF-36 and QLS-AA to 306 patients with AA in two hospitals in China.

Results

The ceiling and floor effects of SF-36 (range 0%–38.89% and 0%–56.54%, respectively) were higher than those of QLS-AA (range 0.65%–1.31% and 0%, respectively). The Cronbach’s α coefficients for SF-36 ranged from 0.622 to 0.911, with principal component analysis (PCA) identifying two factors accounting for 62.481% of the variance. For QLS-AA, Cronbach’s α coefficients ranged from 0.793 to 0.932, and PCA revealed a single factor explaining 79.815% of the variance. There was a significant positive correlation between two scales (r = 0.743; p < 0.001). Both scales had discriminant validity in disease duration, work/study situation, economic dependence, blood transfusion situation, and degree of anemia. In addition, the QLS-AA showed sensitivity to the marital status.

Conclusions

Both the SF-36 and the QLS-AA are viable instruments for assessing the QoL in patients with AA. Nevertheless, the QLS-AA exhibited superior performance in psychometric testing.

Trial Registration

ClinicalTrials.gov identifier: ChiCTR2100047575

Background

Alcohol has been associated with cardiovascular disease, and excessive amounts are implicated in worsening heart failure outcomes. The knowledge, patterns, and associations of alcohol use among heart failure patients have not been established in Ghana.

Methods

This descriptive, cross-sectional study was conducted at the Ho Teaching Hospital among adult patients with acutely decompensated heart failure in the medical and emergency wards. All patients who presented with heart failure to the facility from September 2022 to August 2023 were recruited. Information needed was obtained using a structured questionnaire. The systolic and diastolic functions were determined using 2D echocardiography.

Results

Among the 315 patients, 33.7% used varying types and quantities of alcohol, with the local gin being the most patronized (62.2%).

Additionally, 65.1% of all heart failure patients who used alcohol also used herbal medicines (mostly orally and alcohol-based), and this was statistically significantly different from the patients who did not use alcohol (p < 0.05). There was a higher proportion of more severe forms of diastolic dysfunction among patients who used alcohol compared to those who did not (χ² = 125.039, p = 0.011), and this was also significantly demonstrated in concomitant alcohol and herbal medication use (χ² = 243.039, p = 0.001).

Conclusion

This study revealed that a third of patients with acute heart failure indulge in alcohol use above acceptable limits, with associated moderate to severe diastolic dysfunction in almost all of them. Herbal medication used in alcohol drinking patients was associated with HFpEF.

Objective

Observational studies indicate that psoriasis (PSO) patients have an increased risk of depression; however, potential confounding factors and reverse causality limit these findings, leaving the exact causal relationship between these two conditions remain to be determined. The objective of this study is to investigate the causal relationship between PSO and depression using a two-sample Mendelian randomization (MR) approach.

Methods

Summary statistics from multiple genomewide association studies (GWAS) in European populations were analyzed using Z-scores to assess correlations between PSO and depression. MR design, which uses genetic variants as instrumental variables, was employed to examine causality, with primary analyses conducted using the inverse variance weighted (IVW) method. Additional MR Steiger (testing causal direction) and colocalization (identifying shared genetic variants) analyses were performed to verify the robustness of genetic variants associated with both conditions.

Results

The results revealed a positive relationship, with genetic susceptibility to PSO correlating to a higher depression risk (OR: 1.348, 95% CI: 1.141–1.592, p = 0.004). This finding was consistently supported by multiple MR methods, including MR-Egger and MR-PRESSO. The MR Steiger method supported a causal link, while colocalization identified a shared causal variant (rs12189871) between the two conditions.

Conclusion

These findings suggest a potential causal relationship between PSO and depression, highlighting the need for depression screening in PSO patients.