This work was designed to explore the value of immune and metabolism-related genes (IMRGs) in lung adenocarcinoma (LUAD) prognosis, with the intention of aiding the application of immunotherapy in LUAD patients. Differential gene expression analysis was conducted using The Cancer Genome Atlas (TCGA)-LUAD data. After merging and deduplication, an intersection was taken with LUAD differential genes to acquire IMRGs. 716 IMRGs were utilized for LUAD clustering, resulting in the stratification of LUAD patients into two subtypes. Cluster-1 demonstrated higher immunophenoscore and lower tumor immune dysfunction and exclusion scores, indicating that cancer patients in cluster-1 were more likely to benefit from immune checkpoint inhibitor therapy. Somatic mutation analysis revealed higher mutation rates in both sample and gene levels for cluster-2 compared to cluster-1. Additionally, we predicted ten prospective candidate drugs, including Teniposide and phloretin, for LUAD patients. LUAD was stratified into two subtypes with distinct molecular features based on IMRGs. These subtypes exhibited pronounced differences in immune processes, checkpoints, genetic mutations, and drug sensitivity. Our endeavor has furnished invaluable insights into comprehending the molecular characteristics of LUAD, potentially enhancing the precision of immunotherapeutic strategies tailored for LUAD.
The risk of a second caesarean section with scarred uterus has attracted attention, and this study aimed to find a molecular marker to assist physicians in prenatal screening to better predict postpartum complications. Serum miR-192-5p expression was determined by qRT-PCR and 145 subjects were divided into low expression group (76) and high expression group (69) based on the miR-192-5p levels. The Receiver Operating Characteristic curve (ROC) was plotted with pelvic floor dysfunction (PFD) score, vaginal microecological environment status, and the occurrence of serious complications occurred as dependent variables. miR-192-5p expression was the test variable. Significant differences were found between the high and low MiR-192-5p expression groups in postpartum class I, class II muscle fiber strength, PFD score (p < 0.01), postpartum vaginal leukocyte esterase (p < 0.001), sialyl glycosidase (p = 0.010), acetylglucosaminidase (p = 0.024), and severe complications (p = 0.001). The ROC for predicting PFD showed an AUC of 0.861. The ROC for predicting vaginal microecological environment showed an AUC of 0.934. The ROC for predicting serious complications showed an AUC of 0.882. MiR-192-5p has the potential to be an adjunctive preoperative screening marker for cesarean section in patients with scarred uterus and has potential value in predicting the occurrence of complications after cesarean section, including PFD, vaginal microecological disorders, postoperative hemorrhage, abdominal incision infections, puerperal infections.
As a common metabolic disease, type 2 diabetes mellitus (T2DM) is regulated by the ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1). A functional polymorphism of ENPP1 (rs1044498, K121Q) has been found to contribute to T2DM susceptibility. This study aims to analyze the combined association of ENPP1 rs1044498 polymorphism with T2DM risk. We searched for publications in Embase, Medline, EBSCO, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang databases from January 2010 to December 2023. Pooled association strength was analyzed using either a random-effects or fixed-effects model, and expressed as combined odds ratios (ORs) with 95% confidence intervals (CIs). Data analysis was performed by STAT 12.0. Due to high heterogeneity, a random-effects model was used for the calculation. In the total population, ENPP1 rs1044498 was evidently related to an increased susceptibility to T2DM under the following models: Q vs. K (OR = 1.405, 95% CI = 1.059-1.863), KQ + QQ vs. KK (OR = 1.475, 95% CI = 1.075-2.023), QQ vs. KK + KQ (OR = 2.355, 95% CI = 1.302-4.262), QQ vs. KK (OR = 3.096, 95% CI = 1.393-6.882) and KQ vs. KK (OR = 1.399, 95% CI = 1.038-1.885). In ethnic subgroups, rs1044498 was associated with T2DM risk in Asians under the following models: Q vs. K (OR = 1.480, 95% CI = 1.017-2.154), KQ + QQ vs. KK (OR = 1.578, 95% CI = 1.047-2.379), QQ vs. KK+ KQ (OR = 3.709, 95% CI = 1.727-7.967), QQ vs. KK (OR = 5.049, 95% CI = 1.784-16.397) and KQ vs. KK (OR = 1.478, 95% CI = 1.008-2.167). The distinct association between rs1044498 and T2DM risk was discovered in the diagnostic criteria not shown subgroup and plasma subgroup. This study demonstrated high sensitivity with minimal publication bias. The ENPP1 121Q allele is a risk factor for T2DM, particularly in the Asian population.
Helicobacter pylori (HP) infection is the major cause of gastric cancer (GC). No reports have been published on the effects of HP infection on anxiety for GC, although the majority of HP-positive subjects received eradication therapy intending to reduce their risk of GC in Japan. This study aimed to investigate the relationship between cancer worry (CW) for GC and participants’ HP infection status. The original study was a quantitative, self-administered questionnaire survey to investigate CW for esophageal cancer in Barrett’s esophagus. The present study used the same dataset on CW against GC. Participants were recruited between May 2021 and March 2022 from three health screening facilities in Akita Prefecture, Japan. The Cancer Worry Scale was used to quantitatively assess the fear of developing cancer. Logistic regression analyses were used to investigate factors associated with excessive CW (defined as ≥ 13). A total of 303 respondents were included. Excessive CW accounted for 63.0% (92/146) in HP-negative, 55.0% (11/20) in HP-positive, and 71.5% (98/137) in HP-eradicated patients. While the presence of upper gastrointestinal symptoms and subnormal mental health quality were significantly associated with excessive CW, the status of HP infection did not affect it. There is a significant discrepancy between CW for GC and actual GC risk, defined as their HP infection status, among those undergoing GC screening. It may be necessary to provide appropriate patient education when introducing risk-based (mainly HP-based) stratified screening for GC shortly in Japan.
Radiotherapy for prostate cancer may induce the development of secondary bladder cancer. However, the clinicopathological characteristics and clinical outcomes of this entity have not been fully elucidated. Therefore, this study compared the clinicopathological characteristics and clinical outcomes of patients who developed secondary bladder cancer after radiotherapy with those of controls. The medical records of patients newly diagnosed with non-muscle-invasive bladder cancer were retrospectively analyzed. Newly diagnosed non-muscle-invasive bladder cancer that developed ≥ 5 years after radiotherapy for prostate cancer was defined as secondary non-muscle-invasive bladder cancer during this study. Patients with newly diagnosed non-muscle-invasive bladder cancer who did not meet this criterion were included in the control group. The clinicopathological characteristics and recurrence-free survival rates of patients with secondary non-muscle-invasive bladder cancer were compared with those of controls. A total of 26 (2.6%) of the 1,019 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital who were screened met this criterion for secondary non-muscle-invasive bladder cancer. Clinicopathological characteristics were similar between the secondary non-muscle-invasive bladder cancer and control groups, except for sex and age. Propensity score-matched analysis revealed that the recurrence-free survival rates of patients with secondary non-muscle-invasive bladder cancer may not be poorer than those of control patients. Tumor characteristics and recurrence-free survival rates of patients with secondary non-muscle invasive bladder cancer were comparable with those of controls. Further large-scale studies should be conducted to clarify the tumor characteristics and clinical outcomes of these patients after radiotherapy.
Danshen, Fufang Danshen, Shuxuening and Shuxuetong injections, four traditional Chinese medicine prescriptions, have been widely explored regarding their lipid-lowering property, but the findings were inconsistent and inconclusive. This meta-analysis was to clarify the lipid-lowering effect of the four injections. PubMed, Scopus, Embase, Web of Science, Google Scholar, Cochrane Library and CNKI databases were searched, and data including age, sex, ethnicity, disease type, dose, duration, sample size and blood lipids were extracted from each eligible study. The alterations in lipids from pre- to post-treatment were calculated and compared between control and treatment groups, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the lipid-lowering effect of the injections. Twenty-eight studies (2,624 subjects), 31 studies (3,023 subjects), 17 studies (1,507 subjects) and 54 studies (4,435 subjects) were respectively identified for Danshen, Fufang Danshen, Shuxuening and Shuxuetong injections. All of the four injections could effectively and significantly reduce serum levels of triglycerides (p < 0.001 for all), total cholesterol (p < 0.001 for all) and low-density lipoprotein cholesterol (p < 0.001 for all), and elevate high-density lipoprotein cholesterol level (p ≤ 0.02 for all). Shuxuening injection had the strongest lipid-lowering effect with almost twice that of the other three injections. Danshen, Fufang Danshen and Shuxuening injections showed a good lipid-lowering effect on patients with heart disease, while Shuxuetong injection displayed a powerful lipid-lowering effect among diabetic patients. Unfortunately, all of these injections had a poor lipid-lowering effect in patients with renal disease. The meta-analysis demonstrates that Danshen, Fufang Danshen, Shuxuening and Shuxuetong injections all can effectively reduce blood lipids. Among them, Shuxuening injection has the strongest lipid-lowering effect with almost twice that of the other three injections. In terms of reducing blood lipid levels, Danshen, Fufang Danshen and Shuxuening injections are suitable for patients with cardiovascular disease, Shuxuetong injection is suitable for patients with diabetes, but none of them is suitable for patients with renal disease.
This study aimed to evaluate the diagnostic significance of miR-505-5p in Acute cerebral infarction (ACI) and its prognostic utility following endovascular mechanical thrombectomy. A total of 138 patients with ACI and 120 healthy controls participated. RT-qPCR quantified miR-505-5p levels in serum and cerebrospinal fluid (CSF). The National Institutes of Health Stroke Scale (NIHSS) scores assessed the severity of the disease. Furthermore, the modified Rankin Scale (mRS) score evaluated the prognosis one year after endovascular mechanical thrombectomy. The Pearson coefficient analyzed the correlation between miR-505-5p and NIHSS or mRS scores. Logistic regression determined risk factors associated with poor outcomes. The receiver operating characteristic (ROC) curve assessed diagnostic and prognostic accuracy. miR-505-5p levels in serum and CSF were significantly elevated in ACI patients compared to controls ( P < 0.05). A positive correlation existed between serum miR-505-5p and NIHSS score, which increased with disease severity. miR-505-5p demonstrated 81.88% sensitivity and 85.83% specificity in identifying ACI patients, with levels correlated to mRS scores. Higher levels of miR-505-5p indicated a poor prognosis in ACI patients, suggesting its role as a potential biomarker for adverse outcomes and mortality. Both miR-505-5p and NIHSS scores emerged as risk factors for negative outcomes. Serum miR-505-5p serves as a biomarker for predicting poor prognosis and mortality in patients.In conclusion, elevated serum miR-505-5p may act as a diagnostic biomarker for ACI and correlates with unfavorable prognoses a worse prognosis in patients having endovascular mechanical thrombectomy.
Although the association between the number of deliveries and cognitive impairment has been previously examined, the influence of subclinical cerebrovascular diseases (SCDs), such as silent cerebrovascular lesions and carotid atherosclerosis, on this association remains unclear. This cross-sectional study aimed to examine whether SCDs mediated the association between the number of deliveries and cognitive impairment. Among 627 Japanese women with a mean age of 73 years, the number of deliveries was collected in the 1998 survey and classified into four groups (0-1, 2, 3, ≥ 4), with two deliveries as the reference. At the annual comprehensive medical examinations, cognitive function was assessed using the Mini-Mental State Examination (MMSE), and SCDs were evaluated using brain magnetic resonance imaging and ultrasonography. Each participant’s latest data on these variables and covariates between 1992 and 2018 were used. MMSE scores were divided into three ordinal categories: ≥ 28 (normal), 24-27 (mild cognitive impairment; MCI), and ≤ 23 (severe cognitive impairment). Ordinal logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive impairment. The ORs for cognitive impairment associated with the number of deliveries were 2.13 (95% CI, 1.21-3.76) in the lowest (0-1) group and 1.45 (0.95-2.23) in the highest (≥ 4) group. These association estimates remained similar after adjusting for SCDs but were weaker in the more recent birth year group. We demonstrated a U-shaped association between the number of deliveries and cognitive impairment, independent of SCDs, and the cohort effect confounded the association.
This study aimed to investigate the correlation between plasma brain natriuretic peptide levels and left ventricular shortening fraction in Fukuyama congenital muscular dystrophy. The correlation between brain natriuretic peptide levels and left ventricular shortening fraction in patients with genetically confirmed Fukuyama congenital muscular dystrophy was retrospectively investigated. The patients at Tokyo Women’s Medical University were followed-up from October 2015 to October 2020. The brain natriuretic peptide level was measured using a specific immunoradiometric assay kit. Left ventricular shortening fraction was defined as a degree of left ventricular systolic function within 3 months before and after brain natriuretic peptide measurements. In addition to left ventricular shortening fraction, the ratio of early filling to early diastolic and the maximum velocity of tricuspid regurgitation, which are measures of diastolic function, were investigated. In total, 27 sets of brain natriuretic peptide levels and echocardiography results were obtained from 16 patients with Fukuyama congenital muscular dystrophy. Excellent correlations were found between the brain natriuretic peptide levels and left ventricular shortening fraction (R2 = 0.8755). Patients with a left ventricular shortening fraction of > 20% had low brain natriuretic peptide levels. However, the brain natriuretic peptide values of patients with a left ventricular shortening fraction of < 20% were > 40 pg/mL. In Fukuyama congenital muscular dystrophy, the brain natriuretic peptide level was exponentially correlated with left ventricular shortening fraction. However, it did not elevate until the advanced stage of left ventricular systolic dysfunction.
Diabetic nephropathy (DN) is a prevalent diabetic complication seriously threatening patients’ health and lives. Cornuside is an iridoid glycoside compound with various pharmacological properties. Nonetheless, whether cornuside has a protective effect against DN remains unillustrated. In this study, a rat model for DN was established by streptozotocin (STZ) injection. Rat podocytes were stimulated with high glucose (HG) to mimic a DN microenvironment in vitro. Several indicators linked to kidney function were evaluated. Periodic Acid-Schiff (PAS) and hematoxylin-eosin staining were implemented for renal histologic analysis. Immunofluorescence staining of CD31 was used for the detection of neovascularization. Western blotting was employed to assess levels of angiogenic factors and MAPK signaling-related proteins in the kidney or podocytes. The results showed that cornuside administration alleviated STZ-elicited renal dysfunction, as evidenced by the reduction in fasting blood glucose, proteinuria, serum creatinine, and blood urea nitrogen. Cornuside attenuated renal pathological lesions in DN rats. Cornuside repressed angiogenesis in DN rat kidney tissues and podocytes. Cornuside blocked MAPK signaling in HG-stimulated podocytes. In conclusion, cornuside alleviates renal injury in DN rats possibly by hindering angiogenesis and MAPK signaling.