International journal of clinical and experimental pathology最新文献

Background: Increasing air pollution has drawn our attention to particulate matter (PM2.5), which has been shown to correlate significantly with respiratory and cardiovascular systems. However, whether PM2.5 is causally associated with Alzheimer's syndrome or delirium is unclear.

Methods: We retrieved the genetic summary data of PM2.5 from genome-wide association studies (GWAS). The genetic information for Alzheimer's disease was obtained from the IEU OpenGWAS project, and that for delirium was obtained from FinnGen. We used two-sample Mendelian randomization analysis (MR) to associate PM2.5 with Alzheimer's disease or delirium.

Results: The odds ratio (OR) for Alzheimer's disease was 0.996 with a p-value of 0.443 using the inverse variance weighted algorithm, and the OR associated with the outcome variable of delirium was 0.393 with a p-value of 0.343.

Conclusion: With the exclusion of confounding factors, our findings do not support a genetic association between PM2.5 and Alzheimer's disease or delirium. Further population-based and experimental studies are needed to dissect the complex correlation between PM2.5 and Alzheimer's disease or delirium.

Lung cancer is the most prevalent and lethal disease globally, with approximately 80% of cases being non-small cell lung cancer (NSCLC). NSCLC is primarily composed of lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Despite chemotherapy currently being the primary treatment for NSCLC, chemotherapy resistance remains a significant challenge for patients. Recent studies have proposed immunotherapy as a promising new avenue for treating NSCLC. The association between the lysyl oxidase-like 2 (LOXL2) gene and NSCLC was explored using multiple online tools and bioinformatics analysis software based on the available datasets from TCGA. The immune microenvironment of the tumor was explored by calculating ImmuneScore, StromalScore, and TumorPurity of LUAD and LUSC and analyzing the infiltration of 22 immune cells in lung cancer tissues. LOXL2-related loads were obtained from the Xena database for LUSC and LUAD patients, and relevant prognostic genes were identified by analyzing survival curves. Functional and pathway enrichment analyses of prognostic, predictive genes were performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of LOXL2 in NSCLC was detected by RT-qPCR. LOXL2 may be involved in the progression of LUAD and LUSC and is closely related to the T-lymphocyte subpopulation, T-reg cells. SEMA7A and VEGFC are identified as the genes that interact with LOXL2 and could be used as prognostic signature genes in NSCLC patients. LOXL2 may become a prognostic marker and a new target for immunotherapy.

This study investigates the influence of CYP3A4 gene polymorphisms on postoperative pain sensitivity and analgesic response in lung cancer patients undergoing intercostal nerve block with local anesthetics. Sixty patients (ages 31-74) undergoing thoracoscopic lung cancer surgery were enrolled and divided into two groups based on CYP3A4 gene expression level: Group I (high CYP3A4) and Group II (low CYP3A4). Postoperative pain was assessed using the Visual Analogue Scale (VAS), and patient-controlled intravenous analgesia (PCIA) pump usage, ECG ST-T segment changes, complications, hospital stay, and costs were recorded. Results showed significantly higher VAS scores, PCIA usage, ST-T depression, complications, longer hospital stay, and higher costs in Group I compared to Group II (P < 0.05). These findings suggest that higher CYP3A4 expression is associated with increased postoperative pain, complications, and healthcare cost. According to CYP3A4 gene expression activity, which was determined before surgery, patients with low enzyme activity metabolized local anesthetics slowly, which resulted in better analgesic effect and a longer duration of intercostal nerve block anesthesia. Owing to the impact of CYP3A4 gene expression on local anesthetic metabolism, precise intercostal nerve block anesthesia and individualized pain treatment plans could be formulated for patients undergoing radical thoracoscopic surgery for lung cancer. This may accelerate postoperative recovery from lung cancer and reduce both the length of hospital stay and hospitalization costs.

Background: Previous studies have reported that STAT1 (Signal Transducer and Activator of Transcription 1) is associated with multiple tumor progression. This study aimed to investigate the role and related mechanisms of STAT1 in bladder cancer.

Methods: STAT1 expression in bladder cancer tissues and human bladder cancer cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The bladder cancer cell line T24 was transfected with overexpressing lentivirus targeting STAT1. Cell proliferation, invasion, and apoptosis were measured by Cell Counting Kit-8, Transwell assays, and flow cytometric analysis. Furthermore, RNA-Seq was performed to identify the downstream signaling pathways. Finally, the signaling pathway-related molecules were determined by RT-qPCR and western blot assays.

Results: The overexpression of STAT1 inhibited bladder cancer cell proliferation and invasion while enhancing apoptosis. Moreover, the overexpression of STAT1 in bladder cancer cells delayed tumor tumorigenesis in vitro. Mechanistically, RNA-Seq analysis revealed that the JAK-STAT signaling pathway was up-regulated, especially SOCS1 (suppressor of cytokine signaling 1) and SOCS3 (suppressor of cytokine signaling 3) in STAT1-sufficient cells.

Conclusions: These results indicate the potential of STAT1 as a therapeutic target in bladder cancer.

Objectives: Thyroid hormone (TH) deficiency during pregnancy may affect cardiovascular function in offspring rats. This study aimed to evaluate the effect of TH deficiency during gestation, on the electrocardiogram indices of young and middle-aged offspring of male rats.

Methods: Eight female rats were equally divided into hypothyroid and control groups. The hypothyroid mothers received 0.025% 6-propyl-2-thiouracil (PTU) in drinking water throughout pregnancy, while control mothers consumed only tap water. Following birth, male rats from each group were observed for 4 months (young age) and 12 months (middle-aged). The group known as fetal hypothyroid (FH) consisted of rats born from hypothyroid mothers. The serum T4 and TSH concentrations from mothers and newborn male rats were assayed at the end of gestation. Lead II electrocardiogram (ECG) was recorded for 5 minutes using Power Lab, AD Instruments.

Results: There was a significant rise in the P wave voltage in young FH rats, whereas, it was decreased in middle-aged control and FH rats. The voltage of QRS decreased and its duration increased in the young and middle-aged FH rats compared to the corresponding control groups. Duration and voltage of the T wave were significantly altered in the young and middle-aged FH groups. PR and QT intervals significantly increased in the young and middle-aged FH groups compared to their controls.

Conclusions: Maternal hypothyroidism affected the electrocardiogram indices of offspring rats, possibly signaling cardiovascular problems later in life.

[This retracts the article on p. 11617 in vol. 10, PMID: 31966519.].

Leukemia cutis (LC) is defined as infiltration of the skin by leukemic cells resulting in clinically recognizable cutaneous lesions. The lesions range from violaceous papules, plaques, nodules, blisters, maculopapular rash and as erythroderma. LC can precede or happen after the presentation of leukemia. Here, we report a case of Mixed phenotype Acute leukemia (MPAL) presenting as LC (erythematous & violaceous nodules) which is a rare as well as a grave combination as it carries a worse prognosis. Here, we present a case of MPAL which presented as Leukemia Cutis proven on biopsy. The paper discusses the importance of identifying LC both in a clinical and a pathological pretext as it is important to start the Chemotherapy for MPAL at the earliest for a better outcome.

Background: Urothelial carcinoma (UC) is an aggressive tumor with high recurrence rates and poses a great challenge for clinical management. Programmed death ligand-1 (PD-L1) inhibitors and human epidermal growth factor receptor 2 (HER2) blockers have been approved for the treatment of advanced urothelial carcinoma. PD-L1 and HER2 expression in UC will determine whether patients are likely to respond to these targeted treatments. This study assessed the expressions of HER2 and PD-L1 in UC at our institution and investigated their correlations with gender, tumor location (upper genitourinary (GU) tract vs. lower GU tract), tumor stage, and histologic divergent subtypes.

Design: Patients with UC who had PD-L1 or HER2 immunostains performed in the past 3 years at our institution were included in our analysis. A total of 97 cases were identified. PD-L1 and HER2 scores were provided by two experienced GU pathologists. HER2 scores were given according to the criteria used in breast cancer, while PD-L1 scores were reported as the combined positive score. We assessed correlation of the scores with the patients' gender, tumor location, tumor stage, and histologic divergent subtypes. The data for PD-L1 expression were analyzed using the Mann-Whitney U Test for gender and urinary tract location, and one-way analysis of variance (ANOVA) for stage and histology. The data for HER2 expression were analyzed using the chi-square test. For all analyses, significance was set at P<0.05.

Results: Of the 97 patients, the average age was 69 years. There were 95 patients who had previously reported HER2 results and 86 patients who had PD-L1 results. PD-L1 expression did not show a significant difference among the histological divergent subtypes (P=0.36). However, HER2 status exhibited a significant difference, with more HER2-positive cases observed in the conventional histology (P=0.008). No correlation between HER2 status and either gender or tumor stage was identified. The median PD-L1 combined positive score was significantly higher in lower urinary tract UC than upper (10 and 2, respectively; P=0.049). No significant differences were observed for gender or pathologic stage.

Conclusion: Our data suggest that HER2 is more frequently expressed in conventional UC than in divergent subtypes. Additionally, PD-L1 has a higher expression level in lower urinary tract UC compared to upper. However, PD-L1 and HER2 expression are not related to gender or tumor stage in UC.

Five cases of FISH verified BCOR rearranged high-grade endometrial stromal sarcoma were retrospectively analyzed. The patient age ranged from 33 to 65 years (median, 48.4 years). Most patients presented with irregular vaginal bleeding (3/5) and uterus mass (2/5). Only one patient developed an abdominal wall metastasis and other patients remained in good condition during the follow-up. Pathological findings revealed that the tumors exhibited morphological diversity in terms of cell shape, arrangement pattern and tumor stroma, compared to previous summarized histology of BCOR rearranged high-grade endometrial stromal sarcoma. Detailed description of such morphology changes expanded our understanding of the histology of BCOR rearranged high-grade endometrial stromal sarcoma. Due to the non-specificity of morphology in such malignancies, molecular testing is needed for confirmation in all patients.

Background: Recent evidence suggests that the tumor stem cells that are responsible for the pathogenesis of gliomas have similar properties to those of neural stem cells. We have studied two of the most consistently expressed stem cell markers in gliomas, i.e., CD133 and Nestin, and compared them with respect to p53 expression and IDH status.

Objectives: To assess the level of expression of Nestin and CD133, and identify a correlation among various grades of diffuse glioma with IDH status and expression of p53.

Materials and methods: A cross-sectional retrospective study with 102 subjects for the expression of cancer stem cell markers; CD133 and Nestin and the correlation of their expression with that of p53 and IDH1 status in adult diffuse glioma. The study was conducted in the Departments of Pathology and Neurosurgery. The expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded sections. The scoring of expression of CD133 and Nestin was adapted from Zhang et al. The scoring for p53 was adopted from Aruna et al. Results: The diffuse gliomas were graded based on WHO into grade II (30.3%), grade III (28.4%), and grade IV (41.3%). Among WHO grade IV, 59.4% were primary, and 40.4% were secondary glioblastomas. 73% of the diffuse gliomas were IDH mutant, and p53 showed an overall expression of 76.4%. The expression of CD133 and Nestin were compared with the increasing grades of diffuse gliomas, which, when plotted on ROC curves, had AUCs of 0.6806 and 0.6119, respectively. Their expression showed a positive correlation with the IDH status of the tumor.

Conclusions: Cancer stem cell markers CD133 and Nestin are expressed in diffuse glioma and have a higher expression with increasing WHO grade of malignancy. These cancer stem cell markers have shown significant association with the IDH-1 mutant status of diffuse gliomas. Hence, it can be inferred that diffuse gliomas with a higher expression of CD133 and Nestin have a poorer prognosis. Further, these cancer stem cell markers may be used as therapeutic targets in the future.