Journal of International Medical Research最新文献

Objective: The prognosis of lung adenocarcinoma (LUAD), which is the most common type of lung cancer, remains poor. Little is known about the function and mechanism of whey acidic protein four-disulfide core domain 2 (WFDC2) in LUAD.

Methods: In this study, we used online databases to compare WFDC2 expression between LUAD and normal tissues, to analyze the relationship between WFDC2 and overall survival, and to investigate the potential roles of WFDC2.

Results: We found that WFDC2 protein and mRNA expression levels were significantly higher in LUAD tissue than in normal tissue, and high WFDC2 mRNA expression was associated with better overall survival. WFDC2 mRNA expression was correlated with the mutation status of TP53. The biological function of WFDC2 was associated with the cell cycle, and low WFDC2 mRNA expression was associated with an elevated tumor mutational burden and neoantigen levels. A negative relationship was observed between WFDC2 and immune gene expression, and high WFDC2 mRNA expression was found in patients with LUAD and low programed cell death 1 mRNA expression.

Conclusions: We propose that WFDC2 is associated with clinical benefits of immune checkpoint inhibitors in LUAD.

Haemorrhagic shock, which arises as a complication of pelvic fracture subsequent to severe trauma, represents a perilous state. The utilization of interventional endovascular haemostasis assumes a pivotal role in the management of patients with vascular injury following pelvic fracture. This article reports the treatment of a patient with pelvic fracture caused by a serious work-related vehicle accident. Despite the implementation of timely blood and fluid transfusion to combat shock, the application of aortic balloon obstruction, and interventional iliac artery embolization for haemostasis, the patient's condition failed to display any discernible improvement. Repeat angiography further revealed a displacement of the interventional embolization material, and the patient subsequently died of multiple organ failure. The occurrence of spring coil displacement is infrequent, but the consequences thereof are considered grave, necessitating meticulous discernment in the selection of haemostatic materials for this type of patient. The diagnostic and therapeutic processes encompassing the particular case described here were analysed and are discussed with the objective of augmenting the efficacy and success rate of treatment modalities for patients in similar circumstances.

Objective: In 2012, the Commission on Human Medicines mandated lowering the acetaminophen toxicity nomogram treatment threshold in the UK to 100 µg/ml at 4 h post-ingestion. The present study aim was to evaluate biochemical and liver toxicity patterns in patients who presented with acetaminophen overdose and had low serum acetaminophen concentrations (<150 µg/ml).

Methods: Patients admitted to the emergency department with a clear history of acute acetaminophen overdose with or without other medication or ethanol were consecutively enrolled into this retrospective cohort study. Patients with serum acetaminophen concentration >150 µg/ml or an unknown ingestion time were excluded. Data were extracted from electronic medical records and are presented as mean ± SD or median (interquartile range).

Results: A total of 103 patients were included (median age, 17 [4-21] years) and 80 (78%) were female. The median ingested acetaminophen dose was 5000 (2850-7650) mg. At baseline, the median serum acetaminophen concentration was 42 (4.5-64.8) µg/ml, and median alanine aminotransferase and aspartate aminotransferase levels were 22 (17-28) and 27 (16-45) IU/L, respectively. Twenty patients were treated with acetylcysteine, with none developing adverse reactions. No patient developed hepatotoxicity, including patients with initial multiple product ingestion or other risk factors.

Conclusions: Patients presenting with an acute acetaminophen overdose with acetaminophen level <150 µg/ml, including patients with other risk factors, are at low risk of hepatotoxicity.

Objective: Apart from the role of the retinoblastoma gene, the genomic events associated with poor outcomes in patients with ophthalmic tumors are poorly understood.

Methods: We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis.

Results: We identified four clearly causative genes (TP53, PTCH1, SMO, BAP1). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2, and BRCA2, and high-frequency gene analysis identified several genes, including TP53, TTN, and MUC16. Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD, ELANE, HBA1, and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis.

Conclusions: TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A, and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.

Objective: This study aimed to identify significantly differentially expressed genes (DEGs) related to cervical cancer by exploring extensive gene expression datasets to unveil new therapeutic targets.

Methods: Gene expression profiles were extracted from the Gene Expression Omnibus, The Cancer Genome Atlas, and the Genotype-Tissue Expression platforms. A differential expression analysis identified DEGs in cervical cancer cases. Weighted gene co-expression network analysis (WGCNA) was implemented to locate genes closely linked to the clinical traits of diseases. Machine learning algorithms, including LASSO regression and the random forest algorithm, were applied to pinpoint key genes.

Results: The investigation successfully isolated DEGs pertinent to cervical cancer. Interleukin-24 was recognized as a pivotal gene via WGCNA and machine learning techniques. Experimental validations demonstrated that human interleukin (hIL)-24 inhibited proliferation, migration, and invasion, while promoting apoptosis, in SiHa and HeLa cervical cancer cells, affirming its role as a therapeutic target.

Conclusion: The multi-database analysis strategy employed herein emphasized hIL-24 as a principal gene in cervical cancer pathogenesis. The findings suggest hIL-24 as a promising candidate for targeted therapy, offering a potential avenue for innovative treatment modalities. This study enhances the understanding of molecular mechanisms of cervical cancer and aids in the pursuit of novel oncological therapies.

Objective: To evaluate longitudinal changes in peripapillary vessel density (VD) following coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography.

Methods: As part of a prospective longitudinal observational study, we studied healthy individuals with a history of mild COVID-19 confirmed via real-time polymerase chain reaction. After recovery, we used the Optovue RTVue XR Avanti machine to perform optic nerve head (ONH) imaging. We also assessed the VD of all vessels and of small vessels in the disc and the radial peripapillary capillary (RPC) network at 1 and 3 months post-recovery.

Results: We included 17 patients (34 eyes; mean age: 36.9 ± 10.2 years, range: 24-62 years) who had recovered from COVID-19. No changes were observed in the ONH parameters. However, there was a noticeable trend of increased small vessel VD values in the RPC. These increases were significant for the peripapillary whole, superior hemifield, inferior-temporal, temporal-superior, and superior-temporal small vessels. Moreover, the evaluation of all vessel VD values in the RPC revealed a significant decrease in the inside disc and a significant increase in a grid-based inferior region.

Conclusion: COVID-19 may affect VD of the RPC in the ONH, and should be considered in ONH evaluations.

Objective: Value-focused thinking (VFT) is a decision-making method that places the qualitative elicitation of decisionmakers' objectives at the beginning of the decision-making process. A potential healthcare application of VFT is to elicit patients' objectives to better understand what matters to them. Only then can treatments be tailored accordingly. This is particularly important for patients with life-threatening diseases such as cancer. Thus, this interview study used VFT to elicit the life and treatment objectives of non-terminal oncologic inpatients.

Methods: Fifteen cancer inpatients (median age 66 years) were sampled in a German university hospital in September 2019. The participants completed questionnaires, the data of which were used to semi-structure the subsequent interviews. Data were analysed using inductive category formation to identify objectives in the transcribed interviews.

Results: Sixteen objectives in five life domains (optimising physical wellbeing, optimising mental wellbeing, optimising personal life, optimising family life and optimising financial life) were identified.

Conclusion: Comparison of the findings with previous research indicated that VFT is a reliable approach to elicit patients' objectives. The identified objectives could increase understanding of the outcomes that cancer inpatients care about.

Objective: With mechanical thrombectomy (MT), we investigated the prognostic importance of aortic arch calcification (AoAC) and carotid sinus calcification (CaSC) for symptomatic intracerebral hemorrhage (sICH) and poor outcome in acute large artery occlusion (LAO).

Methods: In this retrospective observational study, we calculated pre-cranial artery calcification burden (PACB) scores (burden score of AoAC and CaSC) using the AoAC grading scale score plus Woodcock visual score. The outcome measure was sICH per the European Cooperative Acute Stroke Study III definition. A 3-month modified Rankin scale score 3-6 was designated as poor outcome.

Results: Compared with patients who had PACB <3, those with PACB ≥3 showed substantially higher risks of sICH (odds ratio [OR] = 2.567, 95% confidence interval [CI] = 1.187-5.550) and poor outcome (OR = 4.777, 95% CI = 1.659-13.756). According to receiver operating characteristic (ROC) curves, adding PACB to the regression model enhanced the predictive value for poor outcome (area under the ROC curve [AUC]: 0.718 vs. 0.519, Z = 2.340) and in patients receiving MT (AUC: 0.714 vs. 0.584, Z = 2.021), independently.

Conclusions: Factors related to PACB were consistent with common risk factors of systemic atherosclerosis. Low PACB scores indicated better prognosis. In patients with LAO following MT, PACB was useful in predicting sICH and poor clinical outcome.

Parathyroid carcinoma (PC) is a rare and aggressive endocrine malignancy with limited treatment options. Current treatments such as chemotherapy and radiotherapy have demonstrated limited efficacy. Here, we report the case of a male patient who presented with symptoms including polydipsia, polyuria, and joint pain. Further examination revealed a neck lump, hypercalcemia, and hyperparathyroidism, leading to a diagnosis of PC after en bloc surgery. Seven months later, the patient developed local recurrence and lung metastases, which were resected via left lateral neck dissection and thoracoscopic wedge resection. A 422-gene panel test revealed the presence of epidermal growth factor receptor (EGFR) p.L858R (c. T2573G) mutation, which may sensitize the EGFR-tyrosine kinase inhibitor response, and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) p.E545KV (c. G1633A) mutation. After multidisciplinary treatment discussions, the patient was treated with the multi-target tyrosine kinase inhibitor, anlotinib, resulting in survival benefits for 19 months. This case highlights the potential of targeted therapy in terms of long-term survival in patients with distant metastatic PC, as well as the importance of precision therapy guided by genome sequencing to identify potential therapeutic targets.

Objective: Existing isokinetic contractions are characterized using standardized angular velocities, which can induce differing adaptations. Here, we characterized the variation in the isokinetic parameters of knee extensors according to individualized angular velocity (IAV).

Methods: We performed a cross-sectional study of 19 young, healthy men. We measured the maximum angular velocity (MAV) of concentric knee extension using the isotonic mode of an isokinetic dynamometer. Isometric and isokinetic (at angular velocities corresponding to 100%, 70%, 40%, and 10% of each individual's MAV) knee extensor contractions were performed, and the peak torque and mean power were recorded.

Results: Peak torque significantly decreased with increasing IAV (129.42 ± 25.04, 84.37 ± 20.97, and 56.42 ± 16.18 Nm at 40%, 70%, and 100%, respectively), except for isometric contraction (233.36 ± 47.85) and at 10% of MAV (208 ± 48.55). At the mean power, 10% of MAV (74.52 ± 20.84 W) was significantly lower than the faster IAV (176.32 ± 49.64, 161.53 ± 56.55, and 145.95 ± 50.64 W at 40%, 70%, and 100%, respectively), and 100% was significantly lower than 40%.

Conclusion: The optimized IAV for isokinetic contraction to improve power output while maintaining torque is 10% to 40% of MAV. IAV may reflect both the velocity and force components of power because individuals do not have the same angular velocity.