Computed tomography radiomics study of invasion and instability of lung adenocarcinoma manifesting as ground glass nodule.

Background: Ground-glass nodule (GGN) is the most common manifestation of lung adenocarcinoma on computed tomography (CT). Clinically, the success rate of preoperative diagnosis of GGN by puncture biopsy and other means is still low. The aim of this study is to investigate the clinical and radiomics characteristics of lung adenocarcinoma presenting as GGN on CT images using radiomics analysis methods, establish a radiomics model, and predict the classification of pathological tissue and instability of GGN type lung adenocarcinoma. Methods: This study retrospectively collected 249 patients with 298 GGN lesions who were pathologically confirmed of having lung adenocarcinoma. The images were imported into the Siemens scientific research prototype software to outline the region of interest and extract the radiomics features. Logistic model A (a radiomics model to identify the infiltration of lung adenocarcinoma manifesting as GGNs) was established using features after the dimensionality reduction process. The receiver operating characteristic (ROC) curve of the model on training set and the verification set was drawn, and the area under the curve (AUC) was calculated. Second, a total of 112 lesions were selected from 298 lesions originating from CT images of at least two occasions, and the time between the first CT and the preoperative CT was defined as not less than 90 days. The mass doubling time (MDT) of all lesions was calculated. According to the different MDT diagnostic thresholds instability was predicted. Finally, their AUCs were calculated and compared. Results: There were statistically significant differences in age and lesion location distribution between the "noninvasive" lesion group and the invasive lesion group (P<0.05), but there were no statistically significant differences in sex (P>0.05). Model A had an AUC of 0.89, sensitivity of 0.75, and specificity of 0.86 in the training set and an AUC of 0.87, sensitivity of 0.63, and specificity of 0.90 in the validation set. There was no significant difference statistically in MDT between "noninvasive" lesions and invasive lesions (P>0.05). The AUCs of radiomics models B1, B2 and B3 were 0.89, 0.80, and 0.81, respectively; the sensitivities were 0.71, 0.54, and 0.76, respectively; the specificities were 0.83, 0.77, and 0.60, respectively; and the accuracies were 0.78, 0.65, and 0.69, respectively. Conclusions: There were statistically significant differences in age and location of lesions between the "noninvasive" lesion group and the invasive lesion group. The radiomics model can predict the invasiveness of lung adenocarcinoma manifesting as GGNs. There was no significant difference in MDT between "noninvasive" lesions and invasive lesions. The radiomics model can predict the instability of lung adenocarcinoma manifesting as GGN. When the threshold of MDT was set at 813 days, the model had higher specificity, accuracy, and diagnostic efficiency.

EFHD2 regulates T cell receptor signaling and modulates T helper cell activation in early sepsis.

EFHD2 (EF-hand domain family, member D2) has been identified as a calcium-binding protein with immunomodulatory effects. In this study, we characterized the phenotype of Efhd2-deficient mice in sepsis and examined the biological functions of EFHD2 in peripheral T cell activation and T helper (Th) cell differentiation. Increased levels of EFHD2 expression accompanied peripheral CD4+ T cell activation in the early stages of sepsis. Transcriptomic analysis indicated that immune response activation was impaired in Efhd2-deficient CD4+ T cells. Further, Efhd2-deficient CD4+ T cells isolated from the spleen of septic mice showed impaired T cell receptor (TCR)-induced Th differentiation, especially Th1 and Th17 differentiation. In vitro data also showed that Efhd2-deficient CD4+ T cells exhibit impaired Th1 and Th17 differentiation. In the CD4+ T cells and macrophages co-culture model for antigen presentation, the deficiency of Efhd2 in CD4+ T cells resulted in impaired formation of immunological synapses. In addition, Efhd2-deficient CD4+ T cells exhibited reduced levels of phospho-LCK and phospho-ZAP70, and downstream transcription factors including Nfat, Nfκb and Nur77 following TCR engagement. In summary, EFHD2 may promote TCR-mediated T cell activation subsequent Th1 and Th17 differentiation in the early stages of sepsis by regulating the intensity of TCR complex formation.

Comparing Balloon Dilation to Non-Balloon Dilation for Access in Ultrasound-Guided Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. RESULTS: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). CONCLUSIONS: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

Comparing Balloon Dilation to Non-Balloon Dilation for Access in Ultrasound-Guided Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis

ABSTRACT Purpose: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). Materials and methods: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. Results: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). Conclusions: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

Relationships between the coronary fat attenuation index for patients with heart-related disease measured automatically on coronary computed tomography angiography and coronary adverse events and degree of coronary stenosis.

Background: Pericoronary artery coronary tissue (PACT) is a type of epicardial fat that can reflect the state of the coronary artery (inflammation, etc.). However, it cannot be reasonably and efficiently utilized in routine computed tomography (CT) examination. The aim of this study was to use artificial intelligence (AI) software to analyze coronary computed tomography angiography (CCTA) and measure the coronary perivascular fat attenuation index (FAI) of patients. The relationship between FAI and the occurrence of coronary adverse events and the degree of coronary stenosis were further analyzed. Methods: This study involved patients who experienced CCTA in West China Hospital, Sichuan University, from January 2012 to December 2012. These patients were followed up to 2020 and classified according to the occurrence of coronary adverse events and the degree of stenosis of the lumen. For all patients, AI software was used to analyze the CCTA images of patients, and the FAI of 3 coronary arteries, the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA), was measured. Moreover, the relationship between FAI and patients with different degrees of coronary stenosis and adverse coronary events was determined. Results: Comparisons between any 2 groups showed that the differences in the FAI among the 4 groups for the LAD were significant (all P values <0.05). There were no significant differences between the group with less-than-moderate stenosis (Mb) without adverse events and the group with moderate-or-above stenosis (M) with no adverse events for the LCX (P>0.05). For the remaining groups, FAI values exhibited statistically significant differences (P<0.05). According to the degree of lumen stenosis, the patients were divided into groups according to LAD, LCX, and RCA and the sum of the 3 vessels. There were significant differences in coronary FAI among the groups with different degrees of lumen stenosis for the sum of the 3 vessels, the LAD, and the LCX (P<0.05). Conclusions: FAI can reflect the state of the coronary artery, which is related to inflammation of the coronary lumen. Moreover, there is a relationship between FAI and the degree of stenosis in the coronary lumen: the narrower the coronary lumen is, the higher the FAI around the lumen.

Clinical characterization of EFHD2 (swiprosin-1) in Glioma-associated macrophages and its role in regulation of immunosuppression.

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.

The Association of Coronary Fat Attenuation Index Quantified by Automated Software on Coronary Computed Tomography Angiography with Adverse Events in Patients with Less than Moderate Coronary Artery Stenosis.

OBJECTIVE: This study analyzed the relationship between the coronary FAI on CCTA and coronary adverse events in patients with moderate coronary artery disease based on machine learning. METHODS: A total of 172 patients with coronary artery disease with moderate or lower coronary artery stenosis were included. According to whether the patients had coronary adverse events, the patients were divided into an adverse group and a non-adverse group. The coronary FAI of patients was quantified via machine learning, and significant differences between the two groups were analyzed via t-test. RESULTS: The age difference between the two groups was statistically significant (p < 0.001). The group that had adverse reactions was older, and there was no statistically significant difference between the two groups in terms of sex and smoking status. There was no statistical significance in the blood biochemical indexes between the two groups (p > 0.05). There was a significant difference in the FAIs between the two groups (p < 0.05), with the FAI of the defective group being greater than that of the nonperforming group. Taking the age of patients as a covariate, an analysis of covariance showed that after excluding the influence of age, the FAIs between the two groups were still significantly different (p < 0.001).

Declaration: Novel SLC3A1 mutation in a cystinuria patient with xanthine stones: a case report.

BACKGROUND: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported. CASE PRESENTATION: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia. The 23-year-old male patient was diagnosed with kidney and ureteral stones, solitary functioning kidney and hyperuricemia after admission to the hospital. The stones were removed by surgery and found to be composed of xanthine. CONCLUSION: Genetic testing by next-generation sequencing technology showed that the patient carried the homozygous nonsense mutation c.1113 C> A (p.Tyr371*) in the SLC3A1 gene, which was judged to be a functionally pathogenic variant. Sanger sequencing revealed that the patient's parents carried this heterozygous mutation, which is a pathogenic variant that can cause cystinuria. The 24-h urine metabolism analysis showed that the cystine content was 644 mg (<320 mg/24 h), indicating that the patient had cystinuria, consistent with the genetic test results. This case shows that cystinuria and xanthine stones can occur simultaneously, and provides evidence of a possible connection between the two conditions. Furthermore, our findings demonstrate the potential value of genetic testing using next-generation sequencing to effectively assist in the clinical diagnosis and treatment of patients with urinary calculi.

Androgen Receptor Transcriptionally Inhibits Programmed Death Ligand-1 Expression and Influences Immune Escape in Bladder Cancer.

In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.

Primary Pulmonary Artery Leiomyosarcoma with Pulmonary Metastasis Depicted on Enhanced Computer Tomography: A Case Description and an Analysis of the Literature.

Pulmonary artery leiomyosarcoma is an extremely rare disease, with only a few dozen cases reported worldwide to date. This disease is easily misdiagnosed as pulmonary thromboembolism, leading to improper treatment and accurate diagnosis in the later stages of the disease. Furthermore, this delayed diagnosis may also be the reason for the extremely high mortality rate of patients suffering from it. Early invasive surgery with the goal of complete surgical resection is the standard treatment method. Chemotherapy and radiation therapy have been tried with variable outcomes.

Comparison of the Efficacy of ShuoTong Ureteroscopy and Simple Flexible Ureteroscopy in the Treatment of Unilateral Upper Ureteral Calculi.

Background: ShuoTong ureteroscopy (Sotn-ureteroscopy, ST-URS), a new lithotripsy operation method developed on the basis of ureteroscopy, is widely used to treat ureteral stones in China. Its composition includes rigid ureteral access sheath, standard mirror, lithotripsy mirror, and ShuoTong perfusion aspirator (ST-APM). Here, we compared the efficacy and safety of the ST-URS and the flexible ureteroscope (F-URS) holmium laser lithotripsy in the treatment of unilateral upper ureteral calculi. Methods: Retrospective analysis was conducted on the clinical data of 280 patients who met the inclusion 1) urinary tract CT was diagnosed with unilateral single upper ureteral calculi above the L4 lumbar spine; 2) patient age was from 18 to 80 years old; 3) patients were informed and consented to this study; and 4) patients were approved by the hospital ethics committee (proof number: KY-2019-020) and the exclusion criteria for unilateral upper ureteral calculi in the First Affiliated Hospital of Xiamen University from January 2018 to November 2020, and they were divided into the ST-URS group and the flexible ureteroscopy (F-URS) group. Results: The stone-free rate of 1 day after operation of the ST-URS group was significantly higher than the F-URS group (63.71 vs. 34.62%, P < 0.0001). The operative time (38.45 vs. 46.18 min, P = 0.005) and hospitalization cost (27,203 vs. 33,220 Yuan, P < 0.0001) of the ST-URS group were significantly lower than the F-URS group. There were no significant differences in the success rate of ureteral access sheath placement, operative blood loss, stone-free rate of 1 month after operation, postoperative complications, postoperative hospital stay, and postoperative visual analog scale (VAS) pain score between the two groups (P > 0.05). In subgroups of a diameter of calculi ≥ 1.5 cm, calculi CT numerical value ≥ 1,000 Hounsfield unit and the preoperative hydronephrosis range ≥ 3.0 cm, ST-URS shows more advantages in the operative time, stone-free rate of 1 day after the operation, the hospitalization cost, and the incidence of postoperative complications. Conclusion: In unilateral upper ureteral stones treated with a holmium laser, compared with the simple F-URS, the ST-URS has a shorter operative time, lower hospitalization cost, and a higher stone-free rate of 1 day after the operation, suggesting that the ST-URS could be more widely applied in clinics.