Effect of Dexmedetomidine on Apoptosis and Early Cognitive Dysfunction in Rats Following Propofol Anesthesia.

Background: To address the intricate interplay between surgical anesthesia, hippocampal apoptosis, and early cognitive dysfunction in rats, this study delves into the impact of dexmedetomidine (DEX). With a focus on understanding the alterations in the PI3K/Akt pathway, our investigation aims to shed light on the comprehensive dynamics of these processes. Methods: Sixty healthy Sprague-Dawley rats were randomly divided into three groups: controls (intraperitoneal saline injection), group A (intraperitoneal propofol injection), and group A + DEX (intraperitoneal propofol and DEX injection), with 20 rats in each group. Cognitive function in the three groups was evaluated using [specify the cognitive function tests, e.g., Morris Water Maze]. The assessment was conducted at various postoperative time points. We employed Hematoxylin-eosin (HE) staining, flow cytometry (FC), Western blot (WB), and real-time fluorescence quantitation polymerase chain reaction (RT-qPCR) to examine hippocampal apoptosis and gene expression. Results: Rats in groups A and A + DEX exhibited higher cognitive scores (NSS) and escape latencies at each postoperative time point, along with a lower proportion of swimming distance (SD) in the target quadrant (TQ) compared to controls. Group A + DEX demonstrated lower NSS and escape latency than controls, accompanied by a higher proportion of SD in TQ. Apoptosis rates of hippocampal cells were higher in groups A and A + DEX than in controls, although they were relatively lower in group A + DEX (P < .05). Regarding gene expression, the relative expression (RE) of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and Bax and caspase3 were altered. Group A + DEX showed higher RE of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and lower Bax and caspase3 than group A (P < .05). For a detailed understanding of the magnitude of these changes, specific values or ranges are provided in the subsequent results section. Conclusion: In conclusion, the combined use of surgical anesthesia with DEX demonstrates a modulatory effect on the PI3K/Akt signaling pathway. This intervention proves effective in reducing hippocampal cell apoptosis post-surgery, thereby alleviating neurological impairments and ameliorating early cognitive dysfunction in rats. Our findings underscore the potential therapeutic impact of DEX in enhancing cognitive outcomes following surgical procedures. The observed reduction in hippocampal cell apoptosis and improvement in cognitive function suggest that DEX may hold promise as a neuroprotective agent in the perioperative setting. These outcomes highlight the clinical relevance of considering DEX as an adjunctive therapy to mitigate cognitive dysfunction associated with surgery. Further investigations and clinical trials are warranted to validate and extend these findings, potentially offering a novel avenue for improving patient outcomes and advancing perioperative care strategies.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

Imaging features of sentinel lymph node mapped by multidetector-row computed tomography lymphography in predicting axillary lymph node metastasis.

INTRODUCTION: Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. METHODS: 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58-91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773-0.939, P < 0.001), respectively. CONCLUSION: ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.

In Vitro Expression of Cytokeratin 19 in Adipose-Derived Stem Cells Is Induced by Epidermal Growth Factor.

BACKGROUND Cytokeratin 19 (CK19) is a typical epithelial marker. In this study, we determined whether epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) could enhance CK19 expression in adipose-derived stem cells (ADSCs), thereby inducing the differentiation of ADSCs into epithelial-like cells. MATERIAL AND METHODS ADSCs were isolated from perinephric fat, and the expression of CD29, CD90, and CD105 was confirmed. Following isolation, ADSCs were cultured in static medium or medium containing EGF or bFGF. RESULTS Flow cytometry revealed that EGF and bFGF could alter mesenchymal stem cell markers as well as the cell cycle of ADSCs. Western blotting and immunofluorescence revealed that after 14 days, EGF treatment enhanced the expression of CK19 in ADSCs. CONCLUSIONS Our findings offer important insight for the clinical use of ADSCs in the generation of epithelial-like cells in the future.

Efficient production of human zona pellucida-3 in a prokaryotic expression system.

The zona pellucida-3 (ZP3) protein plays a pivotal role in oocyte and gamete development. We aimed to produce a recombinant ZP3 peptide using the Escherichia coli secretory system and apply it to a protein chip for detecting anti-ZP3 antibodies. The ZP3 gene was cloned into the pHOA downstream of the phoA promoter and transformed into E. coli YK537. Recombinant ZP3 was secretory expressed by decreasing the inorganic phosphate concentration. Then, rZP3 was purified and coated onto a protein chip, which was used to detect AZP3A in serum samples from 63 infertile patients. The area under the receiver operating characteristic curve was 0.934. The results, in terms of AZP3A detection, of the rZP3-coated protein chip were consistent with those of the ELISA kit. Therefore, our protein chip assay has potential for diagnosis of infertility due to AZP3A, and represents a less costly and simpler assay for clinical and research applications.

Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma.

OBJECTIVES: To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). METHODS: Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. RESULTS: The APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the PBZ were significantly lower in the SBM group than in the GBM group (P < 0.001). The APTwmin values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms. CONCLUSION: As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs. KEY POINTS: • APTw values in the tumour core were not different between SBMs and GBMs. • APTw values in peritumoral brain zone were lower in SBMs than in GBMs. • The APTw min was the best parameter to distinguish SBMs from GBMs.

CT imaging-based determination and classification of anatomic variations of left gastric vein.

BACKGROUND: Precise determination and classification of left gastric vein (LGV) anatomy are helpful in planning for gastric surgery, in particular, for resection of gastric cancer. However, the anatomy of LGV is highly variable. A systematic classification of its variations is still to be proposed. We aimed to investigate the anatomical variations in LGV using CT imaging and develop a new nomenclature system. METHOD: We reviewed CT images and tracked the course of LGV in 825 adults. The frequencies of common and variable LGV anatomical courses were recorded. Anatomic variations of LGV were proposed and classified into different types mainly based on its courses. The inflow sites of LGV into the portal system were also considered if common hepatic artery (CHA) or splenic artery (SA) could not be used as a frame of reference due to variations. RESULTS: Detailed anatomy and courses of LGV were depicted on CT images. Using CHA and SA as the frames of reference, the routes of LGV were divided into six types (i.e., PreS, RetroS, Mid, PreCH, RetroCH, and Supra). The inflow sites were classified into four types (i.e., PV, SV, PSV, and LPV). The new classification was mainly based on the courses of LGV, which was validated with MDCT in the 805 cases with an identifiable LGV, namely type I, RetroCH, 49.8 % (401/805); type II, PreS, 20.6 % (166/805); type III, Mid, 20.0 % (161/805); type IV, RetroS, 7.3 % (59/805); type V, Supra, 1.5 % (12/805); and type VI, PreCH, 0.7 % (6/805). Type VII, designated to the cases in which SA and CHA could not be used as frames of reference, was not observed in this series. CONCLUSIONS: Detailed depiction of the anatomy and courses of LGV on CT images allowed us to evaluate and develop a new classification and nomenclature system for the anatomical variations of LGV.

A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins.

AIM: The accumulation of disease-causing proteins is a common hallmark of many neurodegenerative disorders. Measuring the degradation of such proteins using high-throughput-compatible assays is highly desired for the identification of genetic and chemical modulators of degradation. For example, Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder caused by the cytotoxicity of mutant huntingtin protein (mHTT). The high-throughput measurement of mHTT degradation is important in HD drug discovery and research. Existing methods for such purposes have limitations due to their dependence on protein tags or pan protein synthesis inhibitors. Here, we report a high-throughput-compatible pulse-chase method (CH-chase) for the measurement of endogenous tag-free huntingtin protein (HTT) degradation based on Click chemistry and Homogeneous Time Resolved Fluorescence (HTRF) technologies. METHODS: The pulsed-labeled proteins were conjugated with biotin using the click reaction strain-promoted alkyne-azide cycloaddition (SPAAC), and the chase signals were calculated by measuring the reduction percentage of the HTT HTRF signals after pull-down with streptavidin beads. RESULTS: We validated that the signals were within the linear detection range and were HTT-specific. We successfully measured the degradation of endogenous HTT in a high-throughput-compatible format using 96-well plates. The predicted changes of HTT degradation by known modifiers were observed, which confirmed that the assay is suitable for the identification of HTT degradation modifiers. CONCLUSION: We have established the first high-throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies.

Absence of the superior mesenteric artery in an adult and a new classification method for superior-inferior mesenteric arterial variations.

PURPOSE: This paper aims to report the complete absence of the superior mesenteric artery (SMA) in an adult and to propose a new classification method for the superior-inferior mesenteric arterial variations (SIMAV). METHODS: A 69-year-old female was referred for abdominal pain and change of stool habits and characteristics. Multi-detector computed tomography (MDCT) was performed. Based on the CT findings of the patient and previous reports on the abnormalities of the superior-inferior mesenteric arteries, attempt was made to propose a new classification method for SIMAV. RESULTS: MDCT with enhancement revealed complete absence of SMA and compensatory dilation of the inferior mesenteric artery (IMA). Aneurysm of the splenic artery and both inferior phrenic arteries aberrantly arising from the aorta at the same level of the celiac trunk were also noted. Based on our case and literature reports, we were able to propose a new classification method for SIMAV. Without considering the relationship with the celiac arteries, SIMAV can be divided into 4 types. Type I is the normal type or "textbook" type. In type II, SMA is defective and in type III, IMA is defective. In type IV, there is an aberrant middle mesenteric artery (MMA). CONCLUSIONS: Complete absence of SMA is extremely rare. However, awareness of such a variation is of great importance during operations for rectal and sigmoid cancer. In such patients, ligation of the trunk of IMA, which is the only artery for the entire intestine, will lead to disastrous consequence. The new classification method may be helpful in the scientific and systematic description of SIMAV.

Sinonasal squamous cell carcinoma in the United States: Temporal and geographic patterns associated with HPV testing and positivity.

OBJECTIVES: Human papillomavirus (HPV) has emerged as a potential etiological factor in sinonasal squamous cell carcinoma (SNSCC), but a clear understanding of HPV prevalence and its temporal patterns in SNSCC remains elusive. This study aimed to investigate temporal trends in HPV testing and positivity rates, and explore demographic and geographic factors associated with these trends. METHODS: A retrospective cohort study included patients diagnosed with invasive SNSCC between 2011 and 2017 from the US National Cancer Database (NCDB). Prevalence ratios (PR) of HPV positivity and testing rates were estimated with the corresponding 95% confidence interval (95% CI). RESULTS: The overall HPV testing rate was 45.4 % (N = 1762/3880), and the prevalence of HPV testing significantly decreased during the study period (adjusted PR: 0.97, 95 % CI: 0.95 - 0.99, p < 0.001). Overall HPV positivity frequency was 37.3 % (N = 650/1741), and the overall prevalence of HPV positive tumors significantly increased during the study period (adjusted PR: 1.04, 95 % CI: 1.02 - 1.05, p < 0.001). The increase in HPV positivity rate was observed solely in the white population (unadjusted PR: 1.10, 95 % CI: 1.06 - 1.14; p < 0.001). A significant geographical variation was observed for both HPV testing (range: 28.6 % - 61.7 %) and positivity (range: 28.3 % - 44.7 %). CONCLUSIONS: This study provides novel insights into the temporal trends and demographic factors associated with HPV testing and positivity in SNSCC. Despite increasing HPV positivity rates, disparities in testing rates persist, highlighting the need for standardized testing protocols and targeted interventions.

GABAergic imbalance in Parkinson's disease-related depression determined with MEGA-PRESS.

OBJECTIVE: The pathogenesis of depression in patients with Parkinson's disease (PD) is poorly understood. Therefore, this study aimed to explore the changes in γ-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) levels in patients with PD with or without depression determined using MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS). MATERIALS AND METHODS: A total of 83 patients with primary PD and 24 healthy controls were included. Patients with PD were categorized into depressed PD (DPD, n = 19) and nondepressed PD (NDPD, n = 64) based on the 17-item Hamilton Depression Rating Scale. All participants underwent T1-weighted imaging and MEGA-PRESS sequence to acquire GABA+ and Glx values. The MEGA-PRESS sequence was conducted using 18.48 mL voxels in the left thalamus and medial frontal cortex. The GABA+, Glx, and creatine values were quantified using Gannet 3.1 software. RESULTS: The GABA+ and Glx values were not significantly disparate between patients with PD and controls in the thalamus and medial frontal cortex. However, the levels of N-acetyl aspartate/creatine and choline/creatine in the left thalamus were significantly lower in patients with PD than in controls (P = .031, P = .009). The GABA+/Water and GABA+/Creatine in the medial frontal cortex were higher in DPD than in NDPD (P = .001, P = .004). The effects of depression on Glx or other metabolite levels were not evident, and no significant difference in metabolite values was noted in the left thalamus among all groups (P > .05). CONCLUSIONS: GABA+ levels increased in the medial frontal cortex in DPD, which may be more closely related to depressive pathology. Thus, alterations in GABAergic function in special brain structures may be related to the clinical manifestations of PD symptoms, and hence mediating this function might help in treating depression in PD.

Assessment of BRCA1 and BRCA2 Germline Variant Data From Patients With Breast Cancer in a Real-World Data Registry.

PURPOSE: The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power. METHODS: Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines. RESULTS: In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality. CONCLUSION: We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.

Fecal Impaction and Nonperforated Stercoral Colitis: Red Flags for Poor Outcomes.

Fecal impaction and stercoral colitis are common, yet little research has been performed on the associated mortality risk. We performed a retrospective cohort study of 970 hospital encounters representing 885 unique patients in which fecal impaction or stercoral colitis was identified in CT reports. Among the 535 patients with fecal impaction, 13.3% died or were discharged to hospice, compared to 13.1% among the 428 patients with nonperforated stercoral colitis (p = 0.93). Of the seven patients with perforation, five died or were discharged to hospice. The risk of death or discharge to hospice for patients with fecal impaction or nonperforated stercoral colitis aged 18-49 was 2.9% and rose approximately 4% each decade thereafter to 21.9% for patients 90 and older (p< 0.001). Patients with a body mass index of 25-30 had an 8.1% risk of death or discharge to hospice, compared to 23.4% for those with a BMI < 18.5 (p< 0.001). Patients with at least one ICD-10 code for dementia, paralysis/neuromuscular disease, or malnutrition/failure to thrive had a risk of death or discharge to hospice of 21.6%, compared to 1.9% among patients with none of these risk factors (p< 0.001). ICD-10 codes for sepsis were associated with 90.0% of the deaths and 44.3% of the discharges to hospice. Patients diagnosed in less than three hours had a risk of death or discharge to hospice of 8.0%, compared to a risk of 20.1% for those diagnosed in ≥ 12 hours (p< 0.001).

Racial and Ethnic Variations in Pre-Diagnosis Comorbidity Burden and Health-Related Quality of Life Among Older Women with Breast Cancer.

BACKGROUND: This study examined racial/ethnic differences in comorbidity burden and health-related quality of life (HRQOL) among older women before breast cancer diagnosis. METHODS: From Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked data resource, 2513 women diagnosed with breast cancer at ≥ 65 years between 1998 and 2012 were identified and grouped based on comorbidity burden using latent class analysis. Pre-diagnosis HRQOL was measured using SF-36/VR-12 and summarized to physical (PCS) and mental component summary (MCS) scores. The adjusted least-square means and 95% confidence intervals were obtained according to comorbidity burden and race/ethnicity. The interactions were examined with 2-way ANOVA. RESULTS: The latent class analysis revealed four comorbid burden classes, with Class 1 being the most healthy and Class 4 being the least healthy. African American (AA) and Hispanic women were more likely to be in Class 4 than non-Hispanic white (NHW) women (18.6%, 14.8%, and 8.3%, respectively). The mean PCS was 39.3 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There were no racial/ethnic differences in Classes 1 and 2, while NHW women reported significantly lower PCS scores than AA women in Classes 3 and 4. The mean MCS was 51.4 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There was no racial/ethnic difference in Class 3; however, AA women reported lower MCS scores than Asian/Pacific Islander women in Class 1, and AA and Hispanic women reported lower MCS scores than NHW women in Classes 2 and 4. CONCLUSION: Comorbidity burden negatively affected HRQOL but differentially for racial/ethnic groups. As the comorbidity burden increases, NHW women are more concerned with physical HRQOL, while AA and Hispanic women are more concerned with mental HRQOL.

Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis.

OBJECTIVE: Our current study tried to assay the role of long noncoding RNAs (lncRNAs) TLR8-AS1 in regulating preeclampsia. METHODS: TLR8-AS1 expression was examined in the clinical placental tissues of preeclampsia patients and the trophoblast cells induced by lipopolysaccharide (LPS). Then, different lentivirus was infected into trophoblast cells to study the role of TLR8-AS1 in cell functions. Furthermore, interactions among TLR8-AS1, signal transducer and activator of transcription 1 (STAT1) and toll-like receptor 8 (TLR8) were determined. A rat model of preeclampsia induced by N(omega)-nitro-L-arginine methyl ester was developed to validate the in-vitro findings. RESULTS: High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. In addition, overexpression of TLR8-AS1 arrested the proliferation, migration and invasion of trophoblast cells, which was related to the upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, and thus promoted the transcription of TLR8. Meanwhile, overexpression of TLR8-AS1 was shown to aggravate preeclampsia by elevating TLR8 in vivo . CONCLUSION: Our study confirmed that TLR8-AS1 aggravated the progression of preeclampsia through increasing the expression of STAT1 and TLR8.

Association between adjuvant radiation treatment and breast cancer-specific mortality among older women with comorbidity burden: A comparative effectiveness analysis of SEER-MHOS.

BACKGROUND: The National Comprehensive Cancer Network suggested that older women with low-risk breast cancer (LRBC; i.e., early-stage, node-negative, and estrogen receptor-positive) could omit adjuvant radiation treatment (RT) after breast-conserving surgery (BCS) if they were treated with hormone therapy. However, the association between RT omission and breast cancer-specific mortality among older women with comorbidity is not fully known. METHODS: 1105 older women (≥65 years) with LRBC in 1998-2012 were queried from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource and were followed up through July 2018. Latent class analysis was performed to identify comorbidity burden classes. A propensity score-based inverse probability of treatment weighting (IPTW) was applied to Cox regression models to obtain subdistribution hazard ratios (HRs) and 95% CI for cancer-specific mortality considering other causes of death as competing risks, overall and separately by comorbidity burden class. RESULTS: Three comorbidity burden (low, moderate, and high) groups were identified. A total of 318 deaths (47 cancer-related) occurred. The IPTW-adjusted Cox regression analysis showed that RT omission was not associated with short-term, 5- and 10-year cancer-specific death (p = 0.202 and p = 0.536, respectively), regardless of comorbidity burden. However, RT omission could increase the risk of long-term cancer-specific death in women with low comorbidity burden (HR = 1.98, 95% CI = 1.17, 3.33), which warrants further study. CONCLUSIONS: Omission of RT after BCS is not associated with an increased risk of cancer-specific death and is deemed a reasonable treatment option for older women with moderate to high comorbidity burden.

MR Finding of Extraventricular Neurocytoma.

OBJECTIVE: To determine the MR (magnetic resonance), pathologic, and clinical findings of extraventricular neurocytoma (EVN). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Radiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China, from January 2020 to March 2022. METHODOLOGY: The MR radiological and pathological data of 11 patients with EVNs proved by histopathology after surgery were analysed retrospectively. Above-mentioned features were studied. RESULTS: There were 5 men and 6 women, ages ranging from 16 to 56 years. Seven cases (63.6%) were located in the cerebral hemisphere, three cases (27.3%) in the cerebellar hemisphere, and one case in cervical cord. Ten cases (91.0%) were cystic-solid, and one case was predominantly solid with small cystic components. Six cases (54.5%) had mild peritumoural ooedema. The signal was isointense (8/11, 72.7%) or hypointense (3/11, 27.3%) on T1WI, and isointense (1/11, 9.1%) or hyperintense (10/11, 90.9%) on T2WI; all cases showed hyperintense on FLAIR and restricted diffusion on DWI. Haemorrhage was found in two cases (18.2%) and flow-void was found in one case (9.1%). All the tumours demonstrated contrast enhancement. CONCLUSION: An accurate diagnosis of EVN is difficult to be made preoperatively. It should be considered when a solid-cystic tumour with the solid part showing isointense on T1WI, hyperintense on FLAIR with mild to moderate enhancement especially restricted diffusion on DWI sequence in patients aged 20-30. When the radiologic manifestations are atypical, more aggressive treatment should be chosen. KEY WORDS: Neurocytoma, Extraventricular, Clinical, Imaging characteristics, MRI.

CT-guided core needle biopsy of the lung in patients with primary malignancy suspected of lung metastasis: 5-year experience from a single institution.

PURPOSE: We aimed to evaluate the diagnostic accuracy and safety profile of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) in patients with primary malignancy suspected of lung metastasis and assess possible factors associated with nondiagnostic results. METHODS: All PTNBs with core needle performed in our hospital from January 2014 to January 2019 were retrospectively reviewed. Overall, 108 cases were found to have a history of primary malignancy with suspected lung metastasis. Patient demographics, lesion characteristics, procedure techniques and complications were evaluated as predictors of overall diagnosis, final diagnosis of lung metastasis, and nondiagnostic results. Statistical analysis was performed using univariate analysis. RESULTS: The overall diagnostic accuracy of PTNB was 83.3%. Lung metastasis was found in 52.8% of PTNBs (57 of 108) and nondiagnostic results were present in 27.6% (18 of 108). Of the 18 cases with nondiagnostic results, 11 cases had a final diagnosis of lung metastasis (61.1%), yielding PTNB a sensitivity of 83.8% and specificity of 100% for the detection of lung metastasis. Smaller lesion size (p = 0.014), pneumothorax (p = 0.026), and hemoptysis (p = 0.014) were significantly associated with overall nondiagnostic results. Similarly, smaller lesion size (p = 0.047), pneumothorax (p = 0.019), high-grade pulmonary hemorrhage (p = 0.019), and hemoptysis (p = 0.012) were significantly correlated with unsuccessful biopsies in the diagnosis of lung metastasis. CONCLUSION: CT-guided core needle biopsy of the lung in patients with primary malignancy suspected of lung metastasis has a high diagnostic accuracy with acceptable complication rates. Small lesion size, pneumothorax, high-grade pulmonary hemorrhage, and hemoptysis are significantly associated with nondiagnostic results in the final diagnosis of lung metastasis. Repeat biopsy and clinical/radiological follow-up should be considered in cancer patients with nondiagnostic results due to the high probability of lung metastasis.

Association between coexisting intracranial artery and extracranial carotid artery atherosclerotic diseases and ipsilateral cerebral infarction: a Chinese Atherosclerosis Risk Evaluation (CARE-II) study.

BACKGROUND: To evaluate the association between coexisting intracranial and extracranial carotid artery atherosclerotic diseases and ipsilateral acute cerebral infarct (ACI) in symptomatic patients by using magnetic resonance (MR) vessel wall imaging. METHODS: Symptomatic patients were recruited from a cross-sectional, multicentre study of Chinese Atherosclerosis Risk Evaluation (CARE-II). All patients underwent MR imaging for extracranial carotid arterial wall, intracranial artery and brain. Coexisting intracranial stenosis ≥50% and extracranial carotid artery mean wall thickness (MWT) ≥1 mm and plaque compositions at the same side were evaluated and the ipsilateral ACI was identified. The association between coexisting atherosclerotic diseases and ACI was evaluated using logistic regression. RESULTS: 351 patients were recruited. Patients with ipsilateral ACI had significantly greater prevalence of coexisting intracranial stenosis ≥50% and carotid MWT ≥1 mm (20.5% vs 4.9%, p<0.001), calcification (15.1% vs 4.4%, p=0.001) and lipid-rich necrotic core (LRNC) (19.2% vs 7.8%, p=0.002) compared with those without. Coexisting intracranial artery stenosis ≥50% and carotid MWT ≥1 mm (OR 5.043, 95% CI 2.378 to 10.694; p<0.001), calcification (OR 3.864, 95% CI 1.723 to 8.664; p=0.001) and LRNC (OR 2.803, 95% CI 1.455 to 5.401; p=0.002) were significantly associated with ipsilateral ACI. After adjusting for confounding factors, the aforementioned associations remained statistically significant (intracranial stenosis ≥50% coexisting with carotid MWT ≥1 mm: OR 4.313, 95% CI 1.937 to 9.601, p<0.001; calcification: OR 3.606, 95% CI 1.513 to 8.593, p=0.004; LRNC: OR 2.358, 95% CI 1.166 to 4.769, p=0.017). CONCLUSIONS: Coexistence of intracranial artery severe stenosis and extracranial carotid artery large burden and intraplaque components of calcification and LRNC are independently associated with ipsilateral ACI. TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov/. Unique identifier: NCT02017756.