BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective:To retrieve, evaluate, and summarize the best evidence on ultrasound-guided placement and tip confirmation of peripherally inserted central catheter (PICC) in neonates.Methods:Based on the "6S" evidence pyramid model, literature on ultrasound-guided placement and tip confirmation of PICC in neonates was sequentially searched on guideline websites, professional society websites, and journal databases. The search period was from database establishment to September 30, 2024. Two researchers used uniform criteria for independent quality assessment and evidence extraction from the literature, and the extracted evidence was integrated and summarized.Results:A total of ten articles were included, including five guidelines, one clinical decision, two expert consensus, one Meta-analysis, and one evidence summary. Thirty pieces of evidence were developed in six aspects: personnel qualification and training, catheter selection, assessment of placement veins, ultrasound-guided PICC puncture in neonates, PICC tip confirmation in neonates, and prevention and management of malposition.Conclusions:This study summarizes the best evidence for ultrasound-guided placement and tip confirmation of PICC in neonates. It is recommended that evidence be selected and applied to develop a standardized process for neonatal PICC placement in conjunction with the resource environment of the department and the skill level of the healthcare professionals to improve the quality of nursing and to ensure the safe and effective use of the PICC in clinical practice.

Objective:To retrieve, evaluate, and summarize the best evidence on ultrasound-guided placement and tip confirmation of peripherally inserted central catheter (PICC) in neonates.Methods:Based on the "6S" evidence pyramid model, literature on ultrasound-guided placement and tip confirmation of PICC in neonates was sequentially searched on guideline websites, professional society websites, and journal databases. The search period was from database establishment to September 30, 2024. Two researchers used uniform criteria for independent quality assessment and evidence extraction from the literature, and the extracted evidence was integrated and summarized.Results:A total of ten articles were included, including five guidelines, one clinical decision, two expert consensus, one Meta-analysis, and one evidence summary. Thirty pieces of evidence were developed in six aspects: personnel qualification and training, catheter selection, assessment of placement veins, ultrasound-guided PICC puncture in neonates, PICC tip confirmation in neonates, and prevention and management of malposition.Conclusions:This study summarizes the best evidence for ultrasound-guided placement and tip confirmation of PICC in neonates. It is recommended that evidence be selected and applied to develop a standardized process for neonatal PICC placement in conjunction with the resource environment of the department and the skill level of the healthcare professionals to improve the quality of nursing and to ensure the safe and effective use of the PICC in clinical practice.

Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.

Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.

Objective To investigate the effects of different sterilization methods on the quality of Astragali Radix decoction pieces by comparing the properties,odor,fingerprint,sterilization effect,extract and active component contents of Astragali Radix decoction pieces,and to further optimize the best sterilization process parameters of Astragali Radix decoction pieces.Methods The effects of moist heat sterilization,irradiation sterilization and dry heat sterilization on the quality of Astragali Radix decoction pieces were compared,and the best sterilization method was selected.Based on this,taking the content of astragaloside IV,the content of isoflavone glucoside,the total content of the two and the sterilization rate as the assessment indicators,taking the sterilization temperature,sterilization time and material thickness as the assessment factors,on the basis of the single-factor test,the response surface method was used to optimize the optimal dry heat sterilization process of Astragali Radix decoction pieces.Results The dry heat sterilization method was selected to sterilize Astragali Radix decoction pieces.The best process for dry heat sterilization was as follows:the sterilization temperature of 113℃,sterilization time of 5.1 h,and the material thickness of 19 mm.Conclusion Considering the sterilization effect,the influence on the content of active ingredients,operability and cost,selecting dry heat sterilization is the best sterilization method for Astragali Radix decoction pieces,and the optimal sterilization process is stable and feasible,with good repeatability,which can provide scientific basis for its industrial production application.

Purpose To investigate the clinicopathological and molecular features of colorectal micropapillary carcinoma(MPC),and to provide evidence for the diagnosis and individu-al treatment of colorectal MPC.Methods The clinicopathologi-cal and molecular data of 461 patients with colorectal cancer were collected retrospectively,including 56 cases of colorectal MPC and 405 cases of colorectal adenocarcinoma not otherwise specified(NOS).The expression of 4 mismatch repair proteins(MLH1,PMS2,MSH2,MSH6)and p53 protein was detected by immunohistochemistry.The hot spot mutations of KRAS,NRAS,PIK3CA and BRAF genes were detected by ARMS-PCR,to analyze the difference of clinicopathological and molec-ular features between colorectal MPC and adenocarcinoma NOS.Results The vessel invasion rate and lymph node metastasis rate of colorectal MPC were significantly higher than those of ad-enocarcinoma NOS(42.9％vs 23.0％,P=0.001;67.9％vs 46.2％,P=0.002).The incidence of mismatch repair defi-ciency in colorectal MPC was significantly lower than that in ade-nocarcinoma NOS(3.6％vs 13.8％,P=0.030).The hot spot mutation rate in exon 2,3 and 4 of KRAS gene in colorectal MPC was significantly higher than that in adenocarcinoma NOS(58.9％vs 42.2％,P=0.018),especially in KRAS G13D(17.9％vs 8.1％,P=0.019).The proportion of colorectal MPC components was not associated with clinicopathological and molecular features.There were no significant differences in clin-icopathological and molecular features between colorectal MPC and adenocarcinoma NOS with high-grade tumor budding.Con-clusion The clinicopathologic and molecular features of color-ectal MPC are different from those of adenocarcinoma NOS,and the diagnosis of this subtype may provide help for the formulation of treatment plan and the evaluation of prognosis.

Purpose To investigate the clinicopathological and molecular features of colorectal micropapillary carcinoma(MPC),and to provide evidence for the diagnosis and individu-al treatment of colorectal MPC.Methods The clinicopathologi-cal and molecular data of 461 patients with colorectal cancer were collected retrospectively,including 56 cases of colorectal MPC and 405 cases of colorectal adenocarcinoma not otherwise specified(NOS).The expression of 4 mismatch repair proteins(MLH1,PMS2,MSH2,MSH6)and p53 protein was detected by immunohistochemistry.The hot spot mutations of KRAS,NRAS,PIK3CA and BRAF genes were detected by ARMS-PCR,to analyze the difference of clinicopathological and molec-ular features between colorectal MPC and adenocarcinoma NOS.Results The vessel invasion rate and lymph node metastasis rate of colorectal MPC were significantly higher than those of ad-enocarcinoma NOS(42.9％vs 23.0％,P=0.001;67.9％vs 46.2％,P=0.002).The incidence of mismatch repair defi-ciency in colorectal MPC was significantly lower than that in ade-nocarcinoma NOS(3.6％vs 13.8％,P=0.030).The hot spot mutation rate in exon 2,3 and 4 of KRAS gene in colorectal MPC was significantly higher than that in adenocarcinoma NOS(58.9％vs 42.2％,P=0.018),especially in KRAS G13D(17.9％vs 8.1％,P=0.019).The proportion of colorectal MPC components was not associated with clinicopathological and molecular features.There were no significant differences in clin-icopathological and molecular features between colorectal MPC and adenocarcinoma NOS with high-grade tumor budding.Con-clusion The clinicopathologic and molecular features of color-ectal MPC are different from those of adenocarcinoma NOS,and the diagnosis of this subtype may provide help for the formulation of treatment plan and the evaluation of prognosis.

Objective:To improve the understanding of cervical papillary squamous cell carcinoma (PSCC), and to provide evidence for the diagnosis and treatment of PSCC.Methods:The clinicopathological and follow-up data of 18 patients diagnosed PSCC by preoperative cervical biopsy in Tangshan Gongren hospital were collected, the correlation of preoperative biopsy, liquid-based cells, and human papilloma virus (HPV) with postoperative pathology and prognosis was analyzed.Results:The concordance rate between preoperative biopsy and postoperative pathology was 50% (9/18). 4 patients showed the characteristic features of PSCC in their liquid-based cells of the 9 patients who were diagnosed as PSCC postoperatively (4/9), the HPV infection rate was 44.4% (4/9), the International Federation of Gynecology and Obstetrics stage were IA1-IB1, no lymph node metastasis, recurrence or death occurred in all patients.Conclusions:Cervical biopsy before operation has certain limitations in the diagnosis of PSCC, which requires a clear diagnosis by postoperative pathology. The HPV infection rate is lower, the stage is earlier and the prognosis is better in PSCC. Some patients can choose a less invasive surgical method than radical surgery.

Objective To analyze the correlation between CT characteristics and epidermal growth factor receptor (EGFR)mutations in pulmonary adenocarcinoma.Methods 82 patients (87 lesions)with pulmonary adenocarcinoma were retrospectively collected.All patients were underwent CT examination before operation,and EGFR gene were determined after operation.Results EGFR mutations were found in 44 of 87 lesions (50.57%).The EGFR mutations rate was 50.00% in females and 47.50% in males,there was no statistical difference between genders (P=0.821).The EGFR mutations rate was 46.55% in the right lung and 58.62% in the left lung,while no statistically significant difference was found (P=0.289).Among all the CT characteristics,the mutations rate was 63.89% in spiculated lesions and 60.71% in lesions with pleural indentation,the differences was statistically significant (P<0.05).The mutations rate was 59.25% in lesions containing solid component and 36.36% in pure ground glass opacity lesions,the difference was statistically significant (P=0.011). There were no statistically differences in lobulation,cavitation and lymphadenectasis (P>0.05).The pleural indentation was the highest in sensitivity (77.27%)and negative predictive value (67.74%).The spiculation was the highest in specificity (69.77%)and positive predictive value (63.89%).Conclusion Among all the CT characteristics,pleural indentation,spiculation and the lesion containing solid component are prone to EGFR mutations.