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*

ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF

OBJECTIVE To investigate the application value of narrow-band CE-Chirp ASSR(NB CE-Chirp ASSR)and modulated acoustic ASSR in the assessment of hearing threshold in children with hearing impairment.METHODS Forty-eight children with sensorineural hearing loss were tested by pure tone audiometry(PTA),NB CE-Chirp ASSR and modulated acoustic ASSR.According to the results of pure tone audiometry,they were divided into mild to moderate group(48 ears)and severe to profound group(48 ears).The difference and correlation between pure tone hearing threshold and ASSR response threshold of different stimuli were compared between 500-4 000 Hz.RESULTS The absolute differences between the NB CE-Chirp ASSR response threshold and the PTA threshold in 48 children were all smaller than the differences between the modulated acoustic ASSR response threshold and the PTA threshold,and the differences were statistically significant(P<0.001).Under the same stimulus sound,the absolute difference between ASSR response threshold and pure tone hearing threshold in the mild to moderate group was higher than that in the severe to very severe group.The correlation coefficients between NB CE-Chirp ASSR threshold and pure tone hearing threshold are higher than those between modulated sound ASSR threshold and pure tone hearing threshold at 500-4 000 Hz.The test time of NB CE-Chirp ASSR[(20.92±9.33)min]was significantly shorter than that of modulated acoustic ASSR[(33.68±10.97)min](P=0.004).CONCLUSION NB CE-Chirp ASSR can more accurately assess the hearing threshold of children with different degrees of hearing loss than modulated acoustic ASSR.

Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16％.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P＜0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P＜0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.

Objective:To investigate the effect of uridine diphosphate ceramide galactosyltransferase 8(UGT8)on colorectal cancer(CRC)cell growth and migration,elucidate an underlying mechanism,and assess the potential regulatory role of SRY-box transcription factor 9(SOX9)on UGT8.Methods:UGT8 and SOX9 mRNA expression levels in CRC tissues,and correlation between their expression levels,were analyzed using GEPIA2,UALCAN,and TIMER 2.0 online databases.UGT8 and SOX9 protein expression in CRC and adjacent tissues was detec-ted using immunohistochemistry,and relationships between their expression and clinicopathological characteristics were analyzed.Impact of UGT8 knockdown on CRC cell proliferation was assessed using a CCK-8 assay,and cell migration was evaluated using Transwell and wound healing assays.Western blot was performed to detect expression of epithelial-mesenchymal transition(EMT)markers(E-cadherin and ZEB1).RT-qPCR and Western blot were used to measure UGT8 mRNA and protein expression levels after SOX9 knockdown.The JASPAR online database was used to assess SOX9 potential for binding to the UGT8 promoter.Results:Bioinformatics analyses revealed significantly higher mRNA expression levels of both UGT8 and SOX9 in CRC tissues than in normal tissues.Positive correlation was observed between expres-sion levels.Immunohistochemistry results showed that tumor UGT8 and SOX9 protein levels were significantly higher than those in adjacent tissues.UGT8 protein level was found to correlates with N stage,and SOX9 protein level correlated with T stage.A positive correlation was observed between UGT8 and SOX9 expression levels.Following UGT8 knockdown,cell proliferation capacity was attenuated and cell migra-tion ability was reduced.E-cadherin expression concurrently increased and ZEB1 expression decreased.RT-qPCR and Western blot results showed that SOX9 knockdown significantly reduced UGT8 mRNA and protein levels.The JASPER website predicts that SOX9 will bind to the UGT8 promoter.Conclusions:UGT8 and SOX9 are highly expressed in CRC tissues,and their expression levels correlate with clinicopatholo-gical features.UGT8 and SOX9 expression levels display significant positive correlation.Mechanistically,UGT8 promotes CRC cell prolifera-tion and migration by facilitating epithelial-mesenchymal transition(EMT).SOX9 enhances UGT8 mRNA and protein expression and may bind to the UGT8 promoter region.

Objective To screen specific antibodies to Helicobacter pylori(H.pylori)in serum,and establish antibody panels and discrimination models for different infection status,which are non-invasive and suitable for gastric cancer screening in Chinese population.Methods A total of 300 subjects with different H.pylori statuses were enrolled depending on an endoscopy screening cohort in a high-risk area of gastric cancer,including current,past,and negative infections.The recomLine Helicobacter IgG 2.0 immunoblotting assay was used to analyze and screen 10 H.pylori specific antibodies in serum samples.Results A total of nine antibody reactivity against CagA,VacA,GroEL,FliD,HpaA,gGT,HtrA,NapA,and CtkA showed significant differences among different H.pylori infection status groups(all P＜0.05).A panel comprising the nine antibodies distinguished exposure subjects to H.pylori(current and past infections)from negatives,with an area under the curve(AUC)of 0.935(95%CI:0.907-0.963).The combination of four antibodies(CagA,GroEL,FliD,and gGT)may help to discriminate current and past infection subjects,with an AUC of 0.927(95%CI:0.891-0.964).Conclusion The antibody panels and discriminant models for H.pylori infection status established in the present study may provide a potential and non-invasive screening method for the development of precise gastric cancer prevention strategies.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.