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*

The disease burden of valvular heart disease (VHD) is increasing with the aging of our society. This paper introduces the disease characteristics of VHD, the current status and problems on postoperative cardiac rehabilitation in VHD patients, the difficulties and solutions in the development of postoperative cardiac rehabilitation programs for VHD patients, and proposes future research directions, with a view to providing a reference for carrying out postoperative cardiac rehabilitation in VHD patients.

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

The disease burden of valvular heart disease (VHD) is increasing with the aging of our society. This paper introduces the disease characteristics of VHD, the current status and problems on postoperative cardiac rehabilitation in VHD patients, the difficulties and solutions in the development of postoperative cardiac rehabilitation programs for VHD patients, and proposes future research directions, with a view to providing a reference for carrying out postoperative cardiac rehabilitation in VHD patients.

Objective To explore the influencing factors of gastric cancer and construct the clinical prediction model.Methods From December 2020 to October 2023,the clinical data of 1000 patients with stomach neoplasm admitted to Putuo Hospital,Shanghai U-niversity of Traditional Chinese Medicine and Shuguang Hospital,Shanghai University of Traditional Chinese Medicine were collected.Af-ter data cleaning and eliminating abnormal values,the patients were divided into gastric polyps group(n=487)and gastric cancer group(n=479).Non-parametric test was used to screen out meaningful indicators,Lasso regression to screen out the characteristic factors re-lated to gastric cancer with non-zero coefficient,and stepwise Logistic regression analysis to screen out the factors with significant correla-tion,and Lasso-Logistic regression model was constructed.The receiver operator characteristic(ROC)curve was plotted to calculate the area under the curve(AUC)and the confusion matrix to evaluate the model efficiency.Results The results of multivariate Logistic re-gression analysis showed that age,white blood cell(WBC)count,monocyte(M)count,alanine amiontransferase(ALT),cancer anti-gen 724(CA724),cancer antigen 242(CA242),cancer antigen 50(CA50)and carcinoembryonic antigen(CEA)were independent factors affecting gastric cancer.Based on the results of multivariate Logistic regression analysis,the risk prediction nomogram model of gas-tric cancer was constructed.The AUC of test set was 0.91,the accuracy rate was 100％,and the recall rate was 100％;the AUC of valida-tion set was 0.93,the accuracy rate was 93.63％,and the recall rate was 74.1％.The model has good prediction efficiency.Conclusion In this study,8 common predictors of gastric cancer were constructed,and the Lasso-logistic regression prediction model had good differen-tiation,which could be used to complete the early screening of gastric cancer based on the physical examination reports of patients.

Objective To investigate the effect of Yiqi Jiedu Recipe(YQ)on the proliferation,migration,and invasion of nasopharyngeal carcinoma cells,and to explore its mechanisms of action on proliferation,migration,and invasion through the TGF-β1/SMAD3 signaling pathway.Methods(1)The 5-8F cells were divided into four groups:solvent control group,YQ 0.5 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and 5-fluorouracil 2 μg·mL-1 group.Cell proliferation was monitored using real-time cell analysis(RTCA).Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using the Western Blot method.(2)The 5-8F cells were divided into five groups:solvent control group,TGF-β1 10 ng·mL-1 group,TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and LY3200882 10 μmol·L-1 group.Cell proliferation was monitored using RTCA.Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using Western Blot.(3)The nude mice were randomly assigned into the model group,YQ group,and 5-fluorouracil group.Subcutaneous injection of 5-8F cell suspension was performed to establish the xenograft nude mouse model of nasopharyngeal carcinoma.After the tumors reached a certain size,the 5-fluorouracil group received intraperitoneal injection of 5-Fu once every 2 days,while the other groups were orally administered corresponding drugs once a day for three consecutive weeks.Tumor volume was measured every 3 days.Western Blot was conducted to assess the protein expression levels of β-catenin,E-cadherin,and N-cadherin in the tissues of each group.Results Compared with the solvent control group,the proliferation curves of 5-8F cells in the YQ(0.5 mg·mL-1,1.0 mg·mL-1)groups showed a decrease.The migration and invasion abilities of the cells were both reduced(P＜0.05,P＜0.01).Additionally,the expression of E-cadherin protein significantly increased(P＜0.01),while the protein expression of β-catenin,N-cadherin,TGF-β1,and SMAD3 all decreased(P＜0.05,P＜0.01).Compared with the model group,the transplanted tumor volume of nasopharyngeal carcinoma in the YQ group significantly decreased(P＜0.05).Furthermore,the protein expression of β-catenin and N-cadherin in the transplanted tissues of the YQ group was significantly downregulated(P＜0.05,P＜0.01),while the expression of E-cadherin protein was significantly upregulated(P＜0.01).After the addition of the activator and inhibitor of TGF-β1 signaling pathway,compared with the YQ 1.0 mg·mL-1 group,the TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group showed a significant increase in the expression of TGF-β1,SMAD3,β-catenin,and N-cadherin proteins(P＜0.05,P＜0.01)and obvious enhancement of the abilities of cell proliferation,migration,and invasion(P＜0.01).Conclusion Yiqi Jiedu Recipe can inhibit the proliferation,migration,and invasion by regulating the TGF-β1/SMAD3 signaling pathway.

To improve the effectiveness of bedside localization of nasointestinal tube(NIT)and facilitate the placement of nasointestinal tube into jejunum,we established a procedure and composed a teaching verse for bedside placement of nasointestinal tube based on relevant classical literature and our own practices.Verse content:enteral nutrition means a successful strategy to improve the outcome in critically ill patient management,never hesitate to place nasointestinal tubes when necessary.There are several methods to deal with it,but popularizing it remains a long way off.Half-sitting and swallowing into the esophagus,freely withdrawing signifies the stomach cavity.Passing through the pylorus using light tension on the tube in the right lateral decubitus position.Arriving at the jejunum with low resistance in the left lateral decubitus position.What are the signs of intragastric coiling?Tube return out of nose is the initial observation,Failure of air insufflation indicates tube coiling.Dyeing location surpasses imaging.Vacuum test is the most sensitive,Sequential change from acid to base is specific.Methylene blue test is dramatical for localization.Combining three methods is enough to navigate.Abdominal plain film is the goldan standard and can still be used in ultrasonic era.3-D image establishes overall view.CT reveals the tube route exactly.The teaching verse has become a powerful tool for clinical teaching of manual nasointestinal tube placement in a concise and easy-to-remember form.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

This study aims to obtain two whole-genome sequences of enzootic nasal tumor virus of goats(ENTV-2)from Anhui Province and analyzed the genetic diversity of ENTV-2 gene.Nasal secretion samples and blood samples of six goats with enzootic nasal adenocarcinoma(ENA)were collected from a goat farm in Anhui Province.The total RNA was extracted by the TRIzol method.The DNA interference was removed by the two-step reverse transcription.The ENTV-2 was detec-ted by PCR.Then,two positive samples were selected and five pairs of primers were used to ampli-fy the whole-genome sequences of ENTV-2.After sequencing and splicing,two sequences were up-loaded to the database for comparative analysis with the sequences in the NCBI database.Finally,the genetic evolution tree was constructed.ENTV-2 was detected in the nasal secretion samples,but not in the blood of the six ENA goats.The ENTV-2 genes were approximately 7 400 bp in length,named ENTV-2AH1(DDBJ accession no.:LC762616)and ENTV-2AH2(DDBJ accession no.:LC762617),respectively.Two sequences showed 99.2％and 99.1％homology with the Fujian strain(ENTV-2FJ)and Guangxi strain(ENTV-2-DA0),respectively.They were in the same evo-lutionary branch.In this study,two whole-genome sequences of ENTV-2 were obtained in Anhui for the first time,which can help to further study the genetic diversity of ENTV-2 in China.

Objective:To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.