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*

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

AIM To investigate the flavor technology for Jiannaoning Mixture based on electronic tongue combined with preference index.METHODS Artificial sensory evaluation method was employed to screen the type of flavor agents,electronic tongue was applied to screening the consumption of flavor agents,and double-bottle preference test was adopted in the analysis of effects of rat gender and body weight on taste sensitivity,after which acceleration test was conducted.RESULTS Sucrose,stevioside and xylitol were taken as flavor agents,whose optimal consumptions were 15%,0.08%and 15%,respectively.Male rats demonstrated stable taste perception with the body weights of 220-280 g,and 0.08%stevioside displayed the best flavoring effect.After placed under accelerated condition for 3 months,the preparation exhibited stable appearance,pH value and contents of lobetyolin,salvianolic acid B,schizandrin,ruscogenin.CONCLUSION This stable and reliable method can provide reference for improving the terrible tastes of Jiannaoning Mixture and other oral liquid preparations of traditional Chinese medicines.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m^-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80^th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80^th percentile of estradiol.
Male ; Humans ; Body Mass Index ; Cross-Sectional Studies ; Gonadal Steroid Hormones ; Regression Analysis ; Estradiol ; Testosterone

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

OBJECTIVE: To analyze the factors related to the need for revision surgery due to nonunion or internal fixation failure after the treatment of distal femoral fracture with lateral locking plate (LLP). METHODS: Retrospective analysis was made of the clinical data of 130 cases with distal femoral fracture treated in our hospital from March 2005 to March 2019. SPSS 17.0 software (univariate analysis and Logistic regression analysis) was used to analyze the general condition [gender, age, body mass index (BMI), comorbidities, smoking history], injury related factors (energy of injury, open or closed injury, AO/OTA classification of fracture, fracture area distribution), operation related factors (operation time, reduction quality, postoperative infection) and construct characteristics of internal fixation. RESULTS: Twelve of 130 patients who were included in the study underwent revisional surgery, with a revision rate 9.2%. Univariate analysis showed that there were significant differences in age, BMI, AO/OTA classification, fracture area distribution, operation time, reduction quality, length of plate/fracture area, length of plate/fracture area above condylar between the two groups (P < 0.05). Logistic regression analysis showed that AO/OTA classification (A3), supracondylar involved fracture, operation time, reduction quality and the length of the plate/fracture area above the condylar were the possible related factors (P < 0.05). Destruction of the medial support ability of the femur in comminuted type A3 fracture, supra-condylar cortex area fracture involvement, increase of the bending stress of the LLP due to poor fracture reduction quality, damage of the blood supply of fracture end due to long-time operation, and stress concentration caused by insufficient length of plate might be risk factors of revisional operation after the treatment of distal femoral fracture with LLP. For the patients who needed revision after LLP treatment, additional use of medial minimally invasive plate fixation and autologous bone transplantation, change to intramedullary nail fixation were commonly used clinical treatment strategies. CONCLUSION AO/OTA classification (A3), supracondylar involved fracture, long operation time, poor reduction quality and the length of the plate/fracture area above the condylar were the possible predictive factors of the revision in distal femoral fractures treated with lateral locking plate. The appropriate application of the locking plate and operation strategy are the key to reduce the revision rate in distal femoral fractures.
Humans ; Femoral Fractures/etiology* ; Retrospective Studies ; Femoral Fractures, Distal ; Bone Plates/adverse effects* ; Fracture Fixation, Internal/adverse effects* ; Treatment Outcome

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.
Acupuncture Therapy ; Acupuncture Points