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*

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

Objective:To evaluate the effect of family intervention on self-management and glycaemic control in patients with type 2 diabetes mellitus (T2DM).Methods:Clinical interventional trials on the family intervention for T2DM patients were searched in PubMed, Medline, Embase, Cochrance libraries, the CNKI, and the Wan Fang Database from January 2016 to June 2023. Literature was screened according to the inclusion and exclusion criteria. Self-management behavior, BMI and glycated haemoglobin of T2DM patients were used as outcome indicators. Meta-analysis and mapping were performed using Review Manager 5.3 software. A systematic review of the literature on indicators of self-management behavior measured using other instruments except Summary of Diabetes Self-Care Activities.Results:A total of 1 342 relevant papers were retrieved and 13 papers were included in the analysis, involving 1 454 patients, 740 in the intervention group and 714 in the control group. Meta-analysis showed that the inclusion of home-based intervention helped adult T2DM patients to improve self-management ( WMD=5.03, 95% CI:4.43-5.63, P<0.001) and reduce glycated hemoglobin compared with the hospital-patient dichotomous model ( WMD=-0.77, 95% CI:-1.32--0.21, P=0.007), but the effect on BMI was unclear ( WMD=-0.38, 95% CI:-1.04-0.28, P=0.25). The results of the systematic review supported that home-based intervention improving self-management behaviors of adult T2DM patients. Conclusion:Family intervention can improve self-management behaviors and reduce glycated haemoglobin levels in adults T2DM patients.

Background Schizophrenic patients have metabolic disorders,impaired language and information processing function.Inflammatory factors may play an important role in the occurrence and development of schizophrenia.Objective To explore the relationship of the inflammatory factor levels with metabolic levels,language fluency and information processing function in patients with schizophrenia,so as to provide references for clinical understanding of the neuropathological mechanisms of schizophrenia.Methods A total of 96 patients with schizophrenia were included in the study group,who were hospitalized in the Fourth People's Hospital of Hefei from January 2021 to December 2022 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)and Mini-International Neuropsychiatric Interview(MINI)6.0.Meanwhile,population who underwent physical examination at the same hospital were included in the control group(n=42).A high-sensitivity multi factor electrochemiluminescence analyzer was used to detect the levels of inflammatory factors IL-4,IL-5,IL-7,IL-8,IL-10 and IL-13.A fully automated biochemical analyzer was used to detect the levels of metabolic indicators such as fasting blood glucose,triglycerides,high-density lipoprotein,apolipoprotein A,creatinine and urea nitrogen.Verbal fluency and information processing function of all participants were assessed by using Verbal Fluency Test(VFT)and Stroop Color Word Test(SCWT).Results There were statistically significant differences in the levels of IL-4,IL-5,IL-7,IL-8,IL-10,IL-13 and IL-15 between the study group and the control group(P<0.05).There were statistically significant differences in BMI,waist circumference,fasting blood glucose,triglycerides,high-density lipoprotein,urea nitrogen,apolipoprotein A and creatinine levels between the two groups(P<0.05).The differences in the correct number of household appliances,animals,fruits,vegetables,names starting with"water"and"self"in VFT between the two groups were statistically significant(P<0.05).The differences in point reaction time,character reaction time and character color reaction time in SCWT between the two groups were statistically significant(P<0.05).Correlation analysis showed that except for creatinine levels,the levels of IL-4 and IL-5 in patients with schizophrenia were correlated with other indicators(P<0.05).IL-7 levels were correlated with creatinine levels,household appliances,animals,fruits,correct number of names starting with"water"in VFT,point reaction time and word reaction time in SCWT(P<0.05).IL-8 levels were correlated with triglyceride levels,household appliances,animals,fruits,vegetables,correct number of names starting with"water"and"self"in VFT and word reaction time in SCWT(P<0.05).Except for creatinine levels and the correct number of names starting with"self",IL-10 levels were correlated with all other indicators(P<0.05).Except for creatinine and urea nitrogen levels,IL-13 levels were correlated with other indicators(P<0.05).Conclusion The levels of inflammatory factors in patients with schizophrenia may be related to their metabolic levels,language fluency and information processing function.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective:To survey the teaching ability of general practitioners(GPs) in community health centers of Shanghai, and its influencing factors.Methods:A questionnaire survey on the teaching ability of general practice trainers was conducted from January to February 2017. The participants of the survey were GPs with teaching experiences from community health centers in Shanghai selected by a stratified and proportional cluster sampling method. The questionnaire included two aspects: the general information and teaching ability of the participants. The influencing factors of teaching ability were analyzed by univariate and multivariate regression analysis.Results:A total of 1 138 GPs from 116 selected community health centers participated in the questionnaire survey, among whom 63.6% (724/1 138) worked in community teaching bases and 78.5% (893/1 138) had received training for trainers. The total score of teaching ability was 38.00 (30.00, 40.00). The score of the item"interesting in teaching"was (3.46±0.80), 75%—80% of the other questions answered "yes". The score of"application of multi-teaching methods"was (3.78±0.72). Multivariate analyses showed that working for 5—9 and 10—19 years [ OR=7.14 (2.47—11.81), P=0.003; OR=5.32 (1.30—9.33), P=0.009], working in community teaching bases [ OR=13.23 (9.88—16.57), P<0.001] and receiving training for trainers [ OR=17.76 (13.80—21.71), P<0.001] were influencing factors of teaching ability. Conclusion:The main problems related to teaching ability in community GPs are lack of teaching interest and the poor application of multi-teaching methods, the relevant training is necessary for them in the future.

With the increasing prevalence of atrial fibrillation (AF), the incidence of its complications, such as ischemic stroke and thromboembolism is also increasing. According to the two-way referral system proposed by health authorities, AF management should be carried out mainly in primary care settings;and studies show that general practitioners play an indispensable role in AF management. At present,however,the inappropriate anticoagulation,AF complications and risk awareness are three major problems in the primary care of AF management in China. This article reviews the status quo and future prospect of AF management in primary care to provide suggestions for better management of AF in primary care level.

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

Objective To explore the clinical features of cerebral hemorrhage associated with nephrotic syndrome (NS) as well as its underlying pathogenesis. Methods The clinical material of seven NS patients with cerebral hemorrhage were analyzed. Results The age of the seven patients was ranged from 5 to 56 years, including four male and three female. There were four patients with coagulopathy, six patients with elevated level of D-dimer and four patients with renal function impairment. Six patients had hyperlipidemia and four patients had severe proteinuria (>5 g/d). In the acute phase of hemorrhage onset, five patients developed cerebral hemorrhage in the lobes, two patients in the basal ganglia. Three patients were in coma on the first day of hemorrhage. On the 30th day after cerebral hemorrhage onset, four patients died and two patients had moderate cognitive dysfunction (modifed Rankin Scale, 3-5). Conclusion The patients of cerebral hemorrhage associated with NS may be in a serious illness state and have poor prognosis. Most of patients have elevated level of D-dimer, hyperlipidemia, and severe proteinuria, the biochemical abnormalities associated with NS. Most hemorrhages occur in the lobes which may be caused by coagulopathy.

Objective To survey the status and related demands of advanced clinical training among community general practitioners (GPs) in Shanghai.Methods A survey on the status and demands of advanced clinical training was conducted with a self-designed questionnaire among GPs in Minhang District and Jiading District of Shanghai from January to May 2016.The questionnaire included basic information , experience of advanced clinical training , satisfaction with training and training demands .Results Total 526 questionnaire were distributed and 478 valid questionnaires were returned with a response rate of 90.9%. Among the participants 202 (42.3%) had experience of advanced clinical study ; the training units were mainly secondary hospitals in Shanghai (69.3%, 140/202); 67.2%(131/195) participants considered that the previous training did not fully meet the needs of the community .There was significant difference in the training demands among participants with different ages , professional titles, and working years ( χ2＝12.754, 7.912, 4.501, all P＜0.01); those with younger age, higher education and shorter working years had higher training demands .Survey showed that 57.3%( 274/478 ) of participants demanded further studies in the future; 58.3%( 239/410) of them chose tertiary hospitals in Shanghai as training unit , 79.0%(321/406) chose internal medicine and geriatrics as training specialties , particularly in outpatient clinic (73.2%, 298/407); the length of study should be 3 months (32.8%, 132/402) or 6 months (27.6%, 111/402), and completed in segments (61.5%, 253/411).The purpose of training was mainly to upgrade clinical competence (94.2%, 258/272); busy working schedule (53.4%, 66/116) was the main reason for not intending the advanced clinical studies .Conclusions The community general practitioners in Shanghai have high demands for advanced clinical training .The training should meet the needs of clinical practice in community and the mode of study should be more flexible .