Objective To investigate the effect and mechanism of miR-195-5p on myocardial fibro-sis in rats with atrial fibrillation(AF).Methods A total of 72 male SD rats were randomly divid-ed into control group,AF group,negative control group,miR-195-5p inhibitor group,recombinant adeno-associated virus serotype 9(rAAV9)group(miR-195-5p inhibitor+rAAV9-negative con-trol),and combination group[miR-195-5p inhibitor+rAAV9-siRNA-SMAD homolog 7(Smad)],with 12 rats in each group.Except for the control group,the rats in the other groups were inflicted to construct AF model.After receiving corresponding intervention measures,elec-trocardiography was conducted to record the incidence and the duration of AF.HE staining and Masson staining were used to observe the pathological changes and fibrosis in the myocardial tis-sues,respectively.qRT-PCR was applied to detect the mRNA levels of miR-195-5p and Smad7,and Western blotting was performed to detect the expression of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,Collagen-Ⅰ and Collagen-Ⅲ in the myocardial tissues.Dual luciferase assay was used to verify the regulatory effect of miR-195-5p on Smad7.Results Compared with the control group,the AF group had significantly higher AF incidence(75.0％vs 0)and longer duration(27.02±2.65 s vs 0 s),larger collagen volume fraction(CVF)[(14.47±0.89)％vs(2.12±0.35)％],and increased expression levels of miR-195-5p(3.27±0.21 vs 1.00±0.10),TGF-β1(0.76±0.08 vs 0.23±0.04),Collagen-Ⅰ(0.58±0.07 vs 0.20±0.04),Collagen-Ⅲ(0.46±0.05 vs 0.11±0.02),p-Smad2/Smad2(0.92±0.10 vs 0.37±0.05),and p-Smad3/Smad3(0.65±0.06 vs 0.14±0.03),but notably decreased expression of Smad7 at mRNA(0.32±0.06 vs 1.02±0.09)and protein(0.19±0.03 vs 0.58±0.07)levels in the myocardial tissues(P＜0.05).The AF incidence and duration,CVF,miR-195-5p level,and protein levels of TGF-β1,Collagen-Ⅰ,Colla-gen-Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 were significantly decreased,and the mRNA and protein levels of Smad7 were significantly increased in the miR-195-5p inhibitor group than the AF group and the negative control group(P＜0.05).The combined treatment increased the inci-dence and duration of AF,CVF,myocardial TGF-β1,Collagen-Ⅰ,Collagen-Ⅲ,p-Smad2/Smad2 and p-Smad3/Smad3 expression levels,and decreased the mRNA and protein expressions of Smad7 when compared with the miR-195-5p inhibitor group and the rAAV9 group(P＜0.05).Conclusion Down-regulation of miR-195-5p alleviates myocardial fibrosis in AF rats probably by targeting Smad7 to inhibit TGF-β1 signaling.

Objective To investigate the effect and mechanism of miR-195-5p on myocardial fibro-sis in rats with atrial fibrillation(AF).Methods A total of 72 male SD rats were randomly divid-ed into control group,AF group,negative control group,miR-195-5p inhibitor group,recombinant adeno-associated virus serotype 9(rAAV9)group(miR-195-5p inhibitor+rAAV9-negative con-trol),and combination group[miR-195-5p inhibitor+rAAV9-siRNA-SMAD homolog 7(Smad)],with 12 rats in each group.Except for the control group,the rats in the other groups were inflicted to construct AF model.After receiving corresponding intervention measures,elec-trocardiography was conducted to record the incidence and the duration of AF.HE staining and Masson staining were used to observe the pathological changes and fibrosis in the myocardial tis-sues,respectively.qRT-PCR was applied to detect the mRNA levels of miR-195-5p and Smad7,and Western blotting was performed to detect the expression of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,Collagen-Ⅰ and Collagen-Ⅲ in the myocardial tissues.Dual luciferase assay was used to verify the regulatory effect of miR-195-5p on Smad7.Results Compared with the control group,the AF group had significantly higher AF incidence(75.0％vs 0)and longer duration(27.02±2.65 s vs 0 s),larger collagen volume fraction(CVF)[(14.47±0.89)％vs(2.12±0.35)％],and increased expression levels of miR-195-5p(3.27±0.21 vs 1.00±0.10),TGF-β1(0.76±0.08 vs 0.23±0.04),Collagen-Ⅰ(0.58±0.07 vs 0.20±0.04),Collagen-Ⅲ(0.46±0.05 vs 0.11±0.02),p-Smad2/Smad2(0.92±0.10 vs 0.37±0.05),and p-Smad3/Smad3(0.65±0.06 vs 0.14±0.03),but notably decreased expression of Smad7 at mRNA(0.32±0.06 vs 1.02±0.09)and protein(0.19±0.03 vs 0.58±0.07)levels in the myocardial tissues(P＜0.05).The AF incidence and duration,CVF,miR-195-5p level,and protein levels of TGF-β1,Collagen-Ⅰ,Colla-gen-Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 were significantly decreased,and the mRNA and protein levels of Smad7 were significantly increased in the miR-195-5p inhibitor group than the AF group and the negative control group(P＜0.05).The combined treatment increased the inci-dence and duration of AF,CVF,myocardial TGF-β1,Collagen-Ⅰ,Collagen-Ⅲ,p-Smad2/Smad2 and p-Smad3/Smad3 expression levels,and decreased the mRNA and protein expressions of Smad7 when compared with the miR-195-5p inhibitor group and the rAAV9 group(P＜0.05).Conclusion Down-regulation of miR-195-5p alleviates myocardial fibrosis in AF rats probably by targeting Smad7 to inhibit TGF-β1 signaling.

Objective To assess the prevalence and clinical features of nonalcoholic fatty liver disease(NAFLD)and its risk factors in patients with CHF,so as to provide the reference for early identification of NAFLD.Methods The data from 1120 CHF patients aged 14～89 was collected,including the general demographic information(age,gender,smoking status,height,weight,BMI,etc.),clinical diagnosis and treatment data(blood pressure,NYHA heart function classification,blood biochemical indicators,etc.),and medication use status.SPSS 27.0 was applied to analyze the clinical characteristics of CHF combined with NAFLD,and binary multivariate logistic regression was used to analyze the independent risk factors of CHF combined with NAFLD.Results Among the 1120 patients,634(56.6%)were male and 486(43.4%)were female.The prevalence of CHF patients with NAFLD was 25.0%.The results of univariate analysis showed that the weight of NAFLD patients BMI,systolic blood pressure,diastolic blood pressure,FPG,UA,left room expansion ratio,ALT,CHO,TG,obesity rate,hyperuricemia rate and β-blocker usage rate were all higher than those of non NAFLD patients.The age,BNP,HDL and ACEI/ARB/ARNI usage rate of NAFLD patients were lower than those of non NAFLD patients(all P<0.05).Logistic regression analysis showed that age(OR=0.988),FPG(OR=1.099),overweight(OR=3.497)and obesity(OR=9.193)were independent risk factors for CHF patients with NAFLD.Conclusion NAFLD may be a common complication in CHF patients,especially those who are young,have high FPG,overweight and obese.In the clinical practice,NAFLD screening,evaluation and management should be focused on CHF patients who are young,have high fasting blood sugar,overweight,and obese.

With the optimization of surgical technologies and postoperative management regimens, the number of lung transplantation has been significantly increased, which has become an important treatment for patients with end-stage lung disease. However, due to the impact of comprehensive factors, such as bronchial ischemia and immunosuppression, the incidence of airway stenosis after lung transplantation is relatively high, which severely affects postoperative survival and quality of life of lung transplant recipients. In recent years, with the improvement of perioperative management, organ preservation and surgical technologies, the incidence of airway stenosis after lung transplantation has been declined, but it remains at a high level. Early diagnosis and timely intervention play a significant role in enhancing clinical prognosis of patients with airway stenosis. In this article, the general conditions, diagnosis, treatment and prevention of airway stenosis after lung transplantation were reviewed, aiming to provide reference for comprehensive management of airway stenosis after lung transplantation and improving clinical prognosis of lung transplant recipients.

OBJECTIVE To construct a risk prediction model for non-compliance with inhaled medication in patients with chronic obstructive pulmonary disease （COPD）. METHODS A retrospective analysis was conducted on 365 COPD patients admitted to the cough and wheeze pharmaceutical care clinic of the First Hospital of Qinhuangdao from October 2021 to October 2023. The patients admitted from October 2021 to June 2023 were selected as the model group （n＝303）， and the patients admitted from July to October 2023 were selected as the validation group （n＝62）. The model group was divided into compliance subgroup （n＝126） and non-compliance subgroup （n＝177）. Univariate analysis combined with multivariate Logistic regression analysis were used to analyze the risk factors for non-compliance with inhaled formulations in patients； the risk prediction model was established through regression analysis， and the accuracy of the model prediction was evaluated based on the validation group of patients. RESULTS Multivariate Logistic regression analysis showed that simultaneous use of 2 inhaled formulations （OR＝3.730， 95%CI 1.996-6.971， P＜0.001）， the number of acute exacerbations within one year ≥2 （OR＝2.509， 95%CI 1.509-4.173， P＜0.001）， smoking （OR＝2.167， 95%CI 1.309-3.588， P＝0.003）， complicated with anxiety/depression （OR＝2.112， 95%CI 1.257-3.499， P＝0.004） and mMRC grading≥2 levels （OR＝1.701， 95%CI 1.014-2.853， P＝0.044） were risk factors for non-compliance with inhaled preparations. Based on this， a risk prediction model was established and the ROC curve was drawn. The areas under the curve of the model group and validation group were 0.836 and 0.928， and the overall accuracy of the model’s prediction was 88.71%. CONCLUSIONS The predictive model based on the simultaneous use of 2 inhaled formulations， the number of acute exacerbations within one year ≥2， smoking， complicated with anxiety/depression， mMRC grading ≥2 levels has certain predictive value for the risk of non-compliance with inhaled formulations for COPD patients.

OBJECTIVE To construct a risk prediction model for non-compliance with inhaled medication in patients with chronic obstructive pulmonary disease （COPD）. METHODS A retrospective analysis was conducted on 365 COPD patients admitted to the cough and wheeze pharmaceutical care clinic of the First Hospital of Qinhuangdao from October 2021 to October 2023. The patients admitted from October 2021 to June 2023 were selected as the model group （n＝303）， and the patients admitted from July to October 2023 were selected as the validation group （n＝62）. The model group was divided into compliance subgroup （n＝126） and non-compliance subgroup （n＝177）. Univariate analysis combined with multivariate Logistic regression analysis were used to analyze the risk factors for non-compliance with inhaled formulations in patients； the risk prediction model was established through regression analysis， and the accuracy of the model prediction was evaluated based on the validation group of patients. RESULTS Multivariate Logistic regression analysis showed that simultaneous use of 2 inhaled formulations （OR＝3.730， 95%CI 1.996-6.971， P＜0.001）， the number of acute exacerbations within one year ≥2 （OR＝2.509， 95%CI 1.509-4.173， P＜0.001）， smoking （OR＝2.167， 95%CI 1.309-3.588， P＝0.003）， complicated with anxiety/depression （OR＝2.112， 95%CI 1.257-3.499， P＝0.004） and mMRC grading≥2 levels （OR＝1.701， 95%CI 1.014-2.853， P＝0.044） were risk factors for non-compliance with inhaled preparations. Based on this， a risk prediction model was established and the ROC curve was drawn. The areas under the curve of the model group and validation group were 0.836 and 0.928， and the overall accuracy of the model’s prediction was 88.71%. CONCLUSIONS The predictive model based on the simultaneous use of 2 inhaled formulations， the number of acute exacerbations within one year ≥2， smoking， complicated with anxiety/depression， mMRC grading ≥2 levels has certain predictive value for the risk of non-compliance with inhaled formulations for COPD patients.

Notoginseng Radix et Rhizoma as a traditional Chinese herbal medicine has now been recognized and paid attention to by the pharmaceutical community.Modern phytochemical studies have shown that Panax notoginseng saponin is the main chemical compo-nent of Notoginseng Radix et Rhizoma.Modern pharmacological studies and clinical applications have revealed that it has anti-cancer,antioxidant and cardiovascular disease effects.In this study,we reviewed the research progress of the main chemical components and pharmacological effects of Notoginseng Radix et Rhizoma,with the aim of providing assistance for the clinical application and later stud-ies of Notoginseng Radix et Rhizoma.

Objective To explore the chain mediating effects of perceived stress and depression between Type D personality and quality of life in patients with Crohn's disease.Methods A total of 270 patients who visited our hospital for Crohn's disease from September 2022 to July 2023 were enrolled in this study with convenience sampling method.Perceived stress scale(PSS),patient health questionnaire 9(PHQ-9),Type D personality scale(DS-14),22-item inflammatory bowel disease quality-of-life questionnaire(IBDQOL-22)and the Crohn's disease activity index(CDAI)were employed in the survey.Pearson correlation or Spearman correlation analysis was used to explore the correlation between Type D personality,perceived stress,depression and quality of life in patients with Crohn's disease.Structural equation modelling was conducted using MPLUS 8.0 software,and confidence intervals were calculated using Bootstrap method for chain mediation analysis.Results A total of 269 patients with Crohn's disease had completed the survey.Total scores for IBDQOL,PHQ-9 and PSS were(82.7±13.7),3.0(1.0-7.0)and(24.4±7.5),respectively and the scores for the dimensions of negative emotion and social inhibition of DS-14 were(10.3±5.9)and(11.6±5.5),respectively.A total of 117(43.5%)patients were identified with Type D personality among 269 patients with Crohn's disease.The structural equation model revealed that Type D personality did not directly or significantly affect the quality of life(effect value=0.034,95%CI:-0.130 to 0.206).However indirectly,perceived stress and depression significantly mediated the relationship between Type D personality and quality of life,with a total indirect effect size of-0.307(95%CI:-0.423 to-0.207),a chain mediation effect size of-0.048(95%CI:-0.079 to-0.016),accounting for 15.6%of the total indirect effect.Conclusions The quality of life in patients with Crohn's disease is moderate.Perceived stress and depression both play a significant role between Type D personality and quality of life of the patients.Attention should be paid to the patients with Type D personality,hence the quality of life of patients could be improved through the intervention of stress perception and depression.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

OBJECTIVE: To explore the genetic basis for two patients from a family with BCL11A-related intellectual disability (BCL11A-ID). METHODS: Clinical data of the proband and her family members was analyzed. Chromosomal karyotyping analysis, trio-whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were carried out. For the suspected genetic variants, Sanger sequencing was used to verify, and pathogenicity assessment was conducted. RESULTS: The proband and her mother both had intellectual and language impairment, and their fetal hemoglobin (HbF) was significantly elevated. A heterozygous c.1327_c.1328delTC (p.Ser443Hisfs*128) variant was found in exon 4 of the BCL11A gene by WES, which has resulted in truncated expression of the encoded protein, and Sanger sequencing has verified that the variant was inherited from the mother. The variant was not found in related databases. The variant was predicted as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PM2+PP1). No karyotypic abnormality was found in the proband, her parents and brother, and no pathogenic CNVs was found in the proband and her parents. CONCLUSION The c.1327_c.1328delTC (p.Ser443Hisfs*128) variant may underlay the BCL11A-ID in the proband and her mother. This de novo variant has expanded the mutational spectrum of the BCL11A gene.
Humans ; Male ; Female ; Intellectual Disability/genetics* ; DNA Copy Number Variations ; Pedigree ; Mutation ; Transcription Factors/genetics* ; Mothers ; Repressor Proteins/genetics*