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.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.

Objective:To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD).Methods:A child who was admitted to the Linyi People′s Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46, XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c. 323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 ( NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion:The NR5A1: c. 323delA variant probably underlay the pathogenesis of 46, XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.

Liver failure is a common end-stage liver disease syndrome in clinical practice characterized by massive necrosis of hepatocytes leading to rapid liver failure, and it is currently believed that excessive inflammation and immune response are the core mechanisms of this disease. Endogenous lipid mediators are involved in the regulation of a variety of inflammatory processes, including initiation, maintenance, and regression, and eicosanoids and pro-decomposition lipid mediators, as well as their complex metabolic pathways and transduction signals, play a key role in the regulation of these processes. This article reviews the key role of endogenous lipid mediators in the pathophysiological mechanism of inflammation and immune dysfunction in liver failure and the potential significance and new therapeutic opportunities of lipid immune pathway in liver failure, in order to provide new ideas for the clinical diagnosis and treatment of liver failure.

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*

Objective:To establish a risk assessment model for recurrence and metastasis in patients with advanced nasopharyngeal carcinoma.Methods:A survival follow-up study was conducted using a COX regression model to analyze 242 patients with advanced nasopharyngeal carcinoma who were treated for the first time in the Fudan University Shanghai Cancer Center from March 1, 2012 to August 31, 2020. The mean age was (48.33±11.13) years, with 178 males and 64 females. The mean survival was (3.39±1.42) years. According to the random number table method, the enrolled subjects were divided into two groups, including 192 cases in the modeling group and 50 cases in the validation group. Venous blood was collected from patients before treatment, after the first treatment and during the follow-up period after treatment. The blood cell classification and blood biochemical indicators were analyzed. T test and Chi-square test were used to analyze the difference in indicators in prognosis of patients with recurrence and metastasis as the outcome of the study. Multivariate COX regression analysis was used to screen out the independent prognostic factors affecting the recurrence and metastasis of nasopharyngeal carcinoma patients, and the Nomogram models of recurrence and metastasis risk of patients in 2 years, 4 years and 6 years were constructed. The model C-Index of the modeling group and the validation group were calculated to evaluate the performance of the predictive model.Results:White blood cells ( P=0.028), lymphocyte counts ( P<0.001), neutrophils ( P=0.001), platelets ( P=0.046), albumin ( P<0.001), neutrophil/lymphocyte ratio ( P<0.001), platelet/lymphocyte ratio ( P<0.001), lymphocyte/monocyte ratio ( P<0.001), systemic immune inflammatory response index ( P<0.001), systemic inflammatory response index ( P<0.001), and prognostic nutritional index ( P=0.004) had statistically significant differences in the efficacy monitoring of patients; through multivariate COX regression analysis, it was found that the platelet/lymphocyte ratio ( HR 2.537, 95% CI 1.439-4.473) and the prognostic nutritional index ( HR 0.462, 95% CI 0.236-0.903) are important factors to predict the risk of recurrence and metastasis of patients. Combining the above indicators, the Nomogram risk assessment model was established. The C index of the modeling group was 0.698, and the C index of the validation group was 0.739. The calibration curves of the two groups showed good consistency. Conclusion:The Nomogram evaluation model can accurately predict the risk of recurrence and metastasis in patients with nasopharyngeal carcinoma, and provide a theoretical basis for evaluating the prognosis of clinical treatment.

Liver failure is a common severe liver disease syndrome in clinical practice and is one of the critical medical conditions in internal medicine. Massive hepatocyte death is the main pathological feature of liver failure, and its core mechanisms include endotoxin, immune response, and inflammatory cascade reaction. Effective regeneration of hepatocytes to compensate liver function is the physiological basis for promoting the good prognosis of liver failure, which directly affects the prognosis and quality of life of patients with liver failure. It has been found in clinical practice that liver failure patients with a low serum level of cholesterol tend to have an extremely high mortality rate, but as an index of hepatocyte anabolism, the association between cholesterol and hepatocyte regeneration has not been taken seriously. Based on the association between cholesterol and liver regeneration, this article reviews its significance and potential value in the clinical treatment of liver failure, in order to understand the pathogenesis of liver failure from another perspective and provide new ideas for the diagnosis and treatment of liver failure and the development of drugs.

Glycolysis plays an important role in the development and progression of liver diseases and shows varying degrees of enhancement in different liver diseases, and it is closely associated with mitochondrial dysfunction (oxidative phosphorylation deficiency and reactive oxygen species production), which helps to fill energy production deficiency caused by impaired oxidative phosphorylation. Therefore, it might be possible to search for potential new therapies for liver diseases through targeted regulation of the key factors in aerobic glycolysis, such as hexokinase 2, pyruvate kinase M2, and other regulatory pathways. From the perspective of the association between glycolysis and liver diseases, this article elaborates on the therapeutic significance and potential value of glycolysis in liver diseases, in order to provide new ideas for the diagnosis and treatment of liver diseases.

Objective:To search, evaluate and integrate the best evidence of exercise rehabilitation intervention after PCI in patients with acute myocardial infarction, so as to provide evidence-based basis for clinical doctors and nurses to intervene in exercise rehabilitation of patients.Methods:We searched PubMed, China National Knowledge Infrastructure, Wanfang Data and other domestic and foreign databases, guide websites and professional association websites about the evidence of exercise rehabilitation intervention in patients with acute myocardial infarction after PCI. The search period is from January 2010 to June 2021. The quality of the included literature was evaluated by two researchers, and the literature evidence in accordance with the quality standard was extracted.Results:A total of 20 articles were included, and 39 pieces of evidence were summarized from 11 aspects, such as the establishment of multidisciplinary team, evaluation, exercise prescription, exercise monitoring and so on.Conclusions:This study summarized the best evidence of exercise rehabilitation intervention in patients with acute myocardial infarction after PCI, and provided theoretical support for clinical practice. It is suggested to combine the clinical situation and patients' wishes to promote the transformation of the best evidence to clinical practice.

Acute liver failure is a serious and complex liver disease with a high short-term mortality rate. Its pathogenesis remains unknown and there is still a lack of effective drugs. Animal models play an important role in further revealing the pathogenesis of acute liver failure and the therapeutic mechanism of drugs, and the selection of experimental animals and preparation methods is the key to the effective implementation of research. This article summarizes the commonly used and new animal models of acute liver failure in recent years and the corresponding preparation methods and divides the animal models of acute liver failure into following four categories: chemical drug model, surgical model, infection model, and other models. Meanwhile, the above models are evaluated based on Terblanche and Hickman evaluation criteria for liver failure models, hoping to provide a reference for model selection and evaluation in basic research on this disease.