Background and Objectives: Long-term pathological myocardial hypertrophy (MH) seriously affects the normal function of the heart. Dronedarone was reported to attenuate left ventricular hypertrophy of mice. However, the molecular regulatory mechanism of dronedarone in MH is unclear. Methods: Angiotensin II (Ang II) was used to induce cell hypertrophy of H9C2 cells.Transverse aortic constriction (TAC) surgery was performed to establish a rat model of MH.Cell size was evaluated using crystal violet staining and rhodamine phalloidin staining.Reverse transcription quantitative polymerase chain reaction and western blot were performed to detect the mRNA and protein expressions of genes. JASPAR and luciferase activity were conducted to predict and validate interaction between forkhead box O3 (FOXO3) and protein kinase inhibitor alpha (PKIA) promoter. Results: Ang II treatment induced cell hypertrophy and inhibited sirtuin 1 (SIRT1) expression, which were reversed by dronedarone. SIRT1 overexpression or PKIA overexpression enhanced dronedarone-mediated suppression of cell hypertrophy in Ang II-induced H9C2 cells. Mechanistically, SIRT1 elevated FOXO3 expression through SIRT1-mediated deacetylation of FOXO3 and FOXO3 upregulated PKIA expression through interacting with PKIA promoter. Moreover, SIRT1 silencing compromised dronedaronemediated suppression of cell hypertrophy, while PKIA upregulation abolished the influences of SIRT1 silencing. More importantly, dronedarone improved TAC surgery-induced MH and impairment of cardiac function of rats via affecting SIRT1/FOXO3/PKIA axis. Conclusions Dronedarone alleviated MH through mediating SIRT1/FOXO3/PKIA axis, which provide more evidences for dronedarone against MH.

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

Objective To investigate the influencing factors for prognosis in patients with ST-segment elevation myocardial infarction(STEMI)with cardiogenic shock(CS)treated with extracorporeal membrane oxygenation(ECMO)combined with percutaneous coronary intervention(PCI).Methods The clinical data of patients with STEMI and CS who received ECMO combined with PCI treatment in the cardiology department of our hospital from May 2019 to July 2023 were retrospectively analyzed.According to the clinical outcome,the patients were divided into death group and survival group.The clinical data of the two groups was compared.Results The study analyzed a total of 37 patients,including 34 males with an average age of(52.4±11.7)years.There were 15 survivors and 22 deaths,with a survival rate of 40.5％.Compared with the death group,the survival group had higher systolic blood pressure[(100.6±17.7)mmHg vs.(84.6±22.0)mmHg,P=0.025]and diastolic blood pressure[(64.5±11.8)mmHg vs.(54.3±16.0)mmHg,P=0.043]at admission,and longer time from shock to ECMO support[4.0(3.0,10.0)h vs.2.8(1.9,5.1)h,P=0.048]and shorter time from ECMO support to passage of guide wire[1.5(0.5,3.0)h vs.3.8(2.3,7.0)h,P=0.008].The proportion of thrombolysis in myocardial infarction(TIMI)blood flow classification reaching level Ⅲ in the first frame is higher[9(60.0％)vs.5(22.7％),P=0.038].The level of serum alanine aminotransferase[261.8(100.1,944.9)U/L vs.106.6(27.4,193.3)U/L,P=0.033]and shorter time from aspartate aminotransferase[753.6(432.7,1533.0)U/L vs.244.7(113.7,594.3)U/L,P=0.009]in the death group are significantly higher than that in the survival group.Conclusions This study suggests that the time from ECMO support and ECMO support to passage of guide wire,and the first frame TIMI blood flow grading are important factors affecting the prognosis of STEMI patients with CS treated with ECMO combined with PCI.

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.
Rats ; Female ; Animals ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Kidney ; Arginine ; Water

OBJECTIVES: To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. METHODS: A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. RESULTS: Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. CONCLUSIONS Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.
Child ; Humans ; Retrospective Studies ; Syndrome ; Kidney Diseases, Cystic/genetics* ; Mutation ; Phenotype

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ²=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ²=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Shock, Septic/therapy* ; Hospitalization ; Intensive Care Units, Pediatric ; Hospitals, Pediatric

OBJECTIVE To explore the efficacy of Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction on adult chronic insomnia and its effect on hypnotic withdrawal.METHODS 187 patients with chronic insomnia were included for anal-ysis,including 102 in the traditional Chinese medicine(TCM)group and 85 in the western medicine group.The TCM group was trea-ted with Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction,while the western medicine group was treated with benzodiazepine under the consideration of doctor.The intervention period was 1 month,with assessments using the Pittsburgh Sleep Quality Index(PSQI)conducted before and after the intervention.Follow-up evaluations were performed at 3 months and 6 months re-spectively after the intervention.RESULTS There was no significant difference between the two groups at baseline.After the inter-vention,the PSQI scores of patients in both groups were significantly improved(P<0.01).Among them,the TCM group was better than the western medicine group in the improvement of sleep quality and sleeping pills,total PSQI score reduction(P<0.01).The re-sults of linear regression analysis showed that after controlling for confounding factors,the regression coefficients of the TCM group in two different models were1.821 and 1.922 respectively,and the former was statistically significant(P<0.05).By screening patients who took hypnotics at baseline in the TCM group and comparing them with those in the western medicine group,the influencing factors of hypnotic withdrawal were analyzed.During the 3-month follow-up,25 out of 39 patients in the TCM group and 17 out of 80 patients in the western medicine group had hypnotic withdrawal(χ2= 19.25,P<0.001);during the 6-month follow-up,23 of the 39 patients in the TCM group and 18 of the 79 patients in the western medicine group had hypnotic withdrawal(χ2= 13.53,P<0.001),the with-drawal rate of patients in the TCM group was significantly higher than that in the western medicine group.Further regression analysis showed that after adjusting for confounding factors,the results showed that the western medicine group had a significantly higher rate of not withdrawal than the TCM group at 3 months(OR=5.50,95%CI:2.30～13.72)and 6 months(OR=6.43,95%CI:2.54～17.77),and the results were statistically different(P<0.05).CONCLUSION Sour Jujube Seed Decoction combined with Huangli-an Wendan Decoction is effective in treating adult chronic insomnia and assisting in hypnotic withdrawal.

OBJECTIVE: To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics. METHODS: Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A RESULTS: Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA CONCLUSION Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.
Animals ; Diabetes Mellitus, Experimental ; Drugs, Chinese Herbal ; Glycolipids ; Liver ; Metabolic Diseases ; Rats ; Rats, Sprague-Dawley ; Transcriptome/genetics*

Abstract: Objective To analyze the industry characteristics of new occupational pneumoconiosis in Foshan from 2007 to Methods 2021. The data of new cases of occupational pneumoconiosis in Foshan City from 2007 to 2021 were obtained from “ ” ， “ the China Disease Prevention and Control Information System subsystem the Occupational Disease and Health Hazardous ”， Results Factors Monitoring Information System and the industry characteristics of the cases were analyzed. From 2007 to ， ， （ ） 2021 there were 886 new cases of occupational pneumoconiosis in Foshan mainly include silicosis 68.3% in males （ ）， （ ） 94.2% and stage Ⅰ pneumoconiosis cases 75.9% . The median age of cases at the time of diagnosed disease was 47 years ， old and the median working age of dust exposure was 11.2 years. The enterprises where all cases are located involve eight top ， ； ， - industry categories of which manufacturing industry accounted for 97.6% and 30 major industry categories of which non （ ） ， metallic mineral products industry was the highest 60.5% . There were 554 sporadic cases and 332 cluster cases and the ， ， Conclusion industries were mainly non-metallic mineral products accounting for 55.0% and 69.6% respectively. ， - Occupational pneumoconiosis in Foshan is dominated by silicosis and the key industries are non metallic mineral products.

OBJECTIVE: To investigate the changes of bone mineral density (BMD) and serum bone turnover factor in newly diagnosed systemic lupus erythematous (SLE) patients. METHODS: Eighty newly diagnosed SLE patients and 80 age and gender matched healthy controls were enrolled. None of the SLE patients had ever received glucocorticoid, immunosuppressive agents or vitamin D. BMD was measured at radius,lumbar spine and hip by dual X ray absorptiometry (DXA). Bone turnover markers including serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b),bone alkaline phosphatase (BAP) and 25-hydroxy vitamin D3 (25-OH-VD3) were measured by enzyme-linked immunosorbent assay (ELISA). Logistic regression was employed to analyze the risk factors associated with decreased BMD. RESULTS: Mean age of the SLE patients was (32.8±12.4) years, and 85% were female, none of whom were post-menopausal. BMD was significantly reduced in all the measured sites, compared with the healthy controls. Sixteen (20%) of the patients were osteopenic in at least one site measured locations. The serum levels of 25-OH-VD3 were markedly reduced in the newly diagnosed SLE patients than those of the normal controls [(46.1+12.3) nmol/L vs. (25.4+11.2) nmol/L, P<0.001)]. The serum levels of 25-OH-VD3 in the SLE patients with nephritis were much lower than those without nephritis (P=0.04). A significant negative correlation was demonstrated between the serum concentration of 25-OH-VD3 and the disease activity scores as measured by SLE disease activity index (SLEDAI) (r=-0.3,P=0.001). The serum TRAP5b concentration was positively correlated with SLEDAI (r=0.435,P=0.003). Age (P=0.058) and SLEDAI (P=0.085) were probably associated with decreased BMD in Logistic regression analysis. CONCLUSION The study showed reduced BMD in untreated SLE patients. The role of chronic inflammation was of probable importance in bone metabolism.
Absorptiometry, Photon ; Adult ; Bone Density ; Bone Diseases, Metabolic ; Bone Remodeling ; Female ; Humans ; Lupus Erythematosus, Systemic/physiopathology* ; Male ; Middle Aged ; Young Adult